Domain Wall Motion Across Various Grain Boundaries in Ferroelectric Thin Films

Domain wall movement at and near engineered 10°, 15°, and 24° tilt and 10° and 30° twist grain boundaries was measured by band excitation piezoresponse force microscopy for Pb(Zr,Ti)O₃ films with Zr/Ti ratio of 45/55 and 52/48. A minimum in nonlinear response was observed at the grain boundary for the highest angle twist and tilt grain boundaries, while a maximum in nonlinear response was observed at the 10° tilt grain boundaries. The observed nonlinear response was correlated with the domain configurations imaged in cross section by transmission electron microscopy.     

Selective oxidation of styrenes under oxygen catalyzed by cobalt chloride

The cobalt(II) chloride-catalyzed oxidative cleavage of -methylstyrene with oxygen in t-BuOH gives acetophenone and formaldehyde in good yield. The competing reactions between C=C cleavage and formation of polymeric products are strongly affected by the solvent, cobalt catalyst and concentration used, as well as the reaction temperature. A free radical mechanism involving a cyclic peroxide intermediate is proposed to give the cleavage products. Oxidation of various alkenes using CoCl₂/t-BuOH/O₂ system shows that only activated styrenes can be oxidized effectively. The reactivity of various styrenes and their selectivity towards giving cleavage products or polymers are strongly influenced by the electronic and steric properties of the substrate.     

Elucidating enzyme-based cleaning of protein soils (gelatine and egg yolk) using a scanning fluid dynamic gauge

The enzyme-based cleaning of two model protein soils was investigated using a scanning fluid dynamic gauge (sFDG). The sFDG device allows data to be collected from more than one sample or location during a single experiment and therefore makes a range of comparative studies feasible. The sFDG was modified to allow the forces imposed on the surface to be controlled during a test. Gelatine films on stainless steel swelled in the presence of alkali at 20 °C but were not removed. Enzymes from a commercial dishwasher product interrupted swelling when the mean water volume fraction of the film reached ∼0.9 and promoted removal. The enzyme effectiveness decreased over time. Egg yolk deposits (spray dried on mica) were studied in a protease/buffer solution at 40 °C. The deposits swelled on contact with alkali, and removal started after ∼40 min. Some flow over the deposit was required to achieve complete cleaning, but the time taken to clean exhibited a weak dependence on the shear stress imposed by the flow for shear stresses above 10 Pa. The cleaning behaviour was strongly influenced by the nature of the deposit. Baking the deposit at 150 °C reduced the rate and extent of swelling as well as the rate of removal, and could result in the formation of a residual film that exhibited yield stress characteristics.     

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.     

Phytochemical Composition of <Emphasis Type="Italic">Oryza sativa</Emphasis> (Rice) Bran Oil Bodies in Crude and Purified Isolates

We describe a procedure for isolating and purifying oil bodies (OBs) from Oryza sativa bran, and present evidence that strongly suggests a physical association between the OB organelles and several antioxidant phytochemicals (γ-oryzanol and several tocochromanols). This suggestion arises from work showing that despite comprehensive washing steps (9 M urea, water), the majority of the tocotrienols and tocopherols (77 and 73 %, respectively) and oryzanols (91 %) remain integral to the oil bodies, not being released unless the latter are sacrificed. This in turn provides a valuable comparison with similar analyses of tocochromanols in other plant species, as well as indicating that rice bran, normally a waste product from the rice industry, may provide a valuable source of antioxidants as well as protein and unsaturated fat.     

Targeting tumour proliferation with a small-molecule inhibitor of AICAR transformylase homodimerization

Aminoimidazole carboxamide ribonucleotide transformylase/ inosine monophosphate cyclohydrolase (ATIC) is a bifunctional homodimeric enzyme that catalyzes the last two steps of de novo purine biosynthesis. Homodimerization of ATIC, a protein–protein interaction with an interface of over 5000 Ų, is required for its aminoimidazole carboxamide ribonucleotide (AICAR) transformylase activity, with the active sites forming at the interface of the interacting proteins. Here, we report the development of a small‐molecule inhibitor of AICAR transformylase that functions by preventing the homodimerization of ATIC. The compound is derived from a previously reported cyclic hexapeptide inhibitor of AICAR transformylase (with a K_i of 17 μM ), identified by high‐throughput screening. The active motif of the cyclic peptide is identified as an arginine‐tyrosine dipeptide, a capped analogue of which inhibits AICAR transformylase with a K_i value of 84 μM . A library of nonnatural analogues of this dipeptide was designed, synthesized, and assayed. The most potent compound inhibits AICAR transformylase with a K_i value of 685 nM , a 25‐fold improvement in activity from the parent cyclic peptide. The potential for this AICAR transformylase inhibitor in cancer therapy was assessed by studying its effect on the proliferation of a model breast cancer cell line. Using a nonradioactive proliferation assay and live cell imaging, a dose‐dependent reduction in cell numbers and cell division rates was observed in cells treated with our ATIC dimerization inhibitor.     

Computational Analysis of the Solid-State and Solvation Properties of Carbamazepine in Relation to its Polymorphism

The solvent-dependent polymorphism of the active pharmaceutical ingredient (API) carbamazepine is interpreted from calculations of the solid-state and API-solvent intermolecular interactions. These simulations suggested that apolar solute-solute interactions could be disrupted by apolar solvents. In contrast, the polar solute-solute interactions were found to be easily disrupted by polar and protic solvents. This is consistent with experimental observations that the crystallization of the metastable form II is more dominant in apolar solvents. The Mercury program remains the gold standard in terms of usability; however, further expansion into more complex simulation techniques could make this package of even greater use in pharmaceutical manufacturing workflows.     

Investigation of fluidized bed behaviour using electrical capacitance tomography

The temporal and cross-sectional distributions of particles in a 127 mm diameter fluidized bed have been obtained using a new generation, high-speed electrical capacitance tomography. Two planes of eight electrodes were used and mounted at 160 and 660 mm from the gas distributor which was a 3 mm thick porous plastic plate (maximum pore size of 50-70 μ m). 3 mm diameter, nearly-spherical polyethylene granules made up the bed. Experiments at sampling frequencies of 200-2000 cross-sections per second and gas superficial velocities from just below the minimum fluidization to 83% above minimum fluidization velocities were used. The time series of the cross-sectional average void fractions have been examined both directly and in amplitude and frequency space. The last two used probability density functions and power spectral densities. The information gathered shows that the fluidized bed was operating in the slugging mode, which is not surprising given the size of the particles. It has been found that an increase in the excess gas velocity above the minimum fluidization velocity resulted in an increase in the mean void fraction, an increase in the length and velocity of the slug bubbles as well as the bed height, and a slight decrease in the slug frequency. The results are presented in a level of detail suitable for comparison with later numerical simulation.     

Regulatory RNAs: A Universal Language for Inter-Domain Communication

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota.