Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC₅₀ value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.     

Polymer confinement and bacterial gliding motility

Cyanobacteria and myxobacteria use slime secretion for gliding motility over surfaces. The slime is produced by the nozzle-like pores located on the bacteria surface. To understand the mechanism of gliding motion and its relation to slime polymerization, we have performed molecular dynamics simulations of a molecular nozzle with growing inside polymer chains. These simulations show that the compression of polymer chains inside the nozzle is a driving force for propulsion. There is a linear relationship between the average nozzle velocity and the chain polymerization rate with a proportionality coefficient dependent on the geometric characteristics of the nozzle such as its length and friction coefficient. This minimal model of the molecular engine was used to explain the gliding motion of bacteria over surfaces.     

Bandgap engineering of self-assembled InAs quantum dots with a thin AlAs barrier

We investigate the effects of a thin AlAs layer with different position and thickness on the optical properties of InAs quantum dots (QDs) by using transmission electron microscopy and photoluminescence (PL). The energy level shift of InAs QD samples is observed by introducing the thin AlAs layer without any significant loss of the QD qualities. The emission peak from InAs QDs directly grown on the 4 monolayer (ML) AlAs layer is blueshifted from that of reference sample by 219 meV with a little increase in FWHM from 42–47 meV for ground state. In contrast, InAs QDs grown under the 4 ML AlAs layer have PL peak a little redshifted to lower energy by 17 meV. This result is related to the interdiffusion of Al atom at the InAs QDs caused by the annealing effect during growing of InAs QDs on AlAs layer.     

Structural and electrical properties of core–shell structured GaP nanowires with outer Ga2O3 oxide layers

This paper presents a review of our current experimental research on GaP nanowires grown by a vapor deposition method. Their structural, electrical, opto-electric transport, and gas-adsorption properties are reviewed. Our structural studies showed that a GaP nanowire consisted of a core–shell structure with a single-crystalline GaP core and an outer Ga₂O₃ layer. The individual GaP nanowires exhibited n-type field effects. Their electron mobilities were in the range of about 6 to 22 cm²/V s at room temperature. When the nanowires were illuminated with an ultraviolet light source, an abrupt increase of conductance occurred resulting from carrier generation in the nanowire and de-adsorption of adsorbed OH^- or O₂ ^- ions on the Ga₂O₃ surface shell. Using an intrinsic Ga₂O₃ shell layer as a gate dielectric, top-gated GaP nanowire field-effect transistors were fabricated and characterized. Like other metal oxide nanowires, the carrier concentration and mobility of GaP nanowires were significantly affected by the surface molecular adsorption of OH or O₂. The GaP nanowire devices were fabricated as sensors for NO₂, NH₃, and H₂ gases by using a simple metal decoration technique. PACS 73.63.-b; 72.80.Ey; 85.35.-p     

Temperature effect on deposition rate of silicon nitride films

Temperature effects on deposition rate of silicon nitride films were characterized by building a neural network prediction model. The silicon nitride films were deposited by using a plasma enhanced chemical vapor deposition system and process parameter effects were systematically characterized by 2⁶⁻¹ fractional factorial experiment. The process parameters involved include a radio frequency power, pressure, temperature, SiH₄, N₂, and NH₃ flow rates. The prediction performance of generalized regression neural network was drastically improved by optimizing multi-valued training factors using a genetic algorithm. Several 3D plots were generated to investigate parameter effects at various temperatures. Predicted variations were experimentally validated. The temperature effect on the deposition rate was a complex function of parameters but N₂ flow rate. Larger decreases in the deposition rate with the temperature were only noticed at lower SiH₄ (or higher NH₃) flow rates. Typical effects of SiH₄ or NH₃ flow rate were only observed at higher or lower temperatures. A comparison with the refractive index model facilitated a selective choice of either SiH₄ or NH₃ for process optimization.     

A micro/nanocasting method for replicating soft micro/nanosurface structures using a dynamic electrical field

We propose a new electric field-induced micro/nanocasting method to replicate soft patterns using micro/nanocasting techniques without pressure. The process uses an alternating current (AC) electrical field and rotation of one electrode, generating a dynamic electrical field that induces electrokinetic flow motion in a dielectric solution (polydimethylsilane, PDMS). We used a lotus leaf as a replication template and characterised the PDMS flow motion to observe the effects of various process parameters (e.g., electrical field strength, rotation speed of an electrode, and electrode shape). The unstable flow motion was significantly dependent on the processing parameters, especially the rotation speed of the electrode. Using the optimised processing conditions, the replication efficiency was about 88%. We believe that this method has potential for fabricating soft micro/nanosized structures.     

Electrical characterization of nylon-6 composite nanofibers

The electrical characteristics of nylon-6 nanofibers incorporated with TiO₂ and Fe₃O₄ nanoparticles were investigated. The resultant nanofibers exhibited good incorporation of nanoparticles. The impregnated TiO₂ and Fe₃O₄ nanoparticles into the nylon-6 nanofibers were confirmed by high resolution transmission electron microscopy (HR-TEM) and energy dispersive X-ray (EDX) spectroscopy studies. The electrical conductivity of the nylon-6 incorporated with TiO₂ and Fe₃O₄ composite nanofibers were higher than that of the pristine nylon-6 nanofibers. The impregnation of TiO₂ and Fe₃O₄ nanoparticles significantly enhanced the electrical property of the composite nanofibers. These polymeric/nanoparticles composite nanofibers structure may open a new direction for future organic electronics.     

Characterization of the variation of the material properties in a freestanding inhomogeneous thin film

This Letter presents a new technique for measuring the variation of the material properties along the thickness in a freestanding inhomogeneous thin film. The analytical results reveal a simple relation between the material properties and the set of cut-off frequencies of Lamb waves. The influence of the graded properties on the variation of cut-off frequencies in three different kinds of models, including artificial FGM model, sub-surface damage model, and nano-porous thin film model, is discussed. These results provide theoretical guidance for characterizing the material property variations of MEMS/NEMS.