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Most of the domestic car ferries departing from Jeju Port in Korea were replaced through the construction of new ships or the introduction of new used ships starting in 2018 after the Sewol Ferry accident. Amid this trend of ship replacement, the size of passenger ship has also become larger than in the past to increase passenger sales and cargo transportation profits, but the passenger ship berth configuration at Jeju Port have not improved significantly. In this study, the current status of passenger ships at Jeju Port was investigated, and a mooring safety assessment was conducted on car ferries exceeding the design berth capacity of the pier. Risk factors of the target ship were identified through mooring safety assessment. Through the sensitivity analysis of each improvement plan, a plan to improve mooring configuration was proposed and its effect was confirmed. As a result, the in case of Arion Jeju which is berthed at No. 2 pier, improvement plan scenario case 1 to 4 from the operator’s perspective did not secure the mooring safety due to the problem of exceeding maximum traction force with the size of the mooring post. However in case of scenario case 5 of the improvement plan through the additional installation of High Height Bitt, it was analyzed that a load of about 23% or less of the breaking strength of all lines acts on the mooring line and the load of 44% or less of the maximum traction force of the mooring post acts that the mooring safety was evaluated to be secured. The results of this study are expected to be used as reference materials for the establishment of safe passenger ship berth mooring configuration and the development of guidelines for mooring a car ferry.

Flexible and stretchable conductive thin films are required for the development of soft electronics; however, few existing films satisfy the requirements for both electrical/mechanical performances...

Solution-processed organic semiconductor thin films with high charge carrier mobility are necessary for development of next-generation electronic applications, but the rapid processing speed demanded for the industrial-scale production of these thin films poses a challenge to control of their thin-film properties, such as crystallinity, morphology, and film-to-film uniformity. Here, we show a new solution coating method that is compatible with a roll-to-roll printing process at a rate of 2 mm s

In article number 2002606, Seung Goo Lee, Kilwon Cho, and co‐workers demonstrate a finger padinspired multimodal mechanoelectric sensor for material discrimination and texture recognition. By integrating various electrical working mechanisms of piezoelectric, triboelectric, and piezoresistive, the sensor can identify and distinguish the external stresses from a single stimulus to a combination of multiple stimuli, enabling a potential application of artificial sensory systems for biomimetic prosthesis and robotic skins. [Image: see text]

In article number 2001184, Seung Goo Lee, Kilwon Cho, and co‐workers demonstrate a user‐interactive thermotherapeutic electronic skin by integrating thermochromic composite and a stretchable strain sensor. Both heat and color of the device are easily controlled by external mechanical strain. This device exhibits a potential application in effective connective tissue injury rehabilitation, while avoiding skin burns. [Image: see text]

A sweat sensor is expected to be the most appropriate wearable device for noninvasive healthcare monitoring. However, the practical use of sweat sensors is impeded by irregular and low sweat secretion rates. Here, a sweat-collecting patch that can collect sweat efficiently for fast and continuous healthcare monitoring is demonstrated. The patch uses cactus-spine-inspired wedge-shaped wettability-patterned channels on a hierarchical microstructured/nanostructured surface. The channel shape, in combination with the superhydrophobic/superhydrophilic surface materials, induces a unidirectional Laplace pressure that transports the sweat to the sensing area spontaneously even when the patch is aligned vertically. The patch demonstrates superior sweat-collecting efficiency and reduces the time required to fill the sensing area by transporting sweat almost without leaving it inside the channel. Therefore, a sensor based on the patch responds quickly to biochemicals in sweat, and the patch enables the continuous monitoring of changes in sweat biochemicals according to their changes in the wearer's blood.

SummaryBackground Although microneedles are one of the best transdermal drug delivery systems for active compounds, few clinical trials have examined the safety and efficacy of brightening microneedle patches. Aims To determine the efficacy and safety of a newly developed whitening microneedle patch. Patients/Methods A split-face study was designed for efficacy assessment with 34 Korean women applying the tested product (a whitening microneedle patch) on one cheek and a control whitening essence on the other. We objectively measured changes in melanin index values and skin brightness by mexameter and chromameter. Each participant also used global assessment to determine skin whitening. In addition, 55 participants were selected for primary skin irritation tests and repeated insult patch tests for safety assessments. Results Mean skin brightness and melanin indexes improved (P

Organometal halide perovskites (OHPs) exhibit superior charge transport characteristics and ultralow thermal conductivities. However, thermoelectric (TE) applications of OHPs have been limited because of difficulties in controlling their carrier concentration, which is a key to optimizing their TE properties. Here, facile control of the carrier concentration in Sn-based OHPs is achieved by developing 2D crystal structures. The 2D OHP crystals are laterally oriented using a mixed solvent, and the morphology and crystal structure of the coexisting 2D/3D hybrid structures are systematically controlled via doping with methylammonium chloride. The effective number neff of inorganic octahedron layers in the 2D OHPs shows a strong positive correlation with the carrier concentration. Moreover, the 2D structure induces the quantum confinement effect, which enhances both the Seebeck coefficient and the electrical conductivity. A 2D OHP shows a high power factor of 111 µW m-1 K-2 , which is an order of magnitude greater than the power factor of its 3D counterpart.

Pressure-sensitive electronic skin composed of a hierarchical structural array exhibits outstanding linear and high sensitivity in the pressure range exerted by gentle touch. By virtue of monolayer graphene acting as electrode material, this device can be operated with low voltage. Especially, its high transparency enables an accurate placement of the device on the target position when it is used for health monitoring.

This study proposed a satisfactory bonding formation mechanism between inter-crystallites fabricated by a vacuum kinetic spray (VKS). This paper confirmed the necessity of high-velocity impact for particle deposition. Based on both experimental (coating trials) and numerical approaches (ANSYS AUTODYN), the impact behavior of Y2O3 particles at different impact velocities was carefully analyzed. There existed a critical impact velocity above which a successive coating buildup with nanocrystal size was possible according to coating thickness measurement. Microstructural observations showed that dynamic fragmentation (creation of non-contaminated faying surface) of the impacting particle and consolidation of the pre-deposited layer occurred favorably at a high impact velocity. The localized deformation at the crystallite surface was attributed to inter-crystallite bonding (frictional heat generation during crystallite rotation). A numerical approach also supported the generation of sufficient energy for strong bonding by high von Mises stress, pressure, and temperature in the contact region at high velocity. Proper kinetic energy of the impact particle is key to successful Y2O3 coating deposition.

Human skin hyperpigmentation disorders occur when the synthesis and/or distribution of melanin increases. The distribution of melanin in the skin is achieved by melanosome transport and transfer. The transport of melanosomes, the organelles where melanin is made, in a melanocyte precedes the transfer of the melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by decreasing melanosome transport. In this study, we found that an extract of Saururus chinensis Baill (ESCB) and one of its components, manassantin B, inhibited melanosome transport in Melan-a melanocytes and normal human melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting the interaction between melanophilin and myosin Va. Manassantin B is neither a direct nor an indirect inhibitor of tyrosinase. The total melanin content was not reduced when melanosome transport was inhibited in a Melan-a melanocyte monoculture by manassantin B. Manassantin B decreased melanin content only when Melan-a melanocytes were co-cultured with SP-1 keratinocytes or stimulated by α-MSH. Therefore, we propose that specific inhibitors of melanosome transport, such as manassantin B, are potential candidate or lead compounds for the development of agents to treat undesirable hyperpigmentation of the skin.

Near-fields of non-resonantly laser-excited nanostructures enable strong localization of ultrashort light fields and have opened novel routes to fundamentally modify and control electronic strong-field processes. Harnessing spatiotemporally tunable near-fields for the steering of sub-cycle electron dynamics may enable ultrafast optoelectronic devices and unprecedented control in the generation of attosecond electron and photon pulses. Here we utilize unsupported sub-wavelength dielectric nanospheres to generate near-fields with adjustable structure and study the resulting strong-field dynamics via photoelectron imaging. We demonstrate field propagation-induced tunability of the emission direction of fast recollision electrons up to a regime, where nonlinear charge interaction effects become dominant in the acceleration process. Our analysis supports that the timing of the recollision process remains controllable with attosecond resolution by the carrier-envelope phase, indicating the possibility to expand near-field-mediated control far into the realm of high-field phenomena., The localized enhancement of laser light in optical near-fields of nanostructures enables the steering of ultrafast electronic motion. Here, the authors employ field propagation in nanospheres to obtain directional tunability and attosecond control of near-field-induced strong-field photoemission.

Anaplastic thyroid carcinomas are a highly aggressive and extremely lethal form of human cancer, but the biological characteristics related to their aggressive nature are not understood. Moreover, Gadd45 family proteins have been implicated in a variety of growth-regulatory mechanisms, including DNA replication and repair, G(2)/M checkpoint control, and apoptosis. In this study we found that Gadd45gamma RNA was present at significantly lower levels in anaplastic cancer cells, compared with normal primary cultured thyrocytes. In addition, the adenovirus-mediated reexpression of Gadd45gamma significantly inhibited the proliferation of anaplastic thyroid carcinoma cells, ARO, FRO, and NPA cells, which was attributed to apoptosis. Furthermore, the adenovirus-mediated delivery of Gadd45gamma gene in anaplastic thyroid cancer resulted in the inhibition of tumor growth in vivo. This in vitro and in vivo activity of the adenovirus-mediated transduction of CR6/Gadd45gamma, on anaplastic thyroid cancer cell growth suppression, was reminiscent of the effects of p53. This study demonstrates that the Gadd45gamma gene has potential use as a candidate gene for gene therapy in anaplastic thyroid cancer.

Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water-binding potential, and stimulates fibroblasts, causing collagen synthesis, with short- and long-term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt-face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation.

The Gadd45γ (growth arrest and DNA damage-inducible) gene is activated transcriptionally by at least two kinds of agents: DNA damaging agent such as methyl methanesulfonate (MMS) and UV radiation, or cytokines such as interleukin (IL)-6, IL-2 and granulocyte colony-stimulating factor (G-CSF). To investigate the sequences and transcription factors involved in induction of Gadd45γ after treatment with IL-6, the human gene was cloned and sequenced. We found C/EBP (CCAAT/enhancer-binding protein) family proteins, major transcription factors in the IL-6 signal transduction pathway, could regulate the transcriptional activity of the Gadd45γ promoter. In addition, a noncanonical C/EBP-binding site within the Gadd45γ promoter where C/EBPβ and C/EBPδ could bind, was identified by electrophoretic mobility shift assay (EMSA) and reporter gene analysis. Furthermore, we found a coordinated expression profile between Gadd45γ mRNA and C/EBPs (β and δ) protein during the differentiation of M1 cells: the amount of Gadd45γ transcripts became maximal when both C/EBPβ and C/EBPδ levels were high, on day 1 of differentiation of M1 cells after treatment with IL-6. These findings suggest that mitotic growth arrest coupled to M1 cell differentiation is mediated by C/EBPs stimulation of growth arrest-associated genes such as Gadd45γ.

Gadd45 family genes encode nuclear acidic proteins composed of Gadd45, MyD118, and CR6. Sequence analysis showed that Gadd45 family proteins (Gadd45, MyD118, and CR6) contain LXXLL signature motifs considered necessary and sufficient for the binding of several coactivators to nuclear receptors. Interaction between Gadd45 or CR6 and RXR alpha was confirmed by a two-hybrid test in yeast. Results from a series of GST pulldown assays showed that these Gadd45 family proteins interact with several nuclear hormone receptors including RXR alpha, RAR alpha, ER alpha, PPAR alpha, PPAR beta, and PPAR gamma2 in vitro. Interaction between Gadd45 family proteins and nuclear hormone receptors resulted in modest activation of transactivating function of nuclear hormone receptors in reporter systems. When fused to DNA binding domain of GAL4, Gadd45 and CR6 activated the UAS-mediated transcription in mammalian cells. These results suggest that Gadd45 family proteins bind to nuclear hormone receptors and act as nuclear coactivators.

Differentiation of PC12 cells triggered by nerve growth factor (NGF) is characterized by several well-defined events including induction of a set of neuron-specific genes, gain of membrane excitability, and morphological changes such as neurite outgrowth. Here we report that K252a, a protein kinase inhibitor, converts the proliferation signal of epidermal growth factor (EGF) into the morphological differentiation signal without inducing the sustained activation of ERK and the expression of neurofilament. Major effects of EGF/K252a, found also in the NGF-treated cells, are the sustained mobility shift of paxillin in SDS-PAGE and the promoted association of Crk-II with paxillin. These effects explain the prominent and robust development of peripheral focal adhesion assembly and stress fiber-like structures observed in the early stages of PC12 cell differentiation. These results suggest a model that cytoskeletal reorganization via focal adhesion assembly triggered by NGF provides a signal required for the morphological differentiation of PC12 cells.

During myogenesis, mononucleated myoblasts form multinucleated myotubes by membrane fusion. Efficiency of this intercellular process can be maximized by a simultaneous progress, with a time window, of other neighboring myoblasts in the differentiation program. This phenomenon has been described as the community effect. It proposes the existence of a molecule that acts as a differentiation-inducing signal to a group of identical cells. Here, we show that neuregulin is a strong candidate for this molecule in myoblast differentiation. The expression of neuregulin increased rapidly but transiently at early stage of differentiation of rat L6 cells. Neuregulin showed a potent differentiation-promoting activity in membrane fusion and expression of myosin heavy chain. The antibodies raised against neuregulin and its cognate receptor ErbB3, which were capable of neutralizing the signal pathway, inhibited myotube formation and expression of myosin heavy chain in both L6 cells and primary rat myoblasts. The progress of differentiation was mostly halted after the expression of myogenin and cell cycle arrest. These results suggest that the activation of an autocrine signaling of neuregulin may provide a basic mechanism for the community effect observed in the differentiation of the embryonic muscle cells.

The biological effects of drug-loaded biodegradable novel membrane for guided bone regeneration (GBR) was evaluated. The membranes were polyglycolic acid mesh coated with poly-L-lactic acid containing flurbiprofen, tetracycline or PDGF-BB. Porous structure was generated in the membranes by using a phase inversion method. The membrane was less toxic, nicely biodegradable and biocompatible for 8 wk after implantation in the dorsal skin of the rat. The drugs released from the membranes were shown to be effective for new bone formation. Tetracycline, flurbiprofen or PDGF-BB loaded membrane was markedly effective for osteoid tissue and new bone formation in the bony defect prepared in rat calvaria to compare with that by unloaded membrane. These results suggested that drug-loaded biodegradable barrier membrane might be a potential tool for GBR in periodontal therapy.

The effects of particle size of core-shell rubber on the fracture toughness of rubber-modified epoxies were investigated. Various sizes of core-shell rubber particles, from 0.16 to 1.2 μm in diameter, were synthesized by seeded emulsion polymerization. Particle size effects were clearly seen for lower crosslinked diglycidyl ether of bisphenol A (DGEBA)/piperidine resin. Fracture toughness increased as the particle size of core-shell rubber decreased from 1.2 to 0.4 μm. On the other hand, fracture toughness was constant in this range of particle sizes for higher crosslinked DGEBA/diaminodiphenylmethane (DDM) resin. Cavitation in the rubbery core and shear deformation in the matrix are the toughening mechanisms for DGEBA/piperidine resin, whereas cavitation is the only mechanism for DGEBA/ DDM resin. Toughening effectiveness decreased with

Human skin hyperpigmentation disorders occur when the synthesis and/or distribution of melanin increases. The distribution of melanin in the skin is achieved by melanosome transport and transfer. The transport of melanosomes, the organelles where melanin is made, in a melanocyte precedes the transfer of the melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by decreasing melanosome transport. In this study, we found that an extract of Saururus chinensis Baill (ESCB) and one of its components, manassantin B, inhibited melanosome transport in Melan-a melanocytes and normal human melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting the interaction between melanophilin and myosin Va. Manassantin B is neither a direct nor an indirect inhibitor of tyrosinase. The total melanin content was not reduced when melanosome transport was inhibited in a Melan-a melanocyte monoculture by manassantin B. Manassantin B decreased melanin content only when Melan-a melanocytes were co-cultured with SP-1 keratinocytes or stimulated by α-MSH. Therefore, we propose that specific inhibitors of melanosome transport, such as manassantin B, are potential candidate or lead compounds for the development of agents to treat undesirable hyperpigmentation of the skin.

Unsaturated polyester (UPE) has been toughened by incorporating novel liquid polyurethane (PU) rubber. PU rubber was synthesized using toluene di-isocyanate and polyols such as poly (propylene glycol) and poly (tetramethylene ether) glycoi, whose molecular weights vary from 650 to 4000. Particle size was varied from 0.1 to 3 μm by changing the polyol and the molecular weight of PU rubber, and the effects of particle size on the fracture toughness of PU rubber-modified UPE were investigated. Hydroxyl terminated PU rubber (HTPU) and isocyanate terminated PU rubber (ITPU) were used to study the effects of rubber-matrix adhesion. The toughening mechanisms observed by scanning electron microscope are debonding between rubber and matrix in HTPU-modified UPE, and cavitation in the rubber particle in ITPU-modified UPE. However, shear bands were not observed as UPE is a highly cross-linked thermoset with very short chain length between the cross-links. A 1.9-times increase in fracture toughness of UPE was achieved with the formation of cavitated particles. In order to measure the process zone size at the crack tip, the thin sections of tested double-notched four-point bending specimens were examined by optical microscope.

Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP- and hormone-sensitive lipase-dependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and down-regulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.

The Gadd45 family of proteins includes Gadd45alpha, MyD118/Gadd45beta, and CR6/OIG37/Gadd45gamma. These proteins play important roles in maintaining genomic stability and in regulating the cell cycle. This study reports the cloning of a novel protein called CR6-interacting factor 1 (CRIF1) which interacts with Gadd45alpha, MyD118/Gadd45beta, and CR6/OIG37/Gadd45gamma. CRIF1 binds specifically to the Gadd45 family proteins, as determined by an in vitro glutathione S-transferase pull-down assay and an in vivo mammalian cell two-hybrid assay along with coimmunoprecipitation assays. CRIF1 mRNA is highly expressed in the thyroid gland, heart, lymph nodes, trachea, and adrenal tissues. CRIF1 localizes exclusively to the nucleus and colocalizes with Gadd45gamma. Recombinant CRIF1 inhibits the histone H1 kinase activity of immunoprecipitated Cdc2-cyclin B1 and Cdk2-cyclin E, and the inhibitory effects were additive with Gadd45 proteins. Overexpression of CRIF1 increases the percentage of cells in G1, decreases the percentage of cells in S phase, and suppresses growth in NIH3T3 cells. The down-regulation of endogenous CRIF1 by the transfection of the small interfering RNA duplexes resulted in the inactivation of Rb by phosphorylation and decreased the G1 phase cell populations. Expression of CRIF1 is barely detectable in adrenal adenoma and papillary thyroid cancer and much lower than in adjacent normal tissue. The results presented here suggest that CRIF1 is a novel nuclear protein that interacts with Gadd45 and may play a role in negative regulation of cell cycle progression and cell growth.

K252a, a protein kinase inhibitor, acts as a neurotrophic factor in several neuronal cells. In this study we show that K252a enhanced the differentiation of C2C12 myoblasts as well as tyrosine phosphorylation of several focal adhesion-associated proteins including p130 Cas , focal adhesion kinase, and paxillin. The tyrosine phosphorylation of these proteins, reaching a maximum at 30 min after K252a treatment, closely correlated with the colocalization of these proteins in focal adhesion complexes and the coimmunoprecipitation of these proteins with p130 Cas . In addition, K252a stimulated longitudinal development of stress fiber-like structures and cell–matrix interaction in postmitotic myoblasts and eventually formation of well-developed myofibrils in multinucleated myotubes. Herbimycin A, a potent inhibitor of Src family kinases, and cytochalasin D, a selective disrupting-agent of actin filament, completely inhibited K252a-induced tyrosine phosphorylation as well as myoblast differentiation. Similar inhibitory effect was observed in the cells scrape loaded with a Rho inhibitor, C3 transferase, and the treatment of K252a induced a rapid translocation of Rho. These results are consistent with the model that Rho-dependent tyrosine phosphorylation of focal adhesion-associated proteins plays an important role in skeletal muscle differentiation.

The oxidation and spin states of the three cations in Co0.6Fe0.9Mn1.5O4, showing a nano-checkerboard structure, were investigated using nuclear magnetic resonance (NMR) and x-ray absorption spectrocopy (XAS) techniques. Comparison of the Co, Fe and Mn 2p XAS spectra with reference spectra suggests the presence of Co2+, Co3+, Fe3+, Mn2+ and Mn3+. Four distinctive NMR peaks were observed in the wide spectral range of 50?610?MHz. The external field dependence of the peaks and comparison of the peaks with those in other spinels also confirm the existence of the cation oxidation states suggested by XAS. Analysis of these results, combined with the magnitude of saturated magnetization, indicates an average chemical formula of (Mn2+xCo1?x2+)A[Cox?0.43+Mn3+1.5?xFe3+0.9]BO4 with x~0.9. Thus, Co0.6Fe0.9Mn1.5O4 appears to be a ferrimagnet with the majority spins from Fe3+, Co2+ and Mn3+ and the minority spins from Co3+ and Mn2+.