Biological Evaluation and X‐ray Co‐crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase,an Enzyme from the Redox Metabolism of Trypanosoma

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure‐based design. The best inhibitors were freely soluble and showed competitive inhibition constants (K_i) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half‐maximal inhibitory concentration, IC₅₀) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X‐ray co‐crystal structures confirmed the binding of the ligands to the hydrophobic wall of the “mepacrine binding site” with the new, solubility‐providing vectors oriented toward the surface of the large active site.     

Cavitation bubble dynamics in non‐Newtonian fluids

Cavitation phenomena play important roles in many areas of science and engineering. The most interesting effect of the non‐Newtonian properties of the liquid is the reduction of cavitation damage and noise. This article reviews experimental and theoretical efforts to understand such phenomena. Two major areas of research are described, namely the dynamics of cavitation bubbles oscillating in a liquid of infinite extent, and the behavior of bubbles collapsing near rigid walls. POLYM. ENG. SCI., 2009. © 2008 Society of Plastics Engineers     

Non-destructive nuclear magnetic resonance image study of belly bursting in herring (Clupea harengus)

Herring (Clupea harengus) captured during the heavy feeding spring season were examined by magnetic resonance imaging (MRI) analysis. MRI was performed at room temperature on the frozen-thawed herring for approximately 50 h. The results showed that the stomachs were filled with prey and that they were very resistant to degradation. The ventral muscle, on the other hand, together with the upper part of the intestine (as confirmed during collection of samples on board fishing vessels), seemed to be the most sensible structures where the autolysis commenced and extended to the rest of the abdominal cavity.     

Domain Switching During Electromechanical Poling in Lead Zirconate Titanate Ceramics

In many polycrystalline piezoelectric ceramics, domain switching during the poling process leads to the development of a macroscopic polarization and piezoelectric behavior. Traditionally, poling involves the application of electric fields across two parallel electrodes. In the present work, a radial mechanical compressive stress is applied transverse to the electric field, increasing the potential for domain alignment during poling by taking advantage of ferroelasticity. Experiments demonstrate that poling of lead zirconate titanate using a combination of an electric field and a transverse mechanical compressive stress increases the d ₃₃ coefficient from 435 to 489 pC/N. Using neutron diffraction and pole figure inversion methods, the degree of non-180° domain switching is described using pole density distributions of the tetragonal c -axis (002). The degree of 002 domain alignment parallel to the electric field after the electromechanical poling process increases from 1.30 multiples of a random distribution (mrd) to >1.40 mrd at stresses exceeding 40 MPa.     

Augmented low-rank methods for gaussian process regression

Applied Intelligence - This paper presents techniques to improve the prediction accuracy of approximation methods used in Gaussian process regression models. Conventional methods such as...     

25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor

4-(2-((2-hydroxybenzyl)amino)ethyl)-2,5-dimethoxybenzonitrile (25CN-NBOH) was first reported as a potent and selective serotonin 2A receptor (5-HT_2AR) agonist in 2014, and it has since found extensive use as a pharmacological tool in a variety of in vitro, ex vivo and in vivo studies. 25CN-NBOH is readily available from a synthetic perspective using standard chemical transformations, and displays favorable physiochemical properties in terms of stability and solubility. Due to its superior selectivity for 5-HT_2AR, 25CN-NBOH has been used to investigate the effects of selective 5-HT_2AR activation in vivo, and has thus become an important pharmacological tool for the exploration of 5-HT_2AR signaling in a range of animal models. In the present review, we outline the discovery of 25CN-NBOH, its pharmacological profile and major findings from studies where it has been used.     

Tracking Twin Boundary Jerky Motion at Nanometer and Microsecond Scales

The jerky motion of twin boundaries in the ferromagnetic shape memory alloy Ni-Mn-Ga is studied by simultaneous measurements of stress and magnetic emissions (ME). A careful design of the experimental conditions results in an approximately linear relationship between the measured ME voltage and the nm-scale volumes exhibiting twinning transformation during microsecond-scale abrupt “avalanche” events. This study shows that the same distributions of ME avalanches, related to features of jerky twin boundary motion, are found both during and between stress drop events. Maximum likelihood analysis of statistical distributions of several variables reveals a good fit to power laws truncated by exponential functions. Interestingly, the characteristic cutoffs described by the exponential functions are in the middle of the distribution range. Further, the cutoff values can be related to the physical characteristics of the studied problem. Particularly, the cutoff of amplitudes of ME avalanches matches the value predicted by high rate magnetic pulse tests performed under much larger driving force values. This observation implies that avalanches during slow rate twin boundary motion and velocity changes observed by high rate tests represent the same behavior and can be described by the same theory.     

Structural Explanation of the Dielectric Enhancement of Barium Titanate Nanoparticles Grown under Hydrothermal Conditions

When synthesized under certain conditions, barium titanate (BaTiO₃, BTO) nanoparticles are found to have the non-thermodynamic cubic structure at room temperature. These particles also have a several-fold enhanced dielectric constant, sometimes exceeding 6000, and are widely used in thin-layer capacitors. A hydrothermal approach is used to synthesize BTO nanocrystals, which are characterized by a range of methods, including X-ray Rietveld refinement and the Williamson–Hall approach, revealing the presence of significant inhomogeneous strain associated with the cubic phase. However, X-ray pair distribution function measurements clearly show the local structure is lower symmetry than cubic. This apparent inconsistency is resolved by examining 3D Bragg coherent diffraction images of selected nanocrystals, which show the existence of ≈50 nm-sized domains, which are interpreted as tetragonal twins, and yet cause the average crystalline structure to appear cubic. The ability of these twin boundaries to migrate under the influence of electric fields explains the dielectric anomaly for the nanocrystalline phase.     

Influence of n-alkanes on wettability and zeta potential of quartz

Contact angles were measured in the following systems: quartz/water droplet/saturated vapor of water + n-alkane and quartz/water droplet/saturated vapor of n-alkane. The alkanes tested were from hexane to pentadecane. In both systems non-smooth changes of contact angle as a function of the chain length were observed. These changes are similar to the zeta-potential changes measured previously for two different samples of quartz in the quartz/n-alkana/water system. On the basis of the results and calculations it is suggested that the observed non-smooth changes of contact angle are due to similar changes in film pressures of the water and n-alkanes.