A validated model for a pin-slot clearance joint

The numerical modeling of joints with a certain amount of clearance and a subsequent validation of the model are important for accurate multibody simulations. For such validated modeling, not only the kinematic constraints, but also the contact models, are important. If a joint has no clearance, it is assumed to be ideal. However, in real applications, there is frequently some clearance in the joints. Adding clearance and kinematic conditions to a pin-slot joint significantly increases the number of kinematic and contact parameters. Consequently, the resulting kinematics and the contact forces can vary significantly with regard to the selection of those parameters. This research covers the development of a validated model for a pin-slot clearance joint. Different kinematic constraints and contact models are discussed. The presented model is an experimentally validated one for a pin-slot clearance joint that is commonly used in safety-critical applications like electrical circuit breakers. Special attention is given to the Hertz, Kelvin–Voigt, Johnson, and Lankarani–Nikravesh contact models. When comparing different contact models within numerical approaches and comparing the results with experimental data, significant differences in the results were observed. With a validated model of a pin-slot clearance joint, a physically consistent numerical simulation was obtained.     

A click-flipped enzyme substrate boosts the performance of the diagnostic screening for Hunter syndrome

We report on the unexpected finding that click modification of iduronyl azides results in a conformational flip of the pyranose ring, which led to the development of a new strategy for the design of superior enzyme substrates for the diagnostic assaying of iduronate-2-sulfatase (I2S), a lysosomal enzyme related to Hunter syndrome. Synthetic substrates are essential in testing newborns for metabolic disorders to enable early initiation of therapy. Our click-flipped iduronyl triazole showed a remarkably better performance with I2S than commonly used O-iduronates. We found that both O- and triazole-linked substrates are accepted by the enzyme, irrespective of their different conformations, but only the O-linked product inhibits the activity of I2S. Thus, in the long reaction times required for clinical assays, the triazole substrate substantially outperforms the O-iduronate. Applying our click-flipped substrate to assay I2S in dried blood spots sampled from affected patients and random newborns significantly increased the confidence in discriminating between these groups, clearly indicating the potential of the click-flip strategy to control the biomolecular function of carbohydrates.

Click-triggered flip of the conformation of a sulfated iduronyl azide afforded a superior enzyme substrate to screen for Hunter syndrome.     

Sulfation of deoxynivalenol,its acetylated derivatives,and T2-toxin

The synthesis of several sulfates of trichothecene mycotoxins is presented. Deoxynivalenol (DON) and its acetylated derivatives were synthesized from 3-acetyldeoxynivalenol (3ADON) and used as substrate for sulfation in order to reach a series of five different DON-based sulfates as well as T2-toxin-3-sulfate. These substances are suspected to be formed during phase-II metabolism in plants and humans. The sulfation was performed using a sulfuryl imidazolium salt, which was synthesized prior to use. All protected intermediates and final products were characterized via NMR and will serve as reference materials for further investigations in the fields of toxicology and bioanalytics of mycotoxins.