The dynamics of interdisciplinary research fields: the case of river research

Interdisciplinarity results from dynamics at two levels. Firstly, research questions are approached using inputs from a variety of disciplinary fields. Secondly, the results of this multidisciplinary research feed back into the various research fields. This may either contribute to the further development of these fields, or may lead to disciplinary reconfiguration. If the latter is the case, a new interdisciplinary field may emerge. Following this perspective, the scientific landscape of river research and river science is mapped to assess to which current river research is a multi-disciplinary endeavor, and to which extent it results in a new emerging (inter)disciplinary field of river science. The paper suggests that this two level approach is a useful method to study interdisciplinary research and, more generally, disciplinary dynamics. With respect to river research, we show that it is mainly performed in several fields (limnology, fisheries & fish research, hydrology & water resources, and geomorphology) that hardly exchange knowledge. The different river research topics are multidisciplinary in nature, as they are shared by different fields. However, river science does not emerge as an interdisciplinary field, and often-mentioned new interdisciplinary fields such as hydroecology or hydromorphology are not (yet) visible. There is hardly any involvement of social within river research. Finally, the field of ecology occupies a central position within river research, whereas an expected engineering field is shown absent. This together may signal the acceptance of the ecosystem-based paradigm in river management, replacing the traditional engineering paradigm.     

On the implementation of nonseparable two-dimensional Haar wavelettransforms

We introduce a transformation to localize the equations defining the successive levels of the Mallat (1989) pyramid for two-dimensional (2-D) Haar wavelets. We propose a methodology for implementing these wavelet transforms in parallel architectures like systolic arrays. More specifically, we show that there is a perfect match between the wavelet algorithms and the multiphase multirate array (MPRA) architectures     

α-Galactosidase a Deficiency in Fabry Disease Leads to Extensive Dysregulated Cellular Signaling Pathways in Human Podocytes

Fabry disease (FD) is caused by mutations in the α-galactosidase A (GLA) gene encoding the lysosomal AGAL enzyme. Loss of enzymatic AGAL activity and cellular accumulation of sphingolipids (mainly globotriaosylcermide) may lead to podocyturia and renal loss of function with increased cardiovascular morbidity and mortality in affected patients. To identify dysregulated cellular pathways in FD, we established a stable AGAL-deficient podocyte cell line to perform a comprehensive proteome analysis. Imbalanced protein expression and function were analyzed in additional FD cell lines including endothelial, epithelial kidney, patient-derived urinary cells and kidney biopsies. AGAL-deficient podocytes showed dysregulated proteins involved in thermogenesis, lysosomal trafficking and function, metabolic activity, cell-cell interactions and cell cycle. Proteins associated with neurological diseases were upregulated in AGAL-deficient podocytes. Rescues with inducible AGAL expression only partially normalized protein expression. A disturbed protein expression was confirmed in endothelial, epithelial and patient-specific cells, pointing toward fundamental pathway disturbances rather than to cell type-specific alterations in FD. We conclude that a loss of AGAL function results in profound changes of cellular pathways, which are ubiquitously in different cell types. Due to these profound alterations, current approved FD-specific therapies may not be sufficient to completely reverse all dysregulated pathways.     

Focussing product innovation and fostering economies of scale based on adaptive product platforms

Current concepts to achieve product commonality follow static approaches. To achieve economies of scale, standards are defined across the product program. However, these standards typically need to be compromised at new product introductions due to unforeseen innovations and economies of scale decrease over time. Accordingly platform standards need to be re-defined.This paper presents an approach for adaptive product platforms. Degrees of freedom in product and process design are managed pro-actively based on functional and technological models. This way adaptivity towards product innovation can be ensured. The concept of adaptive modular platforms is explained based on a practical application.     

Size‐Mediated Effects of Water‐Flow Velocity on Riverine Fish Species

We applied species sensitivity distributions (SSDs), commonly used in chemical risk assessment, to quantify the impact of water‐flow velocity on the presence of fish species in a river. SSDs for water‐flow velocity were derived from observational field data (maximal velocity at which species occur, V_max) and laboratory measurements (critical swimming velocity, V_crit). By calculating the potentially affected fraction of the fish species of the river Rhine, effects of water‐flow velocity on different life stages and guilds were estimated. V_max values for adults were significantly higher than those for juveniles and larvae. At water‐flow velocity of 60 cm s⁻¹, half of the adults were affected, while half of the non‐adult life stages were affected at velocities of 25 to 29 cm s⁻¹. There was a positive correlation between body size and fish tolerance to water‐flow. As expected, rheophilic species tolerated higher water‐flow velocities than eurytopic and limnophilic species. Maximal velocities measured in littoral zones of the Rhine were, on average, 10 cm s⁻¹, corresponding to an affected fraction of 2%. An increase in water‐flow velocity up to 120 cm s⁻¹ as a result of passing vessels caused an increase in affected species to 75%. For a successful ecological river management, the SSD method can be used to quantify the trait‐mediated effects of water‐flow alterations on occurring species enabling to compare and rank the effects of chemical and physical stress. Copyright © 2014 John Wiley & Sons, Ltd.     

Generation and Characterization of a Polyclonal Human Reference Antibody to Measure Anti-Drug Antibody Titers in Patients with Fabry Disease

Male patients with Fabry disease (FD) are at high risk for the formation of antibodies to recombinant α-galactosidase A (AGAL), used for enzyme replacement therapy. Due to the rapid disease progression, the identification of patients at risk is highly warranted. However, currently suitable references and standardized protocols for anti-drug antibodies (ADA) determination do not exist. Here we generate a comprehensive patient-derived antibody mixture as a reference, allowing ELISA-based quantification of antibody titers from individual blood samples. Serum samples of 22 male patients with FD and ADAs against AGAL were pooled and purified by immune adsorption. ADA-affinities against agalsidase-α, agalsidase-β and Moss-AGAL were measured by quartz crystal microbalance with dissipation monitoring (QCM-D). AGAL-specific immune adsorption generated a polyclonal ADA mixture showing a concentration-dependent binding and inhibition of AGAL. Titers in raw sera and from purified total IgGs (r² = 0.9063 and r² = 0.8952, both p < 0.0001) correlated with the individual inhibitory capacities of ADAs. QCM-D measurements demonstrated comparable affinities of the reference antibody for agalsidase-α, agalsidase-β and Moss-AGAL (KD: 1.94 ± 0.11 µM, 2.46 ± 0.21 µM, and 1.33 ± 0.09 µM, respectively). The reference antibody allows the ELISA-based ADA titer determination and quantification of absolute concentrations. Furthermore, ADAs from patients with FD have comparable affinities to agalsidase-α, agalsidase-β and Moss-AGAL.     

A test of the "epinephrine hypothesis" in humans

The absorbed gamma dose rate in air 1 m above soil due to natural gamma emitters and 137Cs from the Chernobyl accident was determined inside a Quercus conferta Kit ecosystem in Northern Greece by combination of Monte Carlo simulations with the MCNP code and in-situ gamma spectrometry measurements. The total absorbed gamma dose rate in air is about 64 nGy h(-1), where 40% of this value is due to 137Cs and 60% to natural gamma emitters. The Monte Carlo simulations indicated that the gamma absorbed dose rate in air due to 137Cs is mainly due (70%) to unscattered radiation and to a lesser extent (30%) to the scattered radiation. The results obtained with the Monte Carlo simulations for the unscattered radiation were in very good agreement with the experimental values deduced by in-situ gamma spectrometry measurements. From the combination of the Monte Carlo simulations and in-situ gamma spectrometry measurements a conversion factor C = 1 nGy h(-1)/kBq m(-2) was deduced for 137Cs. This factor must be used with caution and only for forest sites similar to the one used for this work.