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Background and Purpose: The promotion of hair regeneration and growth heavily depends on the activation of Wnt/β-catenin signaling in the hair follicle including dermal papilla (DP). KY19382, one of the newly synthesized analogs of indirubin-3’-monoxime (I3O) was identified as a Wnt/β-catenin signaling activator via inhibition of the interaction between CXXC-type zinc finger protein 5 (CXXC5) and Dishevelled (Dvl) interaction. Given the close relationship between the Wnt/β-catenin signaling and hair regeneration, we investigated the effect of KY19382 on hair re-growth and hair follicle neogenesis. Experimental Approach: In vitro hair induction effects of KY19382 was performed in human dermal papilla cells. The hair elongation effects of KY19382 was confirmed through the vibrissa culture system. In vivo hair regeneration abilities of KY19382 was identified in three models: hair regrowth, wound-induced hair follicle neogenesis (WIHN), and hair patch assays using C57BL/6 mice. The hair regeneration abilities were analyzed by immunoblotting, alkaline phosphatase (ALP) and immunohistochemical staining. Key results: KY19382 activated Wnt/β-catenin signaling and elevated the expression of ALP and proliferation marker PCNA in DP cells. KY19382 also increased hair length in ex vivo cultured mouse vibrissa follicles and induced hair regrowth in mice. Moreover, KY19382 significantly promoted the generation of de novo hair follicles as shown by WIHN and hair patch assays. Conclusion and Implications: These results indicate that KY19382 is a potential therapeutic drug that exhibits effective hair regeneration ability via activation of the Wnt/β-catenin signaling for alopecia treatments.

In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.

Biomass hydrolysate, rich in glucose, was used to produce an important platform chemical, 5-hydroxymethylfurfural (HMF). By separating the solid biomass from solution after autohydrolysis, most of the inhibitors were removed from hydrolysate. Biphasic system, which prevents the HMF degradation, was optimized with HCl and AlCl3 catalysts. The yield of HMF conversion using biomass hydrolyzate under the optimized reaction conditions is comparable to the yield using pure glucose as a feedstock. This lab-generated HMF was purified via activated charcoal and oxidized to high value-added chemical, 2,5-furandicarboxylic acid (FDCA). The final FDCA yield of 65% was achieved. The results suggest that, with the separation of nonsugar components such as dissolved lignin and sugar degradation products, biomass hydrolysate is a promising source for HMF and FDCA production.

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities within a single biocompatible platform remains a challenge. Here, we introduce a device composed of an optical waveguide, six electrodes, and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes, while providing collocated neural recording and optical stimulation. The miniature (< 200 μm) footprint and modest weight (

FMS-like receptor tyrosine kinase-3 (FLT3) is expressed on acute leukemia cells and is implicated in the survival, proliferation and differentiation of hematopoietic cells in most acute myeloid leukemia (AML) patients. Despite recent achievements in the development of FLT3-targeted small-molecule drugs, there are still unmet medical needs related to kinase selectivity and the progression of some mutant forms of FLT3. Herein, we describe the discovery of novel orally available type 1 FLT3 inhibitors from structure-activity relationship (SAR) studies for the optimization of indirubin derivatives with biological and pharmacokinetic profiles as potential therapeutic agents for AML. The SAR exploration provided important structural insights into the key substituents for potent inhibitory activities of FLT3 and in MV4-11 cells. The profile of the most optimized inhibitor (36) showed IC50 values of 0.87 and 0.32 nM against FLT3 and FLT3/D835Y, respectively, along with potent inhibition against MV4-11 and FLT3/D835Y expressed MOLM14 cells with a GI50 value of 1.0 and 1.87 nM, respectively. With the high oral bioavailability of 42.6%, compound 36 displayed significant in vivo antitumor activity by oral administration of 20 mg/kg once daily dosing schedule for 21 days in a mouse xenograft model. The molecular docking study of 36 in the homology model of the DFG-in conformation of FLT3 resulted in a reasonable binding mode in type 1 kinases similar to the reported type 1 FLT3 inhibitors Crenolanib and Gilteritinib.

This study was designed to investigate the inhibitory activities of 5,7-dimethoxy-3-(2′hydro-xybenzyl)-4-chromanone (5,7-D chromanone) isolated from Portulaca oleracea L. on carbohydrate digesting enzymes and its ability to improve postprandial hyperglycemia in streptozotocin-induced diabetic mice. 5,7-D chromanone strongly inhibited α-glucosidase and α-amylase (half-maximal inhibitory concentration, IC50; 15.03 ± 2.59 μM and 12.39 ± 2.16 μM, respectively). The inhibitions were more effective than acarbose, which was the positive control. The increase in blood glucose level after ingesting starch was more significantly alleviated in the 5,7-D chromanone ingested group than in the control group of diabetic mice. In the control group, blood glucose levels were 24.64 ± 1.73, 27.22 ± 1.58, and 26.37 ± 1.41 mM, and in the 5,7-D chromanone ingested group were 23.87 ± 1.10, 23.38 ± 1.32, and 21.42 ± 1.36 mM at 30, 60, and 120 min, respectively. In addition, the area under the curve of blood glucose significantly declined with 5,7-D chromanone ingestion in diabetic mice. The results indicate that 5,7-D chromanone can help lower postprandial hyperglycemia by inhibiting carbohydrate digesting enzymes.

We demonstrate high light extraction efficiency of GaN-based light-emitting diodes (LEDs) using the selective growth of ZnO nanorods (NRs). The chemical wet-etched hexagonal patterns of ZnO transparent conductive film were used to achieve the selective growth of ZnO NRs, which could be grown at the non-etched hexagonal pattern regions due to the wet-etching effect. The optical transmittance of GaN-based LEDs was decreased by forming additional different types of ZnO transparent conductive films, such as the hexagonal ZnO patterns and the ZnO NRs selectively grown on hexagonal ZnO patterns. However, the light output power of GaN-based LEDs increased on decreasing the optical transmittance by employing a hexagonal ZnO transparent conductive film and selectively grown ZnO NRs. Based on these results, we suggest that the combined structure of the surface hexagonal patterns and the selectively grown ZnO NRs decreases the optical transmittance, but is more effective in improving the light extraction efficiency in the GaN-based LEDs.

Background: Exercise training-induced adaptation of central Blood Pressure (BP) depends on exercise mode. Kendo, a traditional Japanese martial art, is a unique exercise mode because its training encompasses anaerobic and resistance training components. However, the effects of habitual kendo training on central BP have not been established. Objective: The aim of this study was to compare the central BP of high-level kendo athletes and age-matched controls without exercise habits. Methods: Thirty-six young university kendo athletes (the kendo athlete group) and 29 young sedentary individuals (the control group) participated in this cross-sectional study. Central hemodynamics were estimated from carotid arterial waveforms via a generalized transfer function. Stroke volume was computed from brachial arterial waveforms using the Modelflow method. Results: Central systolic BP and Central Pulse Pressure (cPP) were higher in the kendo athlete group than in the control group (both, p < 0.01). Central diastolic BP did not differ between the two groups. Stroke Volume Index (SVI; stroke volume adjusted for body surface area) and the maximum rate of aortic pressure rise during systole (dP/dTmax), which reflects left ventricle contractility, were significantly higher in the kendo athlete group than in the control group (p < 0.05), and these parameters showed a significant positive correlation with cPP (SVI: r = 0.34, p < 0.01; dP/dTmax: r = 0.79, p < 0.01). Conclusion: These results suggest that habitual kendo training may increase central pulse pressure through increases in left ventricular systolic function. •Kendo is ideal for investigating of training adaptation since it induces the characteristics of anaerobic exercise training and resistance training; that is, kendo athletes had both high anaerobic capacity and high muscle strength compared with sedentary controls. •In the present study, central blood pressure (central systolic blood pressure and central pulse pressure) was significantly higher in the kendo athlete group than in the control group. •Stroke Volume Index (SVI; stroke volume adjusted for body surface area) and the maximum rate of aortic pressure rise during systole (dP/dTmax) but not augmented pressure in the kendo athlete group were also significantly higher than those in the control group. •In addition, SVI and dP/dTmax showed a significant positive correlation with central pulse pressure. •These results suggest that combined anaerobic exercise and muscular strength training may increase central blood pressure through increases in left ventricular systolic function.

This study is to investigate the effect of biological seawater properties on sea spray aerosols (SSA). Concentrations of chlorophyll-a and bacteria were measured at coastal site in Korea in fall and summer seasons. Also, aerosol mass spectrometer (AMS) was used to determine chemical constituents (organics, sulfate, nitrate, ammonium, and chloride) of non-refractory submicrometer aerosols sprayed from seawaters using a bubble bursting system. The average concentration of chlorophyll-a in seawater in fall was 1.75±0.78μg/l, whereas it significantly increased to 5.11±2.16μg/l in summer. It was found that the fraction of organics in the submicrometer SSA was higher in summer (68%) than fall (49%), and that the organic fraction in the SSA increased as the concentration of chlorophyll-a increased in seawater, suggesting that the high phytoplankton biomass in seawater could lead to the enhancement of organic species in the SSA.

A variety of adsorbent materials have been developed to extract uranium from seawater as an alternative traditional terrestrial mining. A large-scale deployment of these adsorbents would be necessary to recover useful quantities of uranium, and this raises a number of concerns regarding potential impacts on the surrounding marine environment. Two concerns are whether or not the adsorbent materials are toxic and any potentially harmful effects that may result from depleting uranium or vanadium (also highly concentrated by the adsorbents) from the local environment. To test the potential toxicity of the adsorbent with or without bound metals, Microtox assays were used to test both direct contact toxicity and the toxicity of any leachate in the seawater. The Microtox assay was chosen because it detected nonspecific mechanisms of toxicity. Toxicity was not observed with leachates from any of the 68 adsorbent materials that were tested, but direct contact with some adsorbents at very high adsorbent concentrati...

The Pacific Northwest National Laboratory (PNNL) is evaluating the performance of adsorption materials to extract uranium from natural seawater. Testing consists of measurements of the adsorption of uranium and other elements from seawater as a function of time using flow-through columns and a recirculating flume to determine adsorbent capacity and adsorption kinetics. The amidoxime-based polymer adsorbent AF1, produced by Oak Ridge National Laboratory (ORNL), had a 56-day adsorption capacity of 3.9 ± 0.2 g U/kg adsorbent material, a saturation capacity of 5.4 ± 0.2 g U/kg adsorbent material, and a half-saturation time of 23 ± 2 days. The ORNL AF1 adsorbent has a very high affinity for uranium, as evidenced by a 56-day distribution coefficient between adsorbent and solution of log KD,56day = 6.08. Calcium and magnesium account for a majority of the cations adsorbed by the ORNL amidoxime-based adsorbents (61% by mass and 74% by molar percent), uranium is the fourth most abundant element adsorbed by mass an...

The Marine Science Laboratory at the Pacific Northwest National Laboratory evaluated the impact of biofouling on the performance or uranium adsorbents. A surface-modified polyethylene adsorbent fiber provided by Oak Ridge National Laboratory, AF adsorbent, was tested in either the presence or absence of light to simulate deployment in shallow or deep marine environments. Samples of the adsorbent fiber were exposed to seawater as loose fibers packed with glass beads in columns and as >10-cm-long braids of fiber placed in a flume that provided a continuous flow representative of natural ocean currents. Exposure tests (42 days) in column and flume settings showed that biofouling resulted in decreased uranium uptake by the adsorbent fiber. Uranium uptake was reduced by up to 30%, in the presence of simulated sunlight, which also increased biomass accumulation and altered the microbial community composition on the fibers. These results suggest that deployment below the photic zone would mitigate the effects of...

Three homoisoflavonoids and one dimethoxychalcone from Portulaca oleracea L. were isolated using bioassay-guided fractionation and HPLC. Among the compounds 1-4, (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (compound 3) had the most effect on glucose uptake in the adipocytes. We investigated how (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone contributed to increase glucose uptake in 3T3-L1 adipocytes. Levels of the glucose transporters GLUT-4, as well as glucose uptake, and key proteins of the insulin pathway, namely PI3K/AKT and AMPK pathway are analyzed using glucose uptake assay and western blot analysis. Our results show that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone significantly increased glucose uptake by stimulating translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. High levels of expression of GLUT4 in the plasma membrane resulted from IRS-1 phosphorylation, PI3K activation, Akt phosphorylation and phosphorylation of AMPK, resulting in increased glucose uptake by the cells. The increase in glucose uptake due to (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone was significantly inhibited by the PI3K inhibitor and the AMPK inhibitor in 3T3-L1 adipocytes. These findings suggest that (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone may increase glucose uptake by stimulating GLUT4 translocation to the plasma membrane via activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes.

The characteristics of drinking groundwater at west Gyeong-nam were analyzed by investigating 3,698 cases which were carried out from January 2008 to september 2013. 24.5% of the observed data exceeded the drinking water quality standards. Among the drinking water quality standards, 40 parameters were found to exceed. and most problematic were total coliform and HPC(Heterotrophic Plate Count). The unfit ratio of each region for drinking water were 23.1% at Geoje, 18.7% at Geochang, 28.5% at Goseong, 24.1% at Namhae, 32.8% at Sacheon, 20.5% at Sancheong, 36.9% at Uiryeong, 29.2% at Jinju, 40.9% at Tongyeong, 24.7% at Hadong, 20.6.% at Hamyang, 20.1% at Hapcheon. The result of correlation showed that rainfall and unfit ratio of HPC may be associated with the hydrologic durability and season. The coefficient of correlation between them was 0.304. During the summer, the coefficient of correlation was 0.699. But the significant correlation between total coliform and rainfall was not found.

Recently, with increasing use of smartphones, the security threats also have increased rapidly. Especially, the compromised smartphone is very dangerous because it could be exploited in a DDOS attacks such as cyberterrorism as well as in the leakage of personal information. However, most bot detection mechanisms are still unsuitable for smartphone with its lower computing capability and limited battery capacity because they incur additional computational overheads or require pre-defined signatures. In this paper, we present an efficient bot detection mechanism in smartphones. Our mechanism detects effectively bots in outgoing traffic by using a correlation between user events and network traffic. We have implemented its prototype in Android smartphone and measured its performance. The evaluation results show that our mechanism provides low overhead to detect bots in smartphones.

The impact of authentic mineral dust particles sourced from the Gobi Desert (GDD) on the kinetic uptake coefficient of SO

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNFα, are currently used as promising therapeutic agents against the disease. Stabilization of the tran- script is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an im- portant transcript stabilizer, in tissues from experimental ani mals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dex- tran sodium sulfate (DSS)-treated mice compared to those in con trol tissues from normal mice. Moreover, the expression of HuR was very high only in the mucos al and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-tran- scriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic inves- tigations are warranted to determine the potential use of HuR as a predictive biomarker or a promis- ing target against IBD.

Carrageenan (CGN), a widely used food additive, has been shown to injure the epithelial barrier in animal models. This type of damage is a clinical feature of inflammatory bowel disease (IBD) in humans. In the present study, the effects of CGN on pro-apoptotic responses associated with macrophage inhibitory cytokine 1 (MIC-1) regulation in human enterocytes were evaluated. CGN up-regulated the expression of MIC-1 that promoted epithelial cell apoptosis. Although MIC-1 induction was dependent on pro-apoptotic p53 protein, the pro-survival protein activating transcription factor 3 (ATF3) was negatively regulated by p53 expression. However, MIC-1 enhanced the expression of the pro-survival protein ATF3 in enterocytes exposed to CGN. Functionally, MIC-1-mediated epithelial cell apoptosis was counteracted by the pro-survival action of ATF3 in response to CGN exposure. These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress.

The number concentrations of bacteria, viruses, and insoluble submicrometer particles in seawater were simultaneously measured to investigate the effects of biological activity and anthropogenic sources on the number of submicrometer particles in seawater sampled at various coastal locations during different seasons and at varying tidal levels. It was found that when an anthropogenic source was located near a sampling site, there was an increase in the number concentration of insoluble submicrometer particles, as well as enhancements of anthropogenic elements. The concentration of insoluble submicrometer particles was the highest at the Taean site, which had the strongest biological activity. The particle concentration was two to three times higher in spring than in summer or winter, which aligns with the observation that spring had the highest biological activity, which may be caused by the increase in solar radiation and nutrients. During spring tide, when there is maximum tidal variation, strong mixing and the suspension of accumulated sediments can occur. At this time, there were significant increases in the number concentrations of insoluble particles and viruses in seawater. Data suggest that the location, season, and tidal level have great impacts on the biological materials in seawater, which affects the number of insoluble submicrometer particles, and contributes to primary marine aerosols produced by the bubble bursting process.

Many companies have started to pay attention to the promotion of employee happiness and offer a variety of benefit plans to improve company productivity. Work-life harmony and leader-member exchange are important parts of the quality of working life. Organizational commitment is directly related to organizational performance. The purpose of this study was to examine the effects of work-life harmony and leader-member exchange on organizational commitment through employee happiness at work. Data was collected from 530 workers employed in a variety of organizations. It was found that work-life harmony and leader-member exchange quality were significant predictors of employee happiness at work and that the happiness at work was a significant indicator of organizational commitment. In addition, the happiness at work completely mediated the relationships between work-life harmony and organizational commitment, and partially mediated the relationships between leader-member exchange and organizational commitment. The results of this study will be helpful for employees and organizations as it will offer solutions to promote employee happiness and improve company productivity. In addition, it can be utilized as a basic resource for a corporate welfare system.

최근 여러 기업에서 직원의 행복 증진을 성과를 창출하기 위한 방안으로 보고 있으며, 이에 따라 다양한 복지제도를 시행하고 있다. 본 연구에서는 직장에서의 행복에 지대한 영향을 미치는 것으로 일 영역과 생활 영역에서의 조화와, 상사-부하와의 관계를 꼽았으며, 조직의 성과와 직결되는 중요한 변인으로 조직몰입을 꼽았다. 따라서 본 연구에서는 일과 생활의 조화와 상사-부하 관계가 조직몰입에 미치는 과정과 이러한 관계에서 직장에서의 행복이 매개하는지 검증하고자 하였다. 직장인 530명을 대상으로 조사한 결과 일과 생활의 조화와 상사-부하의 관계는 직장에서의 행복에 정적인 영향을 미치는 것으로 나타났다. 또한 직장에서의 행복은 조직몰입에 정적인 영향을 미치는 것으로 드러났다. 직장에서의 행복은 일과 생활의 조화와 조직몰입 간의 관계를 완전매개하는 것으로 나타났으며, 상사-부하의 관계와 조직몰입과의 간의 관계에서는 부분매개하는 것으로 확인되었다. 일과 생활이 조화로울수록, 상사와 부하 관계가 좋을수록 직장인들은 조직에서 더 행복하고 회사에 더 머무르려 한다는 것을 확인할 수 있었다. 이러한 발견은 개인의 행복 증진과 기업차원의 성과에 유익할 것이므로, 기업의 다양한 복지제도를 위한 기초자료로 활용될 수 있을 것이다.