Acute Intake of Plant Stanol Esters Induces Changes in Lipid and Lipoprotein Metabolism‐Related Gene Expression in the Liver and Intestines of Mice

The kinetics of plant stanol uptake and routing in 8‐week‐old C57BL/6J mice were determined after a plant stanol ester gavage. In addition, acute changes in intestinal and hepatic gene expression were investigated. Mice were fed a plant sterol/stanol poor diet from weaning. At the age of 8 weeks, they received an oral gavage consisting of 0.25 mg cholesterol + 50 mg plant stanol esters dissolved in olive oil. Animals were euthanized at different time points. In a second comparable set‐up, mesenteric lymph‐cannulated versus sham‐operated mice received the same oral gavage, which was now deuterium labeled. Intestinal and hepatic sitostanol concentrations increased within 15 min post‐gavage. This rapid hepatic appearance was absent in lymph‐cannulated mice, suggesting a very fast lymph‐mediated uptake. Hepatic mRNA expression of SREBP2 and its target genes rapidly decreased, whereas expression of LXR target genes increased. The intestinal SREBP2 pathway was increased, whereas the expression of LXR target genes hardly changed. The fivefold and sixfold increased expression of intestinal LDLr and PCSK9 is suggestive of TICE activation. We conclude that in C57BL/6J mice plant stanol kinetics are fast, and affect intestinal and hepatic gene expression within 15 min postprandial after lymph‐mediated uptake.     

Oxidation Potentials of N‐Modified Derivatives of the Analgesic Flupirtine Linked to Potassium KV7 Channel Opening Activity But Not Hepatocyte Toxicity

Openers of neuronal voltage‐gated potassium channels (K_V) are of interest as therapeutic agents for treating pain (flupirtine) and epilepsy (retigabine). In an effort to better understand the mechanisms of action and toxicity of flupirtine, we synthesized nine novel analogues with varying redox behavior. Flupirtine can be oxidatively metabolized into azaquinone diimines; thus, the oxidation potentials of flupirtine and its analogues were measured by cyclic voltammetry. K_V7.2/3 (KCNQ2/3) opening activity was determined by an established assay with HEK293 cells overexpressing these channels. A link was found between the oxidation potentials of the compounds and their EC₅₀ values for potassium channel opening activity. On the other hand, no correlation was observed between oxidation potentials and cytotoxicity in cultures of transgenic mouse hepatocytes (TAMH). These results support the idea that oxidative metabolites of flupirtine contribute to the mechanism of action, similar to what was recently proposed for acetaminophen (paracetamol), but not to hepatotoxicity.     

Preclinical Characterization of Acyl Sulfonimidamides: Potential Carboxylic Acid Bioisosteres with Tunable Properties

Herein we present the preclinical characterization of novel compounds containing the linear acyl sulfonimidamide functionality. Specifically, we studied the pK_a, lipophilicity, in vitro metabolic stability, plasma protein binding, Caco‐2 permeability, and aqueous solubility for nine aryl acyl sulfonimidamides. In comparison with widely used carboxylic acid bioisosteres, the acyl sulfonimidamides were found to be less acidic and more lipophilic depending on the substitution pattern in the studied compounds. Importantly, the pK_a values (5.9–7.6) were significantly influenced by substituents on the nitrogen atom and the aryl substituents. Moreover, the acyl sulfonimidamides displayed membrane permeabilities ranging from moderate to very high, which correlated with decreased pK_a and low to negligible efflux ratios. We foresee that the chiral sulfur center and the two handles for structural diversity of linear acyl sulfonimidamides will offer new opportunities for drug design and for improving the oral bioavailability of acidic drug candidates.     

Micro-solid oxide fuel cells using free-standing 3 mol.% yttria-stabilised-tetragonal-zirconia-polycrystal electrolyte foils

Ultrathin 3 mol.% yttria-stabilised-tetragonal-zirconia-polycrystal (Y-TZP) foils with thicknesses of 1-10 μm are fabricated by a new wet-chemical processing route. The foils are free-standing, semi-transparent and flexible. The in-plane electrical conductivity of the Y-TZP foil is 0.03 S m⁻¹ at 500 °C. Cross-plane impedance measurements with sputtered Pt electrodes yield two arcs, of which the high-frequency arc is attributed to the ohmic resistance of the electrolyte and the low-frequency arc to the electrode-electrolyte interface. A symmetrical micro-solid oxide fuel cell (SOFC) is designed using this ultrathin free-standing Y-TZP foil as the electrolyte and sputtered Pt electrodes. An open-circuit voltage of 0.98 V and a maximum power density of 12 mW cm⁻² are measured at 500 °C. These results prove the feasibility of this approach to the fabrication of miniaturised planar SOFCs without the need for microfabrication.     

Tetrachloroferrate containing ionic liquids: Magnetic- and aggregation behavior

The magnetic behavior of a binary salt of tricaprylylmethylammonium tetrachloroferrate and tricaprylylmethylammonium chloride, [A336][FeCl₄]_0.73[Cl]_0.27, was evaluated. With a magnetic susceptibility of 0.011 emu mol^? 1 this binary salt exhibited a remarkable response to an external magnetic field. Dynamic light scattering (DLS) measurements allowed to study the aggregation behavior of [A336][FeCl₄]_0.73[Cl]_0.27 as well as of further magnetic ionic liquids [PR_6,6,6,14][FeCl₄] and (BMIM)[FeCl₄] in ethylacetate and ethanol.     

Investigation of some factors affecting the antibacterial activity of rosemary extracts in food models by a food microdilution method

The activity of rosemary phenolic extracts against Listeria monocytogenes and Escherichia coli was evaluated in 50% food models of meat, vegetable and dairy products in relation to some factors that can affect MIC (minimal inhibitory concentration) values (inoculum level, proportion of food, temperature) using a new food microdilution method. It was shown that the interactions of meat and milk components with plant extracts reduced the antibacterial effectiveness of rosemary extracts. MIC values for L. monocytogenes were lower than for E. coli in all tested conditions. A lower inoculation level caused a decrease in MIC values for E. coli but an increase in MIC values for L. monocytogenes in control media. In food models, MIC values were higher or equal to MIC values in control media regardless of bacterial type. We showed that the food microdilution method represents a simple, rapid, reproducible and inexpensive method for testing the antimicrobial efficiency of plant extracts in food systems.     

Caching Locator/ID mappings: An experimental scalability analysis and its implications

Victim of its own success, the current Internet is facing scalability issues that lead the research community to explore alternative architectures. In particular, the Locator/ID Split paradigm, based on the idea of separating the identity from the location of end-systems, is gaining momentum and seems to be the most promising candidate for the future Internet architecture. A critical component of any Locator/ID Split approach, from a performance and resources consumption perspective, as well as from a security point of view, is the cache. The cache is meant to temporarily store mappings, i.e., the bindings between identifiers and locations, in order to provide routers with the knowledge of where to forward packets.Taking as reference protocol LISP (Locator/ID Separation Protocol), the most successful proposal currently under discussion at the IETF, this paper presents a thorough analysis of such a component, including the implications of policies to increase the level of security, based on real packet-level traces. Our results prove that even a timeout as short as 60 s provides a high hit ratio and that the impact of using security policies is small. Furthermore, a thorough analysis of the scalability of such a component is provided along with the analysis of which class of applications contributes the major fraction of cache-misses.     

New insights into the antioxidant activity of Trolox in o/w emulsions

The antioxidant activity of Trolox was investigated in emulsions containing different emulsifiers, and decreased in the order Brij 58 > CTAB > SDS. Two degradation products were isolated and identified as Trolox quinone and a keto-derivative. In addition to the stability of Trolox, the effects of the degradation products on lipid oxidation were investigated. In emulsions with SDS, the quinone and the keto-derivative contributed to the overall pro-oxidant effect of Trolox, whereas they had no effect in emulsions containing CTAB or Brij 58. It was concluded that the microenvironment at the o/w interface has a marked influence on the antioxidant and pro-oxidant effects of Trolox and its degradation products via molecular interactions and by affecting its molecular mobility.     

Mechanical characterisation of miniaturised direct inkjet printed 3Y-TZP specimens for microelectronic applications

Direct inkjet printing (DIP) allows the production of small ceramic specimens with special geometries starting from high solids content suspensions. In this work, thin (300 μm thickness) 3Y-TZP specimens were produced with the DIP technique as model materials for microelectronic applications. The mechanical strength of the printed specimens was evaluated under biaxial loading, and the results were interpreted within the framework of the Weibull theory. Hot-pressed 3Y-TZP specimens with the same geometry and dimensions were tested for comparison. The fracture surfaces were subsequently examined using scanning electron microscopy (SEM). The inkjet printed materials revealed high mechanical reliability (m ≈ 10 for σ₀ ≈ 1400 MPa), which was ascribed to the uniform and defect free microstructure generated by the DIP technique.