Cellular Antisense Activity of PNA–Oligo(bicycloguanidinium) Conjugates Forming Self‐Assembled Nanoaggregates

A series of peptide nucleic acid–oligo(bicycloguanidinium) (PNA–BG_n) conjugates were synthesized and characterized in terms of cellular antisense activity by using the pLuc750HeLa cell splice correction assay. PNA–BG₄ conjugates exhibited low micromolar antisense activity, and their cellular activity required the presence of a hydrophobic silyl terminal protecting group on the oligo(BG) ligand and a minimum of four guanidinium units. Surprisingly, a nonlinear dose–response with an activity threshold around 3–4 μM , indicative of large cooperativity, was observed. Supported by light scattering and electron microscopy analyses, we propose that the activity, and thus cellular delivery, of these lipo‐PNA–BG₄ conjugates is dependent on self‐assembled nanoaggregates. Finally, cellular activity was enhanced by the presence of serum. Therefore we conclude that the lipo‐BG‐PNA conjugates exhibit an unexpected mechanism for cell delivery and are of interest for further in vivo studies.     

Investigation of the collapse of bubbles after the impact of a piston on a liquid free surface

A novel technique based on the impact of a piston on a liquid confined in a vessel is described. Pressure measurements reveal that strong pressure variations (up to 100 atmospheres) with a rich content of frequencies are efficiently transmitted to the liquid. High‐speed camera visualizations show that pre‐existing millimetric bubbles always collapse during the first instants of the impact whereas the behavior of submillimetric bubbles depends on the features of the pressure evolution in the system. In addition to the impact velocity, the amount of gas/vapor trapped between the piston and the liquid's surface plays an important role on how pressure evolves. Only when negative pressure occurs tiny bubbles grow significantly and collapse. The violent collapse of bubbles promote turbulence and mixing at very small length‐scales which renders this technique interesting to intensify processes limited by heat and mass diffusion. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2483–2495, 2017     

Adamantyl Arotinoids That Inhibit IκB Kinase α and IκB Kinase β

A series of analogues of the adamantyl arotinoid (AdAr) chalcone MX781 with halogenated benzyloxy substituents at C2′ and heterocyclic derivatives replacing the chalcone group were found to inhibit IκBα kinase α (IKKα) and IκBα kinase β (IKKβ) activities. The growth inhibitory capacity of some analogues against Jurkat T cells as well as prostate carcinoma (PC‐3) and chronic myelogenous leukemia (K562) cells, which contain elevated basal IKK activity, correlates with the induction of apoptosis and increased inhibition of recombinant IKKα and IKKβ in vitro, pointing toward inhibition of IKK/NFκB signaling as the most likely target of the anticancer activities of these AdArs. While the chalcone functional group present in many dietary compounds has been shown to mediate interactions with IKKβ via Michael addition with cysteine residues, AdArs containing a five‐membered heterocyclic ring (isoxazoles and pyrazoles) in place of the chalcone of the parent system are potent inhibitors of IKKs as well, which suggests that other mechanisms for inhibition exist that do not depend on the presence of a reactive α,β‐unsaturated ketone.     

Effect of compression on the performance of a HT-PEM fuel cell

This paper shows by thorough electrochemical investigation that (1) the performances of high-temperature polymer electrolyte fuel cell membrane electrode assemblies of three suppliers are differently affected by compressive forces. (2) Membrane thickness reduction by compressive pressure takes place less than expected. (3) A contact pressure cycling experiment is a useful tool to distinguish the impact of compression on the contact resistances bipolar plate/gas diffusion layer (GDL) and GDL/catalytic layer. A detailed visual insight into the structural effects of compressive forces on membrane and gas diffusion electrode (GDE) is obtained by micro-computed X-ray tomography (μ-CT). μ-CT imaging confirms that membrane and GDEs undergo severe mechanical stress resulting in performance differences. Irreversible GDL deformation behavior and pinhole formation by GDL fiber penetration into the membrane could be observed.     

New methodology for scaling hydrodynamic data from a 2D-fluidized bed

We present a new method of scaling hydrodynamic data obtained from a 2D gas-solid fluidized bed, establishing links between 2D and 3D geometries. The methodology proposed may also be useful for verifying 3D-3D dynamic scaling. According to the chaos scale-up methodology proposed by Van den Bleek and Schouten [1993. Chemical Engineering Science 48, 2367-2373], the information balance is taken into account. The complexity shown by these systems is measured as the Kolmogorov entropy. Fluidized beds of different geometry (2D, 3D) performing under the bubbling regime were operated at different bed height and bed aspect ratios by fluidizing several particle groups belonging to Geldart groups B and D. Finally, an empirical correlation is proposed to compare fluidized bed hydrodynamics. This correlation relates the global information flow of the system K_G=KFr_r to the relative Reynolds particle number.     

Photocatalytic Inactivation of Legionella Pneumophila and an Aerobic Bacteria Consortium in Water over TiO2/SiO2 Fibres in a Continuous Reactor

A continuous photoreactor, working in a total recycle mode and irradiated by a low-pressure Hg lamp, has been used to study the bactericidal effect of a photocatalyst, formed by TiO₂ embedded in SiO₂ fibres, on Legionella pneumophila and a consortium of common gram-negative aerobic bacteria: (Escherichia coli, Klebsiella sp., Pseudomona sp. and Proteus sp.) in water. The kinetic modeling of the inactivation process, carried out with the measured values of viable bacteria concentration at the outlet of photoreactor, evidenced that for each pass inside the photoreactor the ratio between the outlet and inlet cell concentrations was of order of 0.01 for the inactivation of L. pneumophila. For the other aerobic bacteria, which are usually taken as reference in photocatalytic bacteria inactivation studies, this ratio was of order of 0.3 for the first hour of illumination, while upon prolonged irradiation (up to 9 h) this ratio increased to 0.7. Several factors inducing this latter decrease of efficiency are possible, as e.g. competition for photocatalytic attack between microorganisms and organic compounds released by damaged bacteria or photoinduced alteration of a small fraction of still viable bacteria making them less interactive with the photocatalyst. The inactivation mechanism normally proposed for common bacteria involves an initial attack of the photogenerated radicals to the outer membrane; the consequent membrane dispersion allows the radicals to damage the cytoplasmic membrane. The higher lethality of the photocatalytic method observed towards Legionella: (in comparison to the other aerobic bacteria) is explained considering that the radicals attack the Legionella secretion system, which is adapted for high virulence and would become activated for and through adhesion to the TiO₂ surface. This attack would then be able to inactivate L. pneumophila without dispersing the outer membrane. Apart from this, the water flow through the catalyst fibres can facilitate the bacteria transport towards the anatase surface, and additionally the generated shear stress may help adhesion, at least for some bacteria as E. coli, contributing further to improve the photokilling efficiency; both factors may contribute to the efficiency of this photoreactor configuration.     

Low Temperature Water–Gas Shift/Methanol Steam Reforming: Alkali Doping to Facilitate the Scission of Formate and Methoxy C–H Bonds over Pt/ceria Catalyst

Doping Pt/ceria catalysts with the Group 1 alkali metals was found to lead to an important weakening of the C–H bond of formate and methoxy species. This was demonstrated by a shift to lower wavenumbers of the formate and methoxy ν(CH) vibrational modes by DRIFTS spectroscopy. Li and Na-doped Pt/ceria catalysts were tested relative to the undoped catalyst for low temperature water–gas shift and methanol steam reforming using a fixed bed reactor and exhibited higher catalytic activity. Steaming of formate and methoxy species pre-adsorbed on the catalyst surface during in-situ DRIFTS spectroscopy suggested that the species were more reactive for dehydrogenation steps in the catalytic cycle for the Li and Na-doped catalysts relative to undoped Pt/ceria. However, with increasing atomic number over the series of alkali-doped catalysts, the stability of a fraction of the carbonate species was found to increase. This was observed during TPD-MS measurements of the adsorbed CO₂ probe molecule by a systematic increase of a high temperature peak for a fraction of the CO₂ desorbed. This result indicates that alkali-doping is an optimization problem—that is, while improving the dehydrogenation rates of methoxy and formate species, the carbonate intermediate stability increases, making it difficult to liberate the CO₂. Infrared spectroscopy results of CO adsorbed on Pt and ceria suggest that the alkali dopant is located on, and electronically modifies, both the Pt and ceria components. The results not only lend further support to the role that methoxy and formate species play as intermediates in the catalytic mechanisms, but also provide a path forward for improving rates by means other than resorting to higher noble metal loadings.     

Synthesis of novel DC-SIGN ligands with an alpha-fucosylamide anchor

The dendritic cell-specific intercellular adhesion molecule (ICAM) 3-grabbing nonintegrin (DC-SIGN) is a C-type lectin that appears to perform several different functions. Besides mediating adhesion between dendritic cells and T lymphocytes, DC-SIGN recognizes several pathogens some of which, including HIV, appear to exploit it to invade host organisms. The intriguing diversity of the roles attributed to DC-SIGN and their therapeutic implications have stimulated the search for new ligands that could be used as biological probes and possibly as lead compounds for drug development. The natural ligands of DC-SIGN consist of mannose oligosaccharides or fucose-containing Lewis-type determinants. Using the known 3D structure of the Lewis-x trisaccharide, we have identified some monovalent alpha-fucosylamides that bind to DC-SIGN with inhibitory constants 0.4-0.5 mM, as determined by SPR, and have characterized their interaction with the protein by STD NMR spectroscopy. This work establishes for the first time alpha-fucosylamides as functional mimics of chemically and enzymatically unstable alpha-fucosides and describes interesting candidates for the preparation of multivalent systems able to block the receptor DC-SIGN with high affinity and with potential biomedical applications.     

Examination of organic coatings on metallic substrates by scanning electrochemical microscopy in feedback mode: Revealing the early stages of coating breakdown in corrosive environments

Scanning electrochemical microscopy in feedback mode was used to monitor changes in the surface state of a polymeric film applied on a metallic substrate when exposed to an aqueous electrolytic environment. The protected metal consisted of a carbon steel substrate coated with a polyurethane-based polymeric film. SECM measurements performed in the presence and absence of chloride anions permitted a specific effect caused by Cl⁻ anions at early exposures to be detected. Significant surface roughening is observed for immersion times shorter than 1 day when the electrolyte contains chloride ions. Additionally, the growth of an individual blister could also be investigated.