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Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.

This article presents an output-capacitorless digital low-dropout regulator (OCL-DLDO) for fine-grained on-chip power delivery and management in system-on-chip devices. The proposed OCL-DLDO incorporates three distinct feedback loops: asynchronous, coarse, and fine loops. The asynchronous loop is activated during drastic load transients, rapidly restoring the output voltage and achieving a small voltage undershoot even without any output capacitor. The coarse loop, which is equipped with adaptive gain adjustment logics based on least-mean-square algorithm, adaptively adjusts the connection of power switches for fast and accurate voltage regulation. Lastly, the fine loop, which is implemented with shift-registers-based control, takes over the control in steady-states for low output voltage ripples and quiescent current. The proposed OCL-DLDO was fabricated in 65 nm CMOS process with an active area of 0.041 mm2. The measurement results show that the proposed OCL-DLDO achieves a peak current efficiency of 99.91% and a figure-of-merit as low as 2.87 fs when driving 25 mA of load current.

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

ARG2 has been reported to inhibit autophagy in vascular endothelial cells and keratinocytes. However, studies of its mechanism of action, its role in skin fibroblasts, and the possibility of promoting autophagy and inhibiting cellular senescence through ARG2 inhibition are lacking. We induced cellular senescence in dermal fibroblasts by using H2O2. H2O2-induced fibroblast senescence was inhibited upon ARG2 knockdown and promoted upon ARG2 overexpression. The microRNA miR-1299 suppressed ARG2 expression, thereby inhibiting fibroblast senescence, and miR-1299 inhibitors promoted dermal fibroblast senescence by upregulating ARG2. Using yeast two-hybrid assay, we found that ARG2 binds to ARL1. ARL1 knockdown inhibited autophagy and ARL1 overexpression promoted it. Resolvin D1 (RvD1) suppressed ARG2 expression and cellular senescence. These data indicate that ARG2 stimulates dermal fibroblast cell senescence by inhibiting autophagy after interacting with ARL1. In addition, RvD1 appears to promote autophagy and inhibit dermal fibroblast senescence by inhibiting ARG2 expression. Taken together, the miR-1299/ARG2/ARL1 axis emerges as a novel mechanism of the ARG2-induced inhibition of autophagy. Furthermore, these results indicate that miR-1299 and pro-resolving lipids, including RvD1, are likely involved in inhibiting cellular senescence by inducing autophagy.

LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchymal transition (EMT) of lung cancer cells. A549 and H1299 lung cancer cells were induced to undergo via TGF-β1 treatment, resulting in the downregulation of E-cadherin and upregulation of N-cadherin and Vimentin concurrently with increases in the migration and invasion capacities of the cells. These effects of TGF-β1 were suppressed upon co-treatment of the cells with LW1497. An RNA-seq analysis revealed that LW1497 induced differential expression of genes related to hypoxia, RNA splicing, angiogenesis, cell migration, and metastasis in the A549 lung cancer cell lines. We confirmed the differential expression of Slug, an EMT-related transcription factor. Results from Western blotting and RT-PCR confirmed that LW1497 inhibited the expression of EMT markers and Slug. After orthotopically transplanting A549 cancer cells into mice, LW1497 was administered to examine whether the lung cancer progression was inhibited. We observed that LW1497 reduced the area of cancer. In addition, the results from immunohistochemical analyses showed that LW1497 downregulated EMT markers and Slug. In conclusion, LW1497 suppresses cancer progression through the inhibition of EMT by downregulating Slug.

The effects of an anti-rolling tank (ART) on vessel motions were numerically investigated. The potential-based BEM vessel motion simulation program and particle-based computational fluid dynamics program were dynamically coupled and used to perform a simulation of vessel motions with ART. From the time domain simulation results, the response amplitude operators for sway and roll motions were obtained and compared with the corresponding experimental and numerical results. Because the main purpose of ART was only to reduce roll motions, it was important to show that the natural properties of a floating vessel were not changed by the effects of ART. Various ART filling ratios and several ART positions were considered. In conclusion, ART only reduced the roll motion regardless of its filling ratio and position.

The ocean waves and broken waves can disturbance the sea bed at the near shore. Its disturbance can be calculated by measuring or estimating of wave loads, and then apply the obtained load on the sea bed model. At this time, it has two step, firstly the it needs to calculate wave loads from computational fluid dynamics technique, and the sea bed model as soil are fed this load to calculate the soil movement. In this study, the particle method based on the Lagrangian approach is employed to simulate the wave load estimation and the soil movement simultaneously. The particle method has two forms which are fluid particle model and solid particle model, and two models are dynamically interacted to solve the soil disturbance problem.

In general, multi-fluid multi-interface problems are more complicated than single-phase problems and therefore require sophisticated and robust algorithm development. In this study, a moving particle semi-implicit (MPS) method based on the Lagrangian approach was extended to a multi-phase system with multiple interfaces. Accordingly, several new particle interaction models, including self-buoyancy-correction, surface tension, and interface boundary condition models, were introduced. Representative multi-liquid MPS sloshing simulation results were compared with corresponding experimental results with three liquids. The results agree well for both global behaviors and the much smaller-scale interfacial instability phenomenon called the Kelvin–Helmholtz instability (KHI). The validated multi-phase MPS method was subsequently applied to the classical Poiseuille problem of two fluids flowing with different velocities between two parallel plates The KHI is triggered when the destabilizing effect of a shear across an interface with a sufficient relative velocity overcomes the stabilizing effect of gravity and surface tension. Both viscosity and surface tension tend to limit the growth of KHIs when they are over certain values. For many possible combinations of density ratios and surface tensions producing the same Richardson-number, the body-force component plays a much more important role than the surface-tension component if the interfacial wave number is not very high.

본 연구는 학습자의 개별 특성으로서 다중지능, 정서지능 및 학문적 자아개념 간의 관계를 분석하 고, 다중지능 수준에 따라 정서지능 및 학문적 자아개념 간의 관계를 분석하는 것이다. Gardner(1983) 의 다중지능 이론과 Mayer, Salovey(1997)의 정서지능 이론, Shavelson과 Bolus(1982)의 자아개념 모 형을 바탕으로 연구하였다. 연구를 위하여 서울시에 위치한 초등학교 6학년 학생 총 167명을 대상으 로 검사하였으며, 검사 분석 결과 다중지능과 정서지능 및 학문적 자아개념사이에는 대체적으로 유의 미한 상관이 있는 것으로 나타났으며, 다중지능 수준에 따라 정서지능과 학문적 자아개념에서 유의미 한 차이가 있는 것으로 나타났다. 즉, 다중지능 수준이 높을수록 정서지능과 학문적 자아개념도 높다 고 볼 수 있다. 각 지능들은 서로 영향을 주며 함께 작용하고 있으며, 강점지능은 학습에 대한 태도 와 학교생활의 만족감을 높여 학문적 자아개념에도 긍정적 영향을 줄 수 있다고 본다. 따라서 아동의 개별적 특성으로서 다중지능과 정서지능, 학문적 자아개념의 관계를 이해하여 이를 활용하여 효율적 으로 학습할 수 있도록 도운다면 개인의 학습역량과 잠재적 소질을 잘 발현 할 수 있는 토대가 될 것 이다.

Active anti-rolling tank (ART) is sophisticated equipment on a floating vessel to reduce roll motion for the slender ship-shape vessel. Three-dimensional panel based diffraction and radiation linear potential program employed to obtain hydrodynamic coefficients of floating vessel. For the ship motion, a BEM (Boundary Element Method)-based ship motion program was used and inner sloshing effects were conducted by a particle-based CFD (Computational Fluid Dynamics) program which is the Moving Particle Semi-implicit (MPS). By using panel program, the hydrodynamic coefficients were obtained in frequency domain, and then were converted into time domain ship motion simulation program. In this procedure, time memory effect was considered by Volterra series expansion. The ship motion program and sloshing program was coupled dynamically; inner tank received displacement, velocity and acceleration data from ship motion program and use them for inner tank motion, while the ship motion program was waiting external forces due to sloshing impact loads and inertia forces/moments from sloshing simulation program. Thus, two programs run simultaneously and allowed real time coupling effects of inner sloshing on vessel motion. By comparing response amplitude operator (RAO) of the vessel without anti-rolling tank, it was shown both values have good agreement. And then comparing between vessels with and without anti-rolling tank, it is shown that the effects of ART changed and shift RAOs. Furthermore, by changing the location of ART, location effects of ART were also investigated.

When a liquid cargo tank is partially filled with fluid, internal impact loads can be occurred from the vessel`s motions. In this study, liquid sloshing problems with a thin top layer of particles with a lighter density than water and the coupling effects of the liquid-sloshing/vessel-motion were investigated in order to reduce the sloshing-induced impact loads. The PNU-MPS (Pusan-National-University-modified Moving Particle Simulation) method for solving the liquid motion inside a tank and the CHARM3D BEM (Boundary Element Method) based time-domain ship motion analysis program for vessel-motion simulation were coupled. From the simulation results, we could see that the floaters seemed to be quite effective at reducing the sloshing impact loads in the case of tank-only sloshing problems, but not as much for the coupling problem with vessel motion.

In this paper, the feasibility of ORBCOMM satellite-based automatic identification system (SAT-AIS) is evaluated in the context of ship AIS slot collision probability depending on reporting rate, We evaluate detection probability evaluation of ORBCOMM satellite-based AIS considering link budget, SOTDMA protocol and satellite's swath width. The simulation determines the total number of vessels served by ORBCOMM satellite according to satellite's swath width, AIS slot allocation and reporting rate. By simulation results, the ORBCOMM satellite-based AIS slot collision is increased directly proportional to the total number of vessels and the more detection probability evaluation of ORBCOMM satellite-based AIS degrader, the more sip AIS reporting rate shorter.

For oil/gas production/processing platforms, multiple liquid layers can exist and their respective sloshing motions can also affect operational effectiveness or platform performance. To numerically simulate those problems, a new multiliquid moving particle simulation (MPS) method is developed. In particular, to better simulate the relevant physics, robust self-buoyancy model, interface searching model, and surface-tension model are developed. The developed multiliquid MPS method is validated by comparisons against experiment in which three-liquid-sloshing experiment and the corresponding linear potential theory are given. The validated multiliquid MPS program is subsequently coupled with a vessel-motion program in time domain to investigate their dynamic-coupling effects. In case of multiple liquid layers, there exists a variety of sloshing natural frequencies for respective interfaces, so the relevant physics can be much more complicated compared with the single-liquid-tank case. The simulation program can also reproduce the detailed small-scale interface phenomenon called Kelvin–Helmholtz instability. The numerical simulations also show that properly designed liquid cargo tank can also function as a beneficial antirolling device.

For oil/gas production/processing platforms, multiple liquid layers can exist and their respective sloshing motions can also affect platform performance. To numerically simulate those problems, a new multi-liquid MPS (Moving Particle Simulation) method is developed. In particular, to better simulate the relevant physics, robust self-buoyancy model, interface searching model, and surface-tension model are developed. The developed multi-liquid MPS method is validated by comparisons against Molin et al’s (2012) three-liquid-sloshing experiment and the corresponding linear potential theory. The verified multi-liquid MPS program is subsequently coupled with a vessel-motion program in time domain to investigate their dynamic-coupling effects. In case of multiple liquid layers, there exist more than one sloshing natural frequencies, so the relevant physics can be much more complicated compared with the single-liquid-tank case. The numerical simulations also show that liquid cargo can function as a beneficial anti-rolling device.

Metamifop is a novel herbicide with as yet undetermined properties. To assess its carcinogenicity, metamifop was mixed into standard rodent chow and fed to male and female Wistar rats at doses of 10, 100 and 750ppm for 104weeks. The viability/mortality of these rats was not affected by treatment with metamifop. Treatment had no significant effects on clinical parameters, and food consumption. Males and females fed 750ppm of metamifop for 104weeks showed decreases in body weight and body weight gain. Histopathological examination revealed that treatment with metamifop reduced non-neoplastic findings (chronic progressive nephropathy, tubular basophilia, tubular casts, glomerulosclerosis, basophilic and clear cell foci, senile atrophy, and mesothelial hyperplasia) and reduced neoplastic findings (thymoma, pituitary adenoma, and mammary fibroadenoma and adenocarcinoma in females, and mesenteric lymph node hemangioma in males) compared with control groups. Benign granulosa cell tumors were increased in a dose-dependent manner. As metamifop did not show any genotoxic potential, and there was no correlation between ovarian cancer and increased gonadal hormone levels in humans, the granulosa cell tumors observed in female rats fed a high dose of metamifop were considered not relevant to humans.

The mixed oil and gas including water and sand are extracted from well to offshore structure. This mixed fluid must be separated for subsequent processes by using wash tanks or separators. To design such a system, a proper numerical-prediction tool for multiphase fluids is required. In this regard, a new moving particle simulation (MPS) method is developed to simulate multiliquid-layer sloshing problems. The new MPS method for multifluid system includes extra search methods for interface particles, boundary conditions for interfaces, buoyancy-correction model, and surface-tension model for interface particles. The new particle interaction models are verified through comparisons with published numerical and experimental data. In particular, the multiliquid MPS method is verified against Molin et al’s (2012) experiment with three liquid layers. In case of excitation frequency close to one of the internal-layer resonances, the internal interface motions can be much greater than top free-surface motions. The verified multiliquid MPS program is subsequently used for more nonlinear cases including multichromatic multimodal motions with larger amplitudes, from which various nonlinear features, such as internal breaking and more particle detachment, can be observed. For the nonlinear case, the differences between with and without buoyancy-correction and surface-tension models are also demonstrated.

This paper describes the design and development of a hovering AUV constructed at Cheju National University and analyses the dynamic performance of the vehicle using simulation program. The main purpose of this AUV is to carry out fundamental tests on its station keeping, attitude control, and desired position tracking. Its configuration is similar to the general ROV appearance for underwater works and its dimensions are 0.75 m times 0.5 m times 0.5 m. It has 4 thrusters of 450 watts for longitudinal/lateral/vertical propulsion and is equipped with a pressure sensor for measuring water depth and a magnetic compass for measuring heading angle. The navigation of the vehicle is controlled by an on-board Pentium III-class computer, which runs with the help of the Windows XP operating system. These give us an ideal environment for developing various algorithms needed for developing and advancing hovering AUV.

The Armed Services have undertaken a Joint Services Project to develop prototype methods for measuring job performance and, if feasible, to link enlistment standards to on-the-job performance. As one step toward meeting the first purpose of the project, our study assessed the reliability of scores on four measures of job performance of machinist mates in the Navy: a hands-on performance test, a paper-and-pencil job knowledge test, job task perform- ance ratings, and global ratings. Generalizability theory was used to estimate the reliability of the measures and to improve the design of each. The generalizability analyses investigated the consistency of performance scores over observers, tasks (equipment operation, casualty control, preventative maintenance), and types of raters (supervisor, peer, and self). Recommenda- tions about the optimal designs of studies for decision making (e.g., pre- dicting hands-on performance scores from the other measures of job perform- ance) were based on the findings.

Publisher Summary This chapter discusses the issues, alternative, and consequences of mul;tilevel investigations of systematically varying slopes. Generally, the situations of interest are large-scale non-experimental studies of educational effects. The focus may be on either the program—for example, curricular innovation, school type—the school, the classroom/teacher, or some combination, as the sources of educational effects. Regardless, the intent is to identify the antecedents of student performance and attitude and estimate the magnitude of their effects. The typical study involves two-stage sampling. Either a sample, which can be random, representative, or convenience, of schools is drawn and students are sampled randomly or on a stratified random basis from within schools. Alternatively, a sample of classrooms is chosen, either randomly or exhaustively within a sample of schools, and all the students within the classrooms comprise the total study sample. In either case, this situation yields data with dependencies among observations within the first-stage sampling units; that is, there are correlations among individuals in the same macro units.