Ultra-broadband Polarisers Based on Metastable Free-Standing Aligned Carbon Nanotube Membranes

A carbon nanotube free-standing linearly dichroic polariser is developed using solid-state extrusion. Membrane cohesion is experimentally and numerically demonstrated to derive from inter-tube van der Waals interactions in this family of planar metastable morphologies, controlled by the chemical vapour deposition conditions. Ultra-broadband polarisation (400 nm – 2.5 mm) is shown and corroborated by effective medium and full numerical simulations.

Photo-ionized neon plasmas induced by radiation pulses of a laser-plasma EUV source and a free electron laser FLASH

In this work, a laser-produced plasma extreme ultraviolet source and a free electron laser were used to create Ne photo-ionized plasmas. In both cases, a radiation beam was focused onto a gas stream injected into a vacuum chamber synchronously with the radiation pulse. Extreme ultraviolet radiation from the plasma spanned a wide spectral range with pronounced maximum centered at lambda = 11 +/- 1 nm while the free electron laser pulses were emitted at a wavelength of 32 nm. The power density of the focused plasma radiation was approximately 2 x 10(7) W/cm(2) and was seven orders of magnitude lower compared with the focused free electron laser beam. Radiation fluences in both experimental conditions were comparable. Despite quite different spectral characteristics and extremely different power densities, emission spectra of both photo-ionized plasmas consist of the same spectral lines within a wavelength range of 20 to 50 nm, however, with different relative intensities of the corresponding lines. The dominating spectral lines originated from singly charged ions (Ne II); however, Ne III lines were also detected. Additionally, computer simulations of the emission spectra, obtained for photo-ionized plasmas, driven by the plasma extreme ultraviolet source, were performed. The corresponding measured and calculated spectra are presented. An electron temperature and ionic composition were estimated. Differences between the experimental spectra, obtained for both irradiation conditions, were analyzed. The differences were attributed mainly to different energies of driving photons.

Probing The effects of Experimental Conditions on the Character of Drug-Polymer Phase Diagrams Constructed Using Flory-Huggins Theory

Purpose: Amorphous drug-polymer solid dispersions have been found to result in improved drug dissolution rates when compared to their crystalline counterparts. However, when the drug exists in the amorphous form it will possess a higher Gibb’s free energy than its associated crystalline state and can recrystallize. Drug-polymer phase diagrams constructed through the application of the Flory Huggins (F-H) theory contain a wealth of information regarding thermodynamic and kinetic stability of the amorphous drug-polymer system. This study was aimed to evaluate the effects of various experimental conditions on the solubility and miscibility detections of drug-polymer binary system. Methods: Felodipine (FD)-Polyvinylpyrrolidone (PVP) K15 (PVPK15) and FD-Polyvinylpyrrolidone/vinyl acetate (PVP/VA64) were the selected systems for this research. Physical mixtures with different drug loadings were mixed and ball milled. These samples were then processed using Differential Scanning Calorimetry (DSC) and measurements of melting point (Tend) and glass transition (Tg) were detected using heating rates of 0.5, 1.0 and 5.0°C/min. Results: The melting point depression data was then used to calculate the F-H interaction parameter (χ) and extrapolated to lower temperatures to complete the liquid–solid transition curves. The theoretical binodal and spinodal curves were also constructed which were used to identify regions within the phase diagram. The effects of polymer selection, DSC heating rate, time above parent polymer Tg and polymer molecular weight were investigated by identifying amorphous drug miscibility limits at pharmaceutically relevant temperatures. Conclusion: The potential implications of these findings when applied to a non-ambient processing method such as Hot Melt Extrusion (HME) are also discussed.

Free fatty acid receptors:structural models and elucidation of ligand binding interactions

BACKGROUND: The free fatty acid receptors (FFAs), including FFA1 (orphan name: GPR40), FFA2 (GPR43) and FFA3 (GPR41) are G protein-coupled receptors (GPCRs) involved in energy and metabolic homeostasis. Understanding the structural basis of ligand binding at FFAs is an essential step toward designing potent and selective small molecule modulators.

RESULTS: We analyse earlier homology models of FFAs in light of the newly published FFA1 crystal structure co-crystallized with TAK-875, an ago-allosteric ligand, focusing on the architecture of the extracellular binding cavity and agonist-receptor interactions. The previous low-resolution homology models of FFAs were helpful in highlighting the location of the ligand binding site and the key residues for ligand anchoring. However, homology models were not accurate in establishing the nature of all ligand-receptor contacts and the precise ligand-binding mode. From analysis of structural models and mutagenesis, it appears that the position of helices 3, 4 and 5 is crucial in ligand docking. The FFA1-based homology models of FFA2 and FFA3 were constructed and used to compare the FFA subtypes. From docking studies we propose an alternative binding mode for orthosteric agonists at FFA1 and FFA2, involving the interhelical space between helices 4 and 5. This binding mode can explain mutagenesis results for residues at positions 4.56 and 5.42. The novel FFAs structural models highlight higher aromaticity of the FFA2 binding cavity and higher hydrophilicity of the FFA3 binding cavity. The role of the residues at the second extracellular loop used in mutagenesis is reanalysed. The third positively-charged residue in the binding cavity of FFAs, located in helix 2, is identified and predicted to coordinate allosteric modulators.

CONCLUSIONS: The novel structural models of FFAs provide information on specific modes of ligand binding at FFA subtypes and new suggestions for mutagenesis and ligand modification, guiding the development of novel orthosteric and allosteric chemical probes to validate the importance of FFAs in metabolic and inflammatory conditions. Using our FFA homology modelling experience, a strategy to model a GPCR, which is phylogenetically distant from GPCRs with the available crystal structures, is discussed.

Solid-liquid interfacial free energy out of equilibrium

The properties of the interface between solid and melt are key to solidification and melting, as the interfacial free energy introduces a kinetic barrier to phase transitions. This makes solidification happen below the melting temperature, in out-of-equilibrium conditions at which the interfacial free energy is ill defined. Here we draw a connection between the atomistic description of a diffuse solid-liquid interface and its thermodynamic characterization. This framework resolves the ambiguities in defining the solid-liquid interfacial free energy above and below the melting temperature. In addition, we introduce a simulation protocol that allows solid-liquid interfaces to be reversibly created and destroyed at conditions relevant for experiments. We directly evaluate the value of the interfacial free energy away from the melting point for a simple but realistic atomic potential, and find a more complex temperature dependence than the constant positive slope that has been generally assumed based on phenomenological considerations and that has been used to interpret experiments. This methodology could be easily extended to the study of other phase transitions, from condensation to precipitation. Our analysis can help reconcile the textbook picture of classical nucleation theory with the growing body of atomistic studies and mesoscale models of solidification.

Label-free based quantitative proteomics analysis of primary neonatal porcine Leydig cells exposed to the persistent contaminant 3-methylsulfonyl-DDE

Evidence that persistent environmental pollutants may target the male reproductive system is increasing. The male reproductive system is regulated by secretion of testosterone by testicular Leydig cells, and perturbation of Leydig cell function may have ultimate consequences. 3-Methylsulfonyl-DDE (3-MeSO₂-DDE) is a potent adrenal toxicants formed from the persistent insecticide DDT. Although studies have revealed the endocrine disruptive effect of 3-MeSO₂-DDE, the underlying mechanisms at cellular level in steroidogenic Leydig cells remains to be established. The current study addresses the effect of 3-MeSO₂-DDE on viability, hormone production and proteome response of primary neonatal porcine Leydig cells. The AlamarBlue™ assay was used to evaluate cell viability. Solid phase radioimmunoassay was used to measure concentration of hormones produced by both unstimulated and Luteinizing hormone (LH)-stimulated Leydig cells following 48h exposure. Protein samples from Leydig cells exposed to a non-cytotoxic concentration of 3-MeSO₂-DDE (10μM) were subjected to nano-LC-MS/MS and analyzed on a Q Exactive mass spectrometer and quantified using label-free quantitative algorithm. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) were carried out for functional annotation and identification of protein interaction networks. 3-MeSO₂-DDE regulated Leydig cell steroidogenesis differentially depending on cell culture condition. Whereas its effect on testosterone secretion at basal condition was stimulatory, the effect on LH-stimulated cells was inhibitory. From triplicate experiments, a total of 6804 proteins were identified in which the abundance of 86 proteins in unstimulated Leydig cells and 145 proteins in LH-stimulated Leydig cells was found to be significantly regulated in response to 3-MeSO₂-DDE exposure. These proteins not only are the first reported in relation to 3-MeSO₂-DDE exposure, but also display small number of proteins shared between culture conditions, suggesting the action of 3-MeSO₂-DDE on several targeted pathways, including mitochondrial dysfunction, oxidative phosphorylation, EIF2-signaling, and glutathione-mediated detoxification. Further identification and characterization of these proteins and pathways may build our understanding to the molecular basis of 3-MeSO₂-DDE induced endocrine disruption in Leydig cells.

Insight into CO Activation over Cu(100) under Electrochemical Conditions

The reduction of CO₂ on copper electrodes has attracted great attentions in the last decades, since it provides a sustainable approach for energy restore. During the CO₂ reduction process, the electron transfer to CO_ads is experimentally suggested to be the crucial step. In this work, we examine two possible pathways in CO activation, i.e. to generate COH_ads and CHO_ads, respectively, by performing the state-of-the-art constrained ab initio molecular dynamics simulations on the charged Cu(100) electrode under aqueous conditions, which is close to the realistic electrochemical condition. The free energy profile in the formation of COH_ads via the coupled proton and electron transfer is plotted. Furthermore, by Bader charge analyses, a linear relationship between C-O bond distance and the negative charge in CO fragment is unveiled. The formation of CHO_ads is identified to be a surface catalytic reaction, which requires the adsorption of H atom on the surface first. By comparing these two pathways, we demonstrate that kinetically the formation of COH_ads is more favored than that of CHO_ads, while CHO_ads is thermodynamically more stable. This work reveals that CO activation via COH_ads intermediate is an important pathway in electrocatalysis, which could provide some insights into CO₂ electroreduction over Cu electrodes.