Diamondoid Amino Acid-Based Peptide Kinase A Inhibitor Analogues

The incorporation of diamondoid amino acids (DAAs) into peptide-like drugs is a general strategy to improve lipophilicity, membrane permeability, and metabolic stability of peptidomimetic pharmaceuticals. We designed and synthesized five novel peptidic DAA-containing kinase inhibitors of protein kinase A using a sophisticated molecular dynamics protocol and solid-phase peptide synthesis. By means of a thermophoresis binding assay, NMR, and crystal structure analysis, we determined the influence of the DAAs on the secondary structure and binding affinity in comparison to the native protein kinase inhibitor, which is purely composed of proteinogenic amino acids. Affinity and binding pose are largely conserved. One variant showed 6.5-fold potency improvement, most likely related to its increased side chain lipophilicity. A second variant exhibited slightly decreased affinity presumably due to loss of hydrogen-bond contacts to surrounding water molecules of the first solvation shell.     

Precipitate number density determination in microalloyed steels by complementary atom probe tomography and matrix dissolution

Journal of Materials Science - Particle number densities are a crucial parameter in the microstructure engineering of microalloyed steels. We introduce a new method to determine nanoscale...     

From Emerson-Lei automata to deterministic,limit-deterministic or good-for-MDP automata

Innovations in Systems and Software Engineering - The topic of this paper is the determinization problem of $$omega $$ -automata under the transition-based Emerson-Lei acceptance (called TELA),...     

Relationship Between Ultralow Friction of Mesogenic-Like Fluids and Their Lateral Chain Length

Mesogenic fluids (MFs) may have a great potential for technical applications to increase the energy efficiency and to prevent wear. Aim of the present work was to study a homologous series of mesogenic-like fluids to evaluate the influence of the chemical structure on the tribological behavior. Rheological measurements were additionally performed to correlate the tribological properties with the viscosity and flow behavior. Raman spectroscopy and differential scanning calorimetry measurements were used to characterize the MFs. Furthermore, the surface topography of the wear scar was studied by profilometry. The results were summarized and hence an approach was made to describe the several mechanisms which may lead to the observed tribological results. This work shows that a better understanding of the tribological behavior of these MFs is essential to develop new lubricants.     

A comment to the paper by Waltman et al., Scientometrics, 87, 467–481, 2011

In reaction to a previous critique (Opthof and Leydesdorff, J Informetr 4(3):423–430, 2010), the Center for Science and Technology Studies (CWTS) in Leiden proposed to change their old “crown” indicator in citation analysis into a new one. Waltman (Scientometrics 87:467–481, 2011a) argue that this change does not affect rankings at various aggregated levels. However, CWTS data is not publicly available for testing and criticism. Therefore, we comment by using previously published data of Van Raan (Scientometrics 67(3):491–502, 2006) to address the pivotal issue of how the results of citation analysis correlate with the results of peer review. A quality parameter based on peer review was neither significantly correlated with the two parameters developed by the CWTS in the past citations per paper/mean journal citation score (CPP/JCSm) or CPP/FCSm (citations per paper/mean field citation score) nor with the more recently proposed h-index (Hirsch, Proc Natl Acad Sci USA 102(46):16569–16572, 2005). Given the high correlations between the old and new “crown” indicators, one can expect that the lack of correlation with the peer-review based quality indicator applies equally to the newly developed ones.     

Liquid sensing properties of melt processed polypropylene/poly(ε-caprolactone) blends containing multiwalled carbon nanotubes

The sensing properties of polypropylene (PP)/poly(ε-caprolactone) (PCL) blends containing multiwalled carbon nanotubes (MWNT) were studied in terms of their electrical resistance change in presence of liquids (solvents). The preparation of co-continuous blends based on the double percolation concept was done by melt mixing of electrically conductive PCL composites containing 3 wt.% MWNT and neat PP in ratios of 30:70, 40:60, and 50:50. The electrical resistance change of the PCL-MWNT composites and blends was monitored in a solvent immersion/drying cycle. Various solvents, such as n-hexane, ethanol, methanol, water, toluene, chloroform, and tetrahydrofuran were successfully detected, yielding different responses and reversibility of the resistance changes.PP and PCL were tested separately for solvent sorption using ethanol and n-hexane, both showing a low sorption of n-hexane. Ethanol sorption was large for PCL and almost absent for PP. The 50/50 blend composites with 3 wt.% MWNT in the PCL phase presented larger resistance changes for n-hexane, showing larger sensing ability for this solvent compared to PCL composites with 1 and 3 wt.% loadings. The opposite response was observed for immersion in ethanol where the PCL-MWNT composites showed larger changes than the blends. As the ratio of the conductive PCL phase over PP in the blend composition (i.e. the overall MWNT content) decreased, larger resistance changes were observed. The liquid sensing properties of compression-moulded discs and melt-drawn filaments were compared indicating higher responses for the discs.     

Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates

In vivo transcranial and noninvasive cavitation detection with blood-brain barrier (BBB) opening in nonhuman primates is hereby reported. The BBB in monkeys was opened transcranically using focused ultrasound (FUS) in conjunction with microbubbles. A passive cavitation detector, confocal with the FUS transducer, was used to identify and monitor the bubble behavior. During sonication, the cavitation spectrum, which was found to be region-, pressure-, and bubble-dependent, provided real-time feedback regarding the opening occurrence and its properties. These findings demonstrate feasibility of transcranial, cavitation-guided BBB opening using FUS and microbubbles in noninvasive human applications.