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.     

Misalignment tolerance analysis and fabrication for highly efficient parallel optical-electrical convertor module

A compact, highly efficient, and passively assembled parallel optical-electrical convertor module (POECM) for active optical cable application is proposed. This paper presents our POECM structure, optical design simulation results, fabrication process, and data transmission test results, in sequence. The POECM has a compact size of \(18.5\hbox {mm} \times 10\hbox {mm} \times 2.8\hbox {mm}\) . We confirm a data rate of total throughput at 21.6 Gbps ( \(5.4\hbox {Gbps} \times 4\) channels) with a bit error rate of less than \(10^{-12}\) .     

Migration of indium ions in amorphous indium-gallium-zinc-oxide thin film transistors

Electromigration of In in amorphous indium-gallium-zinc-oxide thin film transistors under repeated switching operation was investigated by analyzing the distribution of component elements. During the repeated switching operations up to 300 times, threshold voltage of this device increased gradually implying alteration to the internal device structures. Energy dispersive X-ray spectroscopy revealed noticeable redistribution of metallic components, especially In, in the channel layer beneath the source electrode during switching operations by the migration of metallic ions away from the source electrode, which is attributed to electromigrations similar to those observed in organic light emitting diodes having indium tin oxide electrodes.     

Preparation of Ga-doped ZnO films by pulsed dc magnetron sputtering with cylindrical rotating target for thin film solar cell applications

Applicability of Ga-doped ZnO (GZO) films for thin film solar cells (TFSCs) was investigated by preparing GZO films via pulsed dc magnetron sputtering (PDMS) with rotating target. The GZO films showed improved crystallinity and increasing degree of Ga doping with increasing thickness to a limit of 1000 nm. The films also fulfilled requirements for the transparent electrodes of TFSCs in terms of electrical and optical properties. Moreover, the films exhibited good texturing potential based on etching studies with diluted HCl, which yielded an improved light trapping capability without significant degradation in electrical propreties. It is therefore suggested that the surface-textured GZO films prepared via PDMS and etching are promising candidates for indium-free transparent electrodes for TFSCs.     

Synthesis of ZnO nanospheres with uniform nanopores by a hydrothermal process

ZnO nanospheres were successfully synthesized by a hydrothermal process (S1 sample) and a wet-chemical method (S2 sample). Following synthesis, calcination treatment at 450 °C was performed for the sample prepared by the wet-chemical method (S3 sample). All of the samples possessed a regular spherical shape. A polycrystalline wurtzite structure was confirmed in the S1 and S3 samples by X-ray diffraction and selected area electron diffraction, whereas a mixture of ZnO nanoparticles and amorphous materials was observed in the sample S2. The surface area and pore structure of the samples were investigated by nitrogen adsorption–desorption measurements. Uniform nanopores with a diameter of 4.07 nm were present in the S1 sample while a broad pore size distribution was obtained for the S2 and S3 samples. The highest surface area was obtained for the S1 sample and a possible formation mechanism was studied.     

Different ocular dominance map formation influenced by orientation preference columns in visual cortices

In animal experiments, the observed orientation preference and ocular dominance columns in the visual cortex of the brain show various pattern types. Here, we show that the different visual map formations in various species are due to the crossover behavior in anisotropic systems composed of orientational and scalar components such as easy-plane Heisenberg models. We predict the transition boundary between different pattern types with the anisotropy as a main bifurcation parameter, which is consistent with experimental observations.     

Hydrophobic Shielding of Outer Surface: Enhancing the Chemical Stability of Metal–Organic Polyhedra

Metal–organic polyhedra (MOP) are a promising class of crystalline porous materials with multifarious potential applications. Although MOPs and metal–organic frameworks (MOFs) have similar potential in terms of their intrinsic porosities and physicochemical properties, the exploitation of carboxylate MOPs is still rudimentary because of the lack of systematic development addressing their chemical stability. Herein we describe the fabrication of chemically robust carboxylate MOPs via outer‐surface functionalization as an a priori methodology, to stabilize those MOPs system where metal–ligand bond is not so strong. Fine‐tuning of hydrophobic shielding is key to attaining chemical inertness with retention of the framework integrity over a wide range of pH values, in strong acidic conditions, and in oxidizing and reducing media. These results are further corroborated by molecular modelling studies. Owing to the unprecedented transition from instability to a chemically ultra‐stable regime using a rapid ambient‐temperature gram‐scale synthesis (within seconds), a prototype strategy towards chemically stable MOPs is reported.     

Observable Structures of Small Neutral and Anionic Gold Clusters

Since gold clusters have mostly been studied theoretically by using DFT calculations, more accurate studies are of importance. Thus, small neutral and anionic gold clusters (Au_n and Au_n^?, n=4–7) were investigated by means of coupled cluster with singles, doubles, and perturbative triple excitations [CCSD(T)] calculations with large basis sets, and some differences between DFT and CCSD(T) results are discussed. Interesting isomeric structures that have dangling atoms were obtained. Structures having dangling atoms appear to be stable up to n=4 for neutral gold clusters and up to n=7 for anionic clusters. The relative stabilities and electronic properties of some isomers and major structures are discussed on the basis of the CCSD(T) calculations. This accurate structure prediction of small gold clusters corresponding to experimental photoelectron spectral peaks is valuable in the field of atom‐scale materials science including nanocatalysts.     

Hemoglobin as a Diagnosing Molecule for Biological Effects of Atmospheric-Pressure Plasma

The studies with proteins are necessary to understand the biological effects of atmospheric pressure plasma (APP). Among proteins, those with transient metal ions play key roles in many biological events and they are very sensitive to environmental redox states. Iron-containing hemoglobin (Hb) is investigated in this study, after APP treatments under two environmental gas conditions of pure N₂ and N₂?+?O₂ mixture. Monitoring the intensity change for absorption spectra could lead to a quantitative assessment of the effect of discharge plasma on Hb. Redox states of Hb are classified into five states including O₂-bound Hb (oxy-Hb), deoxy-Hb, met-Hb, NO-bound Hb (NO-Hb), and hemichrome. Chemically generated reactive species and some scavengers are applied to understand the chemical reactions. Our experimental results confirm the complex chemical reactions of APP and suggest the possible use of Hb as a model protein for the visualization of APP biological effects.