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Fermented foods have several advantages, including increased nutritional value, improved bioavailability, and functional health properties. We examined that these outcomes were also observed in fermented mixed grains (FMG) containing wheat germ, wheat bran, oats, brown rice, barley, quinoa, and lentils following solid-state fermentation (SSF) by Bacillus amyloliquefaciens 245. The metabolic profile during fermentation was screened using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). The amino acids were quantitatively measured for the validation of the changes in metabolites. The activity of enzymes (e.g., amylase, protease, and fibrinolysis) and antioxidant capacity was also assessed to elucidate the functionality of FMG. The essential amino acid contents gradually increased as fermentation progressed. As the metabolites involved in the urea cycle and polyamine pathway were changed by fermentation, arginine was used as a substance to produce citrulline, ornithine, and agmatine. FMG showed dramatic increases in enzyme activity. FMG incubated for 36 h also displayed higher total phenolic contents and free radical scavenging ability than MG. The data suggest that FMG produced by Bacillus amyloliquefaciens 245 possess improved nutritional and functional quality, leading to their potential use as dietary supplements.

Fermented foods have several advantages, including increased nutritional value, improved bioavailability, and functional health properties. We examined that these outcomes were also observed in fermented mixed grains (FMG) containing wheat germ, wheat bran, oats, brown rice, barley, quinoa, and lentils following solid-state fermentation (SSF) by Bacillus amyloliquefaciens 245. The metabolic profile during fermentation was screened using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). The amino acids were quantitatively measured for the validation of the changes in metabolites. The activity of enzymes (e.g., amylase, protease, and fibrinolysis) and antioxidant capacity was also assessed to elucidate the functionality of FMG. The essential amino acid contents gradually increased as fermentation progressed. As the metabolites involved in the urea cycle and polyamine pathway were changed by fermentation, arginine was used as a substance to produce citrulline, ornithine, and agmatine. FMG showed dramatic increases in enzyme activity. FMG incubated for 36 h also displayed higher total phenolic contents and free radical scavenging ability than MG. The data suggest that FMG produced by Bacillus amyloliquefaciens 245 possess improved nutritional and functional quality, leading to their potential use as dietary supplements.

Mesoporous silica nanoparticles (MSN) have several advantages as carriers for drug delivery, including high drug loading capacity, good biocompatibility, excellent stability, and easily tailorable surface properties. This study describes the design of an MSN-based carrier for use in a heat shock responsive drug delivery system. MSN were functionalized with the temperature-sensitive PEG/PCL multiblock copolymer, as gatekeepers, allowing the release of entrapped drugs in response to heat shock stimuli (MBC-MSN). In the absence of heat shock, doxorubicin (Dox)-loaded MBC-MSN showed very low cytotoxicity, as PEG/PCL inhibited the premature release of Dox from MBC-MSN. In response to heat-shock stimuli, however, these Dox@MBC-MSN showed significant cytotoxicity, similar to that of free Dox. Dox release was due to the loosening of the structure of the gatekeeper, PEG/PCL, in response to the heat shock stimuli. Taken together, these findings suggest that MBC-MSN are a strong candidate to act as a carrier in heat shock responsive drug delivery.

Cancer is a life-threatening disease, and the occurrence of metastasis, which increases the lethality of primary tumors, is increasing. The epithelial-to-mesenchymal transition (EMT) is a biological process by which epithelial cells lose cell-cell adhesion properties and acquire mesenchymal properties, including motility and invasiveness. EMT is considered an early stage of metastasis; therefore, inhibiting EMT may be an effective anticancer therapy. In the present study, the antimetastatic effect of piperlongumine (PL) was assessed in human cancer cells. PL is a single component isolated from long pepper (Piper longum) and it has been studied for its antibacterial, antiangiogenic, and antidiabetic activities. Migration assays (wound healing assay) and transwell invasion assays showed that PL inhibited the migration and invasion of cancer cells. Western blotting and immunofluorescence imaging showed that TGF-β upregulated the transcription factors Snail1 and Twist1 and downregulated E-cadherin, a marker of epithelial cells, inducing EMT. PL might inhibit TGF-β-induced EMT by downregulating Snail1 and Twist1 and upregulating E-cadherin in cancer cells. In summary, PL might inhibit TGF-β-induced EMT, suggesting that it is a promising anticancer agent.

Objectives Patients with bilateral vocal fold paralysis (BVFP) theoretically have difficulty producing voiceless consonants. However, perceptual studies have revealed clear production of voiceless consonants with good articulation scores in nontracheostomized patients. The purpose of this study was to clarify the production of voiceless stops during articulation in patients with BVFP compared to normal speakers. Methods The perceptual, acoustic, and aerodynamic characteristics of patients with BVFP and those with normal speech were investigated with special reference to voiceless stop consonants. Test words were prepared to place the stop consonants in different phonological environments, and were all nonsense words. Results The patients with BVFP perceptually produced the three types of stops successfully. However, they acoustically varied voice onset time to produce phonetically representative stops but decreased voice onset time of /ph/ and /p/ compared to those of normal speakers. These patients may properly control air pressure to produce the three types of stop consonants similar to normal speakers. Conclusion The patients with BVFP realized the distinctions between the three types of stops similar to the normal speakers. Although vocal mobility was absent in the patients with BVFP, voice onset time, vowel duration, closure duration, and air pressure were similar to those of normal speakers.

Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor β (TGF-β) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-β treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-β. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.

Objectives Voice and speech alterations after total thyroidectomy may be associated with other extralaryngeal factors, such as neck muscle dysfunction and neck scar contracture. We evaluated the acoustic characteristics of oral vowel sounds and changes in hyoid bone movement before and after thyroidectomy. Methods Twenty-nine female patients undergoing total thyroidectomy were included. Fundamental frequencies (Fo), formants and vowel space areas were evaluated before surgery and 7 days and 3 months after surgery to acoustically analyze the oral vowel sounds. Videofluoroscopic images were taken at the same times to evaluate hyoid bone movement. Results The Fo levels of seven vowels decreased significantly after surgery. The vowel formant changes the F1 of vowel /[e]/ decreased significantly from baseline at 3 months postoperatively, and the F3 of vowel /[i]/ decreased significantly from baseline 7 days postoperatively. The change in the vowel space area was not observed. The Y coordinate of the vowels /[i]/ and /[e]/ decreased significantly from baseline 7 days postoperatively due to changes in hyoid movement. Conclusion The damage to the neck muscles after thyroidectomy changes in Fo, formant and hyoid bone position. These quantitative results could be used as basic data for voice management in patients who undergo thyroidectomy.

The gene encoding β-galactosidase was cloned from

This study examined the dry etching characteristics of palladium and GaN/AlGaN superlattices using Cl2/CHF3 and Cl2/Ar chemistry formed by an inductively coupled plasma system for the fabrication of ridges of laser diodes. Although the etch rates of n-GaN and AlGaN/GaN superlattices were similar using Cl2/Ar chemistry, the etch rate of the latter was quenched using Cl2/CHF3 chemistry due to the formation of a non-volatile fluoride layer and/or high bond strength oxide. The ridge pattern was eroded when the Pd was etched at higher source powers, resulting in non-uniform etched features. In addition, Cl2/Ar chemistry could not etch the Pd layer. Using a 2-step etching process combining Cl2/CHF3 chemistry for Pd with Cl2/Ar chemistry for the AlGaN/GaN SLs, a ridge for the laser diodes was formed successfully with a vertical sidewall and a good etched surface morphology.

Performance tests of a 75-tonf liquid rocket engine turbopump were conducted. The performance of sub-components - two pumps and a turbine - and their power matching were measured and examined firstly near the design speed under the LN2 and kerosene enviro nment. In the real propellant - LOX and kerosene - environment tests, design and off-design performance of turbopump were fully verified in regime of the rocket engine operation. During the off-design performance tests, turbopump running time was set longer than the engine operating time to verify the pump operability and set the pump inlet pressure close to design NPSHr to investigate pump suctio n capability in parallel. It has been found that developed-turbopump satisfied all of the engine required performances.초 록 75톤급 액체로켓엔진용 터보펌프 개발 시제에 대한 조립체 성능시험이 터보펌프 실매질 시험설비에서 수행되었다. LN2와 케로신을 적용한 첫 시험에서는 터보펌프 구성품들의 조립체 상태에서의 수력/공력 성능 및 출력 매칭 점검이 설계회전수 근방에서 이루어 졌으며 LOX와 케로신을 적용한 실매질 시험에서는 터보펌프의 설계성능 및 엔진운용영역 탈설계 성능 검증이 이루어졌다. 탈설계시험의 경우, 내구성 검증을 위해 엔진의 운용시간을 초과하여 터보펌프가 운용되었으며 펌프입구압력을 설계 요구유효흡입양정(NPSHr)에 가깝게 설정하여 흡입성능 검증을 병행하였다. 개발된 75톤급 액체로켓용 터보펌프는 성능, 운용시간의 엔진 요구규격을 만족시키는 것으로 확인되었다.Key Words:Liquid Rocket Engine(액체로켓엔진), Turbopump(터보펌프), Performance Test(성능시험), Kerosene(케로신), LOX(액체산소)Received 2 December 2015 / Revised 29 February 2016 / Accepted 7 March 2016

Context: Mutations in the gene encoding Mediator complex subunit MED12 are dominant drivers of uterine fibroids (UFs) in women of diverse racial and ethnic origins. Previously, we showed that UF-linked mutations in MED12 disrupt its ability to activate cyclin C-CDK8/19 in Mediator. However, validation of Mediator kinase disruption in the clinically relevant setting of MED12-mutant UFs is currently lacking. Objective: The objective of this study was twofold. First, to extend the ethnic distribution profile of MED12 mutations by establishing their frequency in UFs from Hispanic women of South Texas. Second, to examine the impact of MED12 mutations on Mediator kinase activity in patient-derived UFs. Methods: We screened 219 UFs from 76 women, including 170 tumors from 57 Hispanic patients, for MED12 exon 2 mutations, and further examined CDK8/19 activity in Mediator complexes immunoprecipitated from MED12 mutation-negative and MED12 mutation-positive UFs. Results: MED12 exon 2 mutations in UFs from Hispanic women are somatic in nature, predominantly monoallelic, and occur at high frequency (54.1%). We identified a minimal cyclin C-CDK8 activation domain on MED12 spanning amino acids 15 through 80 that includes all recorded UF-linked mutations in MED12, suggesting that disruption of Mediator kinase activity is a principal biochemical defect arising from these pathogenic alterations. Analysis of Mediator complexes recovered from patient UFs confirmed this, revealing that Mediator kinase activity is selectively impaired in MED12-mutant UFs. Conclusions: MED12 mutations are important drivers of UF formation in Hispanic women of South Texas. MED12 mutations disrupt Mediator kinase activity, implicating altered CDK8/19 function in UF pathogenesis.

Bifidobacteria are representative probiotics which are defined as live microorganisms that confer a health benefit on the host. Because of their safety and healthfulness when applied to humans, bifidobacteria are suitable as genetically engineered bacteria for applications to benefit human physiology and pathology. However, molecular biological studies of bifidobacteria have been limited due to insufficient genetic tools including effective transformation methods. The aim of this study is to improve the electroporation-mediated transformation efficiency of bifidobacteria to a reproducibly high level. The crucial factors that determine electroporation efficiency are the restriction-modification system, together with the cell wall and cell membrane structure of the bacteria. We optimized the bifidobacterial electroporation conditions by focusing on these factors as well as the amount of plasmid DNA used, the electrical parameters and the bacterial growth phase. As a result, the electroporation efficiency of B. bifidum BGN4 drastically and consistently increased from 103 to 105 CFU / μg DNA. The most significant factor for increasing the electroporation efficiency was the cell wall weakening mediated by NaCl, which improved the electroporation frequency by 20 times. Because the optimized electrotransformation conditions reported here should be widely applicable to other Bifidobacterium species, these could promote the extensive genetic manipulation of the various Bifidobacterium species in future studies.

Shikonin (SK), a natural naphthoquinone isolated from the Chinese medicinal herb, has been known to suppress the proliferation of several cancer cells. However, its role in the epithelial mesenchymal transition (EMT) has yet to be demonstrated. The aim of the present study was to examine the effects of SK on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. SK markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin in MDA-MB‑231 cells, and increased the expression of E-cadherin in MCF-7 cells. SK also inhibited cell migration and invasion in vitro. The effects of SK on the LPS-induced EMT were mediated by the inactivation of the NF-κB-Snail signaling pathway. The results provided new evidence that SK suppresses breast cancer cell invasion and migration by inhibiting the EMT. Therefore, SK is a potentially effective anticancer agent for breast tumors, by inhibiting metastasis.

Background Mediator is a multiprotein interface between eukaryotic gene-specific transcription factors and RNA polymerase II. Mutations in exon 2 of the gene encoding MED12, a key subunit of the regulatory kinase module in Mediator, are extremely frequent in uterine leiomyomas, breast fibroadenomas, and phyllodes tumors. These mutations disrupt kinase module interactions and lead to diminished Mediator-associated kinase activity. MED12 mutations in exon 26, resulting in a substitution of leucine 1224 to phenylalanine (L1224F), have been recurrently observed in prostate cancer. Methods To elucidate the molecular mechanisms leading to tumorigenesis in prostate cancer, we analyzed global interaction profiles of wild-type and L1224F mutant MED12 with quantitative affinity purification-mass spectrometry (AP-MS). Immunoprecipitation and kinase activity assay were used to further assess the interactions between Mediator complex subunits and kinase activity. The presence of L1224F mutation was analyzed in altogether 877 samples representing prostate hyperplasia, prostate cancer, and various tumor types in which somatic MED12 mutations have previously been observed. Results In contrast to N-terminal MED12 mutations observed in uterine leiomyomas, the L1224F mutation compromises neither the interaction of MED12 with kinase module subunits Cyclin C and CDK8/19 nor Mediator-associated CDK activity. Instead, the L1224F mutation was shown to affect interactions between MED12 and other Mediator components (MED1, MED13, MED13L, MED14, MED15, MED17, and MED24). Mutation screening revealed one mutation in a Finnish (Caucasian) prostate cancer patient, whereas no mutations in any other tumor type were observed. Conclusions Specific somatic MED12 mutations in prostate cancer and uterine leiomyomas accumulate in two separate regions of the gene and promote tumorigenesis through clearly distinct mechanisms. Prostate © 2015 Wiley Periodicals, Inc.

Thermal insulation plays a key role in saving energy consumed by buildings. To obtain a high level of insulation performance, repeated thermal bridges should be minimized. These bridges may cause a...

Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)–dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation–induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation–induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs.

Ojeok-san is a frequently used herbal medication for the management of osteoarthritic pain. We evaluated the effect of Ojeok-san on the pharmacokinetics of celecoxib at steady-state in healthy individuals. An open-label, fixed-sequence, two-period, two-treatment cross-over study was conducted. In period I, the individuals received celecoxib capsule 200 mg once daily for 4 days. In period II, only Ojeok-san (14.47 g/pack, three times daily) was administered for 4 days, followed by co-administration with celecoxib for 4 days. On the fourth (final) day of administration, Ojeok-san was administered as a single dose. The blood samples for pharmacokinetic evaluation were collected for up to 48 hr after the administration of celecoxib in each study period. Of the 22 enrolled individuals, 20 individuals completed the study. In the presence of Ojeok-san, the systemic exposure of celecoxib was decreased. The geometric mean ratios ([celecoxib + Ojeok-san]/celecoxib) and the 90% confidence intervals for the maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve during dosing interval (AUCτ ) of celecoxib at steady-state were 0.725 (0.620-0.848) and 0.885 (0.814-0.962), respectively. The changes in the mean of the Cmax and AUCτ of celecoxib were greater in intermediate metabolizers of cytochrome 2C9 (CYP2C9) than in normal metabolizers. Our results suggested that the Cmax and AUCτ of celecoxib were reduced by Ojeok-san co-administration. This finding may be beneficial to determine the required adjustment of celecoxib dosage when co-administered with Ojeok-san.

Laser cordectomy (LC) or radiotherapy (RT) is often recommended in the early stage of laryngeal cancer. We conducted perceptual and acoustic analysis to compare sustained vowel and stop consonants since there is no article evaluating both the sustained vowel and stop consonants. Eventually, we might determine which management is superior in terms of speech production.A total of 28 patients who underwent LC and RT for early T1 glottic cancer were selected. The sustained vowel /a/ and bilabial stop consonants were used to assess the perceptual scores. The fundamental frequency (FThe GRBAS and discrimination scores were not significantly different between two groups. FThe differences may have been due to muscular fibrosis after RT. Movements of vocal cords with fibrosis were sluggish, when impulsion developed to pronounce the initial /p/ sound, so the VOT was shortened and the VD was longer after RT.

Background/Aims: Cyclophosphamide (CP) is a promising treatment for severe cases of paraquat (PQ) poisoning. We investigated the effective dose of CP for mitigating PQ-induced lung injury. Methods: Adult male Sprague-Dawley rats were allocated into five groups: control, PQ (35 mg/kg, intraperitoneal injection), and PQ + CP (1.5, 15, or 30 mg/kg). The dimensions of lung lesions were determined using X-ray microtomography (micro-CT), and histological changes and cytokine levels were recorded. Results: The micro-CT results showed that 15 mg/kg CP was more effective than 1.5 mg/kg CP for treating PQ-induced lung injury. At a dose of 1.5 mg/kg, CP alleviated the histological evidence of inflammation and altered superoxide dismutase activity. Using 15 mg/kg CP reduced the elevated catalase activity and serum transforming growth factor (TGF)-β1 level. Conclusions: A CP dose of > 15 mg/kg is effective for reducing the severity of PQ-induced lung injury as determined by histological and micro-CT tissue examination, possibly by modulating antioxidant enzyme and TGF-β1 levels.

Sprassis crispa was cultivated using soybean curd whey, and its antimicrobial activities were examined against those of eight microorganisms that were foodborne pathogens or food-poisoning bacteria. The culture broth of soybean curd whey was superior in mycelium content (17.76 g/L) to that of the defined culture broth, and the -glucan content was about 10.64 percent (w/w). The antimicrobial activities of the culture broth were confirmed against those of B. cereus, St. aureus, L. monocytogenes and S. typhimurium using the paper disk method. The antimicrobial activity was also maintained after the heat treatment and alcalase treatment. The filtrate with less than 3 kDa M.W. also showed the antimicrobial activity against four strains: B. cereus, St. aureus, L. monocytogenes and S. typhimurium. The minimum inhibitory concentration (MIC) was about 1.26 mg/mL in the B. cereus and 12.6 mg/mL in the St. aureus and L. monocytogenes. The S. typhimurium showed a MIC of 62.8 mg/mL. Thus, the culture of Sparassis crispa using soybean curd whey provides a thermally stable antimicrobial agent that can be used as a natural preservative in the biofood industry.

Background To determine whether initial reactive oxygen species (ROS)-induced endothelial cell injury is involved in early death after paraquat intoxication and concentrations of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and von Willebrand factor (VWF) reflecting endothelial cell injury, we investigated the initial endothelial cell injury marker involved in the pathogenesis of death within 5 days after paraquat ingestion. Material/Methods Sixty patients with paraquat poisoning were prospectively enrolled. Plasma samples were collected at admission. Plasma concentrations of Ang-1, Ang-2, and VWF were measured by enzyme-linked immunosorbent assay. The patients were classified into 3 categories: survivors, early death (died within 5 days after ingestion), and late death (died more than 5 days after ingestion). Results The baseline concentration of Ang-2 and the Ang-2: Ang-1 ratio were significantly higher in patients who died (Ang-2 [pg/mL], 1012.75±468.02 vs. 1986.07±1675.37 [p=0.002]; Ang-2: Ang-1, 0.90±0.49 vs. 2.16±2.28 [p=0.002]). The Ang-2: Ang-1 ratio was significantly higher in the early death group (2.41±2.54) than in the survivors (0.90±0.49) and the late death group (1.33±0.64). The Ang-2: Ang-1 ratio was significantly associated with early death (OR, 2.602; 95% CI, 1.106–6.117; p=0.028) after adjusting for plasma levels of paraquat, age, PCO2, and creatinine. VWF did not predict mortality. Conclusions Endothelial cell damage could be involved in the pathogenesis of early death following paraquat ingestion.

This study presented the development of hydrophobically modified polysialic acid (HPSA) nanoparticles, a novel anticancer drug nanocarrier that increases therapeutic efficacy without causing nonspecific toxicity towards normal cells. HPSA nanoparticles were prepared by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling between N-deacetylated polysialic acid (PSA) and 5β-cholanic acid. The physicochemical characteristics of HPSA nanoparticles (zeta-potential, morphology and size) were measured, and in vitro cytotoxicity and cellular uptake of PSA and HPSA nanoparticles were tested in A549 cells. In vivo cancer targeting of HPSA nanoparticles was evaluated by labeling PSA and HPSA nanoparticles with Cy5.5, a near-infrared fluorescent dye, for imaging. HPSA nanoparticles showed improved cancer-targeting ability compared with PSA. Doxorubicin-loaded HPSA (DOX-HPSA) nanoparticles were prepared using a simple dialysis method. An analysis of the in vitro drug-release profile and drug-delivery behavior showed that DOX was effectively released from DOX-HPSA nanoparticles. In vivo cancer therapy with DOX-HPSA nanoparticles in mice showed antitumor effects that resembled those of free DOX. Moreover, DOX-HPSA nanoparticles had low toxicity toward other organs, reflecting their tumor-targeting property. Hence, HPSA nanoparticles are considered a potential nanocarrier for anticancer agents.

Mediator regulates transcription by connecting gene-specific transcription factors to the RNA polymerase II initiation complex. We recently discovered by exome sequencing that specific exon 2 mutations in mediator complex subunit 12 (MED12) are extremely common in uterine leiomyomas. Subsequent screening studies have focused on this mutational hot spot, and mutations have been detected in uterine leiomyosarcomas, extrauterine leiomyomas and leiomyosarcomas, endometrial polyps, and colorectal cancers. All mutations have been missense changes or in-frame insertions/deletions. Here, we have analyzed 611 samples representing all above-mentioned tumor types for possible exon 1 mutations. Five mutations were observed, all of which were in-frame insertion/deletions in uterine leiomyomas. Transcriptome-wide expression data revealed that MED12 exon 1 and exon 2 mutations lead to the same unique global gene expression pattern with RAD51B being the most upregulated gene. Immunoprecipitation and kinase activity assays showed that both exon 1 and exon 2 mutations disrupt the interaction between MED12 and Cyclin C and CDK8/19 and abolish the mediator-associated CDK kinase activity. These results further emphasize the role of MED12 in uterine leiomyomas, show that exon 1 and exon 2 exert their tumorigenic effect in similar manner, and stress that exon 1 should be included in subsequent MED12 screenings. Uterine leiomyomas are the most common human tumors with highly specific mutations reported in MED12 exon 2. Here, we show that mutations occur recurrently also in MED12 exon 1. Transcriptome-wide gene expression profiling and functional analyses show that exon 1 and 2 mutations promote tumorigenesis through similar mechanism. These results bring new knowledge on MED12 function and highlight the role of MED12 in human tumorigenesis. © 2014 WILEY PERIODICALS, INC.

The IR3535 derivative (LJH158), in which the ethyl ester of IR3535 was converted to methyl ester, was synthesized and studied as a new mosquito repellent. The repellent efficacy of LJH158 was compared with that of DEET against Aedes albopictus, Culex pipiens pallens and Aedes togoi. Also, the aromatic repellent tests were conducted with mixtures of repellents and the essential oils of cinnamon, which were obtained by supercritical fluid extraction. In addition, the safety issues of LJH158 were monitored using single oral dose safety methods and eye irritation, and skin irritation tests. The results of repellent efficacy in both biting and aromatic tests and safety tests demonstrate that LJH158 has high potential to be used as a new repellent or in combination with other repellents.

To produce novel cheese-like fermented soybean, the solid-state fermentation of roasted soybean flour (RSF) was performed using 1.0% inoculum Bacillus subtilis HA and Lactobacillus plantarum, with the initial 60% substrate moisture for 10 hr at 42°C, resulting in pH 6.5, 0.82% acidity, 3.5% mucilage, 14.3 unit/g protease activity, 7.6 unit/g fibrinolytic activity, 216 mg% tyrosine content and 1.7×10(10) CFU/g of viable cell counts. After the second lactic acid fermentation with 10∼30% skim milk powder, the fermented RSF resulted in an increase in acidity with 1.64∼1.99%, tyrosine content with 246∼308 mg% and protease activity in the range of 5.2∼17.5 unit/g and 0.966 water activity. Viable cell counts as probiotics indicated 1.6×10(8) CFU/g of B. subtilis and 7.3×10(10) CFU/g of L. plantarum. The firmness of the first fermented RSF with 2,491 g·ømm(-1) greatly decreased to 1,533 g·ømm(-1) in the second fermented RSF, although firmness was slightly increased by adding a higher content of skim milk. The consistency of the second fermented RSF also decreased greatly from 55,640 to 3,264∼3,998 in the presence of 10∼30% skim milk. The effective hydrolysis of soy protein and skim milk protein in the fermented RSF was confirmed. Thus, the second fermented RSF with a sour taste and flavor showed similar textural properties to commercial soft cheese.

Rad9-Rad1-Hus1 (9-1-1) is a checkpoint protein complex playing roles in DNA damage sensing, cell cycle arrest, DNA repair or apoptosis. Human 8-oxoguanine DNA glycosylase (hOGG1) is the major DNA glycosylase responsible for repairing a specific aberrantly oxidized nucleotide, 7,8-dihydro-8-oxoguanine (8-oxoG). In this study, we identified a novel interaction between hOGG1 and human 9-1-1, and investigated the functional consequences of this interaction. Co-immunoprecipitation assays using transiently transfected HEK293 cells demonstrated an interaction between hOGG1 and the 9-1-1 proteins. Subsequently, GST pull-down assays using bacterially expressed and purified hOGG1-His and GST-fused 9-1-1 subunits (GST-hRad9, GST-hRad1, and GST-hHus1) demonstrated that hOGG1 interacted directly with the individual subunits of the human 9-1-1 complex. In vitro excision assay, which employed a DNA duplex containing an 8-oxoG/C mismatch, showed that hRad9, hRad1, and hHus1 enhanced the 8-oxoG excision and beta-elimination activities of hOGG1. In addition, the presence of hRad9, hRad1, and hHus1 enhanced the formation of covalently cross-linked hOGG1-8-oxoG/C duplex complexes, as determined by a trapping assay using NaBH(4). A trimeric human 9-1-1 complex was purified from Escherichia coli cell transformed with hRad9, His-fused hRad1, or His-fused hHus1 expressing vectors. It also showed the similar activity to enhance in vitro hOGG1 glycosylase activity, compared with individual human 9-1-1 subunits. Detection of 8-oxoG in HEK293 cells using flow cytometric and spectrofluorometric analysis revealed that over-expression of hOGG1 or human 9-1-1 reduced the formation of 8-oxoG residues following the H(2)O(2) treatment. The highest 8-oxoG reduction was observed in HEK293 cells over-expressing hOGG1 and all the three subunits of human 9-1-1. These indicate that individual human 9-1-1 subunits and human 9-1-1 complex showed almost the same abilities to enhance the in vitro 8-oxoG excision activity of hOGG1, but that the greatest effect to remove 8-oxoG residues in H(2)O(2)-treated cells was derived from the 9-1-1 complex as a whole.

In this study, we have fabricated polyacrylate substrates having a nano-patterned surface topography using a soft-imprint technique. The planar alignment of liquid crystals (LCs) along the direction of nanogrooves has been generated. Twisting behavior of nematic LCs has been also observed with a perpendicularly assembled LC cell and the cell parameters can be estimated by using the Soutar and Lu method. By comparing the anchoring energies obtained, accordingly, it has been demonstrated that the polymer nanogroove pattern has a comparable influence on LC alignment to the conventional rubbing process. It has been also shown that the artificial topography of the line grooves on the conventionally rubbed surface has a significant influence on the anchoring stability of the LC molecules.

Strain Gsoil 259(T), a beta-glucosidase-producing bacterium, was isolated from a soil sample from a ginseng field in the Republic of Korea and characterized in order to determine its taxonomic position. Cells were Gram-positive, heterotrophic, strictly aerobic, non-motile short rods. 16S rRNA gene sequence analysis revealed that strain Gsoil 259(T) belonged to the genus Microbacterium and was closely related to Microbacterium arborescens IFO 3750(T) (98.5 %) and Microbacterium imperiale IFO 12610(T) (97.9 %). However, it has low values for DNA-DNA relatedness with the above strains (20.7 and 17.5 %, respectively). Strain Gsoil 259(T) possessed chemotaxonomic markers that were consistent with classification in the genus Microbacterium, i.e. MK-11 and MK-12 were the major menaquinones and anteiso-C(17 : 0), anteiso-C(15 : 0) and iso-C(16 : 0) were the predominant cellular fatty acids. The DNA G+C content was 69.4 mol%. The cell-wall sugar was rhamnose and the diamino acid in the cell-wall peptidoglycan was ornithine. On the basis of data from this polyphasic study, strain Gsoil 259(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium ginsengisoli sp. nov. is proposed. The type strain is Gsoil 259(T) (=KCTC 19189(T) =DSM 18659(T)).

An integrated multidisciplinary analysis and design system plays a critical role in the preliminary design of an aircraft. In this work a system based on the CATIA is developed for multidisciplinary computational design; aerodynamics, elasticity, and radar frequency stealth. Common data base of geometry and rectangular grids is generated and used for aerodynamic and structural analysis, while derivative triangular grids are generated for the RCS calculation. The panel method (PANAIR), FEM (NASTRAN), and PO technique are used for aerodynamic, structural, and RF stealth computations, respectively, and several additional algorithms are developed for the effective communication of the common data.

Epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Prunella vulgaris (PV) inhibits the proliferation of various cancer cells; however, its possible role in EMT has not been demonstrated. In the present study, we explored the effect of PV aqueous extract (PVAE), a typical medicine for decoction, on EMT. Lipopolysaccharide (LPS) induced EMT-like phenotype changes in cancer cell lines that enhanced cell migration and invasion. PVAE markedly inhibited these effects and produced accompanying changes in the expression of EMT markers, including decreased expression of N-cadherin and vimentin, and increased expression of β-catenin. We found that PVAE effects on LPS-induced EMT were mediated by inhibition of the NF-κB/Snail signaling pathway. Our findings provide new evidence that PVAE suppresses cancer invasion and migration by inhibiting EMT. Therefore, we suggest that PVAE is an effective dietary chemopreventive agent with antimetastatic activity against malignant tumors.

Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy.

The epithelial-mesenchymal transition (EMT) is a pivotal event in the invasion and metastasis of cancer cells. Psoralea corylifolia L. (PC) inhibits the proliferation of various cancer cells. However, its possible role in EMT has not been identified. In the present study, we examined the effects of an aqueous extract of Psoralea corylifolia L. (PCAE), a typical medicinal decoction, on the EMT. Lipopolysaccharide (LPS) induced EMT-like phenotypic changes, enhancing cell migration and invasion. However, PCAE markedly reduced the expression of the LPS-induced EMT markers, including N-cadherin and vimentin, and increased the expression of β-catenin. PCAE also inhibited cell migration and invasion in vitro. The effects of PCAE on the LPS-induced EMT were mediated by the inactivation of the NF-κB-SNAIL signaling pathway. The results provide new evidence that PCAE suppresses cancer cell invasion and migration by inhibiting EMT. Therefore, PCAE is a potentially effective dietary chemopreventive agent for malignant tumors since it inhibits metastasis.

Here we describe a method of patterning electroluminescent (EL) polymers using micromolding in capillary (MIMIC). MIMIC is the one of the lithographic methods based on the microfludics among the soft lithography using a patterned poly(dimethylsiloxane) (PDMS) elastomer. The patterned microstructures of poly(dioctylfluorene) (PDOF), poly( p -phenylenevinylene) (PPV), and poly(2-methoxy-5-2′-ethylhexyloxy)- p -phenylenevinylene) (MEH-PPV) were fabricated by MIMIC for polymer light-emitting diodes (PLEDs). In addition, the solution viscosity effect on MIMIC process was studied. Finally, a PLED device was fabricated using the patterned EL polymer microstructure and a patterned emission image was obtained.

Expensive herbs like ginseng are always a possible target for fraudulent labeling. Korean ginseng (Panax ginseng) is among the most popular and expensive plant species in many countries, including China, Japan, Korea, Russia, Canada, and the USA. Polymerase chain reaction (PCR) analysis of the internal transcribed spacer (ITS) has proven an appropriate method for the identification of the most popular species (P. ginseng) in the Panax ginseng genus (Panax). A single nucleotide polymorphism (SNP) has been identified between P. ginseng and other Panax species. Specific PCR primers were designed from this SNP site within the sequence data, and were used to detect Korean ginseng (P. ginseng) via multiplex PCR. The established multiplex-PCR method for the simultaneous detection of Korean ginseng and foreign ginseng in a single reaction was determined to be effective. The described method has important implications in both the production and sale of commercial ginseng products, allowing for the prevention of fraud, and also revealing the possible presence of other, cheaper ginseng species.

For most practical applications, it is essential to fabricate micro- or nano-scale polymer electroluminescent (EL) devices and pixel arrays. Microcontact printing, which uses a patterned elastomer (usually PDMS) as the mold to generate or transfer the pattern offers immediate advantages. Here we describe a method of patterning polymeric EL materials based on microcontact printing using PDMS mold. In this technique, we use the self-assembled monolayer (SAM) system of alkanephosphonic acids on ITO substrate, and patterned EL polymer is formed on the SAM-modified ITO substrate.

Solar observations support that magnetic reconnect ion ubiquitously occurs in the chromosphere as well as in the corona. It is now widely accepted that coronal magnetic reconnect ion is fast reconnect ion of the Petschek type, and is the main driver of solar flares. On the other hand, it has been thought that the traditional Sweet-Parker model may describe chromospheric reconnect ion without difficulty, since the electric conductivity in the chromoshphere is much lower than that in the corona. However, recent observations of cancelling magnetic features have suggested that chromospheric reconnect ion might proceed at a faster rate than the Sweet-Parker model predicts. We have applied the Sweet-Parker model and Petschek model to a well-observed cancelling magnetic feature. As a result, we found that the inflow speed of the Sweet-Parker reconnect ion is too small to explain the observed converging speed of the feature. On the other hand, the inflow speeds and outflow speeds of the Petschek reconnect ion are well compatible with observations. Moreover, we found that the Sweet-Parker type current sheet is subject to the ion-acoustic instability in the chromosphere, implying the Petschek mechanism may operate there. Our results strongly suggest that chromospheric reconnect ion is of the Petschek type.

SummarySomatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at very high frequency (∼70%) in uterine leiomyomas. However, the influence of these mutations on Mediator function and the molecular basis for their tumorigenic potential remain unknown. To clarify the impact of these mutations, we used affinity-purification mass spectrometry to establish the global protein-protein interaction profiles for both wild-type and mutant MED12. We found that uterine leiomyoma-linked mutations in MED12 led to a highly specific decrease in its association with Cyclin C-CDK8/CDK19 and loss of Mediator-associated CDK activity. Mechanistically, this occurs through disruption of a MED12-Cyclin C binding interface that we also show is required for MED12-mediated stimulation of Cyclin C-dependent CDK8 kinase activity. These findings indicate that uterine leiomyoma-linked mutations in MED12 uncouple Cyclin C-CDK8/19 from core Mediator and further identify the MED12/Cyclin C interface as a prospective therapeutic target in CDK8-driven cancers.

Background: The skin prick test (SPT) for detecting atopic sensitization is not preferred in young infants with atopic dermatitis (AD) because of concerns about poor skin reactivity. This study aimed to evaluate whether the results of SPT agreed well with those of specific serum immunoglobulin E (sIgE) antibody test in young infants with AD. Methods: This study included 2,077 eligible infants (age

This paper documents findings from evaluating performances of three different methods for segmenting freeway sites for the purpose of identifying high collision concentration locations: Sliding Moving Window (SMW), Peak Searching (PS) and Continuous Risk Profile (CRP). The traffic collision data from sites segmented in each method under two different roadway definitions were used to estimate excess expected average crash frequency with Empirical Bayes adjustment with respect to two different sets of Safety Performance Functions (SPFs). The estimates from each of the methods were then used to prioritize the detected sites for safety investigation and these lists were compared with previously confirmed high collision concentration locations (or hot spots). The input requirements for each of three methods were identical, yet their performance markedly varied. The findings revealed that CRP method has the lowest false positive (i.e., requiring a site for safety investigation while it is not needed) rate. The performances of SMW and PS significantly varied when different sets of SPFs were used while that of CRP was less affected.

Ribosomal protein S3 (rpS3) is a multifunctional protein involved in translation, DNA repair, and apoptosis. The relationship between rpS3 and cyclin-dependent kinases (Cdks) involved in cell cycle regulation is not yet known. Here, we show that rpS3 is phosphorylated by Cdk1 in G2/M phase. Co-immunoprecipitation and GST pull-down assays revealed that Cdk1 interacted with rpS3. An in vitro kinase assay showed that Cdk1 phosphorylated rpS3 protein. Phosphorylation of rpS3 increased in nocodazole-arrested mitotic cells; however, treatment with Cdk1 inhibitor or Cdk1 siRNA significantly attenuated this phosphorylation event. The phosphorylation of a mutant form of rpS3, T221A, was significantly reduced compared with wild-type rpS3. Decreased phosphorylation and nuclear accumulation of T221A was much more pronounced in G2/M phase. These results suggest that the phosphorylation of rpS3 by Cdk1 occurs at Thr221 during G2/M phase and, moreover, that this event is important for nuclear accumulation of rpS3.

Natural killer (NK) cells are important innate effector cells which can irradicate tumor cells through specific interactions between activating receptors on NK cells and their cognate ligands on cancer cells. Recently, it has been known that induction of activating NKG2D ligands including MHC class I chain-related (MIC) and UL16-binding protein (ULBP) families on tumor cells by various stresses makes them more susceptible to NK cell-mediated cytotoxicity. Therefore, it was investigated whether sublethal dose of hematoporphyrin-based photodynamic therapy (PDT) could up-regulate NKG2D ligands on tumor cells and increase the susceptibility of cancer cells against NK cells. Treatment with sublethal dose of hematoporphyrin-based PDT increased mRNA transcription and surface expression of ULBP1 and ULBP2 genes in SNU-1 human gastric tumor cell line and MICA/B, ULBP1, ULBP2 and ULBP3 genes in SW-900 human lung cancer cell line. These results were followed by increased susceptibility of cancer cells to NK cell-mediated cytotoxicity after sublethal PDT, which was abolished by addition of a blocking NKG2D mAb. Therefore, it could be suggested that the effect of hematoporphyrin-based PDT might be mediated in part by the increased susceptibility to NK cells via induction of NKG2D ligands on tumor cells, which survived after treatment with PDT.

Strain DCY24(T), a Gram-reaction-positive, aerobic, rod-shaped, motile bacterium, was isolated from soil of a ginseng field in South Korea. According to 16S rRNA gene sequence analysis, it was closely related to Nocardioides aromaticivorans DSM 15131(T) (95.1 % similarity), Nocardioides simplex KCTC 9106(T) (95.0 %), Nocardioides nitrophenolicus DSM 15529(T) (94.8 %) and Nocardioides kongjuensis DSM 19082(T) (94.7 %). Chemotaxonomic data revealed that strain DCY24(T) possessed MK-8(H(4)) as the predominant menaquinone, ll-2,6-diaminopimelic acid as the diagnostic diamino acid, phosphatidylglycerol and diphosphatidylglycerol as predominant polar lipids and iso-C(16 : 0), iso-C(17 : 0) and C(18 : 1)omega9c as predominant fatty acids. The DNA G+C content was 71.0 mol%. Based on evidence from this polyphasic study, strain DCY24(T) (=KCTC 19265(T) =LMG 24128(T)) should be classified as the type strain of a novel Nocardioides species, for which the name Nocardioides humi sp. nov. is proposed.