Synthesis and Structure–Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents

P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurological disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clinical trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chemical entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chemical Bank, which had an IC₅₀ value of 1030 nM, studies of structure–activity and structure–property relationships enabled further optimization toward improving the antagonistic activities as well as the drug’s physicochemical properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC₅₀ value of 375 nM at P2X3R with more than 23-fold selectivity versus P2X2/3R, along with properties of metabolic stability and improved solubility. In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mechanical withdrawal threshold as measured by von Frey filament following intravenous administration.     

Butterworth Window for Power Spectral Density Estimation

The power spectral density of a signal can be estimated most accurately by using a window with a narrow bandwidth and large sidelobe attenuation. Conventional windows generally control these characteristics by only one parameter, so there is a trade-off problem: if the bandwidth is reduced, the sidelobe attenuation is also reduced. To overcome this problem, we propose using a Butterworth window with two control parameters for power spectral density estimation and analyze its characteristics. Simulation results demonstrate that the sidelobe attenuation and the 3 dB bandwidth can be controlled independently. Thus, the trade-off problem between resolution and spectral leakage in the estimated power spectral density can be overcome.     

Development of Methodology with Excellent Reproducibility for Evaluating Stretch-Flangeability Using a Sheared-Edge Tensile Test

Stretch-flangeability is an important formability factor for advanced high-strength steels (AHSS) when manufacturing automotive parts. However, the reproducibility of the hole expansion test (HET), a standard testing method established by the international organization for standardization, is quite poor compared with other mechanical testing methods. In this study, we propose a new method, the sheared-edge tensile test (SETT), for evaluating stretch-flangeability with excellent reproducibility. SETT takes into account the deformation behavior during the HET and the critical extrinsic factors influencing the hole expansion ratio (HER). The correlation between the sheared-edge surface characteristics, the tensile properties of the SETT specimen, and stretch-flangeability were investigated to gain in-depth understanding of the proposed evaluation method. Although the correlation between HER and the post-uniform elongation of the SETT specimen with an HER >80% was ambiguous, the SETT results exhibited good reproducibility, and the stretch-flangeability indicated by HER tended to increase linearly with increases in the post-uniform elongation of the SETT specimen. Furthermore, the roughness of the sheared-edge surface had a significant effect on the local deformation behavior of the materials. The proposed method requires only a small amount of specimen, as compared with the HET and can evaluate stretch-flangeability with good reproducibility.     

Agglomeration,sedimentation, and cellular toxicity of alumina nanoparticles in cell culture medium

The cytotoxicity of alumina nanoparticles (NPs) was investigated for a wide range of concentration (25–200 μg/mL) and incubation time (0–72 h) using floating cells (THP-1) and adherent cells (J774A.1, A549, and 293). Alumina NPs were gradually agglomerated over time although a significant portion of sedimentation occurred at the early stage within 6 h. A decrease of the viability was found in floating (THP-1) and adherent (J774A.1 and A549) cells in a dose-dependent manner. However, the time-dependent decrease in cell viability was observed only in adherent cells (J774A.1 and A549), which is predominantly related with the sedimentation of alumina NPs in cell culture medium. The uptake of alumina NPs in macrophages and an increased cell-to-cell adhesion in adherent cells were observed. There was no significant change in the viability of 293 cells. This in vitro test suggests that the agglomeration and sedimentation of alumina NPs affected cellular viability depending on cell types such as monocytes (THP-1), macrophages (J774A.1), lung carcinoma cells (A549), and embryonic kidney cells (293).     

End-to-end framework for 4-D broadcasting based on MPEG-V standard

Advances in media technologies brought so-called 4-D movies to your neighbour. The 4-D movies represent movies (preferably in 3-D) with additional sensory effects such as motion chairs and wind effects. We present an end-to-end framework to provide sensory effects for home theaters based on MPEG-V standard. The key technologies of the 4-D broadcasting framework, required to provide sensory effect through home theaters consist of creating sensory effects synchronized with audiovisual contents, delivering the sensory effects with content to home theater devices, recognizing home devices for rendering sensory effects, and rendering contents through home theater system with connected sensory devices in a synchronized way. This paper proposes end-to-end technology required, in addition to the conventional broadcasting framework, based on international standard of MPEG-V, specifically Part 2 to describe capabilities of the home sensory devices, Part 3 to provide contents with sensory effects, and Part 5 to command the sensory devices among other parts of MPEG-V standard.     

Road sign tracking for adaptive cruise control under nonlinear conditions

A vision-based system is described for adaptive cruise control to track road signs from within a moving vehicle. The proposed system has the standard architecture with a particle filter due to its robust tracking performance in a complex environment. In the case of tracking road signs in a real environment, it has great difficulty in predicting time series data by reason of its nonlinear characteristics. To overcome this problem, proposed is a state transition model to which the differences of affine parameters and a fuzzy-autoregressive model are applied. Also, to make an observation model, the Parzen window is used at a measurement step in the particle filter.     

Study of Low-Temperature Thermocompression Bonding in Ag-In Solder for Packaging Applications

Low-temperature solders have wide applications in integrated circuits and micro-electromechanical systems packaging. In this article, a study on Ag-In solder for chip-to-chip thermocompression bonding was carried out. The resulting joint consists of AgIn₂ and Ag₉In₄ phases, with the latter phase having a melting temperature higher than 400°C. Complete consumption of In solder into a Ag-rich intermetallic compound is achieved by applying a bond pressure of 1.4 MPa at 180°C for 40 min. We also observe that the bonding pressure effect enables a Ag-rich phase to be formed within a shorter bonding duration (10 min) at a higher pressure of 1.6 MPa. Finally, prolonged aging leads to the formation of the final phase of Ag₉In₄ in the bonded joints.