Relaxation of functionals with linear growth: Interactions of emerging measures and free discontinuities

For an integral functional defined on functions ( u , v ) ∈ W 1 , 1 × L 1 {(u,v)\in W^{1,1}\times L^{1}} featuring a prototypical strong interaction term between u and v, we calculate its relaxation in the space of functions with bounded variations and Radon measures. Interplay between measures and discontinuities brings various additional difficulties, and concentration effects in recovery sequences play a major role for the relaxed functional even if the limit measures are absolutely continuous with respect to the Lebesgue one.

High-Dose Benzodiazepines Positively Modulate GABAA Receptors via a Flumazenil-Insensitive Mechanism

Benzodiazepines (BZDs) produce versatile pharmacological actions through positive modulation of GABAA receptors (GABAARs). A previous study has demonstrated that high concentrations of diazepam potentiate GABA currents on the α1β2γ2 and α1β2 GABAARs in a flumazenil-insensitive manner. In this study, the high-concentration effects of BZDs and their sensitivity to flumazenil were determined on synaptic (α1β2γ2, α2β2γ2, α5β2γ2) and extra-synaptic (α4β2δ) GABAARs using the voltage-clamp electrophysiology technique. The in vivo evaluation of flumazenil-insensitive BZD effects was conducted in mice via the loss of righting reflex (LORR) test. Diazepam induced biphasic potentiation on the α1β2γ2, α2β2γ2 and α5β2γ2 GABAARs, but did not affect the α4β2δ receptor. In contrast to the nanomolar component of potentiation, the second potentiation elicited by micromolar diazepam was insensitive to flumazenil. Midazolam, clonazepam, and lorazepam at 200 µM exhibited similar flumazenil-insensitive effects on the α1β2γ2, α2β2γ2 and α5β2γ2 receptors, whereas the potentiation induced by 200 µM zolpidem or triazolam was abolished by flumazenil. Both the GABAAR antagonist pentylenetetrazol and Fa173, a proposed transmembrane site antagonist, abolished the potentiation induced by 200 µM diazepam. Consistent with the in vitro results, flumazenil antagonized the zolpidem-induced LORR, but not that induced by diazepam or midazolam. Pentylenetetrazol and Fa173 antagonized the diazepam-induced LORR. These findings support the existence of non-classical BZD binding sites on certain GABAAR subtypes and indicate that the flumazenil-insensitive effects depend on the chemical structures of BZD ligands.

Alkali Concentration and Diluent Effects on Properties of Grape Cane Fiber-Reinforced Polymer Composites

The main objective of this study was to investigate the properties of polymer composites reinforced with grape cane fibers. The fibers were subjected to a sodium hydroxide (NaOH) treatment at two treatment concentrations to extract the fibers as well as fiber surface treatment. Panels were fabricated by hand lay-up and compression molding according to different fiber types, namely outer bark (OB) and whole (W) fibers. The whole fiber was a mixture of OB and inner bark (IB) fibers. Grape cane fibers were used as the reinforcement material for unsaturated polyester (UPE) resin panels. Acrylated epoxidized soybean oil (AESO) was used as a reactive diluent material with the UPE resin, and the results were compared with panels prepared with commercial styrene–UPE. There were inconsistent alkali treatment concentration effects on the mechanical properties and water absorption. However, panels fabricated with the whole bark fibers that have been treated with 1 wt % NaOH and had AESO–UPE resin resulted in the best tensile and flexural strength.

Modulatory Actions of the Glycine Receptor β Subunit on the Positive Allosteric Modulation of Ethanol in α2 Containing Receptors

Alpha1-containing glycine receptors (GlyRs) are major mediators of synaptic inhibition in the spinal cord and brain stem. Recent studies reported the presence of α2-containing GlyRs in other brain regions, such as nucleus accumbens and cerebral cortex. GlyR activation decreases neuronal excitability associated with sensorial information, motor control, and respiratory functions; all of which are significantly altered during ethanol intoxication. We evaluated the role of β GlyR subunits and of two basic amino acid residues, K389 and R390, located in the large intracellular loop (IL) of the α2 GlyR subunit, which are important for binding and functional modulation by Gβγ, the dimer of the trimeric G protein conformation, using HEK-293 transfected cells combined with patch clamp electrophysiology. We demonstrate a new modulatory role of the β subunit on ethanol sensitivity of α2 subunits. Specifically, we found a differential allosteric modulation in homomeric α2 GlyRs compared with the α2β heteromeric conformation. Indeed, while α2 was insensitive, α2β GlyRs were substantially potentiated by ethanol, GTP-γ-S, propofol, Zn2+ and trichloroethanol. Furthermore, a Gβγ scavenger (ct-GRK2) selectively attenuated the effects of ethanol on recombinant α2β GlyRs. Mutations in an α2 GlyR co-expressed with the β subunit (α2AAβ) specifically blocked ethanol sensitivity, but not propofol potentiation. These results show a selective mechanism for low ethanol concentration effects on homomeric and heteromeric conformations of α2 GlyRs and provide a new mechanism for ethanol pharmacology, which is relevant to upper brain regions where α2 GlyRs are abundantly expressed.