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We report an improved approach for the integration of flow synthesis and continuous chromatography, for applications in the end-to-end preparation of pharmaceutically-relevant small molecules. It involves the combination of sequential microreactors and twin-column counter-current chromatography based on the often-used C18 columns. The column loading method ensures that the product breaking through a fully loaded first column is loaded onto the second one, avoiding waste of precious material and technological complexity associated with the use of four-to-six columns typical of simulated moving bed chromatography. The system was applied to synthesize biphenyl via Suzuki–Miyaura reaction, and was also demonstrated for other structurally-different compounds. Compared to the discontinuous and other traditional approaches, our method leads to higher isolated yields (ca. +60%), higher productivity (ca. +30%), and reduced solvent consumption (ca. −80%). A circularity and life-cycle analysis was also conducted to demonstrate the environmental benefits of the flow process. Funding from the European Commission (GV, grant agreement 101031710), Bracco Imaging (AS, VR, and GV), Fondazione Bracco (GV), and YMC Japan (TKK and MS) is gratefully acknowledged.

Background: Tumor-derived exosomal microRNAs are key elements of the cell-cell communications response to lots of stimuli. However, various functions of the exosome in tumor suppression by radiotherapy (RT) are not clearly understood. Our study showed a previously unknown interaction of p53 and histone deacetylase 5 (HDAC5) by radiation exposure in hepatocellular carcinoma (HCC). Methods: Using serial ultracentrifugation methods, radiation and non-radiation exosomes were purified to investigate the radioresistance of miRNA151a-3p. Radiation doses were treated in 2gy and 4gy using radiation equipment X-RAD 320 to observe the expression of HDAC5 and p53 in hepatic cancer cells. Exosomal miRNA bioinformatics analysis was conducted to find a variation in the miRNA configuration inside Exosome after radiation exposure.Results: HDAC5 and p53 interacted by exposure to radiation, which increased exosome release and altered microRNAs' composition within exosomes. Also, we have described the intercommunication occurring between irradiated and untreated cells via exosomal microRNAs that affect tumor proliferation. In particular, the expression of exosomal microR151a-3p was markedly reduced by radiation treatment. We confirmed that inhibition of exosomal microR151a-3p promotes suppression of non-irradiated cancer cells, thereby increasing RT sensitivity. Conclusion: our present findings demonstrated HDAC5 is a key component of the p53-mediated release of exosomes resulting in tumor suppression through exosomal microRNA-151a-3p in response to radiation. Finally, we highlight the important role of exosomal microRNA 151a-3p as a biomarker in enhancing RT sensitivity.

Tumor-derived exosomes (TEXs) contain enriched miRNAs, and exosomal miRNAs can affect tumor growth, including cell proliferation, metastasis, and drug resistance through cell-to-cell communication. We investigated the role of exosomal miR-1260b derived from non-small cell lung cancer (NSCLC) in tumor progression. Exosomal miR-1260b induced angiogenesis by targeting homeodomain-interacting protein kinase-2 (HIPK2) in human umbilical vein endothelial cells (HUVECs). Furthermore, exosomal miR-1260b or suppression of HIPK2 led to enhanced cellular mobility and cisplatin resistance in NSCLC cells. In patients with NSCLC, the level of HIPK2 was significantly lower in tumor tissues than in normal lung tissues, while that of miR-1260b was higher in tumor tissues. HIPK2 and miR-1260b expression showed an inverse correlation, and this correlation was strong in distant metastasis. Finally, the expression level of exosomal miR-1260b in plasma was higher in patients with NSCLC than in healthy individuals, and higher levels of exosomal miR-1260b were associated with high-grade disease, metastasis, and poor survival. In conclusion, exosomal miR-1260b can promote angiogenesis in HUVECs and metastasis of NSCLC by regulating HIPK2 and may serve as a prognostic marker for lung cancers.

A segmented-core (SC) structure has been widely used for high-power-density (HP) motors. However, the SC motor is associated with a number of problems due to the complexity of both the structure and the manufacturing process. To address these issues, a novel structure of a HP motor is proposed, referred to as the ring-coupled segmented-stator (RSS) model here. The proposed RSS can increase the reliability, the stability, and the manufacturability of motor. Furthermore, useful thermal analysis and design flow which take into account the RSS and asymmetric overhang structure of the motor are proposed in this research. The proposed lumped parameter thermal network (LPTN) for the thermal analysis shows a good agreement with experimental data within 9.8% difference. The proposed analysis and design method can be used for the diverse kinds of motor requiring the HP. The usefulness of the proposed RSS motor, the analysis method, and the design method are verified through the experiment in this research.

Label-free optical diffraction tomography (ODT), an imaging technology that does not require fluorescent labeling or other pre-processing, can overcome the limitations of conventional cell imaging technologies, such as fluorescence and electron microscopy. In this study, we used ODT to characterize the cellular organelles of three different stem cells-namely, human liver derived stem cell, human umbilical cord matrix derived mesenchymal stem cell, and human induced pluripotent stem cell-based on their refractive index and volume of organelles. The physical property of each stem cell was compared with that of fibroblast. Based on our findings, the characteristic physical properties of specific stem cells can be quantitatively distinguished based on their refractive index and volume of cellular organelles. Altogether, the method employed herein could aid in the distinction of living stem cells from normal cells without the use of fluorescence or specific biomarkers.

The cell nucleus is a three-dimensional, dynamic organelle organized into subnuclear compartments such as chromatin and nucleoli. The structure and function of these compartments are maintained by diffusion and interactions between related factors as well as by dynamic and structural changes. Recent studies using fluorescent microscopic techniques suggest that protein factors can access and are freely mobile in heterochromatin and in mitotic chromosomes, despite their densely packed structure. However, the physicochemical properties of the chromosome during cell division are not fully understood. In the present study, characteristic properties such as the refractive index (RI), volume of the mitotic chromosomes, and diffusion coefficient (D) of fluorescent probes inside the chromosome were quantified using an approach combining label-free optical diffraction tomography with complementary confocal laser-scanning microscopy and fluorescence correlation spectroscopy. Variations in these parameters correlated with osmotic conditions, suggesting that changes in RI are consistent with those of the diffusion coefficient for mitotic chromosomes and cytosol. Serial RI tomography images of chromosomes in live cells during mitosis were compared with three-dimensional confocal micrographs to demonstrate that compaction and decompaction of chromosomes induced by osmotic change were characterized by linked changes in chromosome RI, volume, and the mobilities of fluorescent proteins.

// Je-won Ryu 1, * , Sung Sik Choe 2, * , Seung-Hee Ryu 1 , Eun-Young Park 1 , Byoung Wook Lee 3 , Tae Keun Kim 4 , Chang Hoon Ha 3 , Sang-wook Lee 1 1 Department of Radiation Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea 2 Department of Biological Sciences, Institute of Molecular Biology and Genetics, National Creative Research Institutive Center for Adipose Tissue Remodeling, Seoul National University, Seoul, Republic of Korea 3 Asan Institute for Life Science, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Republic of Korea 4 Department of Life Science, College of Natural Science, Hallym University, Kyeongki Province, Republic of Korea * These authors contributed equally to this work Correspondence to: Chang Hoon Ha, email: chhoonha@gmail.com Sang-Wook Lee, email: lsw@amc.seoul.kr Keywords: Epidermal Growth Factor (EGF), Purinergic Receptor 2(P2Y), Redox Factor-1(Ref-1), Zinc Finger-containing Transcriptional Regulator 1(EGR1), Phosphatase and Tensin Homolog (PTEN) Received: September 30, 2016 Accepted: November 24, 2016 Published: December 07, 2016 ABSTRACT Epidermal growth factor (EGF) signaling promotes cell proliferation and survival in several types of cancer. Here, however, we showed that EGF inhibits proliferation and promotes programmed cell death in non-small cell lung cancer (NSCLC) cells. In A549 cells, EGF increased redox factor-1 (Ref-1) expression and the association of Ref-1 with zinc finger-containing transcriptional regulator (EGR1) via activation of p22 phox , RAC1, and an NADPH oxidase subunit. EGF increased p22 phox and RAC1 expression through activation of purinergic receptors (P2Y). Elevated Ref-1/EGR1 levels increased phosphatase and tensin homolog (PTEN) levels, leading to inhibition of the Akt pathway. EGF-induced PTEN upregulation increased apoptosis and autophagy-induced damage in A549 cells, whereas Ref-1 knockdown blocked EGF-induced PTEN upregulation in an NADPH oxidase p22 phox subunit-independent manner. In addition, p22 phox knockdown restored EGF-induced effects, implying that changes in P2Y activity caused by EGF, which activates NADPH oxidase via RAC1, influenced Ref-1-mediated redox regulation. Finally, EGF similarly attenuated cell proliferation and promoted autophagy and apoptosis in vivo in a xenograft model using A549 cells. These findings reveal that EGF-induced redox signaling is linked to Ref-1-induced death in NSCLC cells.

The instability of recombinant basic fibroblast growth factor (bFGF) is a major disadvantage for its therapeutic use and means frequent applications to cells or tissues are required for sustained effects. Originating from silkworm hemolymph, 30Kc19α is a cell-penetrating protein that also has protein stabilization properties. Herein, it was investigated whether fusing 30Kc19α to bFGF could enhance the stability and skin penetration properties of bFGF, which may consequently increase its therapeutic efficacy. The fusion of 30Kc19α to bFGF protein increased protein stability, as confirmed by ELISA. 30Kc19α-bFGF also retained the biological activity of bFGF as it facilitated the migration and proliferation of fibroblasts and angiogenesis of endothelial cells. It was discovered that 30Kc19α could improve the transdermal delivery of a small molecular fluorophore through the skin of hairless mice. Importantly, it increased the accumulation of bFGF and further facilitated its translocation into the skin through follicular routes. Finally, when applied to a skin wound model in vivo, 30Kc19α-bFGF penetrated the dermis layer effectively, which promoted cell proliferation, tissue granulation, angiogenesis, and tissue remodeling. Consequently, our findings suggest that 30Kc19α improves the therapeutic functionalities of bFGF, and would be useful as a protein stabilizer and/or a delivery vehicle in therapeutic applications.

This study was performed to establish a production system for in situ and ex situ conservation of Elsholtzia minima Nakai, an endemic plant grown in Jeju Island. Moreover, this study aimed to identify root-growth characteristics according to the use of pre-treatment agents and seedling growth effect according to fertilizer application. The mean temperature was similar in greenhouse and vinyl-moist chamber, but air humidity was higher in vinyl-moist chamber than in greenhouse. After stem planting of Elsholtzia minima Nakai, initial root growth was observed after 10 days in greenhouse and after 7 days in vinyl-moist chamber. Root growth rate was more rapid in vinyl-moist chamber. Moreover, survival rate, root growth rate and root number was slightly higher in vinyl-moist chamber than in greenhouse, indicating that vinyl-moist chamber is more effective in plant growth. When pre-treatment agents were used to remove root growth-inhibiting substances, a higher root growth rate of more than 95% was found in pre-treatment groups, excluding the group treated with AgNO3 at 77.5%. Thus, Elsholtzia minima Nakai is thought to have less root growth inhibitors. In the analysis of nitrogen application rate and Osmocote application by seedling container, a difference was found in survival rate and growth according to application rate and container conditions. When Osmocote, a slow release fertilizer, was applied to the soil surface around each culture container, survival rate and the growth of aerial and root parts were most favorable. Thus, Osmocote fertilizer is thought to be desirable for seedling propagation of Elsholtzia minima Nakai.

We have researched a gondola typed robot system for building facade maintenance. Its main application is to paint on building facade. To apply a robot system to the painting tool,recognition of building wall shape should be preceded. In this paper, we proposed a limit switch module as a mechanical sensor method. As experiments, we applied the proposed module to window and obstac le on wall with attitude reference sensor (ARS) and laser height sensor (distance sensor).

Hexagonal boron nitride (h-BN) has been previously manufactured using mechanical exfoliation and chemical vapor deposition methods, which make the large-scale synthesis of uniform h-BN very challenging. In this study, we produced highly uniform and scalable h-BN films by plasma-enhanced atomic layer deposition, which were characterized by various techniques including atomic force microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray diffraction. The film composition studied by X-ray photoelectron spectroscopy and Auger electron spectroscopy corresponded to a B:N stoichiometric ratio close to 1:1, and the band-gap value (5.65 eV) obtained by electron energy loss spectroscopy was consistent with the dielectric properties. The h-BN-containing capacitors were characterized by highly uniform properties, a reasonable dielectric constant (3), and low leakage current density, while graphene on h-BN substrates exhibited enhanced electrical performance such as the high carrier mobility and neutral Dirac voltage, which resulted from the low density of charged impurities on the h-BN surface.

Non-point source pollutants in down stream of Nakdong river were simulated by SWAT. GIS was utilized to make input data of SWAT such as landuse pattern and soil. Meteorological data of 2007 and 2009 were applied for the calibration and validation of runoff in SWAT. It was difficult to calibrate and validate the runoff and nutrient results since a study area was influenced by the tidal effects. Jindong site was selected to escape from the bias of runoff simulation in the coastal area. values of calibration and validation were 0.8 and 0.79. However, values of water qualities were very low level in comparison to runoff. These resulted from the concentration scale of water qualities such as BOD, T-N and T-P. Additionally, tidal influence could effected on the measurements of nutrients. The simulated annual averages and patterns of BOD, T-N and T-P in SWAT were similar to the measurement data. 80 ~ 96 % of nonpoint source pollutants at Nakbon M site were released from April to August of 2009. The ratio of T-N and T-P from nonpoint source were above 50 % during the rainy season.

The agricultural area was classified into dry and paddy fields in this study using the near-infrared band of Landsat TM to extract land cover classes that need to the application of Expected Mean Concentration (EMC) in nonpoint source works. The accuracy of image classification of the land cover map from Landsat TM image showed 83.61% and 78.41% respectively by comparing with the large and middle scale land cover map of Ministry of Environment. As the result of Soil Conservation Service (SCS) Curve Number (CN) using the land cover map from image classification

E-mail: kyoohyun@inha.ac.krReceived April 12, 2012, Accepted May 1, 2012Key Words : Furoxan, Furazan, Selective reduction, Substitution, Energetic materialEven though novel candidates for high energetic materialshave been synthesized continuously, higher performance andthermal stability are gradually becoming major concerns forpractical high energetic materials. Moreover, to improvehigh energetic material’s safety and survivability for militaryor industrial explosives and propellants, it is required thathigh energetic materials must be insensitive and be capableof withstanding unwanted stimuli such as heat, frictions,impact and shocks.

Recently, smartphone, notebook, PC and other supporting wireless LAN device have come into wide use. By increasing user that use wireless LAN device, wireless traffic also increased. If wireless traffic through one AP is increase, it causes throughput decrease. To solve this problem, wireless LAN service provider install more AP where overload occurred. But this is not enough. Because stations can't know AP's load factor, and APs do nothing for load balancing. In this paper, we propose Multi-Interface Access Point(MIAP) to solve this problem. MIAP operate same as multiple APs with multi-interface, and MIAP measure each interface's load periodically. If MIAP detect overloaded interface, MIAP transfer station from overloaded interface to under-loaded interface. We conducted an experiment for verifying existing problem, and we found this problem occurred. We plan an experiment scenario for a comparison between existing AP and MIAP, and excute these experiment. In the result, we show MIAP with load balancing can improve total throughput about 72% and stabilize delay jitter than existing AP.

Despite many reports of animals using visual landmarks for homing, surprisingly little is known about construction of landmarks for the purpose of orientation. Semiterrestrial crabs normally use a path integration method for short-range homing, but active courtship or territorial behavior may introduce errors increasing predation risk. We explored the hypothesis that male fiddler crab Uca lactea may build structures for landmark orientation to compensate for errors during courtship. Males without burrows found an artificial burrow with a semidome from a greater distance than one without a semidome. In addition, courting males retreated to the translocated semidome rather than to the original burrow location more frequently than noncourting males did. Finally, the maximum traveling distance from the burrow and the maximum deviation of the longitudinal body axis from the home vector were greater in males with semidomes than males without semidomes. Our results strongly support the hypothesis that male fiddler crabs build structures for landmark homing. Key words: construction, fiddler crab, homing, orientation, visual landmark. [Behav Ecol]

The fiddler crab, Uca lactea, which lives on intertidal mudflats in Korea, exhibits both burrow mating and surface mating. We observed 17 cases of surface mating that occurred on Ganghwa Island, South Korea. Most surface-mating males did not build semidomes, structures that attract searching females for burrow mating. Based on the conclusion of a previous study that semidome building is condition-dependent, we suggest that food availability may influence the mating tactic of this species. In addition, there was a strong correlation between the carapace size of both sexes that surface-mated, which suggests that males use body size of females as a mating cue.

Agency for Defense Development, Yuseong P.O. Box 35-5 (TRC-3-6), Daejeon 305-600, KoreaReceived February 15, 2013, Accepted March 5, 2013Key Words : Imidazole, Furoxan, Dioxadiazine, Dipolar cyclization, Energetic materialSince TNT and its mixture were introduced into warfaretechnology, various explosives have been continuouslydeveloped. Consequently, there has been remarkable successto synthesize much higher energetic materials such as RDX,HMX, HNIW and so on. However, recent interest in muni-tions system focused on lower sensitivities to impact, shockand friction to reduce accidental initiation, along with higherperformance.

High Energy Material Research Center, Department of Chemistry, Inha University, Incheon 402-751, KoreaReceived August 1, 2011, Accepted August 23, 2011Key Words : Furoxan, Dioxadiazine, Nitro compound, Cycloaddition, Energetic materialNitro and amino 1,2,5-oxadiazoles (furazans) have beenconsidered as explosives and propellants, because they havehigh nitrogen content, good oxygen balance, and highenergy density.

Simple furoxans containing nitro groups could not be applied for energetic materials because of their poor thermal stability and nucleophilic displacement of the nitro groups. On the other hand, benzofuroxans are far more stable than the furoxans and more favorable for practical applications.

Even though some azoles were insensitive towa rds accidental impact, their performance is often lower than that of RDX, one of the most widely used explosives. Recently 1,1-diamino-2,2- dinitroethylene (FOX-7) was emerging as a potential candidate for insensitive high explosives. FOX-7 has attracted substantial interest because it was expected that its performance was similar and its sensitivity could be much lower in comparison with RDX.

In the effort to develop an efficient chemotherapy drug for the treatment of non-small-cell lung cancer (NSCLC), we analyzed the anti-tumorigenic effects of a novel small molecule targeting the inhibitor of apoptosis (IAPs), HM90822B, on NSCLC cells. HM90822B efficiently decreased IAP expression, especially that of XIAP and survivin, in several NSCLC cells. Interestingly, cells overexpressing epidermal growth factor receptor (EGFR) due to the mutations were more sensitive to HM90822B, undergoing cell cycle arrest and apoptosis when treated. In xenograft experiments, inoculated EGFR-overexpressing NSCLC cells showed tumor regression when treated with the inhibitor, demonstrating the chemotherapeutic potential of this agent. Mechanistically, decreased levels of EGFR, Akt and phospho-MAPKs were observed in inhibitor-treated PC-9 cells on phosphorylation array and western blotting analysis, indicating that the reagent inhibited cell growth by preventing critical cell survival signaling pathways. In addition, gene-specific knockdown studies against XIAP and/or EGFR further uncovered the involvement of Akt and MAPK pathways in HM90822B-mediated downregulation of NSCLC cell growth. Together, these results support that HM90822B is a promising candidate to be developed as lung tumor chemotherapeutics by targeting oncogenic activities of IAP together with inhibiting cell survival signaling pathways.

[Purpose] This study compared and analyzed use of an existing ankle ramp and a newly developed ankle ramp for stretching exercises. [Subjects] Fourteen subjects were included; they were stroke patients more than 6 months after onset, with no orthopedic or biological problems in the legs, so independent gait was possible. [Methods] The subjects performed stretching exercises for 5 min with an existing ankle ramp and a newly developed ankle ramp; foot pressure was then measured. [Results] The averaged percentage and kilopascal data for weight bearing and foot pressure on the affected side with the newly developed ankle ramp for stretching exercises were significantly higher than those with the existing ankle ramp. [Conclusion] Our results suggest that stretching exercises using the newly developed ankle ramp more effectively increase foot pressure than the existing ankle ramp.

Lipoprotein lipase (LPL) is known to be attached to the luminal surface of vascular endothelial cells in a complex with membrane-bound heparan sulfate, and released into blood stream by heparin. LPL that catalyzes hydrolysis of triglyceride (TGL) on chylomicron and VLDL into two fatty acids and monoacylglycerol, is also implicated to participate in an enhancement of cholesterol uptake by arterial endothelial cells in vitro. But little is known about the LPL-mediated cholesterol uptake in physiological state. In this study, changes in blood lipid composition and levels of lipoproteins were determined after the injection of heparin in human. The level of LPL in plasma was increased from 0 to 11 mU/ml within 30-40 min post-heparin administration and decreased to the basal level within 2 h. The level of TGL in plasma decreased from 70 mg/dl to 20 mg/dl within 1 h and gradually increased to 80 mg/dl within 4 h. However the level of total cholesterol in plasma remained at 140 mg/dl during an experimental period of 4 h. Analysis of Lipoproteins in plasma by NaBr density gradient ultracentrifugation showed that the level of VLDL decreased from 50 mg/dl to 10 mg/dl within 1-2 h and returned to normal plasm level at 4 h. However there were no significant changes in the level of LDL and HDL. These results suggest that, at least, in normo-lipidemic subjects, increased free plasm LPL acts primarily on VLDL and failed to show any significant uptake of cholesterol-rich lipoproteins in human.

not Available.

Materials processing utilizing ultrashort near-infrared (NIR) laser pulses with duration in the range of tens to hundreds of femtoseconds (1fs = 10 15 s) has attracted a great deal of interest in the scientific and industrial world recently. Unfortunately, a number of materials that often exhibit great technological and scientific importance are transparent in NIR, making it very difficult to process them by laser radiation in this spectral range. Here, we present a new method for the efficient structuring of the surface of materials by applying femtosecond NIR laser pulses simultaneously with a weak extreme ultraviolet (XUV) beam, which leads to very strong radiation-matter interaction, bringing a dramatic increase in the surface processing speed. A laser system providing 5mJ, 820nm, 32fs, 10Hz pulses was used to generate high-order harmonics with the strongest spectral line at 21nm and with a conversion efficiency of 5%. The two beams were focused on the samples by using an off-axis paraboloidal multilayer mirror. As an example, we present the results of the surface nanostructuring of thin films of amorphous carbon and poly(methyl methacrylate) deposited on bulk substrates. We discuss the physical mechanisms that lead to the laser-induced periodic surface structures when our method is used.

We demonstrate sub-100-attosecond timing jitter optical pulse trains generated from free-running, 77.6-MHz repetition-rate, mode-locked Er-fiber lasers. At -0.002(\pm0.001) ps2 net cavity dispersion, the rms timing jitter is 70 as (224 as) integrated from 10 kHz (1 kHz) to 38.8 MHz offset frequency, when measured by a 24-as-resolution balanced optical cross-correlator. To our knowledge, this result corresponds to the lowest rms timing jitter measured from any mode-locked fiber lasers so far. The measured result also agrees fairly well with the Namiki-Haus analytic model of quantum-limited timing jitter in stretched-pulse fiber lasers., 4 pages, 2 figures, to appear in Optics Letters