774 research outputs found

    Alloy Design to Prevent Intergranular Corrosion of Low-Cr Ferritic Stainless Steel with Weak Carbide Formers

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    Effect of weak carbide formers, Mo, Mn and Si, on intergranular corrosion (IGC) of low-Cr ferritic stainless steel is analyzed after IGC test using TEM and three dimensional atom probe. The co-addition ofMo, Mn and Si to low-Cr ferritic stainless steel effectively prevents IGC by forming along grain boundaries CMn4MoSi intermetallic compounds, which act not only as carbon trap sites but also as diffusion barrier against solute Cr diffusion toward grain boundaries. The low solubility of Cr in the CMn4MoSi intermetallic compound results in replenishing Cr in the Cr-depleted area. (C) The Author(s) 2015. Published by ECS. All rights reserved.114Ysciescopu

    Angiomyofibroblastoma-Like Tumor of the Scrotum

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    Various tumors can occur in the scrotum. Of them, angiomyofibroblastoma-like tumors are very rare mesenchymal tumors. Angiomyofibroblastoma-like tumors cannot be easily differentially diagnosed from other malignant tumors invading the male genital tract on the basis of clinical characteristics and imaging study. Therefore, surgical removal and a histopathologic diagnosis must also be performed

    Metric for Measuring the Effectiveness of Clustering of DNA Microarray Expression

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    BACKGROUND: The recent advancement of microarray technology with lower noise and better affordability makes it possible to determine expression of several thousand genes simultaneously. The differentially expressed genes are filtered first and then clustered based on the expression profiles of the genes. A large number of clustering algorithms and distance measuring matrices are proposed in the literature. The popular ones among them include hierarchal clustering and k-means clustering. These algorithms have often used the Euclidian distance or Pearson correlation distance. The biologists or the practitioners are often confused as to which algorithm to use since there is no clear winner among algorithms or among distance measuring metrics. Several validation indices have been proposed in the literature and these are based directly or indirectly on distances; hence a method that uses any of these indices does not relate to any biological features such as biological processes or molecular functions. RESULTS: In this paper we have proposed a metric to measure the effectiveness of clustering algorithms of genes by computing inter-cluster cohesiveness and as well as the intra-cluster separation with respect to biological features such as biological processes or molecular functions. We have applied this metric to the clusters on the data set that we have created as part of a larger study to determine the cancer suppressive mechanism of a class of chemicals called retinoids. We have considered hierarchal and k-means clustering with Euclidian and Pearson correlation distances. Our results show that genes of similar expression profiles are more likely to be closely related to biological processes than they are to molecular functions. The findings have been supported by many works in the area of gene clustering. CONCLUSION: The best clustering algorithm of genes must achieve cohesiveness within a cluster with respect to some biological features, and as well as maximum separation between clusters in terms of the distribution of genes of a behavioral group across clusters. We claim that our proposed metric is novel in this respect and that it provides a measure of both inter and intra cluster cohesiveness. Best of all, computation of the proposed metric is easy and it provides a single quantitative value, which makes comparison of different algorithms easier. The maximum cluster cohesiveness and the maximum intra-cluster separation are indicated by the metric when its value is 0. We have demonstrated the metric by applying it to a data set with gene behavioral groupings such as biological process and molecular functions. The metric can be easily extended to other features of a gene such as DNA binding sites and protein-protein interactions of the gene product, special features of the intron-exon structure, promoter characteristics, etc. The metric can also be used in other domains that use two different parametric spaces; one for clustering and the other one for measuring the effectiveness

    A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

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    Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

    Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture

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    A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7–13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0–6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1–4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6–19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea

    Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

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    <p>Abstract</p> <p>Purpose</p> <p>An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.</p> <p>Patients and methods</p> <p>Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis.</p> <p>Results</p> <p>The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; <it>P </it>= .002).</p> <p>Conclusion</p> <p>Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.</p

    Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses

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    <p>Abstract</p> <p>Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI) viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs) 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.</p

    De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

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    Ravichandran N. Murugan, Mija Ahn, Eunha Hwang, Ji-Hyung Seo, Chaejoon Cheong, Jeong Kyu Bang, Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Chung-Buk, Republic of KoreaBinu Jacob, Song Yub Shin, Department of Bio-Materials, Graduate School and Department of Cellular and Molecular Medicine, School of Medicine, Chosun University, Gwangju, Republic of KoreaHoik Sohn, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas, United States of AmericaHyo-Nam Park, Jae-Kyung Hyun, Division of Electron Microscopic Research, Korea Basic Science Institute, Daejeon, Republic of KoreaEunjung Lee, Ki-Woong Jeong, Yangmee Kim, Department of Bioscience and Biotechnology, Institute of SMART Biotechnology, Konkuk University, Seoul, Republic of KoreaKy-Youb Nam, Bioinformatics and Molecular Design Research Center, Yonsei University Research Complex, Seoul, Republic of KoreaBackground: Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability.-- Methodology/Principal Findings: In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. -- Conclusion/Significance: The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.This work was supported in part by the Korea Basic Science Institute's research program grants T33418 (J.K.B) and T33518 (J-k.H.), and the Korea Research Foundation, funded by the Korean Government (KRF-2011-0009039 to S.Y.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.ChemistryBiochemistryEmail: [email protected] (JKB)Email: [email protected] (SYS
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