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Despite the large efforts in international cancer genome consortium studies, there are still a large proportion of tumors with complex genomic rearrangement often remained without a clinically relevant molecular characterization. Integration of multi-omic data helps elucidating evolutionary history of such cases and identifying predictive molecular markers. Here we present the findings of our proof-of-principle study that investigated the evolutionary history of complex rearrangements in primary head and neck tumor genomes integrating long-read whole-genome, Hi-C, and RNA sequencing. We report a HPV-positive case with development of complex genomic rearrangements tracing back to HPV-mediated genomic instability and a HPV-negative case with an enhancer hi-jacking in a region of chromothripsis predicted to co-occur with a neoloop and a super-enhancer. These structural alterations resulted in overexpression of the oncogenes CCND1 and ALK, respectively, validated with immunohistochemistry assay. Furthermore, we introduce a novel analytic approach utilizing long-read whole-genome data distinguishing somatic mutations before and after structural variants. Our findings highlight the need for multi-modal sequencing strategies to increase our understanding of cancer evolution and rare biomarkers in poorly understood cancers.

Computational fluid dynamics (CFD) has become an essential tool for optimizing the design and diagnosing the operation of a boiler. However, the validity of the results depends on the degree of numerical diffusion as well as the reliability of the submodels. This study aims to assess mesh sensitivity in the reacting two-phase flow of pulverized coal in a common tangential-firing boiler. Three mesh versions were constructed for the boiler with the number of cells ranging between 1.2 million and 5.4 million, corresponding to 0.0114 -0.0022 m3 per cell in the burner zone. The velocity distribution was found to be highly sensitive compared to temperature, heat flux, and NO concentration. By contrast, the use of key performance parameters such as total wall heat absorption, exit NOx concentration, and carbon conversion, was not appropriate criteria for the mesh sensitivity test. These parameters were determined by integration over the entire surface or volume, which made them sensitive to the overall reaction stoichiometry instead of the mesh fineness. It suggests that the use of a coarse mesh could be acceptable in evaluating the key performance parameters influenced by major operation variables, such as air distribution and fuel properties. However, sufficient mesh fineness is necessary for studies requiring accurate prediction of detailed flow patterns such as the evaluation of burner tilting/yawing or ash deposition on the wall.

To identify candidate gene mutations to significantly predict the risk of survival prognosis after treatment with systemic first-line targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) patients.Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS). Fifty-six patients' medical records including overall survival (OS) and progression-free survival (PFS) at the time of mRCC diagnosis were evaluated. The patients were grouped into favorable (12 months/3 years), intermediate (3-12/12-36 months), and poor groups according to their PFS/OS (3 months/12 months). We identified any significant therapeutic targeted genes relating to the survival with a significance at p0.050.The first line therapeutic response showed 1.8% complete remission, 14.2% partial response, 42.9% stable disease, and 41.1% progressive disease. Among the overall TGS results, the cumulative effect ofThis study reports several significant mutated genes related to the survival prognosis in mRCC patients treated with first-line TT.

Commercial entrained-flow coal gasifiers operate at high temperatures and pressures for increased efficiency. For reduced operation costs, the start-up burner (SUB) of a gasifier requires fast heating and pressurization by intensive combustion, minimizing damage to the refractory lining and to itself. We evaluated different designs of the SUB adopting diesel-oxygen diffusion flame under the stoichiometric condition to improve the performance of the existing premixed flame burner that has been subjected to frequent failures. Using computational fluid dynamics, the combustion characteristics of the SUB with a thermal input up to 2.28MWth and pressure up to 8 bar were predicted for tests in a pilot-scale cylindrical gasifier. The results showed that the injection of diesel and oxygen through separate multiple inlets can intensify the combustion, leading to short and stable turbulent diffusion flames. Varying the design of the burner tip and inlet arrangement reduced the influence of pressure on the flame length while achieving high heat flux to the wall, which is essential for a fast and stable start-up. Further investigations are required to understand the influence of the reactor geometry on the circulation flow of high-temperature gas back to the burner tip in the actual gasifier.

Somatic genome mutations occur due to combinations of various intrinsic/extrinsic mutational processes and DNA repair mechanisms. Different molecular processes frequently generate different signatures of somatic mutations in their own favored contexts. As a result, the regional somatic mutation rate is dependent on the local DNA sequence, the DNA replication/RNA transcription dynamics and epigenomic chromatin organization landscape in the genome. Here, we propose an online computational framework, termed Mutalisk, which correlates somatic mutations with various genomic, transcriptional and epigenomic features in order to understand mutational processes that contribute to the generation of the mutations. This user-friendly tool explores the presence of localized hypermutations (kataegis), dissects the spectrum of mutations into the maximum likelihood combination of known mutational signatures and associates the mutation density with numerous regulatory elements in the genome. As a result, global patterns of somatic mutations in any query sample can be efficiently screened, thus enabling a deeper understanding of various mutagenic factors. This tool will facilitate more effective downstream analyses of cancer genome sequences to elucidate the diversity of mutational processes underlying the development and clonal evolution of cancer cells. Mutalisk is freely available at http://mutalisk.org.

In this study, the effects of product separation on the distribution of liquid products and the energy efficiency of sewage sludge liquefaction in supercritical alcohol and supercritical alcohol–water mixtures were investigated. While considering alcohol participation in the liquefaction reaction (6–47 wt%), the effects of process parameters such as temperature (300–400 °C), residence time (10–120 min), concentration (9.1–25.0 wt%), and type of supercritical fluid (water, methanol, ethanol, water–alcohol mixture) on the yield and properties of bio-oils were examined. Accounting for alcohol participation and product separation allowed the bio-oil yield, energy recovery, and energy efficiency to be newly defined. Application of the new separation protocol developed in this study realized a 10–25 wt% increase in bio-oil yield because light fractions were efficiently captured. When supercritical methanol was used, the light fractions consisted primarily of methylated short-chain esters, whereas ketones and alcohols were the major species when supercritical ethanol was used. Liquefaction at 400 °C and 20 wt% sewage sludge in a mixture of water–methanol (80:20, v/v) resulted in a bio-oil with a high calorific value (35.8 MJ kg−1), achieving 155% energy recovery and 106% energy efficiency. Computational fluid dynamics (CFD) analysis of bio-oil combustion conducted in a commercial boiler demonstrated that cofiring with a mixture of petroleum heavy oil and bio-oil resulted in a high firing temperature of 1570 °C and a heat transfer rate, which were comparable to that obtained from conventional heavy oil firing.

The effect of reaction parameters (temperature, time and biomass-to-solvent (BS) ratio) on properties (higher heating value (HHV) and O/C and H/C ratios) and yields of bio-oil produced from macroalgae (Saccharina japonica) liquefaction using supercritical ethanol (scEtOH) as a solvent was investigated. At 400 °C using a BS ratio of 1/10 and reaction time of 45 min, a high yield of bio-oil (88 wt%) with a HHV of 35.0 MJ kg−1, O/C ratio of 0.14, and H/C ratio of 1.62 was obtained. Compared with water-based liquefaction, (subcritical water at 300 °C, bio-oil yield of 43 wt%, HHV of 20.7 MJ kg−1, O/C ratio of 0.48, and H/C ratio of 2.01; supercritical water at 400 °C, bio-oil yield of 37 wt%, HHV of 29.0 MJ kg−1, O/C ratio of 0.18, and H/C ratio of 1.76), the yield and energy content of the bio-oil produced using scEtOH were significantly higher. This enhancement was attributed to the reactivity of scEtOH with the intermediates generated from macroalgae. The utility of the generated bio-oil was demonstrated by application in a commercial 100 MWe generation plant. The thermal efficiency of the bio-oil (86.0%) was quite similar to that of heavy fuel oil (HFO) (87.1%), suggesting that the HFO could be fully replaced by the bio-oil.

Liquid biomass derived from food processing, biodiesel production, or fast pyrolysis has good potential for use as fuel to displace diesel or heavy fuel oil (HFO) for heat and power, and a major demonstration was successfully conducted in a 400 MWe HFO-fired power plant with a wall-firing boiler configuration using a BL blend of palm oil, its residue, and animal fat at a 20% co-firing ratio. When compared to a condition with HFO as fuel, the heat transfer rate on the membrane wall significantly decreased, and that of the convective heat exchangers in the upper furnace increased. This trend was different from what was observed at two smaller plants of 100 and 75 MWe, both with a tangential-firing boiler. This study uses computational fluid dynamics (CFD) to investigate the reason for the difference in the heat transfer characteristics. In both boiler types, bioliquid (BL) combustion led to lower soot concentrations and a corresponding decrease in radiation. This directly reduced the heat absorption on the furnace wall by approximately 5% at 20%-BL co-firing in the wall-firing boiler, and it was predicted further decrease linearly by 14% at 100%-BL firing. However, the tangential-firing boilers had less than a 1% decrease in measured heat absorption on the furnace wall at 100%-BL firing. Such differences were attributable to the gas flow pattern of the two boiler configurations. The burner tilting and flue gas recirculation of the tangential-firing boilers also contributed to successful operation at 100%-BL firing. The conclusions indicate that without effective measures to control the heat absorption distribution, the capability of a wall-firing boiler for BL combustion is limited to low co-firing ratios.

Conversion of sewage sludge into fuel was investigated using a catalyst- and external hydrogen-free supercritical fluid route. When dried sewage sludge was treated in supercritical ethanol, an extremely high bio-oil yield of 87.8 wt% and a remarkable higher heating value (HHV) of 34.6 MJ kg −1 were obtained. The possibility of using non-dried sewage sludge as a fuel source was tested using various alcohol–water mixtures; the presence of water resulted in an almost complete (96%) conversion and high HHVs of 36.8 and 37.3 MJ kg −1 for methanol–water (3:7, v/v) and ethanol–water (3:7, v/v) mixtures, respectively. The main chemical compounds in the bio-oils were found to be esters and nitrogenated species. Plausible reaction mechanisms for sewage sludge conversion in each supercritical fluid are discussed.

Autophagy is a cellular process that disrupts and uses unnecessary or malfunctioning components for cellular homeostasis. Evidence has shown a role for autophagy in tumor cell survival, but the molecular determinants that define sensitivity against autophagic regulation in cancers are not clear. Importantly, we found that breast cancer cells with low expression levels of a zinc-finger protein, ZNF143 (MCF7 sh-ZNF143), showed better survival than control cells (MCF7 sh-Control) under starvation, which was compromised with chloroquine, an autophagy inhibitor. In addition, there were more autophagic vesicles in MCF7 sh-ZNF143 cells than in MCF7 sh-Control cells, and proteins related with the autophagic process, such as Beclin1, p62, and ATGs, were altered in cells with less ZNF143. ZNF143 knockdown affected the stability of p53, which showed a dependence on MG132, a proteasome inhibitor. Data from proteome profiling in breast cancer cells with less ZNF143 suggest a role of NAD(P)H quinone dehydrogenase 1(NQO1) for p53 stability. Taken together, we showed that a subset of breast cancer cells with low expression of ZNF143 might exhibit better survival via an autophagic process by regulating the p53&ndash, Beclin1 axis, corroborating the necessity of blocking autophagy for the best therapy.

PURPOSE MicroRNAs (miRNAs) are noncoding RNAs that play roles as tumor suppressors or oncogenes by regulating the expression of target genes via binding to seed-match sequences. Polymorphisms in the miRNA-binding site of a target gene can alter miRNA binding and potentially affect the risk of cancer. The objective of this study was to identify single-nucleotide polymorphisms (SNPs) in miRNA-binding sites and assess their involvement in the risk of colorectal cancer (CRC). MATERIALS AND METHODS SNPs in the 3' untranslated regions of genes were selected and assessed for their effects on CRC risk in Korean population using participants in Korean Cancer Prevention Study-II. A detailed study was carried out with the SNP rs7930 in the 3' untranslated region of the translocase of outer mitochondrial membrane 20 (TOMM20) gene. A case-control study (1,545 controls and 620 CRC cases) was conducted to analyze the relationship between polymorphism at rs7930 and the risk of CRC. An interacting miRNA was predicted using web-based software programs, and its interaction with rs7930 in CRC cell lines was investigated by using a luciferase assay. RESULTS Individuals carrying the rs7930 AG genotype (G allele) had a 1.721-fold increased risk for CRC in comparison with those with the AA genotype (A allele). The miRNA miR-4273-5p was found to specifically interact with the A allele of rs7930 and to suppress the expression of the target gene (TOMM20) in CRC cell lines. CONCLUSION rs7930 is an independent genetic risk factor for CRC susceptibility. Our study suggests a mechanism of how this SNP contributes to CRC carcinogenesis.

Fast pyrolysis bio-oil derived from empty palm fruit bunch was upgraded in supercritical ethanol (scEtOH) without using external catalysts and molecular hydrogen. The effects of the reaction temperature and time on the product yield and the quality of the upgraded oil based on parameters like the elemental content, total acid number (TAN), water content, high heating value (HHV), and viscosity were examined. At 400 °C, almost all of the organic species in the fast pyrolysis bio-oil were converted to the liquid and gas phase in 30 min, resulting in a high yield of the upgraded oil (83.0 wt%) with an enhanced HHV of 34.1 MJ kg −1 and very low values of TAN (4.8 mg KOH g −1 ) and water (1.6 wt%) when compared to the fast pyrolysis bio-oil (HHV, 24.3 MJ kg −1 ; TAN, 69.4 mg KOH g −1 ; water, 14.0 wt%). The major chemical species in the upgraded oil were alcohols, esters, phenols, hydrocarbons, and aromatics. After aging at 80 °C for one week, a marginal increase in the viscosity of the upgraded bio-oil was observed, indicating a significant improvement in the stability of the bio-oil. Computational fluid dynamics (CFD) analysis of the process performed in a commercial boiler demonstrated that the upgraded oil firing exhibited high gas temperature profiles, a high firing peak of 1599 °C, and a high total heat transfer rate of 121.81 MW th . These results are comparable to the performance parameters of conventional heavy oil-firing processes.

Complete fuel switching from heavy fuel oil (HFO) to bioliquid (BL) was demonstrated in a 100 MWe-capacity boiler with a tangential firing configuration. The BL from the residue of palm oil production successfully replaced HFO at the full load (103 MWe) with new atomizers and minor adjustments to the operating parameters. The detailed combustion and heat transfer characteristics of the two fuels were analyzed using computational fluid dynamics (CFD). Compared to the HFO firing case, more uniform distributions of the gas temperature and heat transfer rate were observed in the combustion zone for the BL firing case. The total heat transfer rate was slightly lower on the furnace wall (evaporator), but this disadvantage was offset by the increased convection in the downstream heat exchangers. Because of the low soot concentration, the contribution of convection in the BL-firing case was larger in the lower furnace. A significant reduction in SOx and NOx emissions was achieved due to the low S and N content of BL, which would be the main benefit of fuel switching, in addition to the minimization of greenhouse gas emissions. In the future, the CFD model established in this study could be applied to the evaluation of BL different candidates and various co-firing cases with HFO.

For the construction safety manager, it is expected that job stress is significantly high due to lack of expertise about new technology, new construction methods, and enlargement of scale as well as due to work intensity and unstable work hours. It is probable that such an increase in job stress not only has bad effects on individual, but also the bad effects spread to construction industry at large, resulting in rise in accident rate, increase in direct and indirect loss cost, and loss of reputation. In this context, methods for controlling construction safety manager's job stress are needed at the levels of both government and company. Therefore, this study investigated and analyzed the effects of construction safety manager's job stress on job satisfaction and job commitment, and proposed methods for relieving job stress. In addition, this study was suggested policies for higher job satisfaction and job commitment at the levels of the government and companies.

Colorectal cancer (CRC), the third most common cancer worldwide, also has the highest rate of cancer-related morbidity and mortality. WNT signaling is initiated by binding of WNT to various receptors, including frizzleds (FZDs), and plays a critical role in CRC and other tumor development by regulating proliferation, differentiation, migration, apoptosis, and polarity. Among the members of the FZD family, FZD6 is broadly expressed in various tissues, and its overexpression has been reported in several cancers, suggesting an important role in cancer development. In this study, we investigated the expression of FZD6 in patients with CRC and found it to be increased in tumors, as compared to paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression was negatively regulated by miR199a5p in CRC cells. These results suggest that overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play an important role in the development of CRC. [BMB Reports 2015; 48(6): 360-366]

It is a tendency for enterprises in the domestic construction field to harness the system scaffolding with an aim to securing safety, despite slight increase in terms of the construction cost. Nevertheless, given that putting the system into service in reality is not accurately surveyed by far and that safety standards and methods for safe work therewith are not yet established, hazardous factors involving the system scaffolding remain latent leaving unrecognized. In this regard, the current study attempts to understand the status of implementation and use of the system scaffolding in the local construction sites as for the year 2009 and the year 2013 through questionnaire surveying and in-depth interviewing, while further proposing, based on the result thereof, ways for activating introduction of the system scaffolding in an effective and systematic manner.

Background Hairless ( Hr ), a transcriptional corepressor expressed mainly in the skin, regulates hair follicle (HF) morphogenesis and hair cycling. Recently, we reported a new Hr mutant mouse, "Hairpoor" ( Hr Hp ), that resembles the human hair disorder Marie Unna hereditary hypotrichosis (MUHH) in the heterozygous state. The Wnt/β-catenin signaling pathway is critical for homeostasis in various adult tissues including skin and HFs. One of the Wnt inhibitors, Dickkopf (Dkk), inhibits hair growth during the hair cycle as a catagen inducer of apoptosis, resulting in HF reductions. Objective To investigate regulation of Dkk1 by HR and its effect on hair formation. Methods The relative expression of Dkk1 in + / Hr HP and Hr Hp / Hr Hp mice during the hair cycle was investigated using real time PCR and Western blot analysis. Immunohistochemistry was performed in order to confirm abnormal expression of Dkk1 in HFs of + / Hr HP and Hr Hp / Hr Hp mice. To determine whether Dkk1 expression was also regulated by HR in vitro , an Hr -transient transfection experiment was performed. Alteration of the hair cycle in Hr HP heterozygous mice was identified by determination of the hair cycle and measurement of HF length. Results Dkk1 expression was increased in the skin of + / Hr HP and Hr Hp / Hr Hp mice, as well as in Hr -overexpressing mouse keratinocytes. Additionally, an earlier entrance of HFs into catagen and shortened HF length in + / Hr HP mice compared to wild-type mice was observed. Conclusion Study results suggested that up-regulation of Dkk1 by HR contributed to abnormal development of HFs and failure in regeneration of HFs in Hr Hp / Hr Hp mice. These findings also indicated that alteration of the hair cycle in + / Hr HP mice was related to the up-regulation of Dkk1 by HR.

T-cadherin is frequently down regulated in various cancers, however, the underlying mechanisms responsible have yet to be elucidated. A genome wide association study of a cohort of Korean adults revealed that the T-cadherin rs3865188 single nucleotide polymorphism (SNP) was associated with serum Adiponectin levels and that its genotypic variants were correlated with risk for colorectal cancer (CRC). To test the function of rs12444338, a SNP tightly linked to the rs3865188 SNP, in T-cadherin transcriptional regulation in colorectal cancer, its effect on transcriptional activity and the capacity of binding activity attributable to allelic variation of the rs12444338 SNP was investigated. An electrophoretic-mobility-shift assay (EMSA) revealed a specific nucleoprotein complex unique to the T allele probe, which displayed lower promoter activity when compared to the G allele. Based on the results of the EMSA using mutant probes, the consensus sequence of the putative transcription factor binding site was determined. Additionally, candidates for putative binding factors to the T allele were also identified. Collectively, the study data suggested that the rs12444338 SNP was involved in transcriptional regulation of T-cadherin gene (CDH13) and that the differential binding of transcription factors at the rs12444338 SNP resulted in altered gene expression. These results elucidate, at least in part, the regulation of T-cadherin expression in CRC and provide further information regarding the effect of nucleotide variation in its promoter region.

The Hairless (HR) gene regulates the expression of sev-eral target genes as a transcriptional corepressor of nu-clear receptors. The hair follicle (HF), a small independ-ent organ of the skin, resides in the epidermis and un-dergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss pheno-type in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF develop-ment. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates proliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and dis-cuss the roles of the HR gene in HF development. Keywords: hairless, corepressor, hair follicle, hair cycle, hair loss

Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.

Background Adiponectin levels have been shown to be associated with colorectal cancer (CRC). Furthermore, a newly identified adiponectin receptor, T-cadherin, has been associated with plasma adiponectin levels. Therefore, we investigated the potential for a genetic association between T-cadherin and CRC risk. Result We conducted a case–control study using the Korean Cancer Prevention study-II cohort, which is composed of 325 CRC patients and 977 normal individuals. Study results revealed that rs3865188 in the 5’ flanking region of the T-cadherin gene (CDH13) was significantly associated with CRC (p = 0.0474). The odds ratio (OR) for the TT genotype as compared to the TA + AA genotype was 1.577 (p = 0.0144). In addition, the interaction between CDH13 and the adiponectin gene (APN) for CRC risk was investigated using a logistic regression analysis. Among six APN single nucleotide polymorphisms (rs182052, rs17366568, rs2241767, rs3821799, rs3774261, and rs6773957), an interaction with the rs3865188 was found for four (rs2241767, rs3821799, rs3774261, and rs6773957). The group with combined genotypes of TT for rs3865188 and GG for rs377426 displayed the highest risk for CRC development as compared to those with the other genotype combinations. The OR for the TT/GG genotype as compared to the AA/AA genotype was 4.108 (p = 0.004). Furthermore, the plasma adiponectin level showed a correlation with the gene-gene interaction, and the group with the highest risk for CRC had the lowest adiponectin level (median, 4.8 μg/mL for the TT/GG genotype vs.7.835 μg/mL for the AA/AA genotype, p = 0.0017). Conclusions The present study identified a new genetic factor for CRC risk and an interaction between CDH13 and APN in CRC risk. These genetic factors may be useful for predicting CRC risk. Electronic supplementary material The online version of this article (doi:10.1186/s12929-015-0180-9) contains supplementary material, which is available to authorized users.

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5' untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5' UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5' UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.

PURPOSE Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

Hardy-weinberg equilibrium (HWE) in the control group. Table S2. Differences on the adiponectin level in KCP-II based on the genotype combination between rs3865188- rs2241767, rs3865188- rs382179 and rs3865188- rs6773957. (DOCX 18Â kb)

Purpose: The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans. Materials and Methods: To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a casecontrol study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects. Results: Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069‒2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4±0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant. Conclusion: We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.

Hairless (HR), a transcriptional cofactor, is highly expressed in the skin and brain. To characterize the effects of HR expression in the skin, we examined its capacity for transcriptional regulation of its target genes in mouse skin and keratinocytes. We found that Foxe1 mRNA expression was suppressed in HR-overexpressing skin, as well as in HR-expressing keratinocytes. In turn, Msx1 expression was downregulated contingent on Foxe1 downregulation in skin and keratinocytes. We also found that expression of Sfrp1 was also correlated with that of Foxe1. Further investigation of the mechanisms involved in the transcriptional regulation of these genes will facilitate our understanding of the relationship among genes involved in hair follicle morphogenesis and cycling.

Hairpoor mice (Hr(Hp)) were derived through N-ethyl-N-nitrosourea (ENU) mutagenesis. These mice display sparse and short hair in the Hr(Hp)/+ heterozygous state and complete baldness in the Hr(Hp)/Hr(Hp) homozygous state. This phenotype was irreversible and was inherited in an autosomal semidominant manner. Hair follicles (HFs) of Hr(Hp)/+ mice underwent normal cycling and appeared normal, although smaller than those of the wild-type mice. In contrast, HFs of Hr(Hp)/Hr(Hp) mice became cyst-like structures by postnatal day (P) 21. The number and length of vibrissae decreased in a dose-dependent manner as the number of mutant alleles increased. A positional candidate gene approach was used to identify the gene responsible for the hairpoor phenotype. Genetic linkage analysis determined that the hairpoor locus is 2 cm from D14Mit34 on chromosome 14. Sequence analysis of the exons of the candidate gene hairless revealed a T-to-A transversion mutation at nucleotide position 403 (exon 2), presumably resulting in abolishment of an upstream open reading frame (uORF). In addition, we also found that the near-naked mouse (Hr(N)), a spontaneously arising mutant, harbors a A402G transition in its genome. Both mutations were in the uATG codon of the second uORF in the 5' UTR and corresponded to the mutations identified in Marie Unna Hereditary Hypotrichosis (MUHH) patients. In the present study we describe the phenotype, histological morphology, and molecular etiology of an animal model of MUHH, the hairpoor mouse.

Power system protective relays must be as reliable and fast as possible even though input singals contain fault induced exponentially decaying DC-offset and damped high frequency oscillations. A digital differential relaying system for primary protection of transmission line using travelling wave has been suggested.[1] It was shown that the fault current appears as a difference of two signals – the travelling wave at one terminal and the time delayed travelling wave at the other terminal. The amplitude of fault current was conventionaly computed from each interpolated signal. In this paper signals are transmitted to the other end and the phasor of these quantities are extracted by a correlation method and the fault current are obtained from the phasors. The phasors are computed by correlations of rectagular signals which have half-cycle window and input signals. The correlation integral is equal to the sum of sampled values which are obtained by averaging the input signal during each sampling interval. In the proposed method the phasor of fault current is insensitive to high frequecy transients because it is computed from an analog integral. And the effect of exponentially decaying DC-offset is reduced by using another two sample values. The proposed method has been tested by numerical simulations and the results found to be satisfactory.

Power system protective relays must be as reliable and fast as possible even though input singals contain fault induced exponentially decaying DC-offset and damped high frequency oscillations. A digital differential relaying system for primary protection of transmission line using travelling wave has been suggested.[1] It was shown that the fault current appears as a difference of two signals - the travelling wave at one terminal and the time delayed travelling wave at the other terminal. The amplitude of fault current was conventionaly computed from each interpolated signal. In this paper signals are transmitted to the other end and the phasor of these quantities are extracted by a correlation method and the fault current are obtained from the phasors. The phasors are computed by correlations of rectagular signals which have half-cycle window and input signals. The correlation integral is equal to the sum of sampled values which are obtained by averaging the input signal during each sampling interval. In the proposed method the phasor of fault current is insensitive to high frequecy transients because it is computed from an analog integral. And the effect of exponentially decaying DC-offset is reduced by using another two sample values. The proposed method has been tested by numerical simulations and the results found to be satisfactory.