Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

Antimony triselenide (Sb₂Se₃) nanoflake-based nitrogen dioxide (NO₂) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb₂Se₃ nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO₂ gas concentrations from 0.1 to 100 ppm. These Sb₂Se₃ nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb₂Se₃ nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO₂ gas flow of only 1 ppm. As a result, the Sb₂Se₃ nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.     

A Lane-Level Road Marking Map Using a Monocular Camera

The essential requirement for precise localization of a self-driving car is a lane-level map which includes road markings (RMs). Obviously, we can build the lane-level map by running a mobile mapping system (MMS) which is equipped with a high-end 3D LiDAR and a number of high-cost sensors. This approach, however, is highly expensive and ineffective since a single high-end MMS must visit every place for mapping. In this paper, a lane-level RM mapping system using a monocular camera is developed. The developed system can be considered as an alternative to expensive high-end MMS. The developed RM map includes the information of road lanes (RLs) and symbolic road markings (SRMs). First, to build a lane-level RM map, the RMs are segmented at pixel level through the deep learning network. The network is named RMNet. The segmented RMs are then gathered to build a lane-level RM map. Second, the lane-level map is improved through loop-closure detection and graph optimization. To train the RMNet and build a lane-level RM map, a new dataset named SeRM set is developed. The set is a large dataset for lane-level RM mapping and it includes a total of 25157 pixel-wise annotated images and 21000 position labeled images. Finally, the proposed lane-level map building method is applied to SeRM set and its validity is demonstrated through experimentation.      

Dynamic Oscillation via Negative Differential Resistance in Type III Junction Organic/Two-Dimensional and Oxide/Two-Dimensional Transition Metal Dichalcogenide Diodes

Among many of 2D semiconductor-based devices, type III PN junction diodes are given special attentions due to their unique function, negative differential resistance (NDR). However, it has been found uneasy to achieve well-matched type III PN junctions from 2D–2D van der Waals heterojunctions. Here, the authors present other alternatives of type III heterojunctions, using 2D p-MoTe₂/organic n-type dipyrazino[2,3-f:2′,3′-h]quinoxaline-2,3,6,7,10,11-hexacarbonitrile (HAT-CN) and 2D p-WSe₂/n-MoO_x systems. Those junction diodes appear to well-demonstrate static and dynamic NDR behavior via resonant tunneling and electron–hole recombination. Extended to an inverter circuit, p-MoTe₂/n-HAT-CN diode enables multilevel inverter characteristics as monolithically integrated with p-MoTe₂ channel field effect transistor. The same NDR diode shows dynamic LC oscillation behavior under a constant DC voltage, connected to an external inductor. From p-WSe₂/n-MoO_x oxide diode, similar NDR behavior to those of p-MoTe₂/n-HAT-CN is again observed along with LC oscillations. The authors attribute these visible oscillation results to high peak-to-valley current ratios of their organic or oxide/2D heterojunction diodes.     

Solution‐Processable Photonic Inks of Mie‐Resonant Hollow Carbon–Silica Nanospheres

Hollow carbon–silica nanospheres that exhibit angle‐independent structural color with high saturation and minimal absorption are made. Through scattering calculations, it is shown that the structural color arises from Mie resonances that are tuned precisely by varying the thickness of the shells. Since the color does not depend on the spatial arrangement of the particles, the coloration is angle independent and vibrant in powders and liquid suspensions. These properties make hollow carbon–silica nanospheres ideal for applications, and their potential in making flexible, angle‐independent films and 3D printed films is explored.     

Jig-free laser welding of Eagle XG glasses by using a picosecond pulsed laser

We have performed the jig-free laser welding on the alkaline earth boro-aluminosilicate glass (Eagle XG, Corning), which is commonly used in the display devices, by using a picosecond pulsed laser. Two sheets of Eagle XG glasses with 0.5 mm thickness each were placed one on top of the other. Due to the jig-free laser welding, there was a very thin air gap between the two glasses, and the experiment proceeded by line scanning. The welding performance was evaluated by observing the optical images from the top view and the bottom view and comparing the line images. We could bond the two glass surfaces on the laser spot, and achieve the successful welding of such glasses in the scanning speeds from 10 mm/s to 50 mm/s with the laser irradiance from 50 TW/cm²(500 J/cm²) to 83 TW/cm² (830 J/cm²). We demonstrated the feasibility of jig-free laser welding on the Eagle XG glass with the welding strength up to 50 MPa.

     

Hierarchical sampling optimization of particle filter for global robot localization in pervasive network environment

This paper presents a hierarchical framework for managing the sampling distribution of a particle filter (PF) that estimates the global positions of mobile robots in a large‐scale area. The key concept is to gradually improve the accuracy of the global localization by fusing sensor information with different characteristics. The sensor observations are the received signal strength indications (RSSIs) of Wi‐Fi devices as network facilities and the range of a laser scanner. First, the RSSI data used for determining certain global areas within which the robot is located are represented as RSSI bins. In addition, the results of the RSSI bins contain the uncertainty of localization, which is utilized for calculating the optimal sampling size of the PF to cover the regions of the RSSI bins. The range data are then used to estimate the precise position of the robot in the regions of the RSSI bins using the core process of the PF. The experimental results demonstrate superior performance compared with other approaches in terms of the success rate of the global localization and the amount of computation for managing the optimal sampling size.     

Succinct Palette and Color Model Generation and Manipulation Using Hierarchical Representation

We propose a new method to obtain the representative colors and their distributions of an image. Our intuition is that it is possible to derive the global model from the local distributions. Beginning by sampling pure colors, we build a hierarchical representation of colors in the image via a bottom‐up approach. From the resulting hierarchy, we can obtain satisfactory palettes/color models automatically without a predefined size. Furthermore, we provide interactive operations to manipulate the results which allow the users to reflect their intention directly. In our experiment, we show that the proposed method produces more succinct results that faithfully represent all the colors in the image with an appropriate number of components. We also show that the proposed interactive approach can improve the results of applications such as recoloring and soft segmentation.