Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors

Trypanothione synthetase (TryS) is essential for the survival of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis. It is one of only a handful of chemically validated targets for T. brucei in vivo. To identify novel inhibitors of TbTryS we screened our in-house diverse compound library that contains 62,000 compounds. This resulted in the identification of six novel hit series of TbTryS inhibitors. Herein we describe the SAR exploration of these hit series, which gave rise to one common series with potency against the enzyme target. Cellular studies on these inhibitors confirmed on-target activity, and the compounds have proven to be very useful tools for further study of the trypanothione pathway in kinetoplastids.     

Elevated temperature impact on performance of Low Temperature Co-fired Ceramic dielectrics

The need for electronics to operate at temperatures of 200°C and above continues to grow. These applications include avionics, aerospace, automotive, downhole drilling, mining, and many others. To satisfy this demand, a significant amount of research and development has been conducted. Despite the efforts, the number of new electronic components designed specifically for high-temperature operation is still relatively limited. In Low Temperature Co-fired Ceramic (LTCC) packages, LTCC materials are generally used as the host media for a number of pre-fabricated semiconductor components. As a result, reliability of the entire LTCC package largely depends on the performance of the least robust component. Ferro A6M-E and Ferro L8 are the two well-established and recognized LTCC dielectrics widely used for mid and high frequency LTCC applications, including several high reliability aerospace and defense applications that require demanding Mil-Spec qualifications. This study is our first attempt to characterize and understand basic high-temperature dielectric properties of these two commercial LTCC materials. The secondary objective is to initiate a dialogue in attempt to establish reliability requirements for LTCC packages dedicated for high-temperature operation.     

Anti-biofilm Activity of Human Milk Oligosaccharides in Clinical Strains of Streptococcus agalactiae with Diverse Capsular and Sequence Types

Group B Streptococcus (GBS) is an encapsulated Gram-positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short-chain sugars that have recently been shown to possess antimicrobial and anti-biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO-dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular-type- and sequence-type-specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST-1, ST-12, ST-19, and ST-23 strains. Interestingly, CpsIa as well as ST-7 and ST-17 were not susceptible to the anti-biofilm activity of HMOs, underscoring the strain-specific effects of these important antimicrobial molecules against the perinatal pathogen Streptococcus agalactiae.     

Characterisation and behaviour of Ti/TiO2/noble metal anodes

The morphology, composition and the electrical and electrochemical behaviour of the anodic microporous layer, prepared by the galvanostatic anodisation of Ti after sparking, followed by galvanostatic deposition of Pt or Ir have been investigated. These electrodes are proposed to function as dimensionally stable anodes (DSAs). For Ti/TiO₂/Pt electrodes, Pt is deposited within some of the micropores of the oxide film. In contrast, for Ti/TiO₂/Ir, the metal is deposited preferentially on the top surface. This difference is thought to result from the position of the metal deposition potential with respect to the flat band potential of n-TiO₂. Optical imaging of both types of DSA suggests that only a few sites on the surface are responsible for electron exchange at the DSA-electrolyte interface. C-AFM measurements of Ti/TiO₂/Pt samples subjected to long-term anodic polarisation, suggest that the Ti-noble metal contact is progressively insulated by thickening of the TiO₂ barrier layer, promoting passivation of the DSA. For Ir coated anodes, catalytic activity is directly related to the presence of Ir and to the stability of the catalytic oxide layer. Under Cu electrowinning conditions, the electrochemically formed hydrated Ir oxide was found to be catalytically less stable, than the iridium oxide film subjected to a heat treatment.     

Mechanical properties of a cryogenically mechanically alloyed polycarbonate–poly(aryl ether ether ketone) system

The processing–property relationship of a model cryogenically mechanically alloyed polymer–polymer system [polycarbonate (PC) and poly(aryl ether ether ketone) (PEEK)] was investigated. PC and PEEK powders were cryogenically mechanically alloyed for 10 h, and the resulting two‐phase powder particles were processed into testable coupons with a miniature ram‐injection molder. The bulk mechanical properties of the coupons made from the mechanically alloyed powders and nonmechanically alloyed powders were investigated as a function of mechanical alloying and injection‐molding parameters. The injection‐molded coupons were mechanically tested in the three‐point‐bending mode. The results demonstrated that no measurable improvement was achieved in the energy to break, strain at failure, or failure strength in the coupons made from the mechanically alloyed materials in comparison with those of the coupons made from the nonmechanically alloyed powders. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1196–1202, 2003     

Propellant cohesive fracture during the peel test of a propellant/liner structure

The integrity of propellant/liner structures in rocket motors is critical to ensure controlled combustion of the engine. In an effort to improve the bonding between the liner and the propellant, it is necessary to characterize it well. Therefore, a propellant–liner structure, bounded thanks to co-curing, has been submitted to a peel test while recording the macroscopic fracture energy and the local displacement field on the propellant-free surface. The experimental setup includes two cameras in order to record the displacement field on the propellant-free surface. Upon loading, the peel force stabilizes quickly due to a cohesive fracture in the propellant, providing access to the fracture energy. While the crack propagates through the propellant, it is observed that only a small localized area is submitted to strain, and most of the structure remains unstrained.     

Aryl Bis‐Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum

2‐Methylerythritol 2,4‐cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti‐infectives and herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from Arabidopsis thaliana afforded symmetrical aryl bis‐sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC₅₀ values in the micromolar range. The ortho‐bis‐sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC₅₀ values of 1.4 μm against PfIspF and 240 nm against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha^?1. Molecular modeling studies served as the basis for an in silico search targeted at the discovery of novel, non‐symmetrical sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double‐digit micromolar IC₅₀ range.     

Color harmonies in packaging

The goal of this research was to determine whether or not there was a difference between consumer preferences for color harmonies for products where external labels and visible product existed simultaneously. Using established color theory, transparent packages containing visible products with colored labels were evaluated. Eye tracking metrics and overall preference testing were used to assess these products. Eye tracking data yielded quantitative data that was statistically analyzed using analysis of variance. A post experiment survey was given to participants to collect demographics and additional data was completed through chi‐squared tests for association. No significant difference was found between color harmonies and preference, nor was there significance for the eye tracking metrics. These results of no significance are ideal for designers because it gives them the freedom to use their judgment when designing packaging labels. © 2016 Wiley Periodicals, Inc. Col Res Appl, 42, 50–59, 2017