Improvement of Aglycone π-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists

Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar K_D values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as ¹H,¹⁵N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.     

Gender gaps in scientific performance: a longitudinal matching study of health sciences researchers

Scientometrics - The existence of gender disparities in academia is well documented. Many explanations have been proposed and productivity is one of the most used variables to explain a possible...     

Bio-based polyurethane films using white dextrins

Several new eco-friendly materials have the potential to replace conventional petroleum-derived materials and monomers. Among them are natural polysaccharides. The use of polysaccharides in polyurethane (PU) synthesis has not yet been studied extensively, even though as multihydroxyl compounds, they can easily serve as crosslinkers in PU synthesis. One naturally occurring (hyper-)branched polymer is amylopectin, a component of starch. In this work, we report the PU synthesis and film-forming capacity using the asymmetric cyclic aliphatic diisocyanate—isophorone diisocyanate (IPDI) with acetylated and pristine partially hydrolyzed amylopectin/white dextrin (AVEDEX W80) as a crosslinker. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47454.     

Improved compressed sensing reconstruction for $$^{19}$$ F magnetic resonance imaging

Magnetic Resonance Materials in Physics, Biology and Medicine - In magnetic resonance imaging (MRI), compressed sensing (CS) enables the reconstruction of undersampled sparse data sets. Thus,...     

Quantifying the Error of Light Transport Algorithms

This paper proposes a new methodology for measuring the error of unbiased physically based rendering algorithms. The current state of the art includes mean squared error (MSE) based metrics and visual comparisons of equal‐time renderings of competing algorithms. Neither is satisfying as MSE does not describe behavior and can exhibit significant variance, and visual comparisons are inherently subjective. Our contribution is two‐fold: First, we propose to compute many short renderings instead of a single long run and use the short renderings to estimate MSE expectation and variance as well as per‐pixel standard deviation. An algorithm that achieves good results in most runs, but with occasional outliers is essentially unreliable, which we wish to quantify numerically. We use per‐pixel standard deviation to identify problematic lighting effects of rendering algorithms. The second contribution is the error spectrum ensemble (ESE), a tool for measuring the distribution of error over frequencies. The ESE serves two purposes: It reveals correlation between pixels and can be used to detect outliers, which offset the amount of error substantially.     

Complexity of coordinated beamforming and scheduling for OFDMA based heterogeneous networks

Wireless Networks - Coordination is foreseen to be an important component of future mobile radio networks. It is especially relevant in heterogeneous networks, where high power base stations...     

Understanding the impact of texture on the micromechanical anisotropy of laser powder bed fused Inconel 718

Journal of Materials Science - The manufacturability of metallic alloys using laser-based additive manufacturing methods such as laser powder bed fusion has substantially improved within the last...     

Multidisciplinary shape optimization of ductile iron castings by considering local microstructure and material behaviour

During the casting process and solidification of ductile iron castings, a heterogeneous microstructure is formed throughout the casting. This distribution is strongly influenced by the item geometry and the process related factors, as chemical composition and local solidification conditions. Geometrical changes to the geometry of the casting thus alters the local mechanical behavior and properties, as well as the distribution of stresses and strains when the casting is subjected to load. In order to find an optimal geometry, e.g. with reduced weight and increased load-bearing capacity, this interdependency between geometry and local material behavior needs to be considered and integrated into the optimization method. In this contribution, recent developments in the multidisciplinary integration of casting process simulation, solidification and microstructure modelling, microstructure-based material characterization, finite element structural analyses with local material behavior and structural optimization techniques are presented and discussed. The effect and relevance of considering the local material behavior in shape optimization of ductile iron castings is discussed and evidenced by an industrial application. It is shown that by adopting a multidisciplinary optimization approach by integration of casting simulation and local material behavior into shape optimization, the potential of the casting process to obtain components with high performance and reliability can be enabled and utilized.