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Sample records for 4a 4b 4c

  1. Molecular cloning and subcellular distribution of the novel PDE4B4 cAMP-specific phosphodiesterase isoform.

    PubMed Central

    Shepherd, Malcolm; McSorley, Theresa; Olsen, Aileen E; Johnston, Lee Ann; Thomson, Neil C; Baillie, George S; Houslay, Miles D; Bolger, Graeme B

    2003-01-01

    We have isolated cDNAs encoding PDE4B4, a new cAMP-specific phosphodiesterase (PDE4) isoform with novel properties. The amino acid sequence of PDE4B4 demonstrates that it is encoded by the PDE4B gene, but that it differs from the previously isolated PDE4B1, PDE4B2 and PDE4B3 isoforms by the presence of a novel N-terminal region of 17 amino acids. PDE4B4 contains both of the upstream conserved region 1 (UCR1) and UCR2 regulatory units that are characteristic of 'long' PDE4 isoforms. RNase protection demonstrated that PDE4B4 mRNA is expressed preferentially in liver, skeletal muscle and various regions of the brain, which differs from the pattern of tissue distribution of the other known PDE4B long forms, PDE4B1 and PDE4B3. Expression of PDE4B4 cDNA in COS7 cells produced a protein of 85 kDa under denaturing conditions. Subcellular fractionation of recombinant, COS7-cell expressed PDE4B4 showed that the protein was localized within the cytosol, which was confirmed by confocal microscopic analysis of living COS7 cells transfected with a green fluorescent protein-PDE4B4 chimaera. PDE4B4 exhibited a K(m) for cAMP of 5.4 microM and a V(max), relative to that of the long PDE4B1 isoform, of 2.1. PDE4B4 was inhibited by the prototypical PDE4 inhibitor rolipram [4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidinone] with an IC(50) of 83 nM. Treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which was associated with the phosphorylation of PDE4B4 on Ser-56 within UCR1. The unique tissue distribution and intracellular targeting of PDE4B4 suggests that this isoform may have a distinct functional role in regulating cAMP levels in specific cell types. PMID:12441002

  2. Real-time PCR quantification of human complement C4A and C4B genes

    PubMed Central

    Szilagyi, Agnes; Blasko, Bernadett; Szilassy, Denes; Fust, George; Sasvari-Szekely, Maria; Ronai, Zsolt

    2006-01-01

    Background The fourth component of human complement (C4), an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B) in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different. Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes. Results A novel quantitative real-time PCR (qPCR) technique was developed for rapid and accurate quantification of the C4A and C4B genes applying a duplex, TaqMan based methodology. The reliable, single-step analysis provides the determination of the copy number of the C4A and C4B genes applying a wide range of DNA template concentration (0.3–300 ng genomic DNA). The developed qPCR was applied to determine C4A and C4B gene dosages in a healthy Hungarian population (N = 118). The obtained data were compared to the results of an earlier study of the same population. Moreover a set of 33 samples were analyzed by two independent methods. No significant difference was observed between the gene dosages determined by the employed techniques demonstrating the reliability of the novel qPCR methodology. A Microsoft Excel worksheet and a DOS executable are also provided for simple and automated evaluation of the measured data. Conclusion This report describes a novel real-time PCR method for single-step quantification of C4A and C4B genes. The developed technique could facilitate studies investigating disease association of different C4 isotypes. PMID:16403222

  3. Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo.

    PubMed

    Park, Eun-Hee; Walker, Sarah E; Zhou, Fujun; Lee, Joseph M; Rajagopal, Vaishnavi; Lorsch, Jon R; Hinnebusch, Alan G

    2013-01-25

    Translation initiation factor eIF4F (eukaryotic initiation factor 4F), composed of eIF4E, eIF4G, and eIF4A, binds to the m(7)G cap structure of mRNA and stimulates recruitment of the 43S preinitiation complex and subsequent scanning to the initiation codon. The HEAT domain of eIF4G stabilizes the active conformation of eIF4A required for its RNA helicase activity. Mammalian eIF4B also stimulates eIF4A activity, but this function appears to be lacking in yeast, making it unclear how yeast eIF4B (yeIF4B/Tif3) stimulates translation. We identified Ts(-) mutations in the HEAT domains of yeast eIF4G1 and eIF4G2 that are suppressed by overexpressing either yeIF4B or eIF4A, whereas others are suppressed only by eIF4A overexpression. Importantly, suppression of HEAT domain substitutions by yeIF4B overexpression was correlated with the restoration of native eIF4A·eIF4G complexes in vivo, and the rescue of specific mutant eIF4A·eIF4G complexes by yeIF4B was reconstituted in vitro. Association of eIF4A with WT eIF4G in vivo also was enhanced by yeIF4B overexpression and was impaired in cells lacking yeIF4B. Furthermore, we detected native complexes containing eIF4G and yeIF4B but lacking eIF4A. These and other findings lead us to propose that yeIF4B acts in vivo to promote eIF4F assembly by enhancing a conformation of the HEAT domain of yeast eIF4G conducive for stable binding to eIF4A.

  4. Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression.

    PubMed

    Aguilo, Francesca; Zhou, Ming-Ming; Walsh, Martin J

    2011-08-15

    Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15(INK4b), p14(ARF), and p16(INK4a), and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development. PMID:21828241

  5. Long Noncoding RNA, Polycomb, and the Ghosts Haunting INK4b-ARF-INK4a Expression

    PubMed Central

    Aguilo, Francesca; Zhou, Ming-Ming; Walsh, Martin J.

    2012-01-01

    Polycomb group proteins (PcG) function as transcriptional repressors of gene expression. The important role of PcG in mediating repression of the INK4b-ARF-INK4a locus, by directly binding to the long noncoding RNA (lncRNA) transcript antisense noncoding RNA in the INK4 locus (ANRIL), was recently shown. INK4b-ARF-INK4a encodes 3 tumor-suppressor proteins, p15INK4b, p14ARF, and p16INK4a, and its transcription is a key requirement for replicative or oncogene-induced senescence and constitutes an important barrier for tumor growth. ANRIL gene is transcribed in the antisense orientation of the INK4b-ARF-INK4a gene cluster, and different single-nucleotide polymorphisms are associated with increased susceptibility to several diseases. Although lncRNA-mediated regulation of INK4b-ARF-INK4a gene is not restricted to ANRIL, both polycomb repressive complex-1 (PRC1) and -2 (PRC2) interact with ANRIL to form heterochromatin surrounding the INK4b-ARF-INK4a locus, leading to its repression. This mechanism would provide an increased advantage for bypassing senescence, sustaining the requirements for the proliferation of stem and/or progenitor cell populations or inappropriately leading to oncogenesis through the aberrant saturation of the INK4b-ARF-INK4a locus by PcG complexes. In this review, we summarize recent findings on the underlying epigenetic mechanisms that link PcG function with ANRIL, which impose gene silencing to control cellular homeostasis as well as cancer development. PMID:21828241

  6. Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells

    PubMed Central

    Wu, Liangtang; Wary, Kishore K.; Revskoy, Sergei; Gao, Xiaopei; Tsang, Kitman; Komarova, Yulia A.; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    Summary Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating the expression of fetal liver kinase (Flk)1 and VE-cadherin, respectively, and thereby the transition of mouse ESCs (mESCs) to endothelial cells. KDM4A was shown to bind to histones associated with the Flk1 promoter and KDM4C to bind to histones associated with the VE-cadherin promoter. KDM4A and KDM4C were also both required for capillary tube formation and vasculogenesis in mice. We observed in zebrafish that KDM4A depletion induced more severe vasculogenesis defects than KDM4C depletion, reflecting the early involvement of KDM4A in specifying endothelial cell fate. These findings together demonstrate the essential role of KDM4A and KDM4C in orchestrating mESC differentiation to endothelial cells through the activation of Flk1 and VE-cadherin promoters, respectively. PMID:26120059

  7. SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus.

    PubMed

    Kia, Sima Kheradmand; Gorski, Marcin M; Giannakopoulos, Stavros; Verrijzer, C Peter

    2008-05-01

    Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a variety of human cancers, including malignant rhabdoid tumors (MRTs). MRTs are extremely aggressive cancers caused by the loss of the hSNF5 subunit of the SWI/SNF chromatin-remodeling complex. We found previously that, in MRT cells, hSNF5 is required for p16(INK4a) induction, mitotic checkpoint activation, and cellular senescence. Here, we investigated how the balance between Polycomb group (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b-ARF-INK4a locus in MRT cells. hSNF5 reexpression in MRT cells caused SWI/SNF recruitment and activation of p15(INK4b) and p16(INK4a), but not of p14(ARF). Gene activation by hSNF5 is strictly dependent on the SWI/SNF motor subunit BRG1. SWI/SNF mediates eviction of the PRC1 and PRC2 PcG silencers and extensive chromatin reprogramming. Concomitant with PcG complex removal, the mixed lineage leukemia 1 (MLL1) protein is recruited and active histone marks supplant repressive ones. Strikingly, loss of PcG complexes is accompanied by DNA methyltransferase DNMT3B dissociation and reduced DNA methylation. Thus, various chromatin states can be modulated by SWI/SNF action. Collectively, these findings emphasize the close interconnectivity and dynamics of diverse chromatin modifications in cancer and gene control. PMID:18332116

  8. Human wound infections caused by Neisseria animaloris and Neisseria zoodegmatis, former CDC Group EF-4a and EF-4b

    PubMed Central

    Heydecke, Anna; Andersson, Birgitta; Holmdahl, Torsten; Melhus, Åsa

    2013-01-01

    Background Neisseria animaloris and Neisseria zoodegmatis, former CDC Group EF-4a and -4b, are considered to be rare zoonotic pathogens, usually associated with dog or cat bites. The aim of the study was to phenotypicaly characterize 13 EF-4 isolates from wound infections, determine their antibiotic susceptibility and to follow the clinical outcome of the patients. Methods 13 of the EF-4 isolates were cultured on agar plates. Conventional biochemical tests and the Biolog system were used for phenotypical identification. An arbitrary primed polymerase chain reaction (AP-PCR) was carried out to determine the genetic profiles. Minimum inhibitory concentration (MIC) values were determined for different antibiotics were determined. According to this, clinical data for the patients were recorded. Results 11 isolates were identified as N. animaloris and 2 as N. zoodegmatis due to the production of arginine dihydrolase. A majority of the patients had a history of dog bite. In 6 cases only grewth of N. animaloris or zoodegmatis was registered. When a patient received antibiotic treatment the most common drug of choice was penicillin V. Only 3 patients received treatment for which the isolated EF-4 bacterium was fully susceptible. Conclusion Human infections involving N. animaloris and N. zoodegmatis usually present themselves as local wound infection, but severe complications can occur. Despite their pathogenic potentia, l N. animaloris and N. zoodegmatis are often misidentified, dismissed as skin contaminants or not recognized at all. Due to the fact that N. animaloris and N. zoodegmatis are significant pathogens in animal bites, physicians should keep these bacteria in mind when choosing antibiotic therapy. PMID:23919115

  9. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

    PubMed Central

    Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

    2015-01-01

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  10. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.

    PubMed

    Qiu, Mei-Ting; Fan, Qiong; Zhu, Zhu; Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C; Wong, Kwong-Kwok; Bao, Wei

    2015-10-13

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  11. Coriolis Interactions in the nu2, nu4a, nu4b, and nu3a States of Phosphine-d1

    PubMed

    Kshirsagar; Job

    1997-10-01

    Spectra of the nu4a (HPH bend) and nu4b (HPD bend) bands of the PH2D molecule have been recorded and analyzed. The Coriolis interactions between the two states as well as the various Coriolis interactions of the nu4a and nu4b states with the nu2 state have been included in the analysis. Several new assignments of transitions which occur with enhanced intensity in the nu2 band also have been made. The parameters of the nu4a and nu4b states, improved parameters of the nu2 state, and the interaction parameters have been determined. The data on the nu3a band of PH2D have been reanalyzed by taking into account the b-axis Coriolis interaction of the nu3a state with the 2nu2 state. Copyright 1997 Academic Press. Copyright 1997Academic Press

  12. Contrasting behavior of the p18INK4c and p16INK4a tumor suppressors in both replicative and oncogene-induced senescence.

    PubMed

    Gagrica, Sladjana; Brookes, Sharon; Anderton, Emma; Rowe, Janice; Peters, Gordon

    2012-01-01

    The cyclin-dependent kinase (CDK) inhibitors, p18(INK4c) and p16(INK4a), both have the credentials of tumor suppressors in human cancers and mouse models. For p16(INK4a), the underlying rationale is its role in senescence, but the selective force for inactivation of p18(INK4c) in incipient cancer cells is less clear. Here, we show that in human fibroblasts undergoing replicative or oncogene-induced senescence, there is a marked decline in the levels of p18(INK4c) protein and RNA, which mirrors the accumulation of p16(INK4a). Downregulation of INK4c is not dependent on p16(INK4a), and RAS can promote the loss of INK4c without cell-cycle arrest. Downregulation of p18(INK4c) correlates with reduced expression of menin and E2F1 but is unaffected by acute cell-cycle arrest or inactivation of the retinoblastoma protein (pRb). Collectively, our data question the idea that p18(INK4c) acts as a backup for loss of p16(INK4a) and suggest that the apparent activation of p18(INK4c) in some settings represents delayed senescence rather than increased expression. We propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation.

  13. Gene Expression Status and Methylation Pattern in Promoter of P15INK4b and P16INK4a in Cord Blood CD34+ Stem Cells

    PubMed Central

    Azad, Mehdi; Kaviani, Saeid; Noruzinia, Mehrdad; Mortazavi, Yousef; Mobarra, Naser; Alizadeh, Shaban; Shahjahani, Mohammad; Skandari, Fatemeh; Ahmadi, Mohammad Hosein; Atashi, Amir; Abroun, Saeid; Zonoubi, Zahra

    2013-01-01

    Objective(s) : Stem cell differentiation into different cell lineages depends upon several factors, cell cycle control elements and intracellular signaling elements, including P15INK4b and P16INK4a genes. Epigenetics may be regarded as a control mechanism which is affected by these factors with respect to their promoter structure. Materials and Methods : The CD34 + cord blood stem cells were purified, isolated and then expanded. The undifferentiated day genome was isolated from part of the cultured cells, and the seventh day differentiated genome was isolated from the other part after differentiation to erythroid lineage. The procedure was followed by a separate Real-Time PCR for the two genes using the obtained cDNA. The processed DNA of the former stages was used for MSP (Methylation Specific PCR) reaction. Finally, pre- and post differentiation results were compared.  Results : After performing MSP for each gene, it became clear that P15INK4b gene has undergone methylation and expression in predifferentiation stage. In addition, its status has not been changed after differentiation. P15INK4b gene expression was reduced after the differentiation. The other gene, P16INK4a, showed no predifferentiation methylation. Itwas completely expressed methylated and underwent reduced expression after differentiation. Conclusion : Specific predifferentiation expression of P15INK4b and P16INK4a genes along with reduction in their expression after erythroid differentiation indicated animportant role for these two genes in biology of CD34+ cells in primary stages and before differentiation. In addition, both genes are capable of epigenetic modifications due to the structure of their promoters. PMID:23997911

  14. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

    PubMed

    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers.

  15. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A

    SciTech Connect

    Carroll, M.C.; Fathallah, D.M.; Bergamaschini, L.; Alicot, E.M. ); Isenman, D.E. )

    1990-09-01

    The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)-namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the {alpha} chain. To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of the chemical bond formed. Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not catalytic as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to select binding sites on potential acceptor molecules.

  16. Characterization and expression analyses of five interferon regulatory factor transcripts (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua).

    PubMed

    Inkpen, Sabrina M; Hori, Tiago S; Gamperl, A Kurt; Nash, Gordon W; Rise, Matthew L

    2015-05-01

    The interferon regulatory factor (IRF) family of genes encodes a group of transcription factors that have important roles not only in regulating the expression of Type I interferons (IFNs) and other genes in the IFN pathway, but also in growth, development and the regulation of oncogenesis. In this study, several IRF family members (Irf4a, Irf4b, Irf7, Irf8, Irf10) in Atlantic cod (Gadus morhua) were characterized at the cDNA and putative amino acid levels, allowing for phylogenetic analysis of these proteins in teleost fish, as well as the development of gene-specific primers used in RT-PCR and quantitative PCR (QPCR) analyses. Two Atlantic cod Irf10 splice variants were identified and their presence confirmed by sequencing of the Irf10 genomic region. RT-PCR showed that Irf7, Irf8 and both Irf10 transcripts were expressed in all 15 cod tissues tested, while Irf4a and Irf4b were absent in some tissues. QPCR analysis of spleen expression expanded upon this, and upon previous work. All IRF transcripts in the study were responsive to stimulation by the viral mimic poly(I:C), and all except Irf4a were responsive to exposure to formalin-killed Aeromonas salmonicida (ASAL). These IRF genes, thus, are likely important in the cod immune response to both viral and bacterial infections. Increased temperature (10 °C to 16 °C) was also observed to modulate the antibacterial responses of all IRF transcripts, and the antiviral responses of Irf4b and Irf10-v2. This research supports earlier studies which reported that elevated temperature modulates the expression of many immune genes in Atlantic cod. PMID:25731920

  17. NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology

    PubMed Central

    Rämö, Olli; Kumar, Darshan; Gucciardo, Erika; Joensuu, Merja; Saarekas, Maiju; Vihinen, Helena; Belevich, Ilya; Smolander, Olli-Pekka; Qian, Kui; Auvinen, Petri; Jokitalo, Eija

    2016-01-01

    Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets. PMID:27786289

  18. eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle.

    PubMed

    Harms, Ulf; Andreou, Alexandra Zoi; Gubaev, Airat; Klostermeier, Dagmar

    2014-07-01

    Eukaryotic translation initiation factor eIF4A is a DEAD-box helicase that resolves secondary structure elements in the 5'-UTR of mRNAs during ribosome scanning. Its RNA-stimulated ATPase and ATP-dependent helicase activities are enhanced by other translation initiation factors, but the underlying mechanisms are unclear. DEAD-box proteins alternate between open and closed conformations during RNA unwinding. The transition to the closed conformation is linked to duplex destabilization. eIF4A is a special DEAD-box protein that can adopt three different conformations, an open state in the absence of ligands, a half-open state stabilized by the translation initiation factor eIF4G and a closed state in the presence of eIF4G and eIF4B. We show here that eIF4A alone does not measurably sample the closed conformation. The translation initiation factors eIF4B and eIF4G accelerate the eIF4A conformational cycle. eIF4G increases the rate of closing more than the opening rate, and eIF4B selectively increases the closing rate. Strikingly, the rate constants and the effect of eIF4B are different for different RNAs, and are related to the presence of single-stranded regions. Modulating the kinetics of the eIF4A conformational cycle is thus central for the multi-layered regulation of its activity, and for its role as a regulatory hub in translation initiation. PMID:24848014

  19. AtCCR4a and AtCCR4b are Involved in Determining the Poly(A) Length of Granule-bound starch synthase 1 Transcript and Modulating Sucrose and Starch Metabolism in Arabidopsis thaliana.

    PubMed

    Suzuki, Yuya; Arae, Toshihiro; Green, Pamela J; Yamaguchi, Junji; Chiba, Yukako

    2015-05-01

    Removing the poly(A) tail is the first and rate-limiting step of mRNA degradation and apparently an effective step not only for modulating mRNA stability but also for translation of many eukaryotic transcripts. Carbon catabolite repressor 4 (CCR4) has been identified as a major cytoplasmic deadenylase in Saccharomyces cerevisiae. The Arabidopsis thaliana homologs of the yeast CCR4, AtCCR4a and AtCCR4b, were identified by sequence-based analysis; however, their role and physiological significance in plants remain to be elucidated. In this study, we revealed that AtCCR4a and AtCCR4b are localized to cytoplasmic mRNA processing bodies, which are specific granules consisting of many enzymes involved in mRNA turnover. Double mutants of AtCCR4a and AtCCR4b exhibited tolerance to sucrose application but not to glucose. The levels of sucrose in the seedlings of the atccr4a/4b double mutants were reduced, whereas no difference was observed in glucose levels. Further, amylose levels were slightly but significantly increased in the atccr4a/4b double mutants. Consistent with this observation, we found that the transcript encoding granule-bound starch synthase 1 (GBSS1), which is responsible for amylose synthesis, is accumulated to a higher level in the atccr4a/4b double mutant plants than in the control plants. Moreover, we revealed that GBSS1 has a longer poly(A) tail in the double mutant than in the control plant, suggesting that AtCCR4a and AtCCR4b can influence the poly(A) length of transcripts related to starch metabolism. Our results collectively suggested that AtCCR4a and AtCCR4b are involved in sucrose and starch metabolism in A. thaliana.

  20. Increased expression of a novel splice variant of the complement component 4 (C4A) gene in mastitis-infected dairy cattle.

    PubMed

    Yang, Y; Huang, J M; Ju, Z H; Li, Q L; Zhou, L; Li, R L; Li, J B; Shi, F X; Zhong, J F; Wang, C F

    2012-08-29

    The complement system helps in the direct lysis of invading pathogens and modulates phagocytic, humoral and cellular immune responses. Complement 4 is a critical component in complement activity and protection against many bacterial pathogens because it is essential to classical and lectin activation pathways. We used reverse transcription and PCR to investigate alternative splicing and expression of the complement component 4 (C4A) gene in Chinese Holstein cattle. The PCR products were cloned and sequenced. A novel splice variant involving intron 10 was identified, which we named C4A-AS. To examine how C4A gene activity is affected by bovine mastitis, six Chinese Holstein cattle were divided into healthy (non-mastitic) and Staphylococcus aureus-induced mastitic groups. Real-time quantitative PCR (qRT-PCR) revealed that the C4A-complete and C4A-AS transcripts are expressed at significantly different levels in healthy cows, while there were no significant differences in the mastitic group (P = 0.257). Expression of C4A-AS increased significantly when mastitis developed. We also examined the expression of C4A-complete and C4A-AS in several tissues (liver, heart, spleen, lung, kidney, tongue, and muscle). The two transcripts were expressed in all of these tissues but there were no significant differences in expression between healthy and mastitic cows. We therefore conclude that the C4A-complete transcript is the main transcript under normal physiological conditions, while C4A-AS is augmented when mastitis develops.

  1. APEX-CHAMP+ high-J CO observations of low-mass young stellar objects. III. NGC 1333 IRAS 4A/4B envelope, outflow, and ultraviolet heating

    NASA Astrophysics Data System (ADS)

    Yıldız, Umut A.; Kristensen, Lars E.; van Dishoeck, Ewine F.; Belloche, Arnaud; van Kempen, Tim A.; Hogerheijde, Michiel R.; Güsten, Rolf; van der Marel, Nienke

    2012-06-01

    Context. The NGC 1333 IRAS 4A and IRAS 4B sources are among the most well-studied Stage 0 low-mass protostars, which drive prominent bipolar outflows. Spectrally resolved molecular emission lines provide crucial information about the physical and chemical structure of the circumstellar material as well as the dynamics of the different components. Most studies have so far concentrated on the colder parts (T ≤ 30 K) of these regions. Aims: The aim is to characterize the warmer parts of the protostellar envelope using the new generation of submillimeter instruments. This will allow us to quantify the feedback of the protostars on their surroundings in terms of shocks, ultraviolet (UV) heating, photodissociation, and outflow dispersal. Methods: The dual frequency 2 × 7 pixel 650/850 GHz array receiver CHAMP+ mounted on APEX was used to obtain a fully sampled, large-scale ~4' × 4' map at 9″ resolution of the IRAS 4A/4B region in the 12CO J = 6-5 line. Smaller maps were observed in the 13CO 6-5 and [C i] J = 2-1 lines. In addition, a fully sampled 12CO J = 3-2 map made with HARP-B on the JCMT is presented and deep isotopolog observations are obtained at selected outflow positions to constrain the optical depth. Complementary Herschel-HIFI and ground-based lines of CO and its isotopologs, from J = 1-0 up to 10-9 (Eu/k ≈ 300 K), are collected at the source positions and used to construct velocity-resolved CO ladders and rotational diagrams. Radiative-transfer models of the dust and lines are used to determine the temperatures and masses of the outflowing and photon-heated gas and infer the CO abundance structure. Results: Broad CO emission-line profiles trace entrained shocked gas along the outflow walls, which have an average temperature of ~100 K. At other positions surrounding the outflow and the protostar, the 6-5 line profiles are narrow indicating UV excitation. The narrow 13CO 6-5 data directly reveal the UV heated gas distribution for the first time. The

  2. Theoretical study of isoelectronic molecules: B6H10, 2-CB5H9, 2,3-C2B4H8, 2,3,4-C3B3H7, and 2,3,4,5-C4B2H6.

    PubMed

    Tian, Shan Xi

    2005-07-28

    Isoelectronic molecules regarding B6H10, 2-CB5H9, 2,3-C2B4H8, 2,3,4-C3B3H7, and 2,3,4,5-C4B2H6 are studied by the density functional B3LYP/6-311G(d,p) method and the electron propagator theory in the partial third-order quasiparticale approximation, as well as the extrapolated calculation with the coupled-cluster CCSD(T) theory. The calculated ionization potentials are in good agreement with the experimental data from photoelectron spectroscopy. Valence structures are characterized with natural orbital bond (NBO) theory, exhibiting the multiple three-center two-electron bonds B-H-B, B-B-B, C-B-B, B-C-B, and C-B-C, and chemical bond rearrangements in the cations. PMID:16834005

  3. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19∗4A, ∗4B, and ∗17 alleles: implications for clopidogrel response testing.

    PubMed

    Scott, Stuart A; Tan, Qian; Baber, Usman; Yang, Yao; Martis, Suparna; Bander, Jeffrey; Kornreich, Ruth; Hulot, Jean-Sébastien; Desnick, Robert J

    2013-11-01

    CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.-806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.

  4. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    PubMed

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future.

  5. Carcinogen-specific mutational and epigenetic alterations in INK4A, INK4B and p53 tumour-suppressor genes drive induced senescence bypass in normal diploid mammalian cells.

    PubMed

    Yasaei, H; Gilham, E; Pickles, J C; Roberts, T P; O'Donovan, M; Newbold, R F

    2013-01-10

    Immortalization (senescence bypass) is a critical rate-limiting step in the malignant transformation of mammalian somatic cells. Human cells must breach at least two distinct senescence barriers to permit unfettered clonal evolution during cancer development: (1) stress- or oncogene-induced premature senescence (SIPS/OIS), mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive pathways, and (2) replicative senescence triggered by telomere shortening. In contrast, because their telomerase is constitutively active, cells from small rodents possess only the SIPS/OIS barrier, and are therefore useful for studying SIPS/OIS bypass in isolation. Dermal fibroblasts from the Syrian hamster (SHD cells) are exceptionally resistant to spontaneous SIPS bypass, but it can be readily induced following exposure to a wide range of chemical and physical carcinogens. Here we show that a spectrum of carcinogen-specific mutational and epigenetic alterations involving the INK4A (p16), p53 and INK4B (p15) genes are associated with induced SIPS bypass. With ionizing radiation, immortalization is invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2 locus. In comparison, SHD cells immortalized by the powerful polycyclic hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the DNA-binding domain of p53 coupled with INK4 alterations such as loss of expression of p15. Epimutational silencing of p16 is the primary event associated with immortalization by nickel, a human non-genotoxic carcinogen. As SIPS/OIS bypass is a prerequisite for the immortalization of normal diploid human epithelial cells, our results with the SHD model will provide a basis for delineating combinations of key molecular changes underpinning this important event in human carcinogenesis. PMID:22410783

  6. Boeing F4B-4

    NASA Technical Reports Server (NTRS)

    1932-01-01

    The Boeing F4B-4 was seen to differ from earlier F4Bs in having a vertical fin with slightly more area. The Boeing model 235 was not fitted with a NACA cowling, but rather the less efficient 'Townend' ring around the Pratt & Whitney Wasp radials cylinders. This aircraft was much used by both the Navy and the Army Air Corps in the late 1920's and early 1930's. The Army variation was known as the P-12E. The engine cowling was a British development known as the 'Townend' ring. It differed from the NACA cowling and was less effective in reducing the drag.

  7. Characteristics of potential repository wastes: Volume 4, Appendix 4A, Nuclear reactors at educational institutions of the United States; Appendix 4B, Data sheets for nuclear reactors at educational institutions; Appendix 4C, Supplemental data for Fort St. Vrain spent fuel; Appendix 4D, Supplemental data for Peach Bottom 1 spent fuel; Appendix 4E, Supplemental data for Fast Flux Test Facility

    SciTech Connect

    Not Available

    1992-07-01

    Volume 4 contains the following appendices: nuclear reactors at educational institutions in the United States; data sheets for nuclear reactors at educational institutions in the United States(operational reactors and shut-down reactors); supplemental data for Fort St. Vrain spent fuel; supplemental data for Peach Bottom 1 spent fuel; and supplemental data for Fast Flux Test Facility.

  8. Selective Phosphodiesterase 4B Inhibitors: A Review

    PubMed Central

    Azam, Mohammed Afzal; Tripuraneni, Naga Srinivas

    2014-01-01

    Abstract Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B. PMID:25853062

  9. Phosphodiesterase 4B is essential for TH2-cell function and development of airway hyperresponsiveness in allergic asthma

    PubMed Central

    Catherine Jin, S.-L.; Goya, Sho; Nakae, Susumu; Wang, Dan; Bruss, Matthew; Hou, Chiaoyin; Umetsu, Dale; Conti, Marco

    2010-01-01

    Background Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. Objectives We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and TH2-driven inflammatory responses. Methods Wild-type and PDE4B−/− mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and TH2 cytokine production were determined in cultured bronchial lymph node cells. Results Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased TH2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, TH2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the TH1 cytokine IFN-γ was not affected in PDE4B−/− mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. Conclusion By relieving a cAMP-negative constraint, PDE4B plays an essential role in TH2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment. PMID:21047676

  10. RDR-4B doppler weather radar with forward looking wind shear detection capability

    NASA Technical Reports Server (NTRS)

    Grasley, Steven S.

    1992-01-01

    The topics are presented in viewgraph form and include the following: Bendix/King atmospheric transport and dispersion (ATAD) position; RDR-4A technical baseline; RTA-4A characteristics; RDR-4 antenna characteristics; modification of RDR-4A to RDR-4B; RDR-4A functional block diagram; RDR-4B characteristics; development/test plan; CV-580 testing capability; CV-580 test results; Continental A300 test configuration; Continental Data Recording Program operational considerations; Continental A300 test results; and display considerations.

  11. Structural basis for the design of selective phosphodiesterase 4B inhibitors.

    PubMed

    Fox, David; Burgin, Alex B; Gurney, Mark E

    2014-03-01

    Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor -Tumor Necrosis Factor α (TNFα) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs. PMID:24361374

  12. An assessment of the MCNP4C weight window

    SciTech Connect

    Christopher N. Culbertson; John S. Hendricks

    1999-12-01

    A new, enhanced weight window generator suite has been developed for MCNP version 4C. The new generator correctly estimates importances in either a user-specified, geometry-independent, orthogonal grid or in MCNP geometric cells. The geometry-independent option alleviates the need to subdivide the MCNP cell geometry for variance reduction purposes. In addition, the new suite corrects several pathologies in the existing MCNP weight window generator. The new generator is applied in a set of five variance reduction problems. The improved generator is compared with the weight window generator applied in MCNP4B. The benefits of the new methodology are highlighted, along with a description of its limitations. The authors also provide recommendations for utilization of the weight window generator.

  13. siRNA-mediated silencing of phosphodiesterase 4B expression affects the production of cytokines in endotoxin-stimulated primary cultured microglia

    PubMed Central

    Cheng, Hao; Wu, Zhifang; He, Xiaoyun; Liu, Qingzhen; Jia, Hongbin; Di, Yan; Ji, Qing

    2016-01-01

    Phosphodiesterase 4 (PDE4) has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. The expression of PDE4 subtypes in microglial cells and the specific contribution of each subtype to inflammation remain unclear. In this study, the expression of PDE4 subtypes in primary microglial cells was assayed. Primary microglial cells were then transfected with specific small interfering RNA (siRNA) against each PDE4 subtype. PDE4 subtype A-D knockdown was confirmed by quantitative polymerase chain reaction. Secreted cytokines in the supernatant and intracellular cyclic adenosine monophosphate (cAMP) levels of transfected cells were measured. The effect of PDE4B siRNA on the activation of extracellular regulated protein kinase (ERK) induced by lipopolysaccharide (LPS) in microglia was further tested by western blotting. Results showed that the primary microglial cells expressed all four types of PDE4s at the protein level. Transfection with the four siRNAs inhibited PDE4 subtype A-D mRNA expression, respectively. In primary microglial cells, treatment with PDE4B siRNA significantly inhibited the expression of tumor necrosis factor-α and interleukin (IL)-1β, and enhanced the expression of cAMP, while siRNAs to other subtypes had no significant effects. However, none of the four siRNAs had any significant effect on the expression of IL-10. Furthermore, in the PDE4B group, the level of phosphorylated ERK was reduced. Among the four PDE4 subtypes, PDE4B plays an important role in regulating inflammatory responses in microglia, potentially through initially regulating the intracellular cAMP concentration. PMID:27698721

  14. siRNA-mediated silencing of phosphodiesterase 4B expression affects the production of cytokines in endotoxin-stimulated primary cultured microglia

    PubMed Central

    Cheng, Hao; Wu, Zhifang; He, Xiaoyun; Liu, Qingzhen; Jia, Hongbin; Di, Yan; Ji, Qing

    2016-01-01

    Phosphodiesterase 4 (PDE4) has four subtypes: PDE4A, PDE4B, PDE4C and PDE4D. The expression of PDE4 subtypes in microglial cells and the specific contribution of each subtype to inflammation remain unclear. In this study, the expression of PDE4 subtypes in primary microglial cells was assayed. Primary microglial cells were then transfected with specific small interfering RNA (siRNA) against each PDE4 subtype. PDE4 subtype A-D knockdown was confirmed by quantitative polymerase chain reaction. Secreted cytokines in the supernatant and intracellular cyclic adenosine monophosphate (cAMP) levels of transfected cells were measured. The effect of PDE4B siRNA on the activation of extracellular regulated protein kinase (ERK) induced by lipopolysaccharide (LPS) in microglia was further tested by western blotting. Results showed that the primary microglial cells expressed all four types of PDE4s at the protein level. Transfection with the four siRNAs inhibited PDE4 subtype A-D mRNA expression, respectively. In primary microglial cells, treatment with PDE4B siRNA significantly inhibited the expression of tumor necrosis factor-α and interleukin (IL)-1β, and enhanced the expression of cAMP, while siRNAs to other subtypes had no significant effects. However, none of the four siRNAs had any significant effect on the expression of IL-10. Furthermore, in the PDE4B group, the level of phosphorylated ERK was reduced. Among the four PDE4 subtypes, PDE4B plays an important role in regulating inflammatory responses in microglia, potentially through initially regulating the intracellular cAMP concentration.

  15. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  16. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  17. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  18. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... “Scientific research specimens, 49 CFR 173.4b applies.” (6) Documentation. (i) For transportation by highway... “Scientific research specimens, 49 CFR 173.4b applies” and the number of packages indicated. (iii) For... the statement “Scientific research specimens, 49 CFR 173.4b applies” and the number of...

  19. 49 CFR 173.4b - De minimis exceptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false De minimis exceptions. 173.4b Section 173.4b Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS General § 173.4b De minimis exceptions. (a) Packing Group II and III materials...

  20. Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.

    PubMed

    Yin, Yan; Liu, Liren; Yang, Chenyi; Lin, Congxing; Veith, George Michael; Wang, Caihong; Sutovsky, Peter; Zhou, Pengbo; Ma, Liang

    2016-03-25

    CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis. PMID:26846852

  1. PROCEEDINGS: 1993 SO2 CONTROL SYMPOSIUM - VOLUME 2. SESSIONS 4A, 4B, AND 5A

    EPA Science Inventory

    The report documents more than 100 presentations at the 1993 SO2 Control Symposium in Boston, MA, August 24-27, 1993. The presentations covered a wide range of topics: industry's strategies for dealing with Clean Air Act Amendments of 1990, including Phase I strategies, the emiss...

  2. High resolution crystal structure of human Dim2/TXNL4B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    TXNL4A (thioredoxin like 4A) is an essential protein conserved from yeast to human and is a component of the pre-mRNA splicing machinery. TXNL4B was identified as a TXNL4 family protein that also interacts with prp6, an integral component of the U4/U6•U5 tri-snRNP complex, and was shown to function...

  3. KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism

    PubMed Central

    Xia, Yingfeng; Liu, Mengling; Ye, Bingwei; Choi, Jeong-Hyeon; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Zha, Yunhong; Yang, Liqun; Cui, Hongjuan; Ding, Han-Fei

    2015-01-01

    SUMMARY The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9) trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation. PMID:26774480

  4. Hypovalency--a kinetic-energy density description of a 4c-2e bond.

    PubMed

    Jacobsen, Heiko

    2009-06-01

    A bond descriptor based on the kinetic energy density, the localized-orbital locator (LOL), is used to characterize the nature of the chemical bond in electron deficient multi-center bonds. The boranes B(2)H(6), B(4)H(4), B(4)H(10), [B(6)H(6)](2-), and [B(6)H(7)](-) serve as prototypical examples of hypovalent 3c-2e and 4c-2e bonding. The kinetic energy density is derived from a set of Kohn-Sham orbitals obtained from pure density functional calculations (PBE/TZVP), and the topology of LOL is analyzed in terms of (3,-3) attractors (Gamma). The B-B-B and B-H-B 3c-2e, and the B-B-H-B 4c-2e bonding situations are defined by their own characteristic LOL profiles. The presence of one attractor in relation to the three or four atoms that are engaged in electron deficient bonding provides sufficient indication of the type of 3c-2e or 4c-2e bond present. For the 4c-2e bond in [B(6)H(7)](-) the LOL analysis is compared to results from an experimental QTAIM study. PMID:19452076

  5. Hypovalency--a kinetic-energy density description of a 4c-2e bond.

    PubMed

    Jacobsen, Heiko

    2009-06-01

    A bond descriptor based on the kinetic energy density, the localized-orbital locator (LOL), is used to characterize the nature of the chemical bond in electron deficient multi-center bonds. The boranes B(2)H(6), B(4)H(4), B(4)H(10), [B(6)H(6)](2-), and [B(6)H(7)](-) serve as prototypical examples of hypovalent 3c-2e and 4c-2e bonding. The kinetic energy density is derived from a set of Kohn-Sham orbitals obtained from pure density functional calculations (PBE/TZVP), and the topology of LOL is analyzed in terms of (3,-3) attractors (Gamma). The B-B-B and B-H-B 3c-2e, and the B-B-H-B 4c-2e bonding situations are defined by their own characteristic LOL profiles. The presence of one attractor in relation to the three or four atoms that are engaged in electron deficient bonding provides sufficient indication of the type of 3c-2e or 4c-2e bond present. For the 4c-2e bond in [B(6)H(7)](-) the LOL analysis is compared to results from an experimental QTAIM study.

  6. MCNP4B{sup {trademark}} verification and validation

    SciTech Connect

    Hendricks, J.S.; Court, J.D.

    1996-08-01

    Several new features and bug fixes have been incorporated into the new release of MCNP. As required by the MCNP Software Quality Assurance Plan, these changes to the code and the test set are documented here for user reference. This document summarizes the new MCNP4B features and corrections, separated into major and minor groupings. Also included are a code cleanup section and a section delineating problems identified in LA-12839 which have not been corrected. Finally, we document the MCNP4B test set modifications and explain how test set coverage has been improved.

  7. Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

    SciTech Connect

    Mitchell, Charlotte J.; Ballantine, Stuart P.; Coe, Diane M.; Cook, Caroline M.; Delves, Christopher J.; Dowle, Mike D.; Edlin, Chris D.; Hamblin, J. Nicole; Holman, Stuart; Johnson, Martin R.; Jones, Paul S.; Keeling, Sue E.; Kranz, Michael; Lindvall, Mika; Lucas, Fiona S.; Neu, Margarete; Solanke, Yemisi E.; Somers, Don O.; Trivedi, Naimisha A.; Wiseman, Joanne O.

    2012-05-03

    Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-{alpha} production from isolated human peripheral blood mononuclear cells.

  8. The hypervariable region of K-Ras4B is responsible for its specific interactions with calmodulin.

    PubMed

    Abraham, Sherwin J; Nolet, Ryan P; Calvert, Richard J; Anderson, Lucy M; Gaponenko, Vadim

    2009-08-18

    K-Ras4B belongs to the family of p21 Ras GTPases, which play an important role in cell proliferation, survival, and motility. The p21 Ras proteins, such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry, we demonstrate that the hypervariable region of K-Ras4B contributes in a major way to the interaction with calmodulin, while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca(2+)-loaded calmodulin with micromolar affinity, while the GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal domain of calmodulin.

  9. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression.

    PubMed Central

    Barba, G; Rittner, C; Schneider, P M

    1993-01-01

    The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma. These null alleles are due either to large gene deletions or to nonexpression of the respective genes. In a previous study, evidence was obtained for nonexpressed defective genes at the C4A locus, and for gene conversion at the C4B locus. To further characterize the molecular basis of these non-expressed C4A genes, we selected nine pairs of PCR primers from flanking genomic intron sequences to amplify all 41 exons from individuals with a defective C4A gene. The amplified products were subjected to single-stranded conformation polymorphism (SSCP) analysis to detect possible mutations. PCR products exhibiting a variation in the SSCP pattern were sequenced directly. In 10 of 12 individuals studied, we detected a 2-bp insertion in exon 29 leading to nonexpression due to the creation of a termination codon, which was observed in linkage to the haplotype HLA-B60-DR6 in seven cases. In one of the other two individuals without this mutation, evidence was obtained for gene conversion to the C4B isotype. The genetic basis of C4A nonexpression in the second individual is not yet known and will be subject to further analysis. Images PMID:8473511

  10. Si enhances the growth of B 4C nanowires

    NASA Astrophysics Data System (ADS)

    Zhu, Ming; Hu, Xiaoyang; Wei, Yingnai; Zhang, Yingjiu; Du, Xiwen; Zhang, Xiaozhong

    2009-07-01

    The B 4C nanowires can be easily fabricated by employing an activated carbon, boron and Ni(NO 3) 2 whereas almost no B 4C nanowires can be obtained if activated carbon is replaced by pure carbon. The analyses show that there are Si and Al impurities in the activated carbon, and both Si and Ni are critical to the growth of the B 4C nanowires. Additionally, the yield of the B 4C nanowires is greatly increased if the B 4C nanowires are grown by the carbon nanotubes-confined method when Si is introduced. The mechanism of the Si enhanced growth of B 4C nanowires is discussed.

  11. 4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments.

    PubMed

    Raviram, Ramya; Rocha, Pedro P; Müller, Christian L; Miraldi, Emily R; Badri, Sana; Fu, Yi; Swanzey, Emily; Proudhon, Charlotte; Snetkova, Valentina; Bonneau, Richard; Skok, Jane A

    2016-03-01

    4C-Seq has proven to be a powerful technique to identify genome-wide interactions with a single locus of interest (or "bait") that can be important for gene regulation. However, analysis of 4C-Seq data is complicated by the many biases inherent to the technique. An important consideration when dealing with 4C-Seq data is the differences in resolution of signal across the genome that result from differences in 3D distance separation from the bait. This leads to the highest signal in the region immediately surrounding the bait and increasingly lower signals in far-cis and trans. Another important aspect of 4C-Seq experiments is the resolution, which is greatly influenced by the choice of restriction enzyme and the frequency at which it can cut the genome. Thus, it is important that a 4C-Seq analysis method is flexible enough to analyze data generated using different enzymes and to identify interactions across the entire genome. Current methods for 4C-Seq analysis only identify interactions in regions near the bait or in regions located in far-cis and trans, but no method comprehensively analyzes 4C signals of different length scales. In addition, some methods also fail in experiments where chromatin fragments are generated using frequent cutter restriction enzymes. Here, we describe 4C-ker, a Hidden-Markov Model based pipeline that identifies regions throughout the genome that interact with the 4C bait locus. In addition, we incorporate methods for the identification of differential interactions in multiple 4C-seq datasets collected from different genotypes or experimental conditions. Adaptive window sizes are used to correct for differences in signal coverage in near-bait regions, far-cis and trans chromosomes. Using several datasets, we demonstrate that 4C-ker outperforms all existing 4C-Seq pipelines in its ability to reproducibly identify interaction domains at all genomic ranges with different resolution enzymes.

  12. The hypervariable region of K-Ras4B is responsible for its specific interactions with Calmodulin

    PubMed Central

    Abraham, Sherwin J.; Nolet, Ryan P.; Calvert, Richard J.; Anderson, Lucy M.; Gaponenko, Vadim

    2009-01-01

    K-Ras4B belongs to the family of p21 Ras GTPases, which play an important role in cell proliferation, survival and motility. The p21 Ras proteins such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry we demonstrate that the hypervariable region of K-Ras contributes in a major way to the interaction with calmodulin while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca2+-loaded calmodulin with micromolar affinity, while the GTP-γ-S loaded catalytic domain of K-Ras4B may interact with the N-terminal domain of calmodulin. PMID:19583261

  13. KDM4B as a Target for Prostate Cancer: Structural Analysis and Selective Inhibition by a Novel Inhibitor

    PubMed Central

    2015-01-01

    The KDM4/JMJD2 Jumonji C-containing histone lysine demethylases (KDM4A–KDM4D), which selectively remove the methyl group(s) from tri/dimethylated lysine 9/36 of H3, modulate transcriptional activation and genome stability. The overexpression of KDM4A/KDM4B in prostate cancer and their association with androgen receptor suggest that KDM4A/KDM4B are potential progression factors for prostate cancer. Here, we report the crystal structure of the KDM4B·pyridine 2,4-dicarboxylic acid·H3K9me3 ternary complex, revealing the core active-site region and a selective K9/K36 site. A selective KDM4A/KDM4B inhibitor, 4, that occupies three subsites in the binding pocket is identified by virtual screening. Pharmacological and genetic inhibition of KDM4A/KDM4B significantly blocks the viability of cultured prostate cancer cells, which is accompanied by increased H3K9me3 staining and transcriptional silencing of growth-related genes. Significantly, a substantial portion of differentially expressed genes are AR-responsive, consistent with the roles of KDM4s as critical AR activators. Our results point to KDM4 as a useful therapeutic target and identify a new inhibitor scaffold. PMID:24971742

  14. Retention of deuterium implanted into B 4C-overlaid isotropic graphites and hot-pressed B 4C

    NASA Astrophysics Data System (ADS)

    Jimbou, R.; Saidoh, M.; Ogiwara, N.; Ando, T.; Morita, K.; Muto, Y.

    1992-12-01

    Retention characteristics of two kinds of B 4C-overlaid graphites and hot-pressed B 4C were investigated. An ion beam of 3 keV D 2+ was implanted into the specimens at room temperature. The amount of retained deuteriums was measured as function of the implantation fluence and temperature by elastic recoil detection analysis. Thermal release behavior of implanted deuteriums was also measured by isochronal annealing. The concentration of retained deuterium reaches saturation similarly in three kinds of B 4C-overlaid specimens at the fluences over 10 18 D +/cm 2 as in isotropic graphite. The release temperature, at which the number of retained deuterium decreases to one half in isochronal annealing, are about 250 K lower for three kinds of B 4C specimens than for graphite. The release temperature of deuterium from unsaturated hot-pressed B 4C in isochronal annealing is about 500 K higher than that from saturated one.

  15. PDE4B as a microglia target to reduce neuroinflammation.

    PubMed

    Pearse, Damien D; Hughes, Zoë A

    2016-10-01

    The importance of microglia in immune homeostasis within the brain is undisputed. Their role in a diversity of neurological and psychiatric diseases as well as CNS injury is the subject of much investigation. Cyclic adenosine monophosphate (AMP) is a critical regulator of microglia homeostasis; as the predominant negative modulator of cyclic AMP signaling within microglia, phosphodiesterase 4 (PDE4) represents a promising target for modulating immune function. PDE4 expression is regulated by inflammation, and in turn, PDE4 inhibition can alter microglia reactivity. As the prototypic PDE4 inhibitor, rolipram, was tested clinically in the 1980s, drug discovery and clinical development of PDE4 inhibitors have been severely hampered by tolerability issues involving nausea and emesis. The two PDE4 inhibitors approved for peripheral inflammatory disorders (roflumilast and apremilast) lack brain penetration and are dose-limited by side effects making them unsuitable for modulating microglial function. Subtype selective inhibitors targeting PDE4B are of high interest given the critical role PDE4B plays in immune function versus the association of PDE4D with nausea and emesis. The challenges and requirements for successful development of a novel brain-penetrant PDE4B inhibitor are discussed in the context of early clinical development strategies. Furthermore, the challenges of monitoring the state of microglia in vivo are highlighted, including a description of the currently available tools and their limitations. Continued drug discovery efforts to identify safe and well-tolerated, brain-penetrant PDE4 inhibitors are a reflection of the confidence in the rationale for modulation of this target to produce meaningful therapeutic benefit in a wide range of neurological conditions and injury. GLIA 2016;64:1698-1709. PMID:27038323

  16. Pulmonary cytochrome P450 enzymes belonging to the CYP4B subfamily from an Australian marsupial, the tammar wallaby (Macropus eugenii).

    PubMed

    Milic, Natalie L; Ngo, Suong N T; Marchant, Ceilidh L; Height, Tamara A; McKinnon, Ross A

    2011-01-01

    Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a diverse array of xenobiotics and endogenous substrates. We have previously reported the cloning and characterisation of the koala CYP4A15, the first reported member of the CYP4 family from marsupials, and have demonstrated important species differences in CYP4A activity and tissue expression. In the present study, the cloning of CYP4B1 in the wallaby (Macropus eugenii) and their expression across marsupials is described. Rabbit anti-mouse CYP4B1 antibody detected immunoreactive proteins in lung and liver microsomes from all test marsupials, with relative weak signal detected from the koala, suggesting a species-specific expression. Microsomal 2-aminofluorene bio-activation (a CYP4B1 marker) in wallaby lung was comparable to that of rabbit, with significant higher activities detected in wallaby liver and kidneys compared to rabbit. A 1548bp wallaby lung CYP4B complete cDNA, designated CYP4B1, which encodes a protein of 510 amino acids and shares 72% nucleotide and 69% amino acid sequence identity to human CYP4B1, was cloned by polymerase chain reaction approaches. The results demonstrate the presence of wallaby CYP4B1 that shares several common features with other published CYP4Bs; however the wallaby CYP4B1 cDNA contains four extra amino acid residues at the NH₂-terminal, a fundamentally conserved transmembrane anchor of all eukaryote CYPs.

  17. Boron carbide (B4C) coating. Deposition and testing

    NASA Astrophysics Data System (ADS)

    Azizov, E.; Barsuk, V.; Begrambekov, L.; Buzhinsky, O.; Evsin, A.; Gordeev, A.; Grunin, A.; Klimov, N.; Kurnaev, V.; Mazul, I.; Otroshchenko, V.; Putric, A.; Sadovskiy, Ya.; Shigin, P.; Vergazov, S.; Zakharov, A.

    2015-08-01

    Boron carbide was proposed as a material of in-situ protecting coating for tungsten tiles of ITER divertor. To prove this concept the project including investigation of regimes of plasma deposition of B4C coating on tungsten and tests of boron carbide layer in ITER-like is started recently. The paper contends the first results of the project. The results of B4C coating irradiation by the plasma pulses of QSPU-T plasma accelerator are presented. The new device capable of B4C film deposition on tungsten and testing of the films and materials with ITER-like heat loads and ion- and electron irradiation is described. The results of B4C coating deposition and testing of both tungsten substrate and coating are shown and discussed.

  18. 4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments

    PubMed Central

    Raviram, Ramya; Rocha, Pedro P.; Müller, Christian L.; Miraldi, Emily R.; Badri, Sana; Fu, Yi; Swanzey, Emily; Proudhon, Charlotte; Snetkova, Valentina

    2016-01-01

    4C-Seq has proven to be a powerful technique to identify genome-wide interactions with a single locus of interest (or “bait”) that can be important for gene regulation. However, analysis of 4C-Seq data is complicated by the many biases inherent to the technique. An important consideration when dealing with 4C-Seq data is the differences in resolution of signal across the genome that result from differences in 3D distance separation from the bait. This leads to the highest signal in the region immediately surrounding the bait and increasingly lower signals in far-cis and trans. Another important aspect of 4C-Seq experiments is the resolution, which is greatly influenced by the choice of restriction enzyme and the frequency at which it can cut the genome. Thus, it is important that a 4C-Seq analysis method is flexible enough to analyze data generated using different enzymes and to identify interactions across the entire genome. Current methods for 4C-Seq analysis only identify interactions in regions near the bait or in regions located in far-cis and trans, but no method comprehensively analyzes 4C signals of different length scales. In addition, some methods also fail in experiments where chromatin fragments are generated using frequent cutter restriction enzymes. Here, we describe 4C-ker, a Hidden-Markov Model based pipeline that identifies regions throughout the genome that interact with the 4C bait locus. In addition, we incorporate methods for the identification of differential interactions in multiple 4C-seq datasets collected from different genotypes or experimental conditions. Adaptive window sizes are used to correct for differences in signal coverage in near-bait regions, far-cis and trans chromosomes. Using several datasets, we demonstrate that 4C-ker outperforms all existing 4C-Seq pipelines in its ability to reproducibly identify interaction domains at all genomic ranges with different resolution enzymes. PMID:26938081

  19. Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype

    PubMed Central

    Plog, Stephanie; Klymiuk, Nikolai; Binder, Stefanie; Van Hook, Matthew J.; Thoreson, Wallace B.; Gruber, Achim D.; Mundhenk, Lars

    2015-01-01

    The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype. PMID:26474299

  20. Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.

    PubMed

    Parkinson, Oliver T; Liggitt, H Denny; Rettie, Allan E; Kelly, Edward J

    2013-08-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 (-/-) mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 (-/-) mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 (+/+) animals. Administration of IPO (20mg/kg) to Cyp4b1 (+/+) mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 (-/-) mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 (-/-) mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity. PMID:23748241

  1. Generation and Characterization of a Cyp4b1 Null Mouse and the Role of CYP4B1 in the Activation and Toxicity of Ipomeanol

    PubMed Central

    Kelly, Edward J.

    2013-01-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 −/− mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 −/− mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 +/+ animals. Administration of IPO (20mg/kg) to Cyp4b1 +/+ mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 −/− mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 −/− mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity. PMID:23748241

  2. Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation

    PubMed Central

    Ansseau, Eugénie; Matteotti, Christel; Yip, Cassandre; Liu, Jian; Leroy, Baptiste; Hubeau, Céline; Gerbaux, Cécile; Cloet, Samuel; Wauters, Armelle; Zorbo, Sabrina; Meyer, Pierre; Pirson, Isabelle; Laoudj-Chenivesse, Dalila; Wattiez, Ruddy; Harper, Scott Q.; Belayew, Alexandra; Coppée, Frédérique

    2016-01-01

    Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD). In the present study, we performed yeast two-hybrid screens and protein co-purifications with HaloTag-DUX fusions or GST-DUX4 pull-down to identify protein partners of DUX4, DUX4c (which is identical to DUX4 except for the end of the carboxyl terminal domain) and DUX1 (which is limited to the double homeodomain). Unexpectedly, we identified and validated (by co-immunoprecipitation, GST pull-down, co-immunofluorescence and in situ Proximal Ligation Assay) the interaction of DUX4, DUX4c and DUX1 with type III intermediate filament protein desmin in the cytoplasm and at the nuclear periphery. Desmin filaments link adjacent sarcomere at the Z-discs, connect them to sarcolemma proteins and interact with mitochondria. These intermediate filament also contact the nuclear lamina and contribute to positioning of the nuclei. Another Z-disc protein, LMCD1 that contains a LIM domain was also validated as a DUX4 partner. The functionality of DUX4 or DUX4c interactions with cytoplasmic proteins is underscored by the cytoplasmic detection of DUX4/DUX4c upon myoblast fusion. In addition, we identified and validated (by co-immunoprecipitation, co-immunofluorescence and in situ Proximal Ligation Assay) as DUX4/4c partners several RNA-binding proteins such as C1QBP, SRSF9, RBM3, FUS/TLS and SFPQ that are involved in mRNA splicing and translation. FUS and SFPQ are nuclear proteins, however their cytoplasmic translocation was reported in neuronal cells where they associated with ribonucleoparticles (RNPs). Several other validated or identified DUX4/DUX4c partners are also contained in mRNP granules, and the co-localizations with cytoplasmic DAPI-positive spots is in keeping with such an association. Large muscle RNPs were

  3. Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation.

    PubMed

    Ansseau, Eugénie; Eidahl, Jocelyn O; Lancelot, Céline; Tassin, Alexandra; Matteotti, Christel; Yip, Cassandre; Liu, Jian; Leroy, Baptiste; Hubeau, Céline; Gerbaux, Cécile; Cloet, Samuel; Wauters, Armelle; Zorbo, Sabrina; Meyer, Pierre; Pirson, Isabelle; Laoudj-Chenivesse, Dalila; Wattiez, Ruddy; Harper, Scott Q; Belayew, Alexandra; Coppée, Frédérique

    2016-01-01

    Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD). In the present study, we performed yeast two-hybrid screens and protein co-purifications with HaloTag-DUX fusions or GST-DUX4 pull-down to identify protein partners of DUX4, DUX4c (which is identical to DUX4 except for the end of the carboxyl terminal domain) and DUX1 (which is limited to the double homeodomain). Unexpectedly, we identified and validated (by co-immunoprecipitation, GST pull-down, co-immunofluorescence and in situ Proximal Ligation Assay) the interaction of DUX4, DUX4c and DUX1 with type III intermediate filament protein desmin in the cytoplasm and at the nuclear periphery. Desmin filaments link adjacent sarcomere at the Z-discs, connect them to sarcolemma proteins and interact with mitochondria. These intermediate filament also contact the nuclear lamina and contribute to positioning of the nuclei. Another Z-disc protein, LMCD1 that contains a LIM domain was also validated as a DUX4 partner. The functionality of DUX4 or DUX4c interactions with cytoplasmic proteins is underscored by the cytoplasmic detection of DUX4/DUX4c upon myoblast fusion. In addition, we identified and validated (by co-immunoprecipitation, co-immunofluorescence and in situ Proximal Ligation Assay) as DUX4/4c partners several RNA-binding proteins such as C1QBP, SRSF9, RBM3, FUS/TLS and SFPQ that are involved in mRNA splicing and translation. FUS and SFPQ are nuclear proteins, however their cytoplasmic translocation was reported in neuronal cells where they associated with ribonucleoparticles (RNPs). Several other validated or identified DUX4/DUX4c partners are also contained in mRNP granules, and the co-localizations with cytoplasmic DAPI-positive spots is in keeping with such an association. Large muscle RNPs were

  4. Calorimetric measurements on Li{sub 4}C{sub 60} and Na{sub 4}C{sub 60}

    SciTech Connect

    Inaba, Akira; Miyazaki, Yuji; Michałowski, Paweł P.; Gracia-Espino, Eduardo; Wågberg, Thomas; Sundqvist, Bertil

    2015-04-28

    We show specific heat data for Na{sub 4}C{sub 60} and Li{sub 4}C{sub 60} in the range 0.4-350 K for samples characterized by Raman spectroscopy and X-ray diffraction. At high temperatures, the two different polymer structures have very similar specific heats both in absolute values and in general trend. The specific heat data are compared with data for undoped polymeric and pristine C{sub 60}. At high temperatures, a difference in specific heat between the intercalated and undoped C{sub 60} polymers of 100 J K{sup −1} mol{sup −1} is observed, in agreement with the Dulong-Petit law. At low temperatures, the specific heat data for Li{sub 4}C{sub 60} and Na{sub 4}C{sub 60} are modified by the stiffening of vibrational and librational molecular motion induced by the polymer bonds. The covalent twin bonds in Li{sub 4}C{sub 60} affect these motions to a somewhat higher degree than the single intermolecular bonds in Na{sub 4}C{sub 60}. Below 1 K, the specific heats of both materials become linear in temperature, as expected from the effective dimensionality of the structure. The contribution to the total specific heat from the inserted metal ions can be well described by Einstein functions with T{sub E} = 386 K for Li{sub 4}C{sub 60} and T{sub E} = 120 K for Na{sub 4}C{sub 60}, but for both materials we also observe a Schottky-type contribution corresponding to a first approximation to a two-level system with ΔE = 9.3 meV for Li{sub 4}C{sub 60} and 3.1 meV for Na{sub 4}C{sub 60}, probably associated with jumps between closely spaced energy levels inside “octahedral-type” ionic sites. Static magnetic fields up to 9 T had very small effects on the specific heat below 10 K.

  5. Secondary Eclipse Photometry of WASP-4b with Warm Spitzer

    NASA Astrophysics Data System (ADS)

    Beerer, Ingrid M.; Knutson, Heather A.; Burrows, Adam; Fortney, Jonathan J.; Agol, Eric; Charbonneau, David; Cowan, Nicolas B.; Deming, Drake; Desert, Jean-Michel; Langton, Jonathan; Laughlin, Gregory; Lewis, Nikole K.; Showman, Adam P.

    2011-01-01

    We present photometry of the giant extrasolar planet WASP-4b at 3.6 and 4.5 μm taken with the Infrared Array Camera on board the Spitzer Space Telescope as part of Spitzer's extended warm mission. We find secondary eclipse depths of 0.319% ± 0.031% and 0.343% ± 0.027% for the 3.6 and 4.5 μm bands, respectively, and show model emission spectra and pressure-temperature profiles for the planetary atmosphere. These eclipse depths are well fit by model emission spectra with water and other molecules in absorption, similar to those used for TrES-3 and HD 189733b. Depending on our choice of model, these results indicate that this planet has either a weak dayside temperature inversion or no inversion at all. The absence of a strong thermal inversion on this highly irradiated planet is contrary to the idea that highly irradiated planets are expected to have inversions, perhaps due the presence of an unknown absorber in the upper atmosphere. This result might be explained by the modestly enhanced activity level of WASP-4b's G7V host star, which could increase the amount of UV flux received by the planet, therefore reducing the abundance of the unknown stratospheric absorber in the planetary atmosphere as suggested in Knutson et al. We also find no evidence for an offset in the timing of the secondary eclipse and place a 2σ upper limit on |ecos ω| of 0.0024, which constrains the range of tidal heating models that could explain this planet's inflated radius.

  6. RAMONA-4B development for SBWR safety studies

    SciTech Connect

    Rohatgi, U.S.; Aronson, A.L.; Cheng, H.S.; Khan, H.J.; Mallen, A.N.

    1993-12-31

    The Simplified Boiling Water Reactor (SBWR) is a revolutionary design of a boiling-water reactor. The reactor is based on passive safety systems such as natural circulation, gravity flow, pressurized gas, and condensation. SBWR has no active systems, and the flow in the vessel is by natural circulation. There is a large chimney section above the core to provide a buoyancy head for natural circulation. The reactor can be shut down by either of four systems; namely, scram, Fine Motion Control Rod Drive (FMCRD), Alternate Rod Insertion (ARI), and Standby Liquid Control System (SLCS). The safety injection is by gravity drain from the Gravity Driven Cooling System (GDCS) and Suppression Pool (SP). The heat sink is through two types of heat exchangers submerged in the tank of water. These heat exchangers are the Isolation Condenser (IC) and the Passive Containment Cooling System (PCCS). The RAMONA-4B code has been developed to simulate the normal operation, reactivity transients, and to address the instability issues for SBWR. The code has a three-dimensional neutron kinetics coupled to multiple parallel-channel thermal-hydraulics. The two-phase thermal hydraulics is based on a nonhomogeneous nonequilibrium drift-flux formulation. It employs an explicit integration to solve all state equations (except for neutron kinetics) in order to predict the instability without numerical damping. The objective of this project is to develop a Sun SPARC and IBM RISC 6000 based RAMONA-4B code for applications to SBWR safety analyses, in particular for stability and ATWS studies.

  7. Chromosome Conformation Capture on Chip (4C): Data Processing.

    PubMed

    Leblanc, Benjamin; Comet, Itys; Bantignies, Frédéric; Cavalli, Giacomo

    2016-01-01

    4C methods are useful to investigate dependencies between regulatory mechanisms and chromatin structures by revealing the frequency of chromatin contacts between a locus of interest and remote sequences on the chromosome. In this chapter we describe a protocol for the data analysis of microarray-based 4C experiments, presenting updated versions of the methods we used in a previous study of the large-scale chromatin interaction profile of a Polycomb response element in Drosophila. The protocol covers data preparation, normalization, microarray probe selection, and the multi-resolution detection of regions with enriched chromatin contacts. A reanalysis of two independent mouse datasets illustrates the versatility of this protocol and the importance of data processing in 4C. Methods were implemented in the R package MRA.TA (Multi-Resolution Analyses on Tiling Array data), and they can be used to analyze ChIP-on-chip data on broadly distributed chromatin components such as histone marks. PMID:27659990

  8. Wisconsin Pilot 4-C Training Grant. Final Report.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Center for Extension Programs in Education.

    This report describes the early childhood educator training programs of the 4-C (Community Coordinated Child Care) project, held in Milwaukee and Dane Counties, Wisconsin from 1970 to 1973. The goal of the training programs was to help teacher-directors, teachers, teacher-aides, and parent-assistants become aware of ways to improve and expand…

  9. Blueprints for Complex Learning: The 4C/ID-Model.

    ERIC Educational Resources Information Center

    van Merrienboer, Jeroen J. G.; Clark, Richard E.; de Croock, Marcel B. M.

    2002-01-01

    Describes the four-component instructional design system (4C/ID-model) developed for the design of training programs for complex skills. Discusses the structure of training blueprints for complex learning and associated instructional methods, focusing on learning tasks, supportive information, just-in-time information, and part-task practice.…

  10. Aggregation Properties of the Chromonic Liquid Crystal Benzopurpurin 4B

    NASA Astrophysics Data System (ADS)

    McKitterick, Christopher; Collings, Peter

    2009-03-01

    Benzopurpurin 4B (BPP) is a textile dye very similar to the common indicator Congo Red. As is true for all chromonics, the absorption spectrum is concentration dependent at low concentrations. If this dependence is used to estimate a free energy change for aggregation, it is higher than has been determined for other systems. Unlike other recently investigated chromonic liquid crystals, BPP forms a liquid crystal phase at extremely low concentrations, about 0.5 wt%. Also unlike these other chromonic liquid crystals, the aggregation kinetics are exceedingly slow. X-ray diffraction and light scattering measurements indicate that the aggregates of BPP are much larger than for chromonic systems that form liquid crystals at higher concentrations. BPP aggregates can be imaged using confocal microscopy, revealing a length distribution centered at 3 μm for a solution forced through a 0.2 μm filter. Over days the aggregates lengthen to well over 10 μm. The diameter of the aggregate images is slightly greater than the diffraction limit of the microscope, placing an upper limit on the diameter of 0.14 μm. These dimensions are consistent with the light scattering results.

  11. Generation and characterization of mouse monoclonal antibodies against NS4B protein of dengue virus.

    PubMed

    Xie, Xuping; Zou, Jing; Wang, Qing-Yin; Noble, Christian G; Lescar, Julien; Shi, Pei-Yong

    2014-02-01

    Dengue virus (DENV) non-structural protein 4B (NS4B) has been demonstrated to be an attractive antiviral target. Due to its nature as an integral membrane protein, NS4B remains poorly characterized. In this study, we generated and characterized two monoclonal antibodies (mAb) that selectively bind to DENV NS4B protein. One mAb, 10-3-7, is specific for DENV-2 NS4B, and its epitope was mapped to residues 5-15 of NS4B. The other mAb, 44-4-7, cross-reacts with all the four serotypes of DENV NS4B, and its epitope was mapped to residues 141-147 of NS4B. Using the mAbs, we probed the intracellular orientation of the epitopes of NS4B by an epitope accessibility assay. The results showed that the N-terminus of NS4B is located in the ER lumen, whereas amino acids 130-148 of NS4B are located in the cytosol. The study demonstrates that the two anti-NS4B mAbs will be useful for future structural and functional analyses of DENV NS4B. PMID:24503088

  12. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  13. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  14. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  15. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  16. 26 CFR 11.402(e)(4)(B)-1 - Election to treat an amount as a lump sum distribution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election to treat an amount as a lump sum... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 11.402(e)(4)(B)-1 Election to treat an amount as a lump... is described in section 402(e)(4)(A) and which is not an annuity contract may be treated as a...

  17. Proper Motion of Components in 4C 39.25

    NASA Technical Reports Server (NTRS)

    Guirado, J. C.; Marcaide, J. M.; Alberdi, A.; Elosegui, P.; Ratner, M. I.; Shapiro, I. I.; Kilger, R.; Mantovani, F.; Venturi, T.; Rius, A.; Ros, E.; Trigilio, C.; Whitney, A. R.

    1995-01-01

    From a series of simultaneous 8.4 and 2.3 GHz VLBI observations of the quasar 4C 39.25 phase referenced to the radio source 0920+390, carried out in 1990-1992, we have measured the proper motion of component b in 4C 39.25: mu(sub alpha) = 90 +/- 43 (mu)as/yr, mu(sub beta) = 7 +/- 68 (mu)as/yr, where the quoted uncertainties account for the contribution of the statistical standard deviation and the errors assumed for the parameters related to the geometry of the interferometric array, the atmosphere, and the source structure. This proper motion is consistent with earlier interpretations of VLBI hybrid mapping results, which showed an internal motion of this component with respect to other structural components. Our differential astrometry analyses show component b to be the one in motion. Our results thus further constrain models of this quasar.

  18. Transcriptional and translational mapping and nucleotide sequence analysis of a vaccinia virus gene encoding the precursor of the major core polypeptide 4b.

    PubMed

    Rosel, J; Moss, B

    1985-12-01

    We prepared antiserum that reacted with a major core polypeptide of approximately 62,000 daltons (62K polypeptide), designated 4b, and its 74K precursor, designated P4b. A cell-free translation product of vaccinia virus late mRNA that comigrated with P4b was specifically immunoprecipitated. The late mRNA encoding P4b hybridized to restriction fragments derived from the left end of the HindIII A fragment and to a lesser extent from the right side of the HindIII D fragment. A polypeptide that comigrated with P4a, the precursor of another major core polypeptide, was synthesized by mRNA that hybridized to DNA segments upstream of the P4b gene. Complete nucleotide sequence analysis of the P4b gene revealed an open reading frame, entirely within the HindIII A fragment, that was sufficient to encode a 644-amino-acid polypeptide of 73K. The 5' end of the P4b mRNA was located at or just above the translational initiation site.

  19. Magnitude and range of the RKKy interaction in SmRh4B4

    NASA Astrophysics Data System (ADS)

    Terris, B. D.; Gray, K. E.; Dunlap, B. D.

    1985-04-01

    The superconductive and magnetic transition temperatures taken together are shown to provide a unique probe which separately determines both the magnitude and range of the RKKY interaction in the RERh4B4 magnetic-superconductors (RE = Er, Sm). Experimentally, an unexpected peak is found in the antiferromagnetic ordering temperature of SmRh4B4 vs. electron mean free path, while for ErRh4B4 the ferromagnetic ordering temperature decreases monotonically. These qualitative features, as well as the quanitative differences between SmRh4B4 and ErRh4B4, are in excellent agreement with calculations using a mean free path dependent RKKY interaction.

  20. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    PubMed

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  1. Dosimetrical evaluation of Leksell Gamma Knife 4C radiosurgery unit

    NASA Astrophysics Data System (ADS)

    Sajeev, Thomas; Mustafa, Mohamed M.; Supe, Sanjay S.

    2011-01-01

    A number of experiments was performed using standard protocols, in order to evaluate the dosimetric accuracy of Leksell Gamma Knife 4C unit. Verification of the beam alignment has been performed for all collimators using solid plastic head phantom and Gafchromic™ type MD-55 films. The study showed a good agreement of Leksell Gammaplan calculated dose profiles with experimentally determined profiles in all three axes. Isocentric accuracy is verified using a specially machined cylindrical aluminium film holder tool made with very narrow geometric tolerances aligned between trunnions of 4 mm collimator. Considering all uncertainties in all three dimensions, the estimated accuracy of the unit was 0.1 mm. Dose rate at the centre point of the unit has been determined according to the IAEA, TRS-398 protocol, using Unidose-E (PTW-Freiburg, Germany) with a 0.125 cc ion chamber, over a period of 6 years. The study showed that the Leksell Gamma Knife 4C unit is excellent radiosurgical equipment with high accuracy and precision, which makes it possible to deliver larger doses of radiation, within the limits defined by national and international guidelines, applicable for stereotactic radiosurgery procedures.

  2. BPO4@B2O3 and (BPO4@B2O3):Eu3+: The novel single-emitting-component phosphors for near UV-white LEDs

    NASA Astrophysics Data System (ADS)

    Cao, Xiyu; Liu, Wei; Jiang, Yu; Cao, Lixin; Su, Ge; Gao, Rongjie

    2016-08-01

    Nowadays much effort has been devoted to exploring novel luminescent materials with low-cost, high stability and excellent luminescent properties. In this paper, a new kind of luminescent material BPO4@B2O3 was prepared by using a facile method. The as-obtained samples contain numerous BPO4 nanoparticles enclosed by amorphous and crystalline B2O3 homogeneously, which exhibits a broad emission band ranging from 380 to 700 nm under near-UV irradiation. More importantly, it is worth noting that the BPO4@B2O3 phosphor exhibits the excellent thermal quenching property, which endows it with a promising prospect as phosphors for high power white LEDs. To further promote its application as white light phosphors, Eu3+ ions were doped into the BPO4@B2O3 samples and prepared the (BPO4@B2O3):Eu3+ phosphors with chromaticity coordinates (0.3022, 0.3122). The corresponding packaging of LEDs indicates that both BPO4@B2O3 and (BPO4@B2O3):Eu3+ can be considered as the promising phosphors for WLEDs.

  3. Peripheral vision horizon display testing in RF-4C aircraft

    NASA Technical Reports Server (NTRS)

    Hammond, L. B., Jr.

    1984-01-01

    A test program to assess the capability of the peripheral vision horizon display (PVHD) to provide peripheral attitude cues to the pilot is described. The system was installed in the rear cockpit of a RF-4C aircraft, selected because its poor instrument crosscheck conditions. The PVHD test plan was designed to assess three primary areas: (1) ability of the system to reduce spatial disorientation; (2) ability of the system to aid the pilot in recovering from unusual attitudes; and (3) improvement in pilot performance during instrument landing system (ILS) approaches. Results of preliminary test flights are summarized. The major problem areas concern the distinction of the display itself and the capability of the display to provide pitch motion cues.

  4. Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors.

    PubMed

    Qiu, Zongxing; Kuhn, Bernd; Aebi, Johannes; Lin, Xianfeng; Ding, Haiyuan; Zhou, Zheng; Xu, Zhiheng; Xu, Danqing; Han, Li; Liu, Cheng; Qiu, Hongxia; Zhang, Yuxia; Haap, Wolfgang; Riemer, Claus; Stahl, Martin; Qin, Ning; Shen, Hong C; Tang, Guozhi

    2016-08-11

    ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure-activity relationship (SAR) and protease selectivity are also discussed. PMID:27563406

  5. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.

    PubMed

    Cabrera, Sandra; Fernández, Alvaro F; Mariño, Guillermo; Aguirre, Alina; Suárez, María F; Español, Yaiza; Vega, José A; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M Soledad; Freije, José M P; Kroemer, Guido; López-Otín, Carlos

    2013-08-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b (-/-) mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b (-/-) mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

  6. DNA damage-induced activation of CUL4B targets HUWE1 for proteasomal degradation.

    PubMed

    Yi, Juan; Lu, Guang; Li, Li; Wang, Xiaozhen; Cao, Li; Lin, Ming; Zhang, Sha; Shao, Genze

    2015-05-19

    The E3 ubiquitin ligase HUWE1/Mule/ARF-BP1 plays an important role in integrating/coordinating diverse cellular processes such as DNA damage repair and apoptosis. A previous study has shown that HUWE1 is required for the early step of DNA damage-induced apoptosis, by targeting MCL-1 for proteasomal degradation. However, HUWE1 is subsequently inactivated, promoting cell survival and the subsequent DNA damage repair process. The mechanism underlying its regulation during this process remains largely undefined. Here, we show that the Cullin4B-RING E3 ligase (CRL4B) is required for proteasomal degradation of HUWE1 in response to DNA damage. CUL4B is activated in a NEDD8-dependent manner, and ubiquitinates HUWE1 in vitro and in vivo. The depletion of CUL4B stabilizes HUWE1, which in turn accelerates the degradation of MCL-1, leading to increased induction of apoptosis. Accordingly, cells deficient in CUL4B showed increased sensitivity to DNA damage reagents. More importantly, upon CUL4B depletion, these phenotypes can be rescued through simultaneous depletion of HUWE1, consistent with the role of CUL4B in regulating HUWE1. Collectively, these results identify CRL4B as an essential E3 ligase in targeting the proteasomal degradation of HUWE1 in response to DNA damage, and provide a potential strategy for cancer therapy by targeting HUWE1 and the CUL4B E3 ligase.

  7. TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis

    PubMed Central

    Grive, Kathryn J.; Gustafson, Eric A.; Seymour, Kimberly A.; Baddoo, Melody; Schorl, Christoph; Golnoski, Kayla; Rajkovic, Aleksandar; Brodsky, Alexander S.; Freiman, Richard N.

    2016-01-01

    TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women. PMID:27341508

  8. TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.

    PubMed

    Grive, Kathryn J; Gustafson, Eric A; Seymour, Kimberly A; Baddoo, Melody; Schorl, Christoph; Golnoski, Kayla; Rajkovic, Aleksandar; Brodsky, Alexander S; Freiman, Richard N

    2016-06-01

    TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women.

  9. Histone demethylase KDM4B regulates otic vesicle invagination via epigenetic control of Dlx3 expression.

    PubMed

    Uribe, Rosa A; Buzzi, Ailín L; Bronner, Marianne E; Strobl-Mazzulla, Pablo H

    2015-11-23

    In vertebrates, the inner ear arises from the otic placode, a thickened swathe of ectoderm that invaginates to form the otic vesicle. We report that histone demethylase KDM4B is dynamically expressed during early stages of chick inner ear formation. A loss of KDM4B results in defective invagination and striking morphological changes in the otic epithelium, characterized by abnormal localization of adhesion and cytoskeletal molecules and reduced expression of several inner ear markers, including Dlx3. In vivo chromatin immunoprecipitation reveals direct and dynamic occupancy of KDM4B and its target, H3K9me3, at regulatory regions of the Dlx3 locus. Accordingly, coelectroporations of DLX3 or KDM4B encoding constructs, but not a catalytically dead mutant of KDM4B, rescue the ear invagination phenotype caused by KDM4B knockdown. Moreover, a loss of DLX3 phenocopies a loss of KDM4B. Collectively, our findings suggest that KDM4B play a critical role during inner ear invagination via modulating histone methylation of the direct target Dlx3. PMID:26598618

  10. Standard Neutron, Photon, and Electron Data Libraries for MCNP4B.

    1997-04-01

    Version 00 US DOE 10CFR810 Jurisdiction. DLC-189/MCNPXS is for use with Version 4B and later of the MCNP transport code. This data library provides a comprehensive set of cross sections for a wide range of radiation transport applications using the Monte Carlo code package CCC-660/MCNP4B.

  11. 75 FR 18509 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... 21, 2008 (73 FR 9575), FDA made available a guidance on the Q4B process entitled ``Q4B Evaluation and.... In the Federal Register of August 14, 2009 (74 FR 41143), FDA published a notice announcing the... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference...

  12. LAPTM4B-35 protein is a weak tumor-associated antigen candidate

    PubMed Central

    SHI, GUILAN; ZHOU, CHUNXIA; WANG, DONGMEI; MA, WENBO; ZHANG, SHUREN

    2014-01-01

    Lysosome-associated protein transmembrane 4β (LAPTM4B) is a gene that has been indicated to be involved in cancer. It is located at chromosome 8q22 and is composed of seven exons and six introns. LAPTM4B encodes two protein isoforms: LAPTM4B-35 and LAPTM4B-24. LAPTM4B-35 is markedly upregulated and LAPTM4B-24 is downregulated in several types of cancer. LAPTM4B-35 is 91 amino acids (N91) longer than LAPTM4B-24 at the N-terminus. In the present study, western blotting, enzyme-linked immunosorbent spot analysis and the B16F10-N91 tumor bearing-mice experiments were used to evaluate whether the overexpression of N91 indicates its potential as a candidate tumor-associated antigen. The results revealed that N91 was expressed in a wide range of normal mouse tissues and human peripheral blood mononuclear cells, with varying expression levels. The weak immunogenicity of N91 protein suggested it was a weak candidate antigen; however, the N91 protein was associated with cell proliferation. PMID:24396432

  13. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...

  14. Monoclonal antibodies against NS4B protein of japanese encephalitis virus.

    PubMed

    Ruan, Xindi; Huang, Shaomei; Shao, Lin; Ye, Jing; Chen, Zheng; Chen, Huanchun; Cao, Shengbo

    2013-12-01

    Japanese encephalitis (JE) is one of the most prevalent global viral encephalitis viruses. The functions of JEV (virus) NS4B protein are still under investigation. In our study, NS4B was expressed in Escherichia coli and purified by dialysis. Two clones of monoclonal antibodies (MAbs 1B1 and 1C3) against NS4B protein were generated and their characterizations were investigated. IFA, Western blot, and ELISA results showed that the MAbs were specific against JEV NS4B protein. The epitope of the MAbs was further identified using pairs of synthesized overlapping peptides. These MAbs may provide valuable tools for further exploration of the functions of NS4B and the pathogenesis of Japanese encephalitis virus. PMID:24328740

  15. Interferon regulatory factor 4b (IRF4b) in Japanese flounder, Paralichthys olivaceus: Sequencing, ubiquitous tissue distribution and inducible expression by poly(I:C) and DNA virus.

    PubMed

    Liu, Dahai; Chen, Jinjing; Zhang, Haiyan; Hu, Mengzhu; Lou, Huimin; Liu, Qiuming; Zhang, Shicui; Hu, Guobin

    2016-09-01

    Interferon regulatory factor 4 (IRF4) in mammals is known to be critical in regulation of development and functions of lymphomyeloid cell lineages. Recent studies have demonstrated its involvement in immune responses to bacterial and viral challenges in teleosts. In this study, an IRF4 gene was cloned from Japanese flounder (Paralichthys olivaceus) and its expression in response to polyinosinic:polycytidylic acid [poly(I:C)] and lymphocystis disease virus (LCDV) stimulations was studied in vivo. The cloned gene spans over 5.9 kb, comprises eight exons and seven introns and encodes a putative protein of 456 amino acids. The deduced amino acid sequence possesses a conserved DNA-binding domain (DBD), an IRF-association domain (IAD) and a nuclear localization signal (NLS). Phylogenetic analysis clustered it into the teleost IRF4b clade and, thus, it was named Paralichthys olivaceus (Po)IRF4b. The constitutive expression of PoIRF4b transcripts was detectable in all examined organs, with highest levels found in lymphomyeloid-rich tissues. They were induced by both poly(I:C) and LCDV with a similar inducibility in immune or non-immune organs. Two waves of induced expression of PoIRF4b were observed with the two stimuli during a 7-day time course in the immune organs, with the early-phase induction being stronger. The maximum increases of PoIRF4b transcript levels ranged from 1.3 to 4.0-fold and appeared at day 1-5 post-injection depending on different organs and stimuli. In both stimulation cases, the strongest induction was detected in spleen and the weakest in muscle. These results indicate that PoIRF4b may participate in regulation of immune responses of flounders to both RNA and DNA virus infections. PMID:27084058

  16. Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis

    PubMed Central

    Zeng, Yang; Pan, I-Wen

    2015-01-01

    Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a “coactivator” of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development. PMID:26258622

  17. Smaller tumor size is associated with poor survival in T4b colon cancer

    PubMed Central

    Huang, Ben; Feng, Yang; Mo, Shao-Bo; Cai, San-Jun; Huang, Li-Yong

    2016-01-01

    AIM: To hypothesize that in patients with colon cancer showing heavy intestinal wall invasion without distant metastasis (T4bN0-2M0), small tumor size would correlate with more aggressive tumor behaviors and therefore poorer cancer-specific survival (CSS). METHODS: We analyzed T4bN0-2M0 colon cancer patients in the Surveillance, Epidemiology and End Results (SEER) database. A preliminary analysis of T4bN0-2M0 colon cancer patients at the Fudan University Shanghai Cancer Center is also presented. RESULTS: A total of 1734 T4bN0-2M0 colon cancer patients from the SEER database were included. Kaplan-Meier analysis revealed decreasing CSS with decreasing tumor size (P < 0.001). Subgroup analysis showed a significant association between poorer CSS with smaller tumor size in T4bN0 patients (P = 0.024), and a trend of association in T4bN1 (P = 0.182) and T4bN2 patients (P = 0.191). Multivariate analysis identified tumor size as an independent prognostic factor for CSS in T4bN0-2M0 patients (P = 0.024). Preliminary analysis of Fudan University Shanghai Cancer Center samples suggested the 5-year CSS was 50.0%, 72.9% and 77.1% in patients with tumors ≤ 4.0 cm, 4.0-7.0 cm and ≥ 7.0 cm. CONCLUSION: Smaller tumor size is associated with poorer CSS in the T4bN0-2M0 subset of colon cancer, particularly in the T4bN0M0 subgroup. PMID:27547015

  18. CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.

    PubMed

    Zou, Yongxin; Mi, Jun; Wang, Wenxing; Lu, Juanjuan; Zhao, Wei; Liu, Zhaojian; Hu, Huili; Yang, Yang; Gao, Xiaoxing; Jiang, Baichun; Shao, Changshun; Gong, Yaoqin

    2013-03-18

    Cullin-RING ubiquitin ligases (CRLs) participate in the regulation of diverse cellular processes including cell cycle progression. Mutations in the X-linked CUL4B, a member of the cullin family, cause mental retardation and other developmental abnormalities in humans. Cells that are deficient in CUL4B are severely selected against in vivo in heterozygotes. Here we report a role of CUL4B in the regulation of replication licensing. Strikingly, CDC6, the licensing factor in replication, was positively regulated by CUL4B and contributed to the loading of MCM2 to chromatin. The positive regulation of CDC6 by CUL4B depends on CDK2, which phosphorylates CDC6, protecting it from APC(CDH1)-mediated degradation. Thus, aside being required for cell cycle reentry from quiescence, CDK2 also contributes to pre-replication complex assembly in G1 phase of cycling cells. Interestingly, the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2. Our findings thus establish a CUL4B-CDK2-CDC6 cascade in the regulation of DNA replication licensing.

  19. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

    PubMed Central

    Cabrera, Sandra; Fernández, Álvaro F.; Mariño, Guillermo; Aguirre, Alina; Suárez, María F.; Español, Yaiza; Vega, José A.; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M. Soledad; Freije, José M.P.; Kroemer, Guido; López-Otín, Carlos

    2013-01-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. PMID:23782979

  20. Structure based virtual screening to identify selective phosphodiesterase 4B inhibitors.

    PubMed

    Gangwal, Rahul P; Damre, Mangesh V; Das, Nihar R; Dhoke, Gaurao V; Bhadauriya, Anuseema; Varikoti, Rohith A; Sharma, Shyam S; Sangamwar, Abhay T

    2015-04-01

    Phosphodiesterase 4 (PDE4), is a hydrolytic enzyme, is proposed as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B selective inhibitors are desirable to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. To achieve this goal, ligand based pharmacophore modeling and molecular docking approach is employed. Pharmacophore hypotheses for PDE4B and PDE4D are generated using HypoGen algorithm. The best PDE4B pharmacophore hypothesis (Hypo1_PDE4B) consist of one hydrogen-bond acceptor and two ring aromatic features, whereas PDE4D pharmacophore hypothesis (Hypo1_PDE4D) consist of one hydrogen-bond acceptor, one hydrophobic aliphatic, and two ring aromatic features. The validated pharmacophore hypotheses are used in virtual screening to identify selective PDE4B inhibitors. The hits were screened for their estimated activity, FitValue, and quantitative estimation of drug likeness. After molecular docking analysis, ten hits were purchased for in vitro analysis. Out of these, six hits have shown potent and selective inhibitory activity against PDE4B with IC50 values ranging from 2 to 378nM.

  1. Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells.

    PubMed

    Huygens, Caroline; Liénart, Stéphanie; Dedobbeleer, Olivier; Stockis, Julie; Gauthy, Emilie; Coulie, Pierre G; Lucas, Sophie

    2015-08-14

    Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression.

  2. Comments concerning the crystal structure of B/sub 4/C

    SciTech Connect

    Larson, A.C.

    1985-01-01

    The crystal structure of B/sub 4/C at approx.20 atom% carbon is reported. The space group is R 3m, hexagonal cell lattice constants are a=5.6039(4)A, c=12.0786(14)A, v=109.50A/sup 3/, Z=3, ..mu..(MoK..cap alpha..)=0.05 mm/sup -1/. The excess carbon above the stoichiometric composition of B/sub 13/C/sub 2/ replaces up to 1/6 of the boron in the rhombohedral boron site (B2). The results this refinement are reported and compared with earlier results reported on lower carbon samples. Evidence is that the icosahedron is essentially pure boron at and below carbon compositions of 13.3 a%. 8 refs., 5 tabs.

  3. Modeling of two-phase flow instabilities during startup transients utilizing RAMONA-4B methodology

    SciTech Connect

    Paniagua, J.; Rohatgi, U.S.; Prasad, V.

    1996-10-01

    RAMONA-4B code is currently under development for simulating thermal hydraulic instabilities that can occur in Boiling Water Reactors (BWRs) and the Simplified Boiling Water Reactor (SBWR). As one of the missions of RAMONA-4B is to simulate SBWR startup transients, where geysering or condensation-induced instability may be encountered, the code needs to be assessed for this application. This paper outlines the results of the assessments of the current version of RAMONA-4B and the modifications necessary for simulating the geysering or condensation-induced instability. The test selected for assessment are the geysering tests performed by Prof Aritomi (1993).

  4. TAF4b is required for mouse spermatogonial stem cell development

    PubMed Central

    Lovasco, Lindsay A.; Gustafson, Eric A.; Seymour, Kimberly A.; de Rooij, Dirk G.; Freiman, Richard N.

    2014-01-01

    Long-term mammalian spermatogenesis requires proper development of spermatogonial stem cells (SSCs) that replenish the testis with germ cell progenitors during adult life. TAF4b is a gonadal-enriched component of the general transcription factor complex, TFIID, which is required for the maintenance of spermatogenesis in the mouse. Successful germ cell transplantation assays into adult TAF4b-deficient host testes suggested that TAF4b performs an essential germ cell autonomous function in SSC establishment and/or maintenance. To elucidate the SSC function of TAF4b, we characterized the initial gonocyte pool and rounds of spermatogenic differentiation in the context of the Taf4b-deficient mouse testis. Here we demonstrate a significant reduction in the late embryonic gonocyte pool and a deficient expansion of this pool soon after birth. Resulting from this reduction of germ cell progenitors is a developmental delay in meiosis initiation, as compared to age-matched controls. While GFRα1+ spermatogonia are appropriately present as Asingle and Apaired in wild type testes, TAF4b-deficient testes display an increased proportion of long and clustered chains of GFRα1+ cells. In the absence of TAF4b, seminiferous tubules in the adult testis either lack germ cells altogether or are found to have missing generations of spermatogenic progenitor cells. Together these data indicate that TAF4b-deficient spermatogenic progenitor cells display a tendency for differentiation at the expense of self-renewal and a renewing pool of SSCs fail to establish during the critical window of SSC development. PMID:25727968

  5. VizieR Online Data Catalog: XO-4b 3yr observations with DEMONEX (Villanueva+, 2016)

    NASA Astrophysics Data System (ADS)

    Villanueva, S. Jr; Eastman, J. D.; Gaudi, B. S.

    2016-06-01

    New observations of XO-4b were made using DEdicated MONitor of EXotransits (DEMONEX). DEMONEX monitored bright stars hosting known transiting planets over a 3yr period from 2008 to 2011 in order to provide a homogeneous data set of precise relative photometry for over 40 transiting systems. There are 20 nights of data from 2008 November to 2010 May taken during primary transits of XO-4b. All observations were made in the Sloan z band. (1 data file).

  6. Order Parameter measurements of Chromonic Liquid Crystal Benzopurpurin 4B using polarized Raman scattering

    NASA Astrophysics Data System (ADS)

    Nayani, Karthik; Park, Jung Ok; Srinivasarao, Mohan

    2012-02-01

    Benzopurpurin 4B (BPP4B), a commonly used textile dye, is known to form chromonic liquid crystal phases in aqueous solutions at fairly low concentrations (<0.5 wt%) in comparison with other chromonic liquid crystals. Also the aggregation properties and the structure of the aggregates in aqueous solutions of BPP4B are not well understood. Recently McKitterick et al. reported a study on the aggregation and phase behavior of BPP4B in water.ootnotetextC. B. McKitterick, N. L. Erb-Satullo, N. D. LaRacuente, A. J. Dickson, P. J. Collings. J. Phys. Chem. B. 2010. 114, 1888. Further understanding of the behavior of BPP4B in aqueous solutions can be gained by studying how the order parameter of its liquid crystalline phase varies with some relevant parameters. Planar monodomains of BPP4B were obtained using a flat rectangular capillary. Thermal evolution of the order parameter of these aligned monodomains was carried out using polarized Raman scattering measurements. Further, the concentration dependence and the effect of salt on the order parameter were studied. The variation of the order parameter with the above parameters was correlated to the structure of the aggregates using the UV-Vis absorption data.

  7. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    PubMed Central

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  8. Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B

    PubMed Central

    Woodfield, Sarah E.; Guo, Rong Jun; Liu, Yin; Major, Angela M.; Hollingsworth, Emporia Faith; Indiviglio, Sandra; Whittle, Sarah B.; Mo, Qianxing; Bean, Andrew J.; Ittmann, Michael; Lopez-Terrada, Dolores; Zage, Peter E.

    2016-01-01

    Background UBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology. Methods We evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines. Results Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK. Conclusions We have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation. PMID:27014418

  9. Insights into K-Ras 4B regulation by post-translational lysine acetylation.

    PubMed

    Knyphausen, Philipp; Lang, Franziska; Baldus, Linda; Extra, Antje; Lammers, Michael

    2016-10-01

    Ras is a molecular switch cycling between an active, GTP-bound and an inactive, GDP-bound state. Mutations in Ras, mostly affecting the off-switch, are found in many human tumours. Recently, it has been shown that K-Ras 4B is targeted by lysine acetylation at K104. Based on results obtained for an acetylation mimetic Ras mutant (K104Q), it was hypothesised that K104-acetylation might interfere with its oncogenicity by impairing SOS-catalysed guanine-nucleotide exchange. We prepared site-specifically K104-acetylated K-Ras 4B and the corresponding oncogenic mutant protein G12V using the genetic-code expansion concept. We found that SOS-catalysed nucleotide exchange, also of allosterically activated SOS, was neither affected by acetylation of K104 in wildtype K-Ras 4B nor in the G12V mutant, suggesting that glutamine is a poor mimetic for acetylation at this site. In vitro, the lysine-acetyltransferases CBP and p300 were able to acetylate both, wildtype and G12V K-Ras 4B. In addition to K104 we identified further acetylation sites in K-Ras 4B, including K147, within the important G5/SAK-motif. However, the intrinsic and the SOS-catalysed nucleotide exchange was not affected by K147-acetylation of K-Ras 4B. Finally, we show that Sirt2 and HDAC6 do neither deacetylate K-Ras 4B if acetylated at K104 nor if acetylated at K147 in vitro.

  10. Structural and functional comparison of the non-structural protein 4B in flaviviridae.

    PubMed

    Welsch, Christoph; Albrecht, Mario; Maydt, Jochen; Herrmann, Eva; Welker, Martin Walter; Sarrazin, Christoph; Scheidig, Axel; Lengauer, Thomas; Zeuzem, Stefan

    2007-09-01

    Flaviviridae are evolutionarily related viruses, comprising the hepatitis C virus (HCV), with the non-structural protein 4B (NS4B) as one of the least characterized proteins. NS4B is located in the endoplasmic reticulum membrane and is assumed to be a multifunctional protein. However, detailed structure information is missing. The hydrophobic nature of NS4B is a major difficulty for many experimental techniques. We applied bioinformatics methods to analyse structural and functional properties of NS4B in different viruses. We distinguish a central non-globular membrane portion with four to five transmembrane regions from an N- and C-terminal part with non-transmembrane helical elements. We demonstrate high similarity in sequence and structure for the C-terminal part within the flaviviridae family. A palmitoylation site contained in the C-terminal part of HCV is equally conserved in GB virus B. Furthermore, we identify and characterize an N-terminal basic leucine zipper (bZIP) motif in HCV, which is suggestive of a functionally important interaction site. In addition, we model the interaction of the bZIP region with the recently identified interaction partner CREB-RP/ATF6beta, a human activating transcription factor involved in ER-stress. In conclusion, the versatile structure, together with functional sites and motifs, possibly enables NS4B to adopt a role as protein hub in the membranous web interaction network of virus and host proteins. Important structural and functional properties of NS4B are predicted with implications for ER-stress response, altered gene expression and replication efficacy.

  11. Environmental Assessment and Finding of No Significant Impact: Transuranic Waste Retrieval from the 218-W-4B and 218-W-4C Low-Level Burial Grounds, Hanford Site, Richland, Washington

    SciTech Connect

    N /A

    2002-03-22

    The U.S. Department of Energy, Richland Operations Office (DOE-RL) needs to improve management of post-1970, contact-handled (CH) suspect transuranic (TRU) waste containers (primarily drums) that are stacked in modules and covered with soil in the Low-Level Burial Grounds (LLBG).

  12. High-Pressure Synthesis and Crystal Structure of Ce4B14O27

    PubMed Central

    Hinteregger, Ernst; Perfler, Lukas; Huppertz, Hubert

    2013-01-01

    Ce4B14O27 was synthesized under conditions of 2.6 GPa and 750 °C in a Walker-type multianvil apparatus. The crystal structure was determined on the basis of single-crystal X-ray diffraction data, collected at room temperature, revealing that Ce4B14O27 is isotypic to La4B14O27. Ce4B14O27 crystallizes monoclinically with four formula units in the space group C2/c (No. 15) and the lattice parameters a = 1117.8(2), b = 640.9(2), c = 2531.7(5) pm, and β = 100.2(1)°. The three-dimensional boron-oxygen framework consists of [BO4]5– tetrahedra and trigonal-planar [BO3]3– groups. The structure contains two crystallographically different cerium ions. Furthermore, Raman spectroscopy was performed on single crystals of Ce4B14O27. PMID:25995523

  13. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

    PubMed

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie

    2015-04-01

    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

  14. TAF4b Promotes Mouse Primordial Follicle Assembly and Oocyte Survival

    PubMed Central

    Grive, Kathryn J.; Seymour, Kimberly A.; Mehta, Rajvi; Freiman, Richard N.

    2014-01-01

    Primary ovarian insufficiency (POI) affects 1% of women under the age of 40 and is associated with premature ovarian follicle depletion. TAF4b deficiency in adult female mouse models results in hallmarks of POI including stereotyped gonadotropin alterations indicative of early menopause, poor oocyte quality, and infertility. However, the precise developmental mechanisms underlying these adult deficits remain unknown. Here we show that TAF4b is required for the initial establishment of the primordial follicle reserve at birth. Ovaries derived from TAF4b-deficient mice at birth exhibit delayed germ cell cyst breakdown and a significant increase in Activated Caspase 3 staining compared to control ovaries. Culturing neonatal TAF4b-deficient ovaries with the pan-caspase inhibitor ZVAD-FMK suppresses the excessive loss of these oocytes around the time of birth. These data reveal a novel TAF4b function in orchestrating the correct timing of germ cell cyst breakdown and establishment of the primordial follicle reserve during a critical window of development. PMID:24836512

  15. A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms.

    PubMed

    Perez-Lorenzo, Rolando; Gill, Kamraan Z; Shen, Che-Hung; Zhao, Feng X; Zheng, Bin; Schulze, Hans-Joachim; Silvers, David N; Brunner, Georg; Horst, Basil A

    2014-05-01

    The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

  16. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.

    PubMed

    Akin, Debra; Wang, S Keisin; Habibzadegah-Tari, Pouran; Law, Brian; Ostrov, David; Li, Min; Yin, Xiao-Ming; Kim, Jae-Sung; Horenstein, Nicole; Dunn, William A

    2014-01-01

    Autophagy has been implicated in the progression and chemoresistance of various cancers. In this study, we have shown that osteosarcoma Saos-2 cells lacking ATG4B, a cysteine proteinase that activates LC3B, are defective in autophagy and fail to form tumors in mouse models. By combining in silico docking with in vitro and cell-based assays, we identified small compounds that suppressed starvation-induced protein degradation, LC3B lipidation, and formation of autophagic vacuoles. NSC185058 effectively inhibited ATG4B activity in vitro and in cells while having no effect on MTOR and PtdIns3K activities. In addition, this ATG4B antagonist had a negative impact on the development of Saos-2 osteosarcoma tumors in vivo. We concluded that tumor suppression was due to a reduction in ATG4B activity, since we found autophagy suppressed within treated tumors and the compound had no effects on oncogenic protein kinases. Our findings demonstrate that ATG4B is a suitable anti-autophagy target and a promising therapeutic target to treat osteosarcoma. PMID:25483883

  17. Lack of Cul4b, an E3 Ubiquitin Ligase Component, Leads to Embryonic Lethality and Abnormal Placental Development

    PubMed Central

    Yuan, Jupeng; Qian, Yanyan; Sun, Wenjie; Zou, Yongxin; Guo, Chenhong; Chen, Bingxi; Shao, Changshun; Gong, Yaoqin

    2012-01-01

    Cullin-RING ligases (CRLs) complexes participate in the regulation of diverse cellular processes, including cell cycle progression, transcription, signal transduction and development. Serving as the scaffold protein, cullins are crucial for the assembly of ligase complexes, which recognize and target various substrates for proteosomal degradation. Mutations in human CUL4B, one of the eight members in cullin family, are one of the major causes of X-linked mental retardation. We here report the generation and characterization of Cul4b knockout mice, in which exons 3 to 5 were deleted. In contrast to the survival to adulthood of human hemizygous males with CUL4B null mutation, Cul4b null mouse embryos show severe developmental arrest and usually die before embryonic day 9.5 (E9.5). Accumulation of cyclin E, a CRL (CUL4B) substrate, was observed in Cul4b null embryos. Cul4b heterozygotes were recovered at a reduced ratio and exhibited a severe developmental delay. The placentas in Cul4b heterozygotes were disorganized and were impaired in vascularization, which may contribute to the developmental delay. As in human CUL4B heterozygotes, Cul4b null cells were selected against in Cul4b heterozygotes, leading to various degrees of skewed X-inactivation in different tissues. Together, our results showed that CUL4B is indispensable for embryonic development in the mouse. PMID:22606329

  18. Protection against Asiatic Taenia solium induced by a recombinant 45W-4B protein.

    PubMed

    Luo, Xuenong; Zheng, Yadong; Hou, Junling; Zhang, Shaohua; Cai, Xuepeng

    2009-02-01

    Taenia solium is a great threat not only to human health but also to the pig-raising industry. Oncospheral stage-specific 45W proteins are good candidates for the development of anticysticercosis vaccines. In this study, a recombinant 45W-4B protein was highly produced and used for vaccination. Two animal trials resulted in a significant reduction in parasite burden induced by the definite protein against Asiatic T. solium, up to 97.0% and 98.4%, respectively. These provide informative results for the development of effective 45W-4B vaccines against cysticercosis caused by both Chinese and Mexican T. solium isolates and even by other isolates.

  19. Potent L-lactic acid assimilation of the fermentative and heterothallic haploid yeast Saccharomyces cerevisiae NAM34-4C.

    PubMed

    Tomitaka, Masataka; Taguchi, Hisataka; Matsuoka, Masayoshi; Morimura, Shigeru; Kida, Kenji; Akamatsu, Takashi

    2014-01-01

    We screened an industrial thermotolerant Saccharomyces cerevisiae strain, KF7, as a potent lactic-acid-assimilating yeast. Heterothallic haploid strains KF7-5C and KF7-4B were obtained from the tetrads of the homothallic yeast strain KF7. The inefficient sporulation and poor spore viability of the haploid strains were improved by two strategies. The first strategy was as follows: (i) the KF7-5C was crossed with the laboratory strain SH6710; (ii) the progenies were backcrossed with KF7-5C three times; and (iii) the progenies were inbred three times to maintain a genetic background close to that of KF7. The NAM12 diploid between the cross of the resultant two strains, NAM11-9C and NAM11-13A, showed efficient sporulation and exhibited excellent growth in YPD medium (pH 3.5) at 35°C with 1.4-h generation time, indicating thermotolerance and acid tolerance. The second strategy was successive intrastrain crosses. The resultant two strains, KFG4-6B and KFG4-4B, showed excellent mating capacity. A spontaneous mutant of KFG4-6B, KFG4-6BD, showed a high growth rate with a generation time of 1.1 h in YPD medium (pH 3.0) at 35°C. The KFG4-6BD strain produced ascospores, which were crossed with NAM11-2C and its progeny to produce tetrads. These tetrads were crossed with KFG4-4B to produce NAM26-14A and NAM26-15A. The latter strain had a generation time of 1.6 h at 35°C in pH 2.5, thus exhibiting further thermotolerance and acid tolerance. A progeny from a cross of NAM26-14A and NAM26-15A yielded the strain NAM34-4C, which showed potent lactic acid assimilation and high transformation efficiency, better than those of a standard laboratory strain.

  20. The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca2+ and Mg2+ dependent-DNase activity and antifungal action on Moniliophthora perniciosa

    PubMed Central

    2014-01-01

    Background The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. Results TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. Conclusion To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively. PMID:24920373

  1. 32 CFR 1630.42 - Class 4-C: Alien or dual national.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Class 4-C: Alien or dual national. 1630.42... CLASSIFICATION RULES § 1630.42 Class 4-C: Alien or dual national. In Class 4-C shall be placed any registrant who... service in the United States. (b) Is an alien and who has departed from the United States prior to...

  2. 32 CFR 1630.42 - Class 4-C: Alien or dual national.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Class 4-C: Alien or dual national. 1630.42... CLASSIFICATION RULES § 1630.42 Class 4-C: Alien or dual national. In Class 4-C shall be placed any registrant who... service in the United States. (b) Is an alien and who has departed from the United States prior to...

  3. 32 CFR 1630.42 - Class 4-C: Alien or dual national.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Class 4-C: Alien or dual national. 1630.42... CLASSIFICATION RULES § 1630.42 Class 4-C: Alien or dual national. In Class 4-C shall be placed any registrant who... service in the United States. (b) Is an alien and who has departed from the United States prior to...

  4. 32 CFR 1630.42 - Class 4-C: Alien or dual national.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Class 4-C: Alien or dual national. 1630.42... CLASSIFICATION RULES § 1630.42 Class 4-C: Alien or dual national. In Class 4-C shall be placed any registrant who... service in the United States. (b) Is an alien and who has departed from the United States prior to...

  5. 32 CFR 1630.42 - Class 4-C: Alien or dual national.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Class 4-C: Alien or dual national. 1630.42... CLASSIFICATION RULES § 1630.42 Class 4-C: Alien or dual national. In Class 4-C shall be placed any registrant who... service in the United States. (b) Is an alien and who has departed from the United States prior to...

  6. Secondary Structure and Membrane Topology of the Full-Length Dengue Virus NS4B in Micelles.

    PubMed

    Li, Yan; Wong, Ying Lei; Lee, Michelle Yueqi; Li, Qingxin; Wang, Qing-Yin; Lescar, Julien; Shi, Pei-Yong; Kang, CongBao

    2016-09-19

    Dengue virus nonstructural protein 4B (NS4B) is a membrane protein consisting of 248 residues with a crucial role in virus replication and interference with the host innate immunity. The dengue virus serotype 3 NS4B was reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Backbone resonance assignment of NS4B was obtained using conventional solution NMR experiments. Further studies suggested that NS4B contained eleven helices and six of them form five potential transmembrane regions. This study provides atomic level information for an important drug target to control flavivirus infections. PMID:27554985

  7. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF NEW SULFONAMIDE ISOXAZOLO[5,4-b]PYRIDINE DERIVATIVES.

    PubMed

    Poręba, Krystyna; Pawlik, Krzysztof; Rembacz, Krzysztof P; Kurowska, Ewa; Matuszyk, Janusz; Długosz, Anna

    2015-01-01

    A series of novel sulfonamide isoxazolo[5,4-b]pyridines were synthesized. The substrates for their synthesis were 3-aminoisoxazolo[5,4-b]pyridine and selected aryl sulfonic chlorides, chlorosulfonic acid and selected amines. Reactions were carried out using the classical and microwave methods. Selected compounds were tested towards antibacterial and antiproliferative activity. The structure of the obtained new derivatives was determined by elemental analysis and acquired IR and 1H NMR spectra. Among the tested compounds: N- isoxazolo[5,4-b]pyridine-3-yl-benzenesulfonamide (2) and N-isoxazolo[5,4-b]pyridine-3-yl-4-methylbenzene-sulfonamide (5) showed antimicrobial activity towards Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922) at doses: 125, 250 and 500 µg. Both compounds showed a 50% inhibition of proliferation of breast carcinoma cell line MCF7 at concentrations of 152.56 µg/mL and 160 161.08 µg/mL, respectively. PMID:26647630

  8. DISC1, PDE4B, and NDE1 at the centrosome and synapse

    SciTech Connect

    Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz; Chubb, Jennifer E.; Carlyle, Becky C.; Christie, Sheila; Claessens, Antoine; Porteous, David J.; Millar, J. Kirsty

    2008-12-26

    Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

  9. Random UV mutagenesis approach for enhanced biodegradation of sulfonated azo dye, Green HE4B.

    PubMed

    Joshi, Swati M; Inamdar, Shrirang A; Jadhav, Jyoti P; Govindwar, Sanjay P

    2013-03-01

    The objective of the study was to execute mutant bacteria for efficient biodegradation of sulfonated azo dye, Green HE4B (GHE4B). UV irradiation was used to introduce random mutations in Pseudomonas sp. LBC1. Genetic alterations induced by UV irradiation in selected mutant bacteria were confirmed by random amplification of polymorphic DNA technique. The mutant bacteria named as Pseudomonas sp. 1 F reduced the time required for complete degradation of recalcitrant dye GHE4B by 25 % when compared with the wild one. The biodegradation was monitored by UV-Vis spectrophotometric analysis. Activities of enzymes like laccase, lignin peroxidase, veratryl alcohol oxidase, and NADH dichlorophenol indophenol reductase were found to be boosted in mutant bacteria as a consequence of UV-induced mutation. Matrix-assisted laser desorption/ionization-time of flight analysis of differentially expressed proteins of mutant bacteria suggested active role of antioxidant enzymes in the degradation of the dye. The degradation product was analyzed by Fourier transform infrared spectroscopy, high-performance thin-layer chromatography, and gas chromatography-mass spectrometry. Results revealed few variations in the degradation end products of wild-type and mutant bacteria. Phytotoxicity study underlined the safer biodegradation of GHE4B by mutant Pseudomonas sp. 1 F.

  10. IcmQ in the Type 4b secretion system contains a novel NAD+ binding domain

    PubMed Central

    Farelli, Jeremiah D.; Gumbart, James C.; Akey, Ildiko V.; Hempstead, Andrew; Amyot, Whitney; Head, James F.; McKnight, C. James; Isberg, Ralph R.; Akey, Christopher W.

    2013-01-01

    A Type4b secretion system (T4bSS) is required for Legionella growth in alveolar macrophages. IcmQ associates with IcmR, binds to membranes and has a critical role in the T4bSS. We have now solved a crystal structure of IcmR-IcmQ to further our understanding of this complex. This structure revealed an amphipathic four-helix bundle, formed by IcmR and the N-terminal domain of IcmQ, which is linked to a novel C-terminal domain of IcmQ (Qc) by a linker helix. The Qc domain has structural homology with ADP ribosyltransferase domains in certain bacterial toxins and binds NAD+ with a Kd in the physiological range. Structural homology and molecular dynamics were used to identify an extended NAD+ binding site on Qc and the resulting model was tested by mutagenesis and binding assays. Based on the data, we suggest that IcmR-IcmQ binds to membranes where it may interact with or perhaps modify a protein in the T4bSS when NAD+ is bound. PMID:23850453

  11. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Component spacing test method for § 1508.4(b). 1508.5 Section 1508.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS § 1508.5 Component spacing test method...

  12. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Component spacing test method for § 1508.4(b). 1508.5 Section 1508.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS § 1508.5 Component spacing test method...

  13. Atg4b-Dependent Autophagic Flux Alleviates Huntington’s Disease Progression

    PubMed Central

    Proenca, Catia C.; Stoehr, Natacha; Bernhard, Mario; Seger, Shanon; Genoud, Christel; Roscic, Ana; Paganetti, Paolo; Liu, Shanming; Murphy, Leon O.; Kuhn, Rainer; Bouwmeester, Tewis; Galimberti, Ivan

    2013-01-01

    The accumulation of aggregated mutant huntingtin (mHtt) inclusion bodies is involved in Huntigton’s disease (HD) progression. Medium sized-spiny neurons (MSNs) in the corpus striatum are highly vulnerable to mHtt aggregate accumulation and degeneration, but the mechanisms and pathways involved remain elusive. Here we have developed a new model to study MSNs degeneration in the context of HD. We produced organotypic cortico-striatal slice cultures (CStS) from HD transgenic mice mimicking specific features of HD progression. We then show that induction of autophagy using catalytic inhibitors of mTOR prevents MSNs degeneration in HD CStS. Furthermore, disrupting autophagic flux by overexpressing Atg4b in neurons and slice cultures, accelerated mHtt aggregation and neuronal death, suggesting that Atg4b-dependent autophagic flux influences HD progression. Under these circumstances induction of autophagy using catalytic inhibitors of mTOR was inefficient and did not affect mHtt aggregate accumulation and toxicity, indicating that mTOR inhibition alleviates HD progression by inducing Atg4b-dependent autophagic flux. These results establish modulators of Atg4b-dependent autophagic flux as new potential targets in the treatment of HD. PMID:23861892

  14. Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy

    PubMed Central

    Lim, Kue Peng; Chun, Nicole Ai Leng; Gan, Chai Phei; Teo, Soo-Hwang; Rahman, Zainal Ariff Abdul; Abraham, Mannil Thomas; Zain, Rosnah Binti; Ponniah, Sathibalan; Cheong, Sok Ching

    2014-01-01

    The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC. PMID:25483651

  15. 20. FOUR 4B17Gs BEING CONVERTED TO F9Cs. Photographic copy of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. FOUR 4B-17Gs BEING CONVERTED TO F-9Cs. Photographic copy of historic photograph. Jan.-June 1947 OAMA (original print located at Ogden Air Logistics Center, Hill Air Force Base, Utah). Photographer unknown. - Hill Field, Airplane Repair Hangars No. 1-No. 4, 5875 Southgate Avenue, Layton, Davis County, UT

  16. Identification of an NTPase motif in classical swine fever virus NS4B protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  17. A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease.

    PubMed

    Rodríguez-Feo, Juan Antonio; Puerto, Marta; Fernández-Mena, Carolina; Verdejo, Cristina; Lara, José Manuel; Díaz-Sánchez, María; Álvarez, Emilio; Vaquero, Javier; Marín-Jiménez, Ignacio; Bañares, Rafael; Menchén, Luis

    2015-06-15

    Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10(-/-) compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10(-/-) mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.

  18. Pr{sub 4}B{sub 10}O{sub 21}: A new composition of rare-earth borates by high-pressure/high-temperature synthesis

    SciTech Connect

    Haberer, Almut; Heymann, Gunter; Huppertz, Hubert

    2007-05-15

    High-pressure chemistry led to the synthesis of the rare-earth borate Pr{sub 4}B{sub 10}O{sub 21} using a Walker-type multianvil apparatus at 3.5 GPa and 1050 deg. C. The tetra-praseodymium(III)-decaborate crystallizes monoclinicly with four formula units in the space group P2{sub 1}/n and lattice parameters of a=710.2(2), b=1948.8(4), c=951.6(2) pm, and {beta}=93.27(3){sup o}. The boron-oxygen network consists of [BO{sub 4}]{sup 5-} tetrahedra and [BO{sub 3}]{sup 3-} groups; however, the [BO{sub 4}]{sup 5-} groups represent the major part (80%) due to the high-pressure conditions during the synthesis. The praseodymium ions are coordinated by 10 and 12 oxygen atoms. Along with a detailed description of the crystal structure, temperature programmed X-ray powder diffraction data are shown, demonstrating the metastable character of this compound. - Graphical abstract: Synthesis of Pr{sub 4}B{sub 10}O{sub 21} via the multianvil high-pressure/high-temperature technique representing a new composition of rare-earth borates.

  19. 29 CFR 4.10 - Substantial variance proceedings under section 4(c) of the Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Act. 4.10 Section 4.10 Labor Office of the Secretary of Labor LABOR STANDARDS FOR FEDERAL SERVICE... under section 4(c) of the Act. (a) Statutory provision. Under section 4(c) of the Act, and under corresponding wage determinations made as provided in section 2(a)(1) and (2) of the Act, contractors...

  20. 29 CFR 4.163 - Section 4(c) of the Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....163 Section 4(c) of the Act. (a) Section 4(c) of the Act provides that no “contractor or subcontractor... Secretary finds after a hearing in accordance with regulations adopted by the Secretary that such wages and... that all service employees are paid no less than the wages and fringe benefits to which such...

  1. 29 CFR 4.163 - Section 4(c) of the Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....163 Section 4(c) of the Act. (a) Section 4(c) of the Act provides that no “contractor or subcontractor... Secretary finds after a hearing in accordance with regulations adopted by the Secretary that such wages and... that all service employees are paid no less than the wages and fringe benefits to which such...

  2. 29 CFR 4.163 - Section 4(c) of the Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....163 Section 4(c) of the Act. (a) Section 4(c) of the Act provides that no “contractor or subcontractor... Secretary finds after a hearing in accordance with regulations adopted by the Secretary that such wages and... that all service employees are paid no less than the wages and fringe benefits to which such...

  3. Two-Dimensional Nb-Based M 4 C 3 Solid Solutions (MXenes)

    DOE PAGES

    Yang, Jian; Naguib, Michael; Ghidiu, Michael; Pan, Li-Mei; Gu, Jian; Nanda, Jagjit; Halim, Joseph; Gogotsi, Yury; Barsoum, Michel W.; Zhou, Y.

    2015-10-15

    Two new two-dimensional Nb4C3-based solid solutions (MXenes), (Nb0.8,Ti0.2)4C3Tx and (Nb0.8,Zr0.2)4C3Tx (where T is a surface termination) were synthesizedas confirmed by X-ray diffractionfrom their corresponding MAX phase precursors (Nb0.8,Ti0.2)4AlC3 and (Nb0.8,Zr0.2)4AlC3. In our report we discuss Zr-containing MXene. We also studied intercalation of Li ions into these two compositions, and Nb4C3Tx in order to determine the potential of those materials for energy storage applications. Lithiation and delithiation peaks at 2.26 and 2.35 V, respectively, appeared in the case of Nb4C3Tx, but were not present in Nb2CTx. After 20 cycles at a rate of C/4, the specific capacities of (Nb0.8,Ti0.2)4C3Txand (Nb0.8,Ti0.2)4C3Tx weremore » 158 and 132 mAh/g, respectively, both slightly lower than the capacity of Nb4C3Tx.« less

  4. Knockdown of CUL4B Suppresses the Proliferation and Invasion in Non-Small Cell Lung Cancer Cells.

    PubMed

    Wang, Xuguang; Chen, Zhe

    2016-01-01

    Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, was found to be overexpressed in many types of tumors. However, the expression pattern and role of CUL4B in non-small cell lung cancer (NSCLC) remain largely unknown. Therefore, in the present study, we investigated the role of CUL4B in NSCLC, and the underlying mechanism was also explored. Our results showed that CUL4B was highly expressed in NSCLC cell lines. Silencing CUL4B obviously inhibited proliferation and migration/invasion of NSCLC cells, and it also suppressed the epithelial-mesenchymal transition (EMT) progress in NSCLC cells. Furthermore, knockdown of CUL4B significantly inhibited the expression of β-catenin, cyclin D1, and c-Myc in NSCLC cells. Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC. PMID:27656838

  5. Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

    PubMed Central

    Tzeng, E; Billiar, T R; Robbins, P D; Loftus, M; Stuehr, D J

    1995-01-01

    Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8524846

  6. Protection against Asiatic Taenia solium Induced by a Recombinant 45W-4B Protein▿

    PubMed Central

    Luo, Xuenong; Zheng, Yadong; Hou, Junling; Zhang, Shaohua; Cai, Xuepeng

    2009-01-01

    Taenia solium is a great threat not only to human health but also to the pig-raising industry. Oncospheral stage-specific 45W proteins are good candidates for the development of anticysticercosis vaccines. In this study, a recombinant 45W-4B protein was highly produced and used for vaccination. Two animal trials resulted in a significant reduction in parasite burden induced by the definite protein against Asiatic T. solium, up to 97.0% and 98.4%, respectively. These provide informative results for the development of effective 45W-4B vaccines against cysticercosis caused by both Chinese and Mexican T. solium isolates and even by other isolates. PMID:19091992

  7. Optical and Near-UV Observations of the Transiting Extrasolar Planet TrES-4b

    NASA Astrophysics Data System (ADS)

    Smith, Carter-Thaxton; Turner, J.; Carleton, T.; Crawford, B.; Guvenen, B.; Hardegree-Ullman, K.; Small, L.; Towner, A. P.; Walker-LaFollette, A.; Henz, T.

    2013-01-01

    Using the Steward Observatory 61” Kuiper Telescope, The University of Arizona Astronomy Club conducted photometric observations of the transiting extrasolar planet TrES-4b as part of the Exoplanet Observation Project. Observations were made in the Bessell U, Harris B, and Harris R filters. Initial observations were made in 2009, with follow up observations in 2011. Basic data reduction and photometry was done using IRAF and determination of transit parameters was done using Transit Analysis Package (TAP) and JKTEBOP transit modeling code. We present an updated planetary mass, radius, density, surface gravity, Safronov number, equilibrium temperature, orbital distance, and orbital inclination for TrES-4b. In addition, we also searched for asymmetries between the near-UV and optical light curves. This project, started in spring 2009, has introduced many undergraduate students to research and given them valuable experience with data reduction and observation techniques.

  8. Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)

    PubMed Central

    REILLY, B D; MOLD, C

    1997-01-01

    Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd ≍ 1.4 10−7M) than C4Bb2 (Kd ≍ 4–8 10−7M), indicating a preferential binding of CR1 for C4A. PMID:9367418

  9. Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation

    PubMed Central

    Thornbrough, Joshua M.; Jha, Babal K.; Yount, Boyd; Goldstein, Stephen A.; Li, Yize; Elliott, Ruth; Sims, Amy C.; Baric, Ralph S.; Silverman, Robert H.

    2016-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage C Betacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage A Betacoronavirus PDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention. PMID:27025250

  10. Fabrication and Characterization of AL-AL4C3 Nanocomposite by Mechanical Alloying

    NASA Astrophysics Data System (ADS)

    Mohammad Sharifi, E.; Enayati, M. H.; Karimzadeh, F.

    Aluminum carbide (Al4C3) seems to be an ideal reinforcement for producing aluminum matrix composites. Al4C3 has high hardness and shear strength as well as a high melting point. The dispersion of Al4C3 particles in the matrix produces a pinning effect that reduces aluminum grain growth, which improves the mechanical properties. In this study, aluminum powders were mixed with 4.5 wt.% graphite and mechanically alloyed using a high-energy ball mill in order to produce Al-Al4C3 nanocomposite. The structural evaluation of powder particles after different milling times was studied by X-ray diffractometry, scanning electron microscopy and microhardness measurements. The aluminum crystallite size estimated with broadening of XRD peaks by Williamson-Hall formula. XRD results suggested that the grain size of aluminum decreased to nanometer range (30 nm) during ball milling. No Al4C3 formed during the mechanical alloying process. Milled powders were then annealed at 300-600 °C for 1 h under argon atmosphere. Annealing at temperatures higher than 300 °C led to formation of Al4C3 phase which increased as annealing temperature increased. Aluminum grain size remained in nanometer range after annealing process. The microhardness of powder particles increased after annealing. Both effects are due to the formation of nanosized Al4C3 particles.

  11. HATS-4b: A dense hot Jupiter transiting a super metal-rich G star

    SciTech Connect

    Jordán, Andrés; Brahm, Rafael; Rabus, M.; Suc, V.; Espinoza, N.; Bakos, G. Á.; Penev, K.; Hartman, J. D.; Csubry, Z.; Bhatti, W.; De Val Borro, M.; Bayliss, D.; Zhou, G.; Mancini, L.; Mohler-Fischer, M.; Ciceri, S.; Csák, B.; Henning, T.; Sato, B.; Buchhave, L.; and others

    2014-08-01

    We report the discovery by the HATSouth survey of HATS-4b, an extrasolar planet transiting a V = 13.46 mag G star. HATS-4b has a period of P ≈ 2.5167 days, mass of M{sub p} ≈ 1.32 M {sub Jup}, radius of R{sub p} ≈ 1.02 R {sub Jup}, and density of ρ {sub p} = 1.55 ± 0.16 g cm{sup –3} ≈1.24 ρ{sub Jup}. The host star has a mass of 1.00 M {sub ☉}, a radius of 0.92 R {sub ☉}, and a very high metallicity [Fe/H]=0.43 ± 0.08. HATS-4b is among the densest known planets with masses between 1 and 2 M {sub J} and is thus likely to have a significant content of heavy elements of the order of 75 M {sub ⊕}. In this paper we present the data reduction, radial velocity measurements, and stellar classification techniques adopted by the HATSouth survey for the CORALIE spectrograph. We also detail a technique for simultaneously estimating vsin i and macroturbulence using high resolution spectra.

  12. DISTRIBUTION OF CH{sub 3}OH IN NGC 1333 IRAS4B

    SciTech Connect

    Sakai, Nami; Yamamoto, Satoshi; Ceccarelli, Cecilia; Bottinelli, Sandrine; Sakai, Takeshi

    2012-07-20

    Distribution of the CH{sub 3}OH (J{sub K} = 2{sub K}-1{sub K}, 96.7 GHz) emission has been investigated toward NGC 1333 IRAS4B, a low-mass Class 0 protostar which harbors a hot corino, with Nobeyama Millimeter Array. The CH{sub 3}OH emission is found to be prominent in the shocked region caused by an impact of the molecular outflow from the protostars. The direction of the outflow which is responsible for the shock seems to be opposite to that of a compact outflow known previously in the CO (J = 2-1), HCN (J = 1-0), H{sub 2}CO (3{sub 12}-2{sub 11}), and CH{sub 3}OH (J{sub K} = 7{sub K}-6{sub K}) emissions, whereas it is the same as that of the faint second outflow found in the H{sub 2}CO emission. This double outflow structure can be interpreted most naturally by the existence of more than two protostars in IRAS4B. On the other hand, a centrally condensed component associated apparently with IRAS4B cannot be recognized in our CH{sub 3}OH observation. Our observation suggests that, in this source, the CH{sub 3}OH (J{sub K} 2{sub K}-1{sub K}) emission preferentially traces the shocked regions rather than the hot corino around the protostar.

  13. Evaulation of B{sub 4}C as an ablator material for NIF capsules. Revision 1

    SciTech Connect

    Burnham, A.K.; Alford, C.S.; Makowiecki, D.M.; Dittrich, T.R.; Wallace, R.J.; Honea, E.C.; King, C.M.; Steinman, D.

    1997-03-26

    Boron carbide (B{sub 4}C) is examined as a potential fuel container and ablator for implosion capsules on the National Ignition Facility (NIF). A capsule of pure B{sub 4}C encasing a layer of solid DT implodes stably and ignites with anticipated NIF x-ray drives, producing 18 MJ of energy. Thin films of B{sub 4}C were found to be resistant to oxidation and modestly transmitting in the infrared (IR), possibly enabling IR fuel characterization and enhancement for thin permeation barriers but not for full-thickness capsules. Polystyrene mandrels 0.5 mm in diameter were successfully coated with 0.15-2.0 micrometers of B{sub 4}C. Thickness estimated from optical density agreed well with those measured by scanning electron microscopy (SEM). The B{sub 4}C microstructure was columnar but finer than for Be made at the same conditions. B{sub 4}C is a very strong material, with a fiber tensile strength capable of holding NIF fill pressures at room temperature, but it is also very brittle, and microscopic flaws or grain structure may limit the noncryogenic fill pressure. Argon (Ar) permeation rates were measured for a few capsules that had been further coated with 5 micrometers of plasma polymer. The B{sub 4}C coatings tended to crack under tensile load. Some shells filled more slowly than they leaked, suggesting that the cracks open and close under opposite pressure loading. As observed earlier for Ti coatings, 0.15-micrometer layers of B{sub 4}C had better gas retention properties than 2-micrometer layers, possibly because of fewer cracks. Permeation and fill strength issues for capsules with a full ablator thickness of B{sub 4}C are unresolved. 21 refs., 6 figs.

  14. Expression, intracellular distribution and basis for lack of catalytic activity of the PDE4A7 isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene.

    PubMed Central

    Johnston, Lee Ann; Erdogan, Suat; Cheung, York Fong; Sullivan, Michael; Barber, Rachael; Lynch, Martin J; Baillie, George S; Van Heeke, Gino; Adams, David R; Huston, Elaine; Houslay, Miles D

    2004-01-01

    PDE4A7 is an isoform encoded by the human PDE4A cAMP-specific phosphodiesterase gene that fails to hydrolyse cAMP and whose transcripts are widely expressed. Removal of either the N- or C-terminal unique portions of PDE4A7 did not reconstitute catalytic activity, showing that they did not exert a chronic inhibitory effect. A chimera (Hyb2), formed by swapping the unique N-terminal portion of PDE4A7 with that of the active PDE4A4C form, was not catalytically active. However, one formed (Hyb1) by swapping the unique C-terminal portion of PDE4A7 with that common to all active PDE4 isoforms was catalytically active. Compared with the active PDE4A4B isoform, Hyb1 exhibited a similar K(m) value for cAMP and IC50 value for rolipram inhibition, but was less sensitive to inhibition by Ro-20-1724 and denbufylline, and considerably more sensitive to thermal denaturation. The unique C-terminal region of PDE4A7 was unable to support an active catalytic unit, whereas its unique N-terminal region can. The N-terminal portion of the PDE4 catalytic unit is essential for catalytic activity and can be supplied by either highly conserved sequence found in active PDE4 isoforms from all four PDE4 subfamilies or the unique N-terminal portion of PDE4A7. A discrete portion of the conserved C-terminal region in active PDE4A isoforms underpins their aberrant migration on SDS/PAGE. Unlike active PDE4A isoforms, PDE4A7 is exclusively localized to the P1 particulate fraction in cells. A region located within the C-terminal portion of active PDE4 isoforms prevents such exclusive targeting. Three functional regions in PDE4A isoforms are identified, which influence catalytic activity, subcellular targeting and conformational status. PMID:15025561

  15. Standard Neutron, Photon, and Electron Data Libraries for MCNP4C.

    2004-02-16

    Version 03 US DOE 10CFR810 Jurisdiction. DLC-200/MCNPDATA is for use with Versions 4C and and 4C2 of the MCNP transport code. This data library provides a comprehensive set of cross sections for a wide range of radiation transport applications using the Monte Carlo code package CCC-700/MCNP4C. See Appendix G of the MCNP report LA-13709-M for information on the libraries and how to select specific nuclides for use in MCNP. Newer MCNP cross sections from LANLmore » are included in CCC-710/MCNP5.« less

  16. Microstructure and magnetic properties of (001) oriented FePt/B{sub 4}C composite films

    SciTech Connect

    Yang, F. J.; Wang Hao; Wang, H. B.; Cao, X.; Yang, C. P.; Li, Q.; Zhou, M. J.; Chong, Y. M.; Zhang, W. J.

    2007-11-15

    FePt/B{sub 4}C multilayer composite films have been prepared by magnetron sputtering and subsequent annealing in vacuum. It was found that the B{sub 4}C layers effectively serve as spacers to separate the FePt layers, enhancing (001) orientation of FePt alloy. Our results show that highly (001) oriented [Fe{sub 45}Pt{sub 55}(8 nm)/B{sub 4}C (4 nm)]{sub 3} film with satisfactory perpendicular coercivity (4.75 kOe) has significant potential as a perpendicular recording medium.

  17. 29 CFR 4.163 - Section 4(c) of the Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the predecessor contractor's agreement allowed a tip credit (§ 4.6(q)), the successor contractor may not take a tip credit toward satisfying the minimum wage requirements under sections 2(a)(1) and 4(c)....

  18. fourSig: a method for determining chromosomal interactions in 4C-Seq data

    PubMed Central

    Williams, Rex L.; Starmer, Joshua; Mugford, Joshua W.; Calabrese, J. Mauro; Mieczkowski, Piotr; Yee, Della; Magnuson, Terry

    2014-01-01

    The ability to correlate chromosome conformation and gene expression gives a great deal of information regarding the strategies used by a cell to properly regulate gene activity. 4C-Seq is a relatively new and increasingly popular technology where the set of genomic interactions generated by a single point in the genome can be determined. 4C-Seq experiments generate large, complicated data sets and it is imperative that signal is properly distinguished from noise. Currently, there are a limited number of methods for analyzing 4C-Seq data. Here, we present a new method, fourSig, which in addition to being precise and simple to use also includes a new feature that prioritizes detected interactions. Our results demonstrate the efficacy of fourSig with previously published and novel 4C-Seq data sets and show that our significance prioritization correlates with the ability to reproducibly detect interactions among replicates. PMID:24561615

  19. Microstructure and Tensile Behaviour of B4C Reinforced ZA43 Alloy Composites

    NASA Astrophysics Data System (ADS)

    Adaveesh, B.; Halesh, G. M.; Nagaral, Madeva; Mohan Kumar, T. S.

    2016-09-01

    The work is carried out to investigate and study the mechanical properties of B4C reinforced ZA43 alloy metal matrix composites. In the present work ZA43 alloy is taken as the base matrix and B4C particulates as reinforcement material to prepare metal matrix composites by stir casting method. For metal matrix composites the reinforcement material was varied from 0 to 6 wt.% in steps of 3 wt.%. For each composite, the reinforcement particulates were preheated to a temperature of 300°C and dispersed into a vortex of molten ZA43 alloy. The microstructural characterization was done using scanning electron microscope. Mechanical properties like hardness, ultimate tensile strength and yield strength were evaluated as per ASTM standards. Further, scanning electron microphotographs revealed that there was uniform distribution of B4C particulates in ZA43 alloy matrix. Hardness, ultimate tensile strength and yield strength increased as wt.% of B4C increased in the base matrix.

  20. Mg{sub 8}Rh{sub 4}B - A new type of boron stabilized Ti{sub 2}Ni structure

    SciTech Connect

    Alekseeva, A.M. . E-mail: alekseev@cpfs.mpg.de; Abakumov, A.M.; Leithe-Jasper, A.; Schnelle, W.; Prots, Yu.; Chizhov, P.S.; Van Tendeloo, G.; Antipov, E.V.; Grin, Yu.

    2006-09-15

    The new magnesium rhodium boron compound Mg{sub 8}Rh{sub 4}B has been synthesized by reaction of the metal powders with crystalline or amorphous boron or the RhB precursor. The crystal structure of Mg{sub 8}Rh{sub 4}B was solved using single-crystal X-ray diffraction data (space group Fd3-bar m, a=12.1711(4)A, Z=8, 174 reflections, R{sub F}=0.016). The crystal structure can be described as a filled Ti{sub 2}Ni type where the interstitial sites 8b (12,12,12), located at the center of two nested Mg{sub 4}Rh{sub 4} tetrahedra, are occupied by boron atoms. Taking into account the absence of the Ti{sub 2}Ni-type phase in the binary Mg-Rh system, the boron atoms can be considered as stabilizing this structural motif. From the bonding analysis with the electron localization function the crystal structure is described as covalently bonded [Rh{sub 4}B]{sup 3-} anions, embedded in a cationic magnesium matrix.

  1. TL and OSL studies of carbon doped magnesium aluminate (MgAl2O4:C)

    NASA Astrophysics Data System (ADS)

    Raj, Sanu S.; Mishra, D. R.; Soni, Anuj; Grover, V.; Polymeris, G. S.; Muthe, K. P.; Jha, S. K.; Tyagi, A. K.

    2016-10-01

    The MgAl2O4:C has been synthesized by using two different methods by electron gun and vacuum assisted melting of MgAl2O4 in presence of graphite. The MgAl2O4:C phosphor thus developed by these two different methods have similar types of the TL/OSL defects with multiple overlapping TL glow peaks from 100 °C to 400 °C. The Computerized Curve De-convolution Analysis (CCDA) has been used to measure TL parameters such as thermal trap depth, frequency factor and order of kinetic associated with charge transfer process in TL phenomenon. The investigated TL/OSL results show that these two methods of incorporating carbon in MgAl2O4 have generated closely resemble the defects of similar types in MgAl2O4:C lattice. However, the MgAl2O4:C synthesized by electron gun shows relatively larger concentration of the TL/OSL defects as compared to MgAl2O4:C synthesized using vacuum assisted melting method. The photo-ionization cross-section (PIC) associated with fastest OSL component of MgAl2O4: C is found to be ∼ 0.5 times than that of fastest OSL component of commercially available dosimetric grade α-Al2O3:C. The MgAl2O4:C thus developed shows good dynamic OSL dose linearity from few mGy to 1 Gy. This work reveals that MgAl2O4:C could be developed as potential tissue equivalent OSL / TL material.

  2. Rhodococcus baikonurensis BTM4c, a boron-tolerant actinobacterial strain isolated from soil.

    PubMed

    Yoon, Jaewoo; Miwa, Hiroki; Ahmed, Iftikhar; Yokota, Akira; Fujiwara, Toru

    2010-01-01

    By screening a bacterial population from the soil in Tokyo, Japan, we isolated a boron-tolerant bacterium, strain BTM4c. Strain BTM4c grew under the boron excess conditions with 100 mM boric acid, which is generally toxic to bacteria. Molecular phylogenetic, chemotaxonomic, and physiological data showed that the strain belongs to the genus Rhodococcus, and is to be identified as Rhodococcus baikonurensis. PMID:20057133

  3. The Top 10 Things I LOVE about p4c Hawai'i

    ERIC Educational Resources Information Center

    Ikeda, Jolyn

    2012-01-01

    In 2001, Dr. Thomas Jackson, or Dr. J as the author and her colleagues affectionately call him, spoke to the faculty at Waikiki Elementary. He described philosophy for children (p4c) Hawai'i and encouraged them to try P4C if something about it "resonated" with them. In the beginning, Dr. J held a p4t (philosophy for teachers) after-school seminar…

  4. Overexpression of Crocus carotenoid cleavage dioxygenase, CsCCD4b, in Arabidopsis imparts tolerance to dehydration, salt and oxidative stresses by modulating ROS machinery.

    PubMed

    Baba, Shoib Ahmad; Jain, Deepti; Abbas, Nazia; Ashraf, Nasheeman

    2015-09-15

    Apocarotenoids modulate vital physiological and developmental processes in plants. These molecules are formed by the cleavage of carotenoids, a reaction catalyzed by a family of enzymes called carotenoid cleavage dioxygenases (CCDs). Apocarotenoids like β-ionone and β-cyclocitral have been reported to act as stress signal molecules during high light stress in many plant species. In Crocus sativus, these two apocarotenoids are formed by enzymatic cleavage of β-carotene at 9, 10 and 7, 8 bonds by CsCCD4 enzymes. In the present study three isoforms of CsCCD4 were subjected to molecular modeling and docking analysis to determine their substrate specificity and all the three isoforms displayed high substrate specificity for β-carotene. Further, expression of these three CsCCD4 isoforms investigated in response to various stresses revealed that CsCCD4a and CsCCD4b exhibit enhanced expression in response to dehydration, salt and methylviologen, providing a clue towards their role in mediating plant defense response. This was confirmed by overexpressing CsCCD4b in Arabidopsis. The transgenic plants developed longer roots and possessed higher number of lateral roots. Further, overexpression of CsCCD4b imparted enhanced tolerance to salt, dehydration and oxidative stresses as was evidenced by higher survival rate, increased relative root length and biomass in transgenic plants as compared to wild type. Transgenic plants also displayed higher activity and expression of reactive oxygen species (ROS) metabolizing enzymes. This indicates that β-ionone and β-cyclocitral which are enzymatic products of CsCCD4b may act as stress signals and mediate reprogramming of stress responsive genes which ultimately leads to plant defense.

  5. The Cry4B toxin of Bacillus thuringiensis subsp. israelensis kills Permethrin-resistant Anopheles gambiae, the principal vector of malaria.

    PubMed

    Ibrahim, Mohamed A; Griko, Natalya B; Bulla, Lee A

    2013-04-01

    Resurgence of malaria has been attributed, in part, to the development of resistance by Anopheles gambiae, a principal vector of the disease, to various insecticidal compounds such as Permethrin. Permethrin, a neurotoxicant, is widely used to impregnate mosquito nets. An alternative strategy to control mosquitoes is the use of Bacillus thuringiensis subsp. israelensis (Bti) because there is no observable resistance in the field to the bacterium. Bti kills mosquitoes by targeting cadherin molecules residing in the midgut epithelium of larvae of the insect. Cry proteins (Cry4A, Cry4B, Cry10A and Cry11A) produced by the bacterium during the sporulation phase of its life cycle bind to the cadherin molecules, which serve as receptors for the proteins. These Cry proteins have variable specificity to a variety of mosquitoes, including Culex and Aedes as well as Anopheles. Importantly, selective mosquitocidal action is occasioned by binding of the respective Cry toxins to cadherins distinctive to individual mosquito species. Differential fractionation of the four Cry proteins from a novel Bti isolate (M1) and cloning and expression of their genes in Escherichia coli revealed that Cry4B is the only Cry protein that exerts insecticidal action against An. gambiae. Indeed, it does so against a Permethrin-resistant strain of the mosquito. The other three Cry proteins are ineffective. Multiple sequence alignments of the four Cry proteins revealed a divergent sequence motif in the Cry4B toxin, which most likely determines binding of the toxin to its cognate receptor, BT-R3, in An. gambiae and to its specific toxicity. A model showing Cry4B toxin binding to BT-R3 is presented. PMID:23760000

  6. Overexpression of Crocus carotenoid cleavage dioxygenase, CsCCD4b, in Arabidopsis imparts tolerance to dehydration, salt and oxidative stresses by modulating ROS machinery.

    PubMed

    Baba, Shoib Ahmad; Jain, Deepti; Abbas, Nazia; Ashraf, Nasheeman

    2015-09-15

    Apocarotenoids modulate vital physiological and developmental processes in plants. These molecules are formed by the cleavage of carotenoids, a reaction catalyzed by a family of enzymes called carotenoid cleavage dioxygenases (CCDs). Apocarotenoids like β-ionone and β-cyclocitral have been reported to act as stress signal molecules during high light stress in many plant species. In Crocus sativus, these two apocarotenoids are formed by enzymatic cleavage of β-carotene at 9, 10 and 7, 8 bonds by CsCCD4 enzymes. In the present study three isoforms of CsCCD4 were subjected to molecular modeling and docking analysis to determine their substrate specificity and all the three isoforms displayed high substrate specificity for β-carotene. Further, expression of these three CsCCD4 isoforms investigated in response to various stresses revealed that CsCCD4a and CsCCD4b exhibit enhanced expression in response to dehydration, salt and methylviologen, providing a clue towards their role in mediating plant defense response. This was confirmed by overexpressing CsCCD4b in Arabidopsis. The transgenic plants developed longer roots and possessed higher number of lateral roots. Further, overexpression of CsCCD4b imparted enhanced tolerance to salt, dehydration and oxidative stresses as was evidenced by higher survival rate, increased relative root length and biomass in transgenic plants as compared to wild type. Transgenic plants also displayed higher activity and expression of reactive oxygen species (ROS) metabolizing enzymes. This indicates that β-ionone and β-cyclocitral which are enzymatic products of CsCCD4b may act as stress signals and mediate reprogramming of stress responsive genes which ultimately leads to plant defense. PMID:26595090

  7. Research Paper: The Future or the Hoffman Paper. Curriculum for English 4A and 4B: College Prep English and English 12A and 12B: Life Communications.

    ERIC Educational Resources Information Center

    Davis, Joyce; And Others

    Written for a 12th grade English program at Wayne Central High School, this curriculum project is designed to take into account the affective dynamics/processes as well as the cognitive processes integral to writing research reports. There are two alternatives for this paper which is required of all 12th graders: The Future, a library based…

  8. New AP4B1 mutation in an African-American child associated with intellectual disability

    PubMed Central

    Lamichhane, Dronacharya

    2013-01-01

    Prevalence of intellectual disability (ID) varies from 1–3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. PMID:27625858

  9. New AP4B1 mutation in an African-American child associated with intellectual disability.

    PubMed

    Lamichhane, Dronacharya

    2013-12-01

    Prevalence of intellectual disability (ID) varies from 1-3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously. PMID:27625858

  10. 75 FR 41871 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... Register of February 21, 2008 (73 FR 9575). Once finalized, the annex will provide guidance to assist... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a draft guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for...

  11. The predominant species of nonstructural protein 4B in hepatitis C virus-replicating cells is not palmitoylated.

    PubMed

    Paul, David; Bartenschlager, Ralf; McCormick, Christopher

    2015-07-01

    Hepatitis C virus (HCV) represents a significant global health burden. Viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4B (NS4B) being a key player in this process. NS4B is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. In order to extend this observation and to establish a functional role for NS4B palmitoylation, we sought to determine the status of this post-translational modification when the protein was expressed as part of a functional viral replicase. We performed direct metabolic labelling and polyethylene glycol-maleimide palmitoylation reporter assays on NS4B expressed in cells containing subgenomic replicons and infectious viral RNA. In a vaccinia virus-based expression system NS4B palmitoylation was detected in a genotype-dependent manner. However, in spite of the high sensitivity of the methods used, no NS4B palmitoylation was found in physiologically more relevant systems. Thus, NS4B palmitoylation is most likely dispensable for HCV RNA replication. PMID:25740959

  12. Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles.

    PubMed

    Sumesh, Remani Vasudevan; Muthu, Muthumani; Almansour, Abdulrahman I; Suresh Kumar, Raju; Arumugam, Natarajan; Athimoolam, S; Jeya Yasmi Prabha, E Arockia; Kumar, Raju Ranjith

    2016-05-01

    The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

  13. The predominant species of nonstructural protein 4B in hepatitis C virus-replicating cells is not palmitoylated

    PubMed Central

    Paul, David

    2015-01-01

    Hepatitis C virus (HCV) represents a significant global health burden. Viral replication is thought to occur in close association with remodelled host cell membranes, with non-structural protein 4B (NS4B) being a key player in this process. NS4B is a poorly characterized integral membrane protein, which has been reported to be palmitoylated at its carboxy-terminal end. In order to extend this observation and to establish a functional role for NS4B palmitoylation, we sought to determine the status of this post-translational modification when the protein was expressed as part of a functional viral replicase. We performed direct metabolic labelling and polyethylene glycol-maleimide palmitoylation reporter assays on NS4B expressed in cells containing subgenomic replicons and infectious viral RNA. In a vaccinia virus-based expression system NS4B palmitoylation was detected in a genotype-dependent manner. However, in spite of the high sensitivity of the methods used, no NS4B palmitoylation was found in physiologically more relevant systems. Thus, NS4B palmitoylation is most likely dispensable for HCV RNA replication. PMID:25740959

  14. Itinerant ferromagnetism and superconductivity in bct ErRh/sub 4/B/sub 4/

    SciTech Connect

    Chaussy, J.; Genicon, J.L.; Lejay, P.; Odin, J.; Shao, L.Q.; Sulpice, A.; Tournier, R.; Chevalier, B.; Etourneau, J.

    1985-04-15

    The body centered tetragonal ErRh/sub 4/B/sub 4/ compound undergoes an itinerant ferromagnetic transition at T/sub m/ = 21 K characterized by a susceptibility equal to the inverse of the demagnetizing coefficient. The itinerant ferromagnetism does not prevent the simultaneous presence of the superconductivity from 7.7 K down to 0 K. The diamagnetic ac susceptibility can be calculated from the ferromagnetic one. The coexistence of itinerant ferromagnetism and superconductivity among d electrons would be one of the most convincing arguments in favor of ''odd-parity'' superconductivity.

  15. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge.

  16. Crystal structure features in a new compound C4B25Mg1.42

    NASA Astrophysics Data System (ADS)

    Konovalikhin, S. V.; Ponomarev, V. I.

    2015-09-01

    The composition of C4B25Mg1.42 crystal obtained by self-propagating high-temperature synthesis was determined using X-ray diffraction. This is the first crystalline structure where all boron atoms in the В12 icosahedron occupy crystallographically independent positions; this circumstance allowed us to analyze the effect of substituents on bond lengths in the icosahedron. The crystal structure features, including the channels filled with disordered Mg atoms and the spread of В—В endo- and exo-bond lengths in the icosahedra, are described. A crystallochemical analysis of pair bonds has been performed for the first time.

  17. Input files with ORNL—mathematical phantoms of the human body for MCNP-4B

    NASA Astrophysics Data System (ADS)

    Krstić, D.; Nikezić, D.

    2007-01-01

    Protection against ionizing radiation requires information on the absorbed doses in organs of the human body. Implantation of many dosimeters in the human body is undesirable (or impossible), so the doses in organs are not measurable and some kind of dose calculation has to be applied. Calculation of doses in organs requests: (a) an exact description of the geometry of organs, (b) the chemical constitution of tissues, and (c) appropriate computer programs. The first two items, (a) and (b), make a so-called "phantom". In another words, the "phantom of a human body" is a mathematical representation of the human body including all other relevant information. All organs are represented with geometrical bodies (like cylinders, ellipsoids, tori, cones etc.), which are described with suitable mathematical equations. A corresponding chemical constitution for various types of organ tissues is also defined. MCNP-4B ( Monte Carlo N- Particle) is often used as transport code. Users of this software prepare an "input file" providing all necessary information for program execution. This information includes: (a) source definition—type of ionizing radiation, energy spectrum, and geometry of the source; (b) target definition—material constitution, geometry, location in respect to the source etc.; (c) characterization of absorbing media between the source and target; (d) output tally, etc. This paper presents input files with "human phantoms" for the MCNP-4B code. The input files with "phantoms" were prepared based on publications issued by the Oak Ridge National Laboratory (ORNL). Seven input files relating to different age groups (newborn, 1, 5, 10, 15 years, as well as, male and female adults) are presented here. A test example and comparison with other data found in literature are also given. Program summaryTitle of program: INPUT FILES, AMALE, AFEMALE, AGE15, AGE10, AGE5, AGE01, NEWB Catalogue identifier:ADYF_v1_0 Program summary URL

  18. Complete Genome Sequence of the Larvicidal Bacterium Lysinibacillus sphaericus Strain OT4b.25

    PubMed Central

    Rey, Andrés; Silva-Quintero, Laura

    2016-01-01

    Lysinibacillus sphaericus OT4b.25 is a native Colombian strain isolated from coleopteran larvae in an oak forest near Bogotá D.C.; this strain has shown high levels of pathogenic activity against Culex quinquefasciatus larvae in laboratory assays compared to that of other members of the same species. Using Pacific Biosciences sequencing technology, we propose a chromosomal contig of 4,665,775 bp that, according to comparative analysis, is highly similar to that of reference strain L. sphaericus C3-41. PMID:27151786

  19. Interface characterization of B4C-based multilayers by X-ray grazing-incidence reflectivity and diffuse scattering.

    PubMed

    Jiang, Hui; Wang, Zhanshan; Zhu, Jingtao

    2013-05-01

    B4C-based multilayers have important applications for soft to hard X-rays. In this paper, X-ray grazing-incidence reflectivity and diffuse scattering, combining various analysis methods, were used to characterize the structure of B4C-based multilayers including layer thickness, density, interfacial roughness, interdiffusion, correlation length, etc. Quantitative results for W/B4C, Mo/B4C and La/B4C multilayers were compared. W/B4C multilayers show the sharpest interfaces and most stable structures. The roughness replications of La/B4C and Mo/B4C multilayers are not strong, and oxidations and structure expansions are found in the aging process. This work provides guidance for future fabrication and characterization of B4C-based multilayers.

  20. Identification of Amino Acid Determinants in CYP4B1 for Optimal Catalytic Processing of 4-Ipomeanol

    PubMed Central

    Wiek, Constanze; Schmidt, Eva M; Roellecke, Katharina; Freund, Marcel; Nakano, Mariko; Kelly, Edward J; Kaisers, Wolfgang; Yarov-Yarovoy, Vladimir; Kramm, Christof M; Rettie, Allan E; Hanenberg, Helmut

    2014-01-01

    Mammalian CYP4B1 enzymes are cytochrome P450 monooxygenases that are responsible for the bioactivation of several exogenous pro-toxins including 4-ipomeanol (4-IPO). In contrast to the orthologous rabbit enzyme, we show here that native human CYP4B1 with a serine at position 427 is unable to bio-activate 4-IPO and does not cause cytotoxicity in HepG2 cells and primary human T-cells that overexpress these enzymes. We also demonstrate that a proline residue in the meander region at position 427 in human CYB4B1 and 422 in rabbit CYP4B1 is important for protein stability and rescues the 4-IPO bioactivation of the human enzyme, but is not essential for the catalytic activity of the rabbit CYP4B1 protein. Systematic substitution of native and p.S427P human CYP4B1 with peptide regions from the highly active rabbit enzyme reveals that 18 amino acids in the wild-type rabbit CYP4B1 protein are key for conferring high 4-IPO metabolizing activity. Introduction of 12 of the 18 amino acids that are also present at corresponding positions in other human CYP4 family members into the p.S427P human CYP4B1 protein results in a mutant human enzyme (P+12) that is as stable and as active as the rabbit wild-type CYP4B1 protein. These 12 mutations cluster in the predicted B–C loop through F-helix regions and reveal new amino acid regions important to P450 enzyme stability. Finally, by minimally re-engineering the human CYP4B1 enzyme for efficient activation of 4-IPO, we have developed a novel human suicide gene system that is a candidate for adoptive cellular therapies in humans. PMID:25247810

  1. Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant.

    PubMed Central

    Erdogan, S; Houslay, M D

    1997-01-01

    The cAMP phosphodiesterase (PDE) 3 and PDE4 isoforms provide the major cAMP-hydrolysing PDE activities in Jurkat T-cells, with additional contributions from the PDE1 and PDE2 isoforms. Challenge of cells with the adenylate cyclase activator forskolin led to a rapid, albeit transient, increase in PDE3 activity occurring over the first 45 min, followed by a sustained increase in PDE3 activity which began after approximately 3 h and continued for at least 24 h. Only this second phase of increase in PDE3 activity was blocked by the transcriptional inhibitor actinomycin D. After approximately 3 h of exposure to forskolin, PDE4 activity had increased, via a process that could be inhibited by actinomycin D, and it remained elevated for at least a 24 h period. Such actions of forskolin were mimicked by cholera toxin and 8-bromo-cAMP. Forskolin increased intracellular cAMP concentrations in a time-dependent fashion and its action was enhanced when PDE induction was blocked with actinomycin D. Reverse transcription (RT)-PCR analysis, using generic primers designed to detect transcripts representing enzymically active products of the four PDE4 genes, identified transcripts for PDE4A and PDE4D but not for PDE4B or PDE4C in untreated Jurkat T-cells. Forskolin treatment did not induce transcripts for either PDE4B or PDE4C; however, it reduced the RT-PCR signal for PDE4A transcripts and markedly enhanced that for PDE4D transcripts. Using RT-PCR primers for PDE4 splice variants, a weak signal for PDE4D1 was evident in control cells whereas, in forskolin-treated cells, clear signals for both PDE4D1 and PDE4D2 were detected. RT-PCR analysis of the PDE4A species indicated that it was not the PDE4A isoform PDE-46 (PDE4A4B). Immunoblotting of control cells for PDE4 forms identified a single PDE4A species of approximately 118 kDa, which migrated distinctly from the PDE4A4B isoform PDE-46, with immunoprecipitation analyses showing that it provided all of the PDE4 activity in control

  2. Generalized transduction of serotype 1/2 and serotype 4b strains of Listeria monocytogenes.

    PubMed

    Hodgson, D A

    2000-01-01

    This is the first report of generalized transduction in the gram-positive, food-borne pathogen Listeria monocytogenes. Bacteriophages were isolated from the environment and from lysogens, or were obtained from other laboratories. Of the 59 bacteriophages tested, 34 proved to be capable of transduction. We exploited the ability of L. monocytogenes to grow at room temperature and isolated bacteriophages that were incapable of growth at 37 degrees C. Transductions at this temperature therefore eliminated transductant killing and lysogeny, as did inclusion of citrate and the use of a low multiplicity of infection. Transducing bacteriophages were found for each of the well-characterized L. monocytogenes strains: EGD, 10403, Mack (serotype1/2a), L028 (serotype 1/2c), Scott A (serotype 4b) and strains from the Jalisco and Halifax, Nova Scotia outbreaks (serotype 4b). P35 (phiLMUP35) is a particularly useful generalized transducing bacteriophage with a wide host range (75% of all serotype 1/2 strains tested). Its disadvantages are that it is small and transduction is relatively infrequent. U153(phiCU-SI153/95) is larger than P35 and transduction frequency increased 100-fold, but it has a very narrow host range. We demonstrated interstrain transduction and used transduction to test linkage between transposon insertions and mutant phenotypes in a variety of strains.

  3. Interfacial microstructure in a B{sub 4}C/Al composite fabricated by pressureless infiltration.

    SciTech Connect

    Luo, Z.; Song, Y.; Zhang, S.; Miller, D. J.

    2012-01-01

    In this work, B{sub 4}C particulate-reinforced Al composite was fabricated by a pressureless infiltration technique, and its interfacial microstructure was studied in detail by X-ray diffraction as well as by scanning and transmission electron microscopy. The B{sub 4}C phase was unstable in Al melt during the infiltration process, forming AlB{sub 10}-type AlB{sub 24}C{sub 4} or Al{sub 2.1}B{sub 51}C{sub 8} as a major reactant phase. The Al matrix was large grains (over 10 {micro}m), which had no definite orientation relationships (ORs) with the randomly orientated B{sub 4}C or its reactant particles, except for possible nucleation sites with {l_brace}011{r_brace}{sub B{sub 4}C} almost parallel to {l_brace}111{r_brace}{sub Al} at a deviation angle of 1.5 deg. Both B{sub 4}C-Al and reactant-Al interfaces are semicoherent and free of other phases. A comparison was made with the SiC/Al composite fabricated similarly by the pressureless infiltration. It was suggested that the lack of ORs between the Al matrix and reinforced particles, except for possible nucleation sites, is the common feature of the composites prepared by the infiltration method.

  4. Fabrication and Tribological Evaluation of Vacuum Plasma-Sprayed B4C Coating

    NASA Astrophysics Data System (ADS)

    Zhu, Huiying; Niu, Yaran; Lin, Chucheng; Huang, Liping; Ji, Heng; Zheng, Xuebin

    2012-12-01

    B4C coating was fabricated by vacuum plasma spraying and the tribological properties of the coating against WC-Co alloy were evaluated by sliding wear tests. Al2O3 coating, one of the most commonly used wear-resistant coatings, was employed as comparison in the tribological evaluation. The results obtained show that, the B4C coating is composed of a large amount of nanostructured particles along with some amorphous phases. Both of the friction coefficient and wear rate of the B4C coating are much lower than those of the Al2O3 coating, and the tribological evaluation reveals a decreasing trend for the B4C coating in friction coefficient as well as wear rate with increasing normal load, which is explained in terms of the formation of a protective transfer layer on its worn surface. Tribofilm wear is found to be the dominant wear mechanism involved in the B4C/WC-Co alloy friction pair.

  5. Mitochondrial haplogroup C4c: a rare lineage entering America through the ice-free corridor?

    PubMed

    Hooshiar Kashani, Baharak; Perego, Ugo A; Olivieri, Anna; Angerhofer, Norman; Gandini, Francesca; Carossa, Valeria; Lancioni, Hovirag; Semino, Ornella; Woodward, Scott R; Achilli, Alessandro; Torroni, Antonio

    2012-01-01

    Recent analyses of mitochondrial genomes from Native Americans have brought the overall number of recognized maternal founding lineages from just four to a current count of 15. However, because of their relative low frequency, almost nothing is known for some of these lineages. This leaves a considerable void in understanding the events that led to the colonization of the Americas following the Last Glacial Maximum (LGM). In this study, we identified and completely sequenced 14 mitochondrial DNAs belonging to one extremely rare Native American lineage known as haplogroup C4c. Its age and geographical distribution raise the possibility that C4c marked the Paleo-Indian group(s) that entered North America from Beringia through the ice-free corridor between the Laurentide and Cordilleran ice sheets. The similarities in ages andgeographical distributions for C4c and the previously analyzed X2a lineage provide support to the scenario of a dual origin for Paleo-Indians. Taking into account that C4c is deeply rooted in the Asian portion of the mtDNA phylogeny and is indubitably of Asian origin, the finding that C4c and X2a are characterized by parallel genetic histories definitively dismisses the controversial hypothesis of an Atlantic glacial entry route into North America.

  6. Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

    PubMed Central

    Kong, Lingbao; Fujimoto, Akira; Nakamura, Mariko; Aoyagi, Haruyo; Matsuda, Mami; Watashi, Koichi; Suzuki, Ryosuke; Arita, Minetaro; Yamagoe, Satoshi; Dohmae, Naoshi; Suzuki, Takehiro; Sakamaki, Yuriko; Ichinose, Shizuko; Suzuki, Tetsuro; Wakita, Takaji

    2016-01-01

    ABSTRACT It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication

  7. The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.

    PubMed

    Pfuhl, Thorsten; Mamiani, Alfredo; Dürr, Matthias; Welter, Susanne; Stieber, Johanna; Ankara, Jasmin; Liss, Michael; Dobner, Thomas; Schmitt, Andrea; Falkai, Peter; Kremmer, Elisabeth; Jung, Volker; Barth, Stephanie; Grässer, Friedrich A

    2008-10-17

    The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human chromosome 11q13.2 and encode highly similar proteins of 363 and 359 amino acids, respectively. They contain two RNA recognition motifs (RRMs) and a retroviral-type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and is also a part of the microRNA-processing RISC complex. In particular, RBM4a is involved in exon 10 inclusion of the tau protein. The function of RBM4b is unknown. With new monoclonal antibodies we show that RBM4a is detectable in virtually all tissues and cell lines tested while RBM4b was only found in kidney and liver. Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5h and 4.5h, respectively. To our knowledge, this is the first description of RBM4b protein in human tissue. In human brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain.

  8. Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

    PubMed Central

    Sillanpää, Maarit; Melén, Krister; Porkka, Päivi; Fagerlund, Riku; Nevalainen, Kaisu; Lappalainen, Maija; Julkunen, Ilkka

    2009-01-01

    Background The viral genome of hepatitis C virus constitutes a 9.6-kb single-stranded positive-sense RNA which encodes altogether 11 viral proteins. In order to study the humoral immune responses against different HCV proteins in patients suffering from chronic HCV infection, we produced three structural (core, E1 and E2) and six nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) in Sf9 insect cells by using the baculovirus expression system. Results The recombinant HCV core, E1, E2, NS2, NS3, NS4A, NS4B, NS5A and NS5B proteins were purified and used in Western blot analysis to determine antibody responses against individual HCV protein in 68 HCV RNA and antibody positive human sera that were obtained from patients suffering from genotype 1, 2, 3 or 4 infection. These sera were also analysed with INNO-LIA Score test for HCV antibodies against core, NS3, NS4AB and NS5A, and the results were similar to the ones obtained by Western blot method. Based on our Western blot analyses we found that the major immunogenic HCV antigens were the core, NS4B, NS3 and NS5A proteins which were recognized in 97%, 86%, 68% and 53% of patient sera, respectively. There were no major genotype specific differences in antibody responses to individual HCV proteins. A common feature within the studied sera was that all except two sera recognized the core protein in high titers, whereas none of the sera recognized NS2 protein and only three sera (from genotype 3) recognised NS5B. Conclusion The data shows significant variation in the specificity in humoral immunity in chronic HCV patients. PMID:19549310

  9. Phosphodiesterase 4B in the cardiac L-type Ca²⁺ channel complex regulates Ca²⁺ current and protects against ventricular arrhythmias in mice.

    PubMed

    Leroy, Jérôme; Richter, Wito; Mika, Delphine; Castro, Liliana R V; Abi-Gerges, Aniella; Xie, Moses; Scheitrum, Colleen; Lefebvre, Florence; Schittl, Julia; Mateo, Philippe; Westenbroek, Ruth; Catterall, William A; Charpentier, Flavien; Conti, Marco; Fischmeister, Rodolphe; Vandecasteele, Grégoire

    2011-07-01

    β-Adrenergic receptors (β-ARs) enhance cardiac contractility by increasing cAMP levels and activating PKA. PKA increases Ca²⁺-induced Ca²⁺ release via phosphorylation of L-type Ca²⁺ channels (LTCCs) and ryanodine receptor 2. Multiple cyclic nucleotide phosphodiesterases (PDEs) regulate local cAMP concentration in cardiomyocytes, with PDE4 being predominant for the control of β-AR-dependent cAMP signals. Three genes encoding PDE4 are expressed in mouse heart: Pde4a, Pde4b, and Pde4d. Here we show that both PDE4B and PDE4D are tethered to the LTCC in the mouse heart but that β-AR stimulation of the L-type Ca²⁺ current (ICa,L) is increased only in Pde4b-/- mice. A fraction of PDE4B colocalized with the LTCC along T-tubules in the mouse heart. Under β-AR stimulation, Ca²⁺ transients, cell contraction, and spontaneous Ca²⁺ release events were increased in Pde4b-/- and Pde4d-/- myocytes compared with those in WT myocytes. In vivo, after intraperitoneal injection of isoprenaline, catheter-mediated burst pacing triggered ventricular tachycardia in Pde4b-/- mice but not in WT mice. These results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa,L during β-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of Ca²⁺-induced Ca²⁺ release in cardiomyocytes.

  10. Human mononuclear cell function after 4 C storage during 1-G and microgravity conditions of spaceflight

    NASA Technical Reports Server (NTRS)

    Meehan, Richard; Taylor, Gerald; Lionetti, Fabian; Neale, Laurie; Curren, Tim

    1989-01-01

    To investigate the possibility of restoring immune competence of crewmembers during a prolonged spaceflight by infusions of autologous blood components, the effect of storage at 4 C aboard Space Shuttle Columbia (Mission 61-c) on the activity of human peripheral blood mononuclear cells (PBMNCs), stored as leukocyte concentrates in autologous plasa, was investigated. The results of preflight storage at 4 C demonstrated a progressive daily loss in mitogen-stimulated protein synthesis, and thymidine uptake, as well as a progressive reduction in the percentage of PBMNCs expressing cell-surface phenotype markers. The ability of PBMNCs stored at 4 C for 8 d in Columbia's middeck, to become activated and proliferate in vitro was similar to that of cells that remained for 7 d on ground.

  11. Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia

    PubMed Central

    Cheung, Ngai; Fung, Tsz Kan; Zeisig, Bernd B.; Holmes, Katie; Rane, Jayant K.; Mowen, Kerri A.; Finn, Michael G.; Lenhard, Boris; Chan, Li Chong; So, Chi Wai Eric

    2016-01-01

    Summary Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia. PMID:26766589

  12. Neutron absorption of Al-Si-Mg-B4C composite

    NASA Astrophysics Data System (ADS)

    Abdullah, Yusof; Ibrahim, Anis Syukriah; Daud, Abdul Razak; Yusof, Mohd Reusmaazran

    2016-01-01

    Al-Si-Mg-B4C composites containing 2-8 wt% of B4C were prepared by stir casting technique. Homogenization treatment was carried out at temperatures of 540°C for 4 houra and followed by ageing at 180°C for 2 houra. Microstructure and phase identification were studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD) respectively. Neutron absorption study was investigated using neutron source Am/Be241. The result indicated that higher B4C content improved the neutron absorption property. Meanwhile homogeneity of the composite was increased by ageing processes. This composite is potential to be used as neutron shielding material especially for nuclear reactor application.

  13. Electronic shell structures of Russian-doll-style Sc 4C 2@C 80

    NASA Astrophysics Data System (ADS)

    Chen, Zhifan; Kah, Cherno B.; Wang, Xiao-Qian

    2011-04-01

    We have studied the electronic properties of a 'Russian-doll'-style endohedral fullerene Sc 4C 2@C 80 based on first-principles density-functional calculations coupled with many-body GW correction. Our calculation results yield a GW rectified gap of 1.8 eV for the 'Russian doll' structured Sc 4C 2@C 80, in very good conformity with experimental observed value of 1.6 eV. The calculated electronic characteristics of the Russian-doll fullerene reveal distinct shell structures, which are embellished in the GW approach. The analysis of vibrational frequency demonstrates profound hybridizations associated with the interactions between the Sc 4C 2 core and C 80 shell.

  14. SLC4A Transporters

    PubMed Central

    Choi, Inyeong

    2016-01-01

    SLC4A gene family proteins include bicarbonate transporters that move HCO3− across the plasma membrane and regulate intracellular pH and transepithelial movement of acid–base equivalents. These transporters are Cl/HCO3 exchangers, electrogenic Na/HCO3 cotransporters, electroneutral Na/HCO3 cotransporters, and Na+-driven Cl/HCO3 exchanger. Studies of the bicarbonate transporters in vitro and in vivo have demonstrated their physiological importance for acid–base homeostasis at the cellular and systemic levels. Recent advances in structure/function analysis have also provided valuable information on domains or motifs critical for regulation, ion translocation, and protein topology. This chapter focuses on the molecular mechanisms of ion transport along with associated structural aspects from mutagenesis of particular residues and from chimeric constructs. Structure/function studies have helped to understand the mechanism by which ion substrates are moved via the transporters. This chapter also describes some insights into the structure of SLC4A1 (AE1) and SLC4A4 (NBCe1) transporters. Finally, as some SLC4A transporters exist in concert with other proteins in the cells, the structural features associated with protein–protein interactions are briefly discussed. PMID:23177984

  15. Monoclonal antibody, mAb 4C13, an effective detoxicant antibody against ricin poisoning.

    PubMed

    Dong, Na; Luo, Longlong; Wu, Junhua; Jia, Peiyuan; Li, Qian; Wang, Yuxia; Gao, Zhongcai; Peng, Hui; Lv, Ming; Huang, Chunqian; Feng, Jiannan; Li, Hua; Shan, Junjie; Han, Gang; Shen, Beifen

    2015-07-31

    Ricin is a glycoprotein produced in castor seeds and consists of two polypeptide chains named Ricin Toxin A Chain (RTA) and Ricin Toxin B Chain (RTB), linked via a disulfide bridge. Due to its high toxicity, ricin is regarded as a high terrorist risk for the public. However, antibodies can play a pivotal role in neutralizing the toxin. In this research, the anti-toxicant effect of mAb 4C13, a monoclonal antibody (mAb) established using detoxicated ricin as the immunized antigen, was evaluated. Compared with mAb 4F2 and mAb 5G6, the effective mechanism of mAb 4C13 was analyzed by experiments relating to its cytotoxicity, epitope on ricin, binding kinetics with the toxin, its blockage on the protein synthesis inhibition induced by ricin and the intracelluar tracing of its complex with ricin. Our result indicated that mAb 4C13 could recognize and bind to RTA, RTB and exert its high affinity to the holotoxin. Both cytotoxicity and animal toxicity of ricin were well blocked by pre-incubating the toxin with mAb 4C13. By intravenous injection, mAb 4C13 could rescue the mouse intraperitoneally (ip) injected with a lethal dose of ricin (20μg/kg) even at 6h after the intoxication and its efficacy was dependent on its dosage. This research indicated that mAb 4C13 could be an excellent candidate for therapeutic antibodies. Its potent antitoxic efficiency was related to its recognition on the specific epitope with very high affinity and its blockage of protein synthesis inhibition in cytoplasm followed by cellular internalization with ricin.

  16. Characterization of an Additional Splice Acceptor Site Introduced into CYP4B1 in Hominoidae during Evolution

    PubMed Central

    Parkinson, Oliver T.; Roellecke, Katharina; Freund, Marcel; Gombert, Michael; Lottmann, Nadine; Steward, Charles A.; Kramm, Christof M.; Yarov-Yarovoy, Vladimir; Rettie, Allan E.; Hanenberg, Helmut

    2015-01-01

    CYP4B1 belongs to the cytochrome P450 family 4, one of the oldest P450 families whose members have been highly conserved throughout evolution. The CYP4 monooxygenases typically oxidize fatty acids to both inactive and active lipid mediators, although the endogenous ligand(s) is largely unknown. During evolution, at the transition of great apes to humanoids, the CYP4B1 protein acquired a serine instead of a proline at the canonical position 427 in the meander region. Although this alteration impairs P450 function related to the processing of naturally occurring lung toxins, a study in transgenic mice suggested that an additional serine insertion at position 207 in human CYP4B1 can rescue the enzyme stability and activity. Here, we report that the genomic insertion of a CAG triplet at the intron 5–exon 6 boundary in human CYP4B1 introduced an additional splice acceptor site in frame. During evolution, this change occurred presumably at the stage of Hominoidae and leads to two major isoforms of the CYP4B1 enzymes of humans and great apes, either with or without a serine 207 insertion (insSer207). We further demonstrated that the CYP4B1 enzyme with insSer207 is the dominant isoform (76%) in humans. Importantly, this amino acid insertion did not affect the 4-ipomeanol metabolizing activities or stabilities of the native rabbit or human CYP4B1 enzymes, when introduced as transgenes in human primary cells and cell lines. In our 3D modeling, this functional neutrality of insSer207 is compatible with its predicted location on the exterior surface of CYP4B1 in a flexible side chain. Therefore, the Ser207 insertion does not rescue the P450 functional activity of human CYP4B1 that has been lost during evolution. PMID:26355749

  17. Formation of a 4c tetraquark in J/{psi}-meson pair production at LHC

    SciTech Connect

    Berezhnoy, A. V.; Likhoded, A. K. Luchinsky, A. V. Novoselov, A. A.

    2012-08-15

    Cross sections for J{psi}-meson pair production in proton-proton interaction at the c.m. collision energy of {radical}a = 7 TeV were theoretically predicted under conditions of various kinematical cuts. The possible contribution to this process from the decays of 4c tetraquarks, new hypothetic particles consisting of two valence c quarks and two valence c-bar antiquarks, was studied. It is shown that at least one such state (tensor 4c tetraquark) can in principle be observed experimentally under conditions of the LNCb experiment.

  18. Brief communication: mitochondrial haplotype C4c confirmed as a founding genome in the Americas.

    PubMed

    Malhi, Ripan S; Cybulski, Jerome S; Tito, Raul Y; Johnson, Jesse; Harry, Harold; Dan, Carrie

    2010-03-01

    Mitochondrial DNA analysis of 31 unrelated Shuswap speakers from a previously poorly sampled region of North America revealed two individuals with haplogroups rarely found in the Americas, C4c and C1d. Comparison of the complete genomes of the two individuals with others found in the literature confirms that C4c is a founding haplotype and gives insight into the evolution of the C1d haplotype. This study demonstrates the importance of collecting and analyzing data from Native North Americans when addressing hypotheses about the peopling of the Americas.

  19. Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.

    PubMed

    Yu, Jun; Fernández-Hernando, Carlos; Suarez, Yajaira; Schleicher, Michael; Hao, Zhengrong; Wright, Paulette L; DiLorenzo, Annarita; Kyriakides, Themis R; Sessa, William C

    2009-10-13

    Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control. PMID:19805174

  20. A new experiment station on beamline 4B7A at Beijing Synchrotron Radiation Facility

    NASA Astrophysics Data System (ADS)

    Zheng, L.; Zhao, Y. D.; Tang, K.; Ma, C. Y.; Hong, C. H.; Han, Y.; Cui, M. Q.; Guo, Z. Y.

    2014-11-01

    A new experiment station was installed on beamline 4B7A at Beijing Synchrotron Radiation Facility (BSRF), making it possible to record X-ray absorption fine structure (XAFS) spectrum in three modes over an energy range from 1750 eV to 6000 eV. A 13-element Si(Li) array detector and a single-element SDD detector were used to acquire data in partial fluorescence yield (PFY) mode. Two low-pressure noble gas ion chambers were adopted for measuring XAFS in transmission mode. In total electron yield (TEY) mode the current of sample is recorded. Solid, wet and liquid samples were suitable for this experimental station. Some representative results obtained from this station were shown and discussed.

  1. BOREAS Level-4b AVHRR-LAC Ten-Day Composite Images: At-sensor Radiance

    NASA Technical Reports Server (NTRS)

    Cihlar, Josef; Chen, Jing; Nickerson, Jaime; Newcomer, Jeffrey A.; Huang, Feng-Ting; Hall, Forrest G. (Editor)

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the National Oceanic and Atmospheric Administration (NOAA-11) and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4b data are gridded, 10-day composites of at-sensor radiance values produced from sets of single-day images. Temporally, the 10- day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files.

  2. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge. PMID:26179097

  3. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    PubMed Central

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

  4. Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B

    PubMed Central

    Rao, Minxi; Smith, Brian C.

    2015-01-01

    ABSTRACT Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. PMID:25944856

  5. Rotation of the optical polarization plane for the blazar 4C +38.41

    NASA Astrophysics Data System (ADS)

    Panopoulou, G. V.; Maragkakis, G. M.; Xexakis, K.

    2016-08-01

    We report on the ongoing rotation of the optical polarization angle (R-band) seen in the monitored blazar 4C +38.41 (RA=16:35:15.5, DEC=38:08:05, J2000) as recorded within the framework of the RoboPol program.

  6. Developing Technical Expertise in Secondary Technical Schools: The Effect of 4C/ID Learning Environments

    ERIC Educational Resources Information Center

    Sarfo, Frederick K.; Elen, Jan

    2007-01-01

    In this study, the effectiveness of learning environments, developed in line with the specifications of the four components instructional design model (4C/ID model) and the additional effect of ICT for fostering the development of technical expertise in traditional Ghanaian classrooms, was assessed. The study had a one-by-one-by-two…

  7. FROM UNTITILED DRAWING "F.A.G.H. 4C, REVISED JUNE 19, 1939." SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FROM UNTITILED DRAWING "F.A.G.H. 4-C, REVISED JUNE 19, 1939." SHOWING PROFILE OF ROADWAY INCLINE AND OR&L AND WAIKELE BRIDGES. Hawaii Department of Transportation, Design Branch, Project ID 7101-001, drawing 4449.8. - Waikele Canal Bridge and Highway Overpass, Farrington Highway and Waikele Stream, Waipahu, Honolulu County, HI

  8. FROM "CANAL BRIDGE, F.A.P. 4C, MAR. 1938." SHOWING WAIKELE BRIDGE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FROM "CANAL BRIDGE, F.A.P. 4-C, MAR. 1938." SHOWING WAIKELE BRIDGE PLAN AND ELEVATION. Hawaii Department of Transportation, Design Branch, Project ID 7101-001, drawing 4449.27. - Waikele Canal Bridge and Highway Overpass, Farrington Highway and Waikele Stream, Waipahu, Honolulu County, HI

  9. Magnetic anisotropy and crystalline electric field effects in RRh{sub 4}B{sub 4} single crystals.

    SciTech Connect

    Zhou, H.; Lambert, S. E.; Maple, M. B.; Dunlap, B. D.; Materials Science Division; Univ. of California at San Diego

    2009-08-01

    Research on polycrystalline RRh{sub 4}B{sub 4} samples has shown that crystalline electric field (CEF) effects play an important role in these compounds. The successful synthesis of single crystal samples of RRh{sub 4}B{sub 4} with R = Y, Sm, Gd, Tb, Dy, Ho, Er, Tm, and Lu has provided an opportunity to further investigate CEF effects in these materials. Magnetization and magnetic susceptibility measurements on the RRh{sub 4}B{sub 4} single crystals revealed strong magnetic anisotropy, and the experimental results could be described well by CEF calculations based on the parameters derived from an analysis of experimental data for ErRh{sub 4}B{sub 4} single crystals. The easy directions of magnetization of these compounds are consistent with the signs of the Stevens factor {alpha}J of the CEF Hamiltonian. A strong influence of magnetic anisotropy on superconductivity was also observed.

  10. Soil Moisture Active Passive Mission L4_C Data Product Assessment (Version 2 Validated Release)

    NASA Technical Reports Server (NTRS)

    Kimball, John S.; Jones, Lucas A.; Glassy, Joseph; Stavros, E. Natasha; Madani, Nima; Reichle, Rolf H.; Jackson, Thomas; Colliander, Andreas

    2016-01-01

    The SMAP satellite was successfully launched January 31st 2015, and began acquiring Earth observation data following in-orbit sensor calibration. Global data products derived from the SMAP L-band microwave measurements include Level 1 calibrated and geolocated radiometric brightness temperatures, Level 23 surface soil moisture and freezethaw geophysical retrievals mapped to a fixed Earth grid, and model enhanced Level 4 data products for surface to root zone soil moisture and terrestrial carbon (CO2) fluxes. The post-launch SMAP mission CalVal Phase had two primary objectives for each science product team: 1) calibrate, verify, and improve the performance of the science algorithms, and 2) validate accuracies of the science data products as specified in the L1 science requirements. This report provides analysis and assessment of the SMAP Level 4 Carbon (L4_C) product pertaining to the validated release. The L4_C validated product release effectively replaces an earlier L4_C beta-product release (Kimball et al. 2015). The validated release described in this report incorporates a longer data record and benefits from algorithm and CalVal refinements acquired during the SMAP post-launch CalVal intensive period. The SMAP L4_C algorithms utilize a terrestrial carbon flux model informed by SMAP soil moisture inputs along with optical remote sensing (e.g. MODIS) vegetation indices and other ancillary biophysical data to estimate global daily net ecosystem CO2 exchange (NEE) and component carbon fluxes for vegetation gross primary production (GPP) and ecosystem respiration (Reco). Other L4_C product elements include surface (10 cm depth) soil organic carbon (SOC) stocks and associated environmental constraints to these processes, including soil moisture and landscape freeze/thaw (FT) controls on GPP and respiration (Kimball et al. 2012). The L4_C product encapsulates SMAP carbon cycle science objectives by: 1) providing a direct link between terrestrial carbon fluxes and

  11. Sesuvium portulacastrum (L.) L.: a potential halophyte for the degradation of toxic textile dye, Green HE4B.

    PubMed

    Patil, Asmita V; Lokhande, Vinayak H; Suprasanna, Penna; Bapat, Vishwas A; Jadhav, Jyoti P

    2012-05-01

    Sesuvium portulacastrum is a common halophyte growing well in adverse surroundings and is exploited mainly for the environmental protection including phytoremediation, desalination and stabilization of contaminated soil. In the present investigation, attempts have been made on the decolorization of a toxic textile dye Green HE4B (GHE4B) using in vitro grown Sesuvium plantlets. The plantlets exhibited significant (70%) decolorization of GHE4B (50 mg l(-1)) that sustain 200 mM sodium chloride (NaCl) within 5 days of incubation. The enzymatic analysis performed on the root and shoot tissues of the in vitro plantlets subjected to GHE4B decolorization in the presence of 200 mM NaCl showed a noteworthy induction of tyrosinase, lignin peroxidase and NADH-DCIP reductase activities, indicating the involvement of these enzymes in the metabolism of the dye GHE4B. The UV-visible spectrophotometer, HPLC and Fourier Transform Infrared Spectroscopy (FTIR) analyses of the samples before and after decolorization of the dye confirmed the efficient phytotransformation of GHE4B in the presence of 200 mM NaCl. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the products revealed the formation of three metabolites such as p -amino benzene, p -amino toluene and 1, 2, 7-amino naphthalene after phytotransformation of GHE4B. Based on the FTIR and GC-MS results, the possible pathway for the biodegradation of GHE4B in the presence of 200 mM NaCl has been proposed. The phytotoxicity experiments confirmed the non-toxicity of the degraded products. The present study demonstrates for the first time the potential of Sesuvium for the efficient degradation of textile dyes and its efficacy on saline soils contaminated with toxic compounds.

  12. Synthesis of B4C from Na2B4O7+Mg+C by SHS Method

    NASA Astrophysics Data System (ADS)

    Jiang, G. J.; Xu, J. Y.; Zhuang, H. R.; Li, W. L.

    2011-05-01

    This paper deals with the formation of Boron Carbide (B4C) powders from Na2B4O7+Mg+C system by self-propagating high-temperature synthesis (SHS) method. B4C without impurities could be obtained after the acid enrichment and distilled water washing. The reaction mechanism of SHS of B4C was proposed: the synthesis of B4C is a process involving the decomposition of Na2B4O7 into the intermediate phase B2O3, which reacts with Mg and Carbon to form B4C.

  13. Effect of Heating Rate on Soft Magnetic Properties in Nanocrystalline Fe80.5Cu1.5Si4B14 and Fe82Cu1Nb1Si4B12 Alloys

    NASA Astrophysics Data System (ADS)

    Ohta, Motoki; Yoshizawa, Yoshihito

    2009-02-01

    The effect of the heating rate in the annealing process of rapidly quenched Fe80.5Cu1.5Si4B14 and Fe82Cu1Nb1Si4B12 amorphous alloys on their soft magnetic properties is investigated. The iron loss in magnetic flux density region of B > 1.55 T in Fe80.5Cu1.5Si4B14 alloy decreases by high-heating-rate annealing (HA). The coercivity Hc and the saturation magnetic flux density Bs in HA specimen of Fe82Cu1Nb1Si4B12 alloy were about 3 A/m and 1.78 T. By applying HA to high-Fe-concentration amorphous alloys such as Fe82Cu1Nb1Si4B12, Fe82Cu1Nb1Si2B12P2, and Fe80.8Cu1.2Si5B11P2, the nanocrystalline alloys with a high Bs of more than 1.75 T and a low Hc of about 3 A/m are obtained.

  14. Adsorption and thermal decomposition of 2-octylthieno[3,4-b]thiophene on Au(111).

    PubMed

    Park, Joon B; Zong, Kyukwan; Jeon, Il Chul; Hahn, Jae Ryang; Stacchiola, Dario; Starr, David; Müller, Kathrin; Noh, Jaegeun

    2012-10-15

    The adsorption and thermal stability of 2-octylthieno[3,4-b]thiophene (OTTP) on the Au(111) surfaces have been studied using scanning tunneling microscopy (STM), temperature programmed desorption (TPD), and X-ray photoelectron spectroscopy (XPS). UHV-STM studies revealed that the vapor-deposited OTTP on Au(111) generated disordered adlayers with monolayer thickness even at saturation coverage. XPS and TPD studies indicated that OTTP molecules on Au(111) are stable up to 450 K and further heating of the sample resulted in thermal decomposition to produce H(2) and H(2)S via C-S bond scission in the thieno-thiophene rings. Dehydrogenation continues to occur above 600 K and the molecules were ultimately transformed to carbon clusters at 900 K. Highly resolved air-STM images showed that OTTP adlayers on Au(111) prepared from solution are composed of a well-ordered and low-coverage phase where the molecules lie flat on the surface, which can be assigned as a (9×2√33)R5° structure. Finally, based on analysis of STM, TPD, and XPS results, we propose a thermal decomposition mechanism of OTTP on Au(111) as a function of annealing temperature. PMID:22818203

  15. High-temperature mass spectrometry - Vaporization of group 4-B metal carbides. [using Knudsen effusion

    NASA Technical Reports Server (NTRS)

    Stearns, C. A.; Kohl, F. J.

    1974-01-01

    The high temperature vaporization of the metal-carbon systems TiC, ZrC, HfC, and ThC was studied by the Knudsen effusion - mass spectrometric method. For each system the metal dicarbide and tetracarbide molecular species were identified in the gas phase. Relative ion currents of the carbides and metals were measured as a function of temperature. Second- and third-law methods were used to determine enthalpies. Maximum values were established for the dissociation energies of the metal monocarbide molecules TiC, ZrC, HfC, and ThC. Thermodynamic functions used in the calculations are discussed in terms of assumed molecular structures and electronic contributions to the partition functions. The trends shown by the dissociation energies of the carbides of Group 4B are compared with those of neighboring groups and discussed in relation to the corresponding oxides and chemical bonding. The high temperature molecular beam inlet system and double focusing mass spectrometer are described.

  16. Study of Historical 4B/X17 Mega Flare on 28 October 2003 (P58)

    NASA Astrophysics Data System (ADS)

    Uddin, W.; Chandra, R.; Ali, S. S.

    2006-11-01

    wuddin_99@yahoo.com We analysed multi-wavelength data of 28 October 2003 4B/X17.2 class extremely energetic parallel ribbon solar flare, which occurred in NOAA 10486. The flare was well observed in H-alpha at ARIES, Nainital and various space (SOHO, TRACE, RHESSI, WIND etc.) and ground based Observatories. The H-alpha observations show the stretching/detwisting and eruption of helically twisted S shaped (sigmoid) filament in the South-West direction of the active region with bright shock front followed by rapid increase in intensity and area of the gigantic flare. The flare is associated with a bright/fast full halo earth directed CME, strong type II, III and IV radio bursts, an intense proton event and GLE. It seems that the filament eruption triggered the halo CME because the helical structure is clearly visible in the SOHO/LASCO C2, C3 images. This indicates helicity transfer from chromosphere to corona and interplanetary medium. The magnetic field of the flaring region was most complex with high magnetic shear. From the above analysis we feel that the energy buildup/release process of this unique flare support helically twisted magnetic flux rope model.

  17. CD4(+)B220(+)TCRγδ(+) T cells produce IL-17 in lupus-prone MRL/lpr mice.

    PubMed

    Qiu, Feng; Li, Tingting; Zhang, Kui; Wan, Jun; Qi, Xiaokun

    2016-09-01

    Systemic lupus erythematosus is an autoimmune disease with comprehensive immune cell disorders. Recent studies suggested that pro-inflammatory cytokine IL-17 plays important role in lupus, leaving the cellular sources and their pathogenic and physiologic characters largely unknown. In the current study, by using lupus-prone MRL/lpr mice, we demonstrated that Th17 response prevails in lupus disease regarding significantly accumulated serum IL-17, increased IL-17-producing splenocytes, and elevated phospho-STAT3 in CD4(+) T cells. Intracellular staining revealed that unusual CD4(+)B220(+) T cells are major IL-17-producing cells, whereas conventional CD4(+)B220(-) T cells are major IFN-γ-producing cells. Subsequent studies showed that CD4(+)B220(+) cells contains both αβ and γδ T cells in the spleen and thymus of MRL/lpr mice. Further study showed that around 60% of γδ T cells in MRL/lpr mice co-express both B220 and CD4 on their surface, and are the major RORγt(+) cells in MRL/lpr mice. Finally, CD4(+)B220(+) T cells alone do not proliferate, but could enhance the proliferation and IFN-γ-production of conventional CD4(+)B220(-) T cells. Our findings suggest the pathogenic role of unusual CD4(+)B220(+) T cells in lupus disease in MRL/lpr mice according to their IL-17-producing ability and stimulatory function for conventional CD4(+)B220(-) T cells. PMID:27235595

  18. Reaction behavior between B4C, 304 grade of stainless steel and Zircaloy at 1473 K

    NASA Astrophysics Data System (ADS)

    Sasaki, Ryosuke; Ueda, Shigeru; Kim, Sun-Joong; Gao, Xu; Kitamura, Shin-ya

    2016-08-01

    For a better understanding of the decommissioning of the Fukushima-daiichi nuclear power plant, the melting behavior of the control blade and the channel box should be clarified. In Fukushima nuclear reactor, the channel box was made of Zircaloy-4, and the control rode is made of B4C together with stainless steel cladding and sheath. In the study, the interaction among B4C, stainless steel (SUS), and Zircaloy-4 was investigated at 1473 K in either argon or air atmosphere. In argon, Zircaloy is melted by the diffusion of elements from SUS, and SUS was melted at 1473 K by the diffusion of C and B. In air, SUS reacted with B2O3 and formed an oxides melt firstly. Then, the oxidized Zircaloy contacted with this melt and fused. Moreover, the progress of core melting process during severe accident under different atmospheres was firstly discussed.

  19. Corrosion and tribocorrosion behavior of Ti-B4C composite intended for orthopaedic implants.

    PubMed

    Toptan, F; Rego, A; Alves, A C; Guedes, A

    2016-08-01

    Poor wear resistance of titanium is a major concern since relative movements due to the cyclic loads in body environment cause wear between the bone and the implant material leading to detachment of the wear debris and release of metal ions due to the simultaneous action of corrosion and wear, defined as tribocorrosion. In order to increase the tribocorrosion resistance, Grade 2 Ti matrix 24vol% B4C particle reinforced composites were processed by hot pressing. Corrosion behaviour was investigated by electrochemical impedance spectroscopy and potentiodynamic polarization in 9g/L NaCl solution at body temperature. Tribocorrosion tests were performed under open circuit potential, as well as under potentiodynamic polarization using a reciprocating ball-on-plate tribometer. Results suggested that the addition of B4C particles provided lower tendency to corrosion and lower corrosion kinetics under sliding, along with significantly reduced wear loss, mainly due to the load carrying effect given by the reinforcement particles.

  20. Determination of Optimum Cutting Parameters for Surface Roughness in Turning AL-B4C Composites

    NASA Astrophysics Data System (ADS)

    Channabasavaraja, H. K.; Nagaraj, P. M.; Srinivasan, D.

    2016-09-01

    Many materials such as alloys, composites find their applications on the basis of machinability, cost and availability. In the present work, machinability of Aluminium 1100 and Boron carbide (AL+ B4C) composite material is examined by using lathe tool dynometers (BANKA Lathe) by varying the cutting parameters like spindle speed, Depth of cut and Feed rate in 3 levels. Also, surface roughness is measured against the weight % of reinforcement in the composite (0, 4 and 8 %). From the study it is observed that the hardness of a composite material increases with increase in weight % of reinforcement material (B4C) by 26.27 and 66.7 % respectively. The addition of reinforcement materials influences the machinability. The cutting force in both X and Z direction were also found increment with the reinforcement percentage.

  1. 4C 39.24: discovery of a `giant' radio galaxy at z=1.88

    NASA Astrophysics Data System (ADS)

    Law-Green, J. D. B.; Eales, S. A.; Leahy, J. P.; Rawlings, S.; Lacy, M.

    1995-12-01

    The radio source 4C 39.24 (6C 0905+399) is shown to be the north-preceding lobe of a 111-arcsec FR II `classical double' with an unusual asymmetric structure. The core of the radio galaxy has been identified with a galaxy at z=1.883+/-0.003, giving a projected linear size of 4C 39.24 of D=(689+/-4) h^-1 kpc (assuming H_0=100 h km s ^-1 Mpc^-1 and Omega=0.04), making it the most distant `giant' radio galaxy known. We suggest that the `quad-like' structure seen in the north-preceding radio lobe is caused by the multiple imaging by gravitational lensing of a single hotspot.

  2. Corrosion and tribocorrosion behavior of Ti-B4C composite intended for orthopaedic implants.

    PubMed

    Toptan, F; Rego, A; Alves, A C; Guedes, A

    2016-08-01

    Poor wear resistance of titanium is a major concern since relative movements due to the cyclic loads in body environment cause wear between the bone and the implant material leading to detachment of the wear debris and release of metal ions due to the simultaneous action of corrosion and wear, defined as tribocorrosion. In order to increase the tribocorrosion resistance, Grade 2 Ti matrix 24vol% B4C particle reinforced composites were processed by hot pressing. Corrosion behaviour was investigated by electrochemical impedance spectroscopy and potentiodynamic polarization in 9g/L NaCl solution at body temperature. Tribocorrosion tests were performed under open circuit potential, as well as under potentiodynamic polarization using a reciprocating ball-on-plate tribometer. Results suggested that the addition of B4C particles provided lower tendency to corrosion and lower corrosion kinetics under sliding, along with significantly reduced wear loss, mainly due to the load carrying effect given by the reinforcement particles. PMID:26866451

  3. Cr/B4C multilayer mirrors: Study of interfaces and X-ray reflectance

    NASA Astrophysics Data System (ADS)

    Burcklen, C.; Soufli, R.; Dennetiere, D.; Polack, F.; Capitanio, B.; Gullikson, E.; Meltchakov, E.; Thomasset, M.; Jérome, A.; de Rossi, S.; Delmotte, F.

    2016-03-01

    We present an experimental study of the effect of layer interfaces on the x-ray reflectance in Cr/B4C multilayer interference coatings with layer thicknesses ranging from 0.7 nm to 5.4 nm. The multilayers were deposited by magnetron sputtering and by ion beam sputtering. Grazing incidence x-ray reflectometry, soft x-ray reflectometry, and transmission electron microscopy reveal asymmetric multilayer structures with a larger B4C-on-Cr interface, which we modeled with a 1-1.5 nm thick interfacial layer. Reflectance measurements in the vicinity of the Cr L2,3 absorption edge demonstrate fine structure that is not predicted by simulations using the currently tabulated refractive index (optical constants) values for Cr.

  4. Cr/B4C multilayer mirrors: Study of interfaces and X-ray reflectance

    DOE PAGES

    Burcklen, C.; Soufli, R.; Gullikson, E.; Meltchakov, E.; Dennetiere, D.; Polack, F.; Capitanio, B.; Thomasset, M.; Jerome, A.; de Rossi, S.; et al

    2016-03-24

    Here, we present an experimental study of the effect of layer interfaces on the x-ray reflectance in Cr/B4C multilayer interference coatings with layer thicknesses ranging from 0.7 nm to 5.4 nm. The multilayers were deposited by magnetron sputtering and by ion beam sputtering. Grazing incidence x-ray reflectometry, soft x-ray reflectometry, and transmission electron microscopy reveal asymmetric multilayer structures with a larger B4C-on-Cr interface, which we modeled with a 1–1.5 nm thick interfacial layer. Reflectance measurements in the vicinity of the Cr L2,3 absorption edge demonstrate fine structure that is not predicted by simulations using the currently tabulated refractive index (opticalmore » constants) values for Cr.« less

  5. Characterization of Al–Al{sub 4}C{sub 3} nanocomposites produced by mechanical milling

    SciTech Connect

    Santos-Beltrán, A.; Morales-Rodriguez, H.; Gallegos-Orozco, V.; Baldenebro-Lopez, F.

    2015-08-15

    In this work, a mixture of Al–C–Al{sub 4}C{sub 3} nanopowder previously synthesized by mechanical milling and subsequent thermal treatment was used to reinforce the Al matrix. The nanocomposites were fabricated via high-energy ball milling and subsequent sintering process for different periods of time at 550 °C. Hardness and compression tests were performed to evaluate the mechanical properties of the nanocomposites in the as-milled and sintered conditions. According to the results the reinforcement located in the grain boundaries is responsible for the brittle behavior observed in the nanocomposites during the compression test. The combined effect of sintering and precipitation mechanisms produced an evident increase of the strength of the Al matrix at a relatively short sintering time. By using the Rietveld method the crystallite size and microstrain measurements were determined and correlated with the microhardness values. For the proper characterization of the nanoparticles present in the Al matrix, atomic force microscopy and high resolution electron microscopy were used. - Highlights: • Nanostructured Al{sub 4}C{sub 3} reinforcement was fabricated via mechanical milling and heat treatment. • We found a significant increase of the mechanical properties at short sintering times. • The formation of Al{sub 4}C{sub 3} with during sintering time restricted the excessive growth of the crystallite. • Al{sub 4}C{sub 3} located in the grain boundaries causes brittle fracture observed in compression tests. • There is a correlation between, crystallite size and microstrain values with microhardness.

  6. 12. 'Erection Plan, 1 180'01/4' c. to c. End ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. 'Erection Plan, 1 - 180'-0-1/4' c. to c. End Pins Sing. Tr. Thro' Span, 16th Crossing over Sacramento River, Pacific System, Southern Pacific Co., Phoenix Bridge Co., C.O. #842, Drawing #13, Scale 1/8' & 1' = 1'-0', Eng'r C. Scheidl, Draftsman D. Sharp, Scale 1' = 1'-0', May 1st 1901.' - Southern Pacific Railroad Shasta Route, Bridge No. 324.99, Milepost 324.99, Shasta Springs, Siskiyou County, CA

  7. 13. 'Portal and Transverse Bracing, 1 180'01/4' c. to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. 'Portal and Transverse Bracing, 1 - 180'-0-1/4' c. to c. end pins S. Tr. Thro. Truss Span, 16th Crossing Sacramento River, Sacramento Division, So. Pac. Co., The Phoenix Bridge Co., C.O. #842, Draw #6, Engineer C. Scheidl, Draftsman Hermanns, Scale 1' = 1', Apr. 26, 1901.' - Southern Pacific Railroad Shasta Route, Bridge No. 324.99, Milepost 324.99, Shasta Springs, Siskiyou County, CA

  8. Regulation of neuropathic pain behavior by amygdaloid TRPC4/C5 channels.

    PubMed

    Wei, Hong; Sagalajev, Boriss; Yüzer, M Anil; Koivisto, Ari; Pertovaara, Antti

    2015-11-01

    Pain per se may increase anxiety and conversely, anxiety may increase pain. Therefore, a positive feedback loop between anxiety and pain possibly contributes to pain and suffering in some pathophysiological pain conditions, such as that induced by peripheral nerve injury. Recent results indicate that transient receptor channels 4 and 5 (TRPC4/C5) in the amygdala have anxiogenic effects in rodents, while their role in chronic pain conditions is not known. Here, we studied whether the amygdaloid TRPC4/C5 that are known to have anxiogenic properties contribute to the maintenance of sensory or affective aspects of pain in an experimental model of peripheral neuropathy. Rats with a spared nerve injury (SNI) model of neuropathy in the left hind limb had a chronic cannula for microinjections of drugs into the right amygdala or the internal capsule (a control site). Sensory pain was assessed by determining mechanical hypersensitivity with calibrated monofilaments and affective pain by determining aversive place-conditioning. Amygdaloid treatment with ML-204, a TRPC4/C5 antagonist, produced a dose-related (5-10 μg) antihypersensitivity effect, without obvious side-effects. Additionally, amygdaloid administration of ML-204 reduced affective-like pain behavior. In the internal capsule, ML-204 had no effect on hypersensitivity or affective-like pain in SNI animals. In healthy controls, amygdaloid administration of ML-204 failed to influence pain behavior induced by mechanical stimulation or noxious heat. The results indicate that the amygdaloid TRPC4/C5 contribute to maintenance of pain hypersensitivity and pain affect in neuropathy. PMID:26432495

  9. AGILE detection of enhanced gamma-ray emission from the FSRQ 4C +01.02

    NASA Astrophysics Data System (ADS)

    Verrecchia, F.; Lucarelli, F.; Pittori, C.; Bulgarelli, A.; Tavani, M.; Fioretti, V.; Zoli, A.; Piano, G.; Striani, E.; Vercellone, S.; Donnarumma, I.; Cardillo, M.; Gianotti, F.; Trifoglio, M.; Giuliani, A.; Mereghetti, S.; Caraveo, P.; Perotti, F.; Chen, A.; Argan, A.; Costa, E.; Del Monte, E.; Evangelista, Y.; Feroci, M.; Lazzarotto, F.; Lapshov, I.; Pacciani, L.; Soffitta, P.; Sabatini, S.; Vittorini, V.; Pucella, G.; Rapisarda, M.; Di Cocco, G.; Fuschino, F.; Galli, M.; Labanti, C.; Marisaldi, M.; Pellizzoni, A.; Pilia, M.; Trois, A.; Barbiellini, G.; Vallazza, E.; Longo, F.; Morselli, A.; Picozza, P.; Prest, M.; Lipari, P.; Zanello, D.; Cattaneo, P. W.; Rappoldi, A.; Colafrancesco, S.; Parmiggiani, N.; Ferrari, A.; Antonelli, A.; Giommi, P.; Salotti, L.; Valentini, G.; D'Amico, F.

    2016-07-01

    AGILE is detecting increased gamma-ray emission above 100 MeV from a position consistent with the flat spectrum radio quasar 4C +01.02 (also known as 5BZQ J0108+0135, PKS 0106+01 and 3FGL J0108.7+0134), recently reported in flaring activity also by Fermi/LAT during the week Jun 6-12 (http://fermisky.blogspot.it).

  10. NIR Brightening of the high redshift Blazar 4C+38.41

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Porras, A.; Recillas, E.; Chavushyan, V.; Mayya, D. Y.

    2016-09-01

    We report on the recent NIR brightening of the high redshift Blazar 4C+38.41 (z=1.814), associated with the Gamma-ray source 2FGLJ1635.2+3810 and the optical source [HB89]1633+382 On September 21st,2016 (MJD 2457652.6733), we found the source with NIR fluxes corresponding to: H = 14.627 +/- 0.04 . On MJD 2457578.8.

  11. Fermi LAT detection of a GeV flare from 4C +01.02

    NASA Astrophysics Data System (ADS)

    Buson, S.

    2013-09-01

    The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, observed a gamma-ray outburst from a source positionally consistent with the flat spectrum radio quasar 4C +01.02, also known as BZQ J0108+0135 (RA: 01h08m38.8s DEC : +01d35m00s, J2000.0, Kenneth et al. 1995) with redshift z=2.099 (Hewett et al. 1995).

  12. Identification of an AAA ATPase VPS4B-Dependent Pathway That Modulates Epidermal Growth Factor Receptor Abundance and Signaling during Hypoxia

    PubMed Central

    Lin, H. Helen; Li, Xu; Chen, Jo-Lin; Sun, Xiuzhu; Cooper, Fariba Norouziyan; Chen, Yun-Ru; Zhang, Wenyu; Chung, Yiyin; Li, Angela; Cheng, Chun-Ting; Yang, Lixin; Deng, XuTao; Liu, Xiyong; Yen, Yun; Johnson, Deborah L.; Shih, Hsiu-Ming; Yang, Austin

    2012-01-01

    VPS4B, an AAA ATPase (ATPase associated with various cellular activities), participates in vesicular trafficking and autophagosome maturation in mammalian cells. In solid tumors, hypoxia is a common feature and an indicator of poor treatment outcome. Our studies demonstrate that exogenous or endogenous (assessed with anchorage-independent three-dimensional multicellular spheroid culture) hypoxia induces VPS4B downregulation by the ubiquitin-proteasome system. Inhibition of VPS4B function by short hairpin VPS4B (sh-VPS4B) or expression of dominant negative VPS4B(E235Q) promotes anchorage-independent breast cancer cell growth and resistance to gefitinib, U0126, and genotoxicity. Biochemically, hyperactivation of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase essential for cell proliferation and survival, accompanied by increased EGFR accumulation and altered intracellular compartmentalization, is observed in cells with compromised VPS4B. Furthermore, enhanced FOS/JUN induction and AP-1 promoter activation are noted in EGF-treated cells with VPS4B knockdown. However, VPS4B depletion does not affect EGFRvIII stability or its associated signaling. An inverse correlation between VPS4B expression and EGFR abundance is observed in breast tumors, and high-grade or recurrent breast carcinomas exhibit lower VPS4B expression. Together, our findings highlight a potentially critical role of VPS4B downregulation or chronic-hypoxia-induced VPS4B degradation in promoting tumor progression, unveiling a nongenomic mechanism for EGFR overproduction in human breast cancer. PMID:22252323

  13. Structural modifications induced by ion irradiation and temperature in boron carbide B4C

    NASA Astrophysics Data System (ADS)

    Victor, G.; Pipon, Y.; Bérerd, N.; Toulhoat, N.; Moncoffre, N.; Djourelov, N.; Miro, S.; Baillet, J.; Pradeilles, N.; Rapaud, O.; Maître, A.; Gosset, D.

    2015-12-01

    Already used as neutron absorber in the current French nuclear reactors, boron carbide (B4C) is also considered in the future Sodium Fast Reactors of the next generation (Gen IV). Due to severe irradiation conditions occurring in these reactors, it is of primary importance that this material presents a high structural resistance under irradiation, both in the ballistic and electronic damage regimes. Previous works have shown an important structural resistance of boron carbide even at high neutron fluences. Nevertheless, the structural modification mechanisms due to irradiation are not well understood. Therefore the aim of this paper is to study structural modifications induced in B4C samples in different damage regimes. The boron carbide pellets were shaped and sintered by using spark plasma sintering method. They were then irradiated in several conditions at room temperature or 800 °C, either by favoring the creation of ballistic damage (between 1 and 3 dpa), or by favoring the electronic excitations using 100 MeV swift iodine ions (Se ≈ 15 keV/nm). Ex situ micro-Raman spectroscopy and Doppler broadening of annihilation radiation technique with variable energy slow positrons were coupled to follow the evolution of the B4C structure under irradiation.

  14. Crystal structure of 7-isopropyl-1,4a,N-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydro-phenanthrene-1-carb-ox-amide.

    PubMed

    Liu, Li; Yan, Xin-Yan; Rao, Xiao-Ping

    2015-10-01

    In the title compound, C26H37NO, a new derivative of di-hydro-abietic acid, the two cyclo-hexene rings adopt half chair conformations, whereas the cyclo-hexane ring has a chair conformation. Each of the methyl groups is in an axial position with respect to the tricyclic hydro-phenanthrene residue. In the crystal packing, methyl-ene-C-H⋯π(phen-yl) inter-actions lead to supra-molecular helical chains along [010]; the amide-H atom does not form a significant inter-molecular inter-action owing to steric pressure.

  15. Crystal structure of 7-isopropyl-1,4a,N-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydro-phenanthrene-1-carb-ox-amide.

    PubMed

    Liu, Li; Yan, Xin-Yan; Rao, Xiao-Ping

    2015-10-01

    In the title compound, C26H37NO, a new derivative of di-hydro-abietic acid, the two cyclo-hexene rings adopt half chair conformations, whereas the cyclo-hexane ring has a chair conformation. Each of the methyl groups is in an axial position with respect to the tricyclic hydro-phenanthrene residue. In the crystal packing, methyl-ene-C-H⋯π(phen-yl) inter-actions lead to supra-molecular helical chains along [010]; the amide-H atom does not form a significant inter-molecular inter-action owing to steric pressure. PMID:26594487

  16. Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

    PubMed Central

    Capalbo, Luisa; Mela, Ioanna; Abad, Maria Alba; Jeyaprakash, A. Arockia; Edwardson, J. Michael

    2016-01-01

    The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission. PMID:27784789

  17. Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets

    PubMed Central

    Yang, Yang; Ye, Fei; Zhu, Na; Wang, Wenling; Deng, Yao; Zhao, Zhengdong; Tan, Wenjie

    2015-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε, and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm, and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production

  18. Newly isolated Penicillium oxalicum A592-4B secretes enzymes that degrade milled rice straw with high efficiency.

    PubMed

    Aoyama, Akihisa; Kurane, Ryuichiro; Matsuura, Akira; Nagai, Kazuo

    2015-01-01

    An enzyme producing micro-organism, which can directly saccharify rice straw that has only been crushed without undergoing the current acid or alkaline pretreatment, was found. From the homology with the ITS, 28S rDNA sequence, the strain named A592-4B was identified as Penicillium oxalicum. Activities of the A592-4B enzymes and commercial enzyme preparations were compared by Novozymes Cellic CTec2 and Genencore GC220. In the present experimental condition, activity of A592-4B enzymes was 2.6 times higher than that of CTec2 for degrading milled rice straw. Furthermore, even when a quarter amount of A592-4B enzyme was applied to the rice straw, the conversion rate was still higher than that by CTec2. By utilizing A592-4B enzymes, improved lignocellulose degradation yields can be achieved without pre-treatment of the substrates; thus, contributing to cost reduction as well as reducing environmental burden.

  19. AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

    PubMed Central

    Johanns, M.; Lai, Y.-C.; Hsu, M.-F.; Jacobs, R.; Vertommen, D.; Van Sande, J.; Dumont, J. E.; Woods, A.; Carling, D.; Hue, L.; Viollet, B.; Foretz, M; Rider, M H

    2016-01-01

    Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation. PMID:26952277

  20. UBE4B Protein Couples Ubiquitination and Sorting Machineries to Enable Epidermal Growth Factor Receptor (EGFR) Degradation*

    PubMed Central

    Sirisaengtaksin, Natalie; Gireud, Monica; Yan, Qing; Kubota, Yoshihisa; Meza, Denisse; Waymire, Jack C.; Zage, Peter E.; Bean, Andrew J.

    2014-01-01

    The signaling of plasma membrane proteins is tuned by internalization and sorting in the endocytic pathway prior to recycling or degradation in lysosomes. Ubiquitin modification allows recognition and association of cargo with endosomally associated protein complexes, enabling sorting of proteins to be degraded from those to be recycled. The mechanism that provides coordination between the cellular machineries that mediate ubiquitination and endosomal sorting is unknown. We report that the ubiquitin ligase UBE4B is recruited to endosomes in response to epidermal growth factor receptor (EGFR) activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0. We identify the EGFR as a substrate for UBE4B, establish UBE4B as a regulator of EGFR degradation, and describe a mechanism by which UBE4B regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR. PMID:24344129

  1. Preparation and characterization of B4C coatings for advanced research light sources.

    PubMed

    Störmer, Michael; Siewert, Frank; Sinn, Harald

    2016-01-01

    X-ray optical elements are required for beam transport at the current and upcoming free-electron lasers and synchrotron sources. An X-ray mirror is a combination of a substrate and a coating. The demand for large mirrors with single layers consisting of light or heavy elements has increased during the last few decades; surface finishing technology is currently able to process mirror lengths up to 1 m with microroughness at the sub-nanometre level. Additionally, thin-film fabrication is able to deposit a suitable single-layer material, such as boron carbide (B4C), some tens of nanometres thick. After deposition, the mirror should provide excellent X-ray optical properties with respect to coating thickness errors, microroughness values and slope errors; thereby enabling the mirror to transport the X-ray beam with high reflectivity, high beam flux and an undistorted wavefront to an experimental station. At the European XFEL, the technical specifications of the future mirrors are extraordinarily challenging. The acceptable shape error of the mirrors is below 2 nm along the whole length of 1 m. At the Helmholtz-Zentrum Geesthacht (HZG), amorphous layers of boron carbide with thicknesses in the range 30-60 nm were fabricated using the HZG sputtering facility, which is able to cover areas up to 1500 mm long by 120 mm wide in one step using rectangular B4C sputtering targets. The available deposition area is suitable for the specified X-ray mirror dimensions of upcoming advanced research light sources such as the European XFEL. The coatings produced were investigated by means of X-ray reflectometry and interference microscopy. The experimental results for the B4C layers are discussed according to thickness uniformity, density, microroughness and thermal stability. The variation of layer thickness in the tangential and sagittal directions was investigated in order to estimate the achieved level of uniformity over the whole deposition area, which is considerably

  2. Preparation and characterization of B4C coatings for advanced research light sources

    PubMed Central

    Störmer, Michael; Siewert, Frank; Sinn, Harald

    2016-01-01

    X-ray optical elements are required for beam transport at the current and upcoming free-electron lasers and synchrotron sources. An X-ray mirror is a combination of a substrate and a coating. The demand for large mirrors with single layers consisting of light or heavy elements has increased during the last few decades; surface finishing technology is currently able to process mirror lengths up to 1 m with microroughness at the sub-nanometre level. Additionally, thin-film fabrication is able to deposit a suitable single-layer material, such as boron carbide (B4C), some tens of nanometres thick. After deposition, the mirror should provide excellent X-ray optical properties with respect to coating thickness errors, microroughness values and slope errors; thereby enabling the mirror to transport the X-ray beam with high reflectivity, high beam flux and an undistorted wavefront to an experimental station. At the European XFEL, the technical specifications of the future mirrors are extraordinarily challenging. The acceptable shape error of the mirrors is below 2 nm along the whole length of 1 m. At the Helmholtz-Zentrum Geesthacht (HZG), amorphous layers of boron carbide with thicknesses in the range 30–60 nm were fabricated using the HZG sputtering facility, which is able to cover areas up to 1500 mm long by 120 mm wide in one step using rectangular B4C sputtering targets. The available deposition area is suitable for the specified X-ray mirror dimensions of upcoming advanced research light sources such as the European XFEL. The coatings produced were investigated by means of X-ray reflectometry and interference microscopy. The experimental results for the B4C layers are discussed according to thickness uniformity, density, microroughness and thermal stability. The variation of layer thickness in the tangential and sagittal directions was investigated in order to estimate the achieved level of uniformity over the whole deposition area, which is

  3. Preparation and characterization of B4C coatings for advanced research light sources.

    PubMed

    Störmer, Michael; Siewert, Frank; Sinn, Harald

    2016-01-01

    X-ray optical elements are required for beam transport at the current and upcoming free-electron lasers and synchrotron sources. An X-ray mirror is a combination of a substrate and a coating. The demand for large mirrors with single layers consisting of light or heavy elements has increased during the last few decades; surface finishing technology is currently able to process mirror lengths up to 1 m with microroughness at the sub-nanometre level. Additionally, thin-film fabrication is able to deposit a suitable single-layer material, such as boron carbide (B4C), some tens of nanometres thick. After deposition, the mirror should provide excellent X-ray optical properties with respect to coating thickness errors, microroughness values and slope errors; thereby enabling the mirror to transport the X-ray beam with high reflectivity, high beam flux and an undistorted wavefront to an experimental station. At the European XFEL, the technical specifications of the future mirrors are extraordinarily challenging. The acceptable shape error of the mirrors is below 2 nm along the whole length of 1 m. At the Helmholtz-Zentrum Geesthacht (HZG), amorphous layers of boron carbide with thicknesses in the range 30-60 nm were fabricated using the HZG sputtering facility, which is able to cover areas up to 1500 mm long by 120 mm wide in one step using rectangular B4C sputtering targets. The available deposition area is suitable for the specified X-ray mirror dimensions of upcoming advanced research light sources such as the European XFEL. The coatings produced were investigated by means of X-ray reflectometry and interference microscopy. The experimental results for the B4C layers are discussed according to thickness uniformity, density, microroughness and thermal stability. The variation of layer thickness in the tangential and sagittal directions was investigated in order to estimate the achieved level of uniformity over the whole deposition area, which is considerably

  4. Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

    PubMed Central

    Sandhu, C; Garbe, J; Bhattacharya, N; Daksis, J; Pan, C H; Yaswen, P; Koh, J; Slingerland, J M; Stampfer, M R

    1997-01-01

    The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited. PMID:9111314

  5. Investigation of the process chain leading to the development of convection during COP IOP 4b

    NASA Astrophysics Data System (ADS)

    Bauer, H.-S.; Schwitalla, T.; Aoshima, F.; Behrendt, A.; Wulfmeyer, V.

    2012-04-01

    The COPS IOP 4b took place from June 20th to June 21st 2007. It was characterized by widespread convection in the COPS domain. The development was steered by a strong low pressure system southwest of the British Isles. On its eastern side warm and moist subtropical air was directed to central Europe. First convection was triggered over the Vosges Mountains around noon on the 20th of June long before the front approached the COPS region. After a calm early afternoon, severe convection was triggered in wide regions of the COPS region in the evening and moved eastwards to Bavaria during the night to the 21st of June. In contrast to other IOPs, the situation was not captured correctly by most of the involved prediction models, no matter whether they were operated with or without sophisticated data assimilation. Aim of this presentation is to unravel the mechanisms responsible for the triggering of convection and to understand the processes preparing the atmosphere for the development of severe convection during the afternoon and night. For this purpose, many different data sets will be investigated ranging from the high resolution Vienna Enhanced Resolution Analysis (VERA), high resolution radar and satellite images and composites to soundings and data as well as retrieved products from the instruments at the COPS supersites. First impression is that the complicated low-level wind field is the major driver for the preparation of the atmosphere and therefore for the development of convection during the day. The inaccuracies in representing the low level wind field are also expected to be the major reason for the failure of the models to correctly predict the situation.

  6. The Dedicated Monitor of Exotransits (DEMONEX): Seven Transits of XO-4b

    NASA Astrophysics Data System (ADS)

    Villanueva, S., Jr.; Eastman, J. D.; Gaudi, B. S.

    2016-04-01

    The DEdicated MONitor of EXotransits (DEMONEX) was a 20-inch robotic and automated telescope to monitor bright stars hosting transiting exoplanets to discover new planets and improve constraints on the properties of known transiting planetary systems. We present results for the misaligned hot Jupiter XO-4b containing seven new transits from the DEMONEX telescope, including three full and four partial transits. We combine these data with archival light curves and archival radial velocity measurements to derive the host star mass {M}*={1.293}-0.029+0.030 {M}⊙ and radius {R}*={1.554}-0.030+0.042 {R}⊙ , the planet mass {M}P={1.615}-0.099+0.10 {M}{{J}} and radius {R}P={1.317}-0.029+0.040\\\\{R}{{J}}, and a refined ephemeris of P=4.1250687+/- 0.0000024 days and {T}0=2,4547,58.18978+/- 0.00024 {{BJD}}{TDB}. We include archival Rossiter-McLaughlin measurements of XO-4 to infer the stellar spin-planetary orbit alignment of λ =-{40.0}-7.5+8.8 degrees. We test the effects of including various detrend parameters, theoretical and empirical mass-radius relations, and Rossiter-McLaughlin models. We infer that detrending against CCD position and time or airmass can improve data quality but can have significant effects on the inferred values of many parameters—most significantly {R}P/{R}* and the observed central transit times TC. In the case of {R}P/{R}* we find that the systematic uncertainty due to detrending can be three times that of the quoted statistical uncertainties. The choice of mass-radius relation has little effect on our inferred values of the system parameters. The choice of Rossiter-McLaughlin models can have significant effects on the inferred values of v{sin}{I}* and the stellar spin-planet orbit angle λ.

  7. Pressure effect on structural, elastic, and thermodynamic properties of tetragonal B{sub 4}C{sub 4}

    SciTech Connect

    Zheng, Baobing; Zhang, Meiguang; Luo, Hong-Gang

    2015-03-15

    The compressibility, elastic anisotropy, and thermodynamic properties of the recently proposed tetragonal B{sub 4}C{sub 4} (t-B{sub 4}C{sub 4}) are investigated under high temperature and high pressure by using of first-principles calculations method. The elastic constants, bulk modulus, shear modulus, Young’s modulus, Vickers hardness, Pugh’s modulus ratio, and Poisson’s ratio for t-B{sub 4}C{sub 4} under various pressures are systematically explored, the obtained results indicate that t-B{sub 4}C{sub 4} is a stiffer material. The elastic anisotropies of t-B{sub 4}C{sub 4} are discussed in detail under pressure from 0 GPa to 100 GPa. The thermodynamic properties of t-B{sub 4}C{sub 4}, such as Debye temperature, heat capacity, and thermal expansion coefficient are investigated by the quasi-harmonic Debye model.

  8. Genome sequence and description of the heavy metal tolerant bacterium Lysinibacillus sphaericus strain OT4b.31

    PubMed Central

    Peña-Montenegro, Tito David; Dussán, Jenny

    2013-01-01

    Lysinibacillus sphaericus strain OT4b.31 is a native Colombian strain having no larvicidal activity against Culex quinquefasciatus and is widely applied in the bioremediation of heavy-metal polluted environments. Strain OT4b.31 was placed between DNA homology groups III and IV. By gap-filling and alignment steps, we propose a 4,096,672 bp chromosomal scaffold. The whole genome (consisting of 4,856,302 bp long, 94 contigs and 4,846 predicted protein-coding sequences) revealed differences in comparison to the L. sphaericus C3-41 genome, such as syntenial relationships, prophages and putative mosquitocidal toxins. Sphaericolysin B354, the coleopteran toxin Sip1A and heavy metal resistance clusters from nik, ars, czc, cop, chr, czr and cad operons were identified. Lysinibacillus sphaericus OT4b.31 has applications not only in bioremediation efforts, but also in the biological control of agricultural pests. PMID:24501644

  9. Pd/B4C/Y multilayer coatings for extreme ultraviolet applications near 10  nm wavelength.

    PubMed

    Windt, David L; Gullikson, Eric M

    2015-06-20

    A new extreme ultraviolet (EUV) multilayer coating has been developed comprising Pd and Y layers with thin B4C barrier layers at each interface, for normal incidence applications near 10 nm wavelength. Periodic, nonperiodic, and dual-stack coatings have been investigated and compared with similar structures comprising either Mo/Y or Pd/B4C bilayers. We find that Pd/B4C/Y multilayers provide higher reflectance than either Mo/Y or Pd/B4C, with much lower film stress than Pd/B4C. We have also investigated the performance of periodic multilayers comprising repetitions of Pd/Y, Ru/Y, or Ru/B4C/Y, as well as Pd/B4C multilayers deposited using reactive sputtering with an Ar:N2 gas mixture in order to reduce stress: these material combinations were all found to provide poor EUV performance. The temporal stability of a periodic Pd/B4C/Y multilayer stored in air was investigated over a period of 16 months, and a slight reduction in peak reflectance was observed. Periodic Pd/B4C/Y multilayers were also found to be thermally stable up to 100°C; at higher temperatures (200°C and 300°C) we observe a slight reduction in peak reflectance and a slight increase in multilayer period. High-resolution transmission electron microscopy and selected area diffraction of an as-deposited Pd/B4C/Y film indicates a fully amorphous structure, with interfaces that are both smoother and more abrupt than those observed in a comparable Pd/B4C multilayer in which the Pd layers are polycrystalline. The new Pd/B4C/Y multilayers are suitable for normal-incidence imaging and spectroscopy applications, including solar physics, plasma physics, high-brightness EUV light sources, and others. PMID:26193039

  10. Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis

    PubMed Central

    2014-01-01

    Background Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. Methods Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. Results We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). Conclusions Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB. PMID:24484408

  11. Bioactivation of 4-ipomeanol by CYP4B1: adduct characterization and evidence for an enedial intermediate.

    PubMed

    Baer, Brian R; Rettie, Allan E; Henne, Kirk R

    2005-05-01

    4-Ipomeanol (IPO) is a pneumotoxin that is bioactivated to a reactive intermediate that binds to DNA and other cellular macromolecules. Despite over 30 years of research in this area, detailed structural information on the nature of the IPO reactive intermediate is still lacking. In the present study, we reacted IPO with rabbit CYP4B1 in the presence of exogenous nucleophiles and analyzed the products by liquid chromatography/electrospray ionization-mass spectrometry. Coincubation of IPO and rabbit CYP4B1 with glutathione gave rise to multiple products due likely to the presence of both sulfur and nitrogen nucleophiles in the same trapping molecule. Reaction mixtures containing equimolar N-acetyl cysteine (NAC) and N-acetyl lysine (NAL) provided a major NADPH- and CYP4B1-dependent product. A combination of high-resolution mass spectrometry and two-dimensional NMR analysis following large-scale isolation of the biologically derived material provided evidence for an N-substituted cysteinyl pyrrole derivative of IPO, analogous to that characterized previously in model chemical studies conducted with cis-2-butene-1,4-dial. Purified native rabbit lung CYP4B1 and purified recombinant rabbit CYP4B1 produced the trapped NAC/NAL-IPO pyrrole adduct at rates of 600-700 nmol/nmol P450/30 min. A panel of 14 commercially available recombinant human CYPs was also studied, and substantial rates of IPO bioactivation (>100 nmol/nmol/30 min) were observed with CYP1A2, CYP2C19, CYP2D6, and CYP3A4. These studies provide evidence for the formation of an enedial reactive intermediate during CYP-mediated IPO bioactivation, identify multiple human liver P450s capable of IPO bioactivation, and demonstrate that the same reactive intermediate is formed by both rabbit CYP4B1 and human P450s. PMID:15892579

  12. Regulation of ATG4B Stability by RNF5 Limits Basal Levels of Autophagy and Influences Susceptibility to Bacterial Infection

    PubMed Central

    Kuang, Ersheng; Varsano, Tal; Shu, Vincent Chih-Wen; Qi, Jianfei; Niesman, Ingrid R.; Yang, Huei-Jiun; López-Otín, Carlos; Yang, Wei Yuan; Reed, John C.; Broday, Limor; Nizet, Victor; Ronai, Ze'ev A.

    2012-01-01

    Autophagy is the mechanism by which cytoplasmic components and organelles are degraded by the lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, and multiple forms of cellular stress. Here, we show that the membrane-associated E3 ligase RNF5 regulates basal levels of autophagy by controlling the stability of a select pool of the cysteine protease ATG4B. RNF5 controls the membranal fraction of ATG4B and limits LC3 (ATG8) processing, which is required for phagophore and autophagosome formation. The association of ATG4B with—and regulation of its ubiquitination and stability by—RNF5 is seen primarily under normal growth conditions. Processing of LC3 forms, appearance of LC3-positive puncta, and p62 expression are higher in RNF5−/− MEF. RNF5 mutant, which retains its E3 ligase activity but does not associate with ATG4B, no longer affects LC3 puncta. Further, increased puncta seen in RNF5−/− using WT but not LC3 mutant, which bypasses ATG4B processing, substantiates the role of RNF5 in early phases of LC3 processing and autophagy. Similarly, RNF-5 inactivation in Caenorhabditis elegans increases the level of LGG-1/LC3::GFP puncta. RNF5−/− mice are more resistant to group A Streptococcus infection, associated with increased autophagosomes and more efficient bacterial clearance by RNF5−/− macrophages. Collectively, the RNF5-mediated control of membranalATG4B reveals a novel layer in the regulation of LC3 processing and autophagy. PMID:23093945

  13. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    SciTech Connect

    Min, Joong Won; Kim, Kwang Il; Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu; Kim, Jae-Sung

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  14. The Bisphenol A analogue Bisphenol S binds to K-Ras4B--implications for 'BPA-free' plastics.

    PubMed

    Schöpel, Miriam; Herrmann, Christian; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-02-01

    K-Ras4B is a small GTPase that belongs to the Ras superfamily of guanine nucleotide-binding proteins. GTPases function as molecular switches in cells and are key players in intracellular signalling. Ras has been identified as an oncogene and is mutated in more than 20% of human cancers. Here, we report that Bisphenol S binds into a binding pocket of K-Ras4B previously identified for various low molecular weight compounds. Our results advocate for more comprehensive safety studies on the toxicity of Bisphenol S, as it is frequently used for Bisphenol A-free food containers. PMID:26867649

  15. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  16. 3,4,6-Trimethyl-1-phenyl-1H-pyrazolo­[3,4-b]pyridine

    PubMed Central

    Hamri, Salha; Hafid, Abderrafia; Zouihri, Hafid; Lazar, Saïd; Khouili, Mostafa

    2010-01-01

    In the title compound, C15H15N3, the 1H-pyrazolo­[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017 (2) and 0.011 (2) Å, respectively; the dihedral angle between the two aromatic systems is 9.33 (10)°. The crystal packing is stabilized by offset π–π stacking between parallel pyrazolo­[3,4-b]pyridine ring systems [face-to-face distance = 3.449 (6) Å]. PMID:21588287

  17. The Bisphenol A analogue Bisphenol S binds to K-Ras4B--implications for 'BPA-free' plastics.

    PubMed

    Schöpel, Miriam; Herrmann, Christian; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-02-01

    K-Ras4B is a small GTPase that belongs to the Ras superfamily of guanine nucleotide-binding proteins. GTPases function as molecular switches in cells and are key players in intracellular signalling. Ras has been identified as an oncogene and is mutated in more than 20% of human cancers. Here, we report that Bisphenol S binds into a binding pocket of K-Ras4B previously identified for various low molecular weight compounds. Our results advocate for more comprehensive safety studies on the toxicity of Bisphenol S, as it is frequently used for Bisphenol A-free food containers.

  18. Probing the water and CO snow lines in the young protostar NGC 1333-IRAS4B

    NASA Astrophysics Data System (ADS)

    Anderl, Sibylle; Maret, Sébastien; André, Philippe; Maury, Anaëlle; Belloche, Arnaud; Cabrit, Sylvie; Codella, Claudio; Lefloch, Bertrand

    2015-08-01

    Today, we believe that the onset of life requires free energy, water, and complex, probably carbon-based chemistry. In the interstellar medium, complex organic molecules seem to mostly form in reactions happening on the icy surface of dust grains, such that they are released into the gas phase when the dust is heated. The resulting “snow lines”, marking regions where ices start to sublimate, play an important role for planet growth and bulk composition in protoplanetary disks. However, they can already be observed in the envelopes of the much younger, low-mass Class 0 protostars that are still in their early phase of heavy accretion. The information on the sublimation regions of different kinds of ices can be used to understand the chemistry of the envelope, its temperature and density structure, and may even hint at the history of the accretion process. Accordingly, it is a crucial piece of information in order to get the full picture of how organic chemistry evolves already at the earliest stages of the formation of sun-like stars. As part of the CALYPSO Large Program (http://irfu.cea.fr/Projets/Calypso/), we have obtained observations of C18O, N2H+ and CH3OH towards the Class 0 protostar NGC 1333-IRAS4B with the IRAM Plateau de Bure interferometer at sub-arcsecond resolution. Of these we use the methanol observations as a proxy for the water snow line, assuming methanol is trapped in water ice. The observed anti-correlation of C18O and N2H+, with N2H+ forming a ring around the centrally peaked C18O emission, reveals for the first time the CO snow line in this protostellar envelope, with a radius of ~300 AU. The methanol emission is much more compact than that of C18O, and traces the water snow line with a radius of ~40 AU. We have modeled the emission using a chemical model coupled with a radiative transfer module. We find that the CO snow line appears further inwards than expected from the binding energy of pure CO ices. This may hint at CO being frozen out

  19. Laboratory Spectra of Mixtures of CH4, C2H6, and CH3OH

    NASA Technical Reports Server (NTRS)

    Mastrapa, Rachel; Berry, Matthew T.; Sandford, Scott

    2011-01-01

    Infrared spectroscopy is commonly used as a tool for identifying the composition of objects in the Solar System and beyond. Using laboratory spectra, optical constants can be calculated and used to create model spectra for comparison to spectra obtained from infrared telescopes. In this study, the optical constants of mixtures of simple organics, including CH4, C2H6, and CH3OH were calculated from 15 to 70 K, in the frequency range of 9000-500 cm(sup -1) (1.1-20 micrometers), at a spectral resolution of 1 cm(sup -1).

  20. Preparation of AlB sub 4 C composites for image analysis

    SciTech Connect

    Kelly, A.M.; Reiswig, R.D.; Hill, M.A.; Blumenthal, W.R.

    1990-01-01

    Composites made by infiltrating B{sub 4}C networks with aluminium, or its alloys are of interest for lightweight armor applications. Image analysis plays an important part in correlating the microstructures of such composites with their mechanical properties. Accurate image analysis requires a high degree of perfection in the metallographic preparation, which is particularly difficult where the phases present have such disparate hardness and reactivities. Two preparation procedures have been developed that produce adequate contrast and definition for analysis of key microstructural features. 8 refs., 5 figs., 1 tab.

  1. Optical outburst of 4C 38.41 (1633+382) observed by the GASP

    NASA Astrophysics Data System (ADS)

    Raiteri, C. M.; Villata, M.; Ehgamberdiev, Sh. A.; Mirzaqulov, D. O.; Holikov, Sh.

    2011-07-01

    The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) reports on the recent observation of a strong optical brightening of the gamma-loud quasar 4C 38.41. This is one of the 28 blazars for which the GASP performs a long-term, multiwavelength monitoring. In the current optical observing season, the source has shown multiwavelength activity (see also ATels #3238, #3333, #3335, #3360), so that the GASP has intensified the observations with a dedicated campaign (contact person: C.

  2. Fermi LAT and Swift flare of the FSRQ 4C +40.25

    NASA Astrophysics Data System (ADS)

    Carpenter, Bryce; Ojha, Roopesh; Pivato, Giovanna; Fermi Large Area Telescope Collaboration

    2015-11-01

    The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope has observed a gamma-ray flare from a source positionally consistent with the flat spectrum radio quasar (FSRQ) 4C +40.25 (also known as B2 1020+40 and 3FGL J1023.1+3952, Acero et al. 2015, ApJS 218, 23) with coordinates RA: 10h 23m 11.5661s, Dec: 39d 48m 15.378s, J2000, (Helmboldt et al. 2007, ApJ, 658, 203) and a redshift of 1.254 (Xu et al. 1994, AJ, 108, 395).

  3. High-strain-rate compression and fracture of B sub 4 C-aluminum cermets

    SciTech Connect

    Blumenthal, W.R.

    1990-01-01

    The compressive behavior of liquid-metal infiltrated boron carbide-aluminum cermets were studied as a function of strain rate, composition, and microstructure. Hopkinson split pressure bar (HSPB) and quasi-static compression tests were conducted using dumb-bell-shaped specimens. Results showed cermet compressive strength to be independent of loading rate. Strength was also found to be independent of the aluminum alloy used to infiltrate pre-sintered 65 vol % B{sub 4}C pre-forms. compositions with the smallest phase size displayed the best strength and ductility. 18 refs., 4 figs.

  4. Inelastic X-ray scattering experiments on B[subscript 4]C under high static pressures

    SciTech Connect

    Kumar, Ravhi S.; Dandekar, Dattatraya; Leithe-Jasper, Andres; Tanaka, Takaho; Xiao, Yuming; Chow, Paul; Nicol, Malcolm F.; Cornelius, Andrew L.

    2010-05-04

    Boron K-edge inelastic X-ray scattering experiments were performed on clean B{sub 4}C and shock impact recovered boron carbide up to 30 GPa and at ambient temperature to understand the pressure induced bonding changes. The spectral features corresponding to the boron site in the interlinking chain remained unchanged up to 30 GPa. The results of our experiments indicate that pressure induces less distortion to the boron sites and the local amorphization observed in the previous reports are due to the rearrangement of carbon atoms under extreme conditions without affecting the boron environment.

  5. Dimeric procyanidins: screening for B1 to B8 and semisynthetic preparation of B3, B4, B6, And B8 from a polymeric procyanidin fraction of white willow bark (Salix alba).

    PubMed

    Esatbeyoglu, Tuba; Wray, Victor; Winterhalter, Peter

    2010-07-14

    Fifty-seven samples have been analyzed with regard to the occurrence of dimeric procyanidins B1-B8 as well as the composition of polymeric procyanidins. Fifty-two samples were found to contain polymeric procyanidins. In most of the samples, (-)-epicatechin was the predominant unit present. In white willow bark (Salix alba), however, large amounts of (+)-catechin (81.0%) were determined by means of phloroglucinolysis. White willow bark has therefore been used for the semisynthetic formation of dimeric procyanidins B3 [(+)-C-4alpha --> 8-(+)-C)], B4 [(+)-C-4alpha --> 8-(-)-EC)], B6 [(+)-C-4alpha --> 6-(+)-C)], and B8 [(+)-C-4alpha --> 6-(-)-EC)]. The reaction mixtures of the semisynthesis were successfully fractionated with high-speed countercurrent chromatography (HSCCC), and dimeric procyanidins B3, B4, B6, and B8 were obtained on a preparative scale.

  6. 28 CFR Appendix to Part 51 - Jurisdictions Covered Under Section 4(b) of the Voting Rights Act, as Amended

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) of the Voting Rights Act, as Amended Appendix to Part 51 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED Pt. 51, App. Appendix to Part 51—Jurisdictions Covered Under Section 4(b) of the Voting Rights...

  7. Establishment of a cell line panel for the detection of antibodies against human platelet antigen 4b.

    PubMed

    Hayashi, Tomoya; Amakishi, Etsuko; Inoue, Masayasu; Hirayama, Fumiya

    2011-02-01

    Antibodies against human platelet antigens (HPAs) play important roles in thrombocytopenia. In Japan, HPA-4b antibody is frequently responsible for HPA-related neonatal alloimmune thrombocytopenia. A highly sensitive assay using platelets has been developed for the detection of antibodies against HPAs. However, it is difficult to obtain the platelets expressing specific HPAs required for the assay. Therefore, an alternative method not requiring platelets would be helpful to detect antibodies against HPAs. Glycoprotein IIIa (GPIIIa) cDNA encoding HPA-4b was individually co-transduced with that of wild-type GPIIb in K562 cells, which is a non-adherent cell line, using a retroviral vector. The expression of transgene products in cultured cells were observed for over 6 months. Next, to evaluating the sensitivity and specificity of this cell line panel, we performed monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay with a serum previously identified by another method. All HPA-4b antibodies in serum samples were positive, and all serum samples, including normal serum and serum containing HLA antibodies were negative. No difference was observed in the specificity and sensitivity between our method and conventional MAIPA using platelets. The present results indicate that this established cell line panel permits highly sensitive detection of specific antibodies against HPA-4b. PMID:21286877

  8. Role of the inositol polyphosphate-4-phosphatase type II Inpp4b in the generation of ovarian teratomas

    PubMed Central

    Balakrishnan, Ashwini; Chaillet, J. Richard

    2012-01-01

    Teratomas are a unique class of tumors composed of ecto- meso- and endodermal tissues, all foreign to the site of origin. In humans, the most common teratoma is the ovarian teratoma. Not much is known about the molecular and genetic etiologies of these tumors. Female carriers of the Tgkd transgene are highly susceptible to developing teratomas. Ovaries of Tgkd/+ hemizygous female mice exhibit defects in luteinization, with numerous corpora lutea, some of which contain central trapped, fully-grown oocytes. Genetically, Tgkd teratomas originate from mature oocytes that have completed meiosis I, suggesting that Tgkd teratomas originate from these trapped oocytes. The insertion of Tgkd 3′ of the Inpp4b gene is associated with decreased expression of Inpp4b and changes in intracellular PI3 Kinase/AKT signaling in follicular granulosa cells. Because Inpp4b is not expressed in fully-grown wild-type or Tgkd oocytes, these findings suggest that hyperactivation of the PI3K/AKT pathway caused by the decrease in INPP4B in granulosa cells promotes an ovarian environment defective in folliculogenesis and conducive to teratoma formation. PMID:23078915

  9. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease.

    PubMed

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-05-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status.

  10. Occurrence of Optic Neuritis and Cervical Cord Schwannoma with Charcot-Marie-Tooth Type 4B1 Disease

    PubMed Central

    Scott, Patrick; Bruwer, Zandre; Al-Kharusi, Khalsa; Meftah, Douja; Al-Murshedi, Fathiya

    2016-01-01

    Charcot-Marie-Tooth neuropathy type 4B1 (CMT4B1) disease is a rare subtype of CMT4 with reported association of facial weakness, vocal cord paresis, chest deformities, and claw hands. We report the unusual occurrence of optic neuritis and cervical cord schwannoma in a male individual with confirmed CMT4B1 disease. Sequencing of the MTMR2 gene revealed a novel nonsense homozygous mutation c.1768C>T (p.Gln590*). The mutation was identified in affected relatives of the proband and a second, apparently unrelated, family. The rare association of optic neuritis or schwannoma with genetically confirmed CMT1A has been individually observed, but never with recessive CMT. To the best of our knowledge, the occurrence of optic neuritis and cervical cord schwannoma in the same patient has never been reported with any form of CMT including CMT4B1. In similar cases, we recommend immediate medical attention to rule out the possibility of schwannomas in patients with all demyelinating CMT subtypes in case of the development of focal neurological signs or acute worsening of clinical status. PMID:27162595

  11. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... Register on September 9, 2009 (74 FR 46453). This revised proposal would include measures for the... Bureau of Reclamation San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and Structural Improvements Project, Merced County, CA AGENCY: Bureau of...

  12. 75 FR 40843 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ..., which was made available in the Federal Register of February 21, 2008 (73 FR 9575). DATES: Although you... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density of Powders...

  13. 75 FR 43172 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... Administration (FDA) is correcting a notice that appeared in the Federal Register of July 14, 2010 (75 FR 40843...-0002, 301-796-9148. SUPPLEMENTARY INFORMATION: In FR Doc. 2010-17055, appearing on page 40843 in the... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference...

  14. VizieR Online Data Catalog: TrES-4b RV and Ic curves (Sozzetti+, 2015)

    NASA Astrophysics Data System (ADS)

    Sozzetti, A.; Bonomo, A. S.; Biazzo, K.; Mancini, L.; Damasso, M.; Desidera, S.; Gratton, R.; Lanza, A. F.; Poretti, E.; Rainer, M.; Malavolta, L.; Affer, L.; Barbieri, M.; Bedin, L. R.; Boccato, C.; Bonavita, M.; Borsa, F.; Ciceri, S.; Claudi, R. U.; Gandolfi, D.; Giacobbe, P.; Henning, T.; Knapic, C.; Latham, D. W.; Lodato, G.; Maggio, A.; Maldonado, J.; Marzari, F.; Martinez Fiorenzano, A. F.; Micela, G.; Molinari, E.; Mordasini, C.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Pepe, F.; Piotto, G.; Santos, N.; Scandariato, G.; Shkolnik, E.; Southworth, J.

    2015-06-01

    The TrES-4 system was observed with HARPS-N on 17 individual epochs between March 2013 and July 2014. We carried out Ic-band precision photometric observations of two complete transit events of TrES-4 b with the CAHA 1.23-m on UT 2013 July 6 and UT 2014 June 30. (2 data files).

  15. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  16. One-Dimensional Al4O4C Ceramics: A New Type of Blue Light Emitter

    PubMed Central

    Sun, Yong; Chen, Yuanzheng; Ding, Cairong; Yang, Guowei; Ma, Yanming; Wang, Chengxin

    2013-01-01

    Ceramic Al4O4C, which has few active functions, has been used as an additive in carbon-containing refractory materials to improve their oxidation resistance and thermal properties. Herein, the crystal and electronic structures of this novel material were systematically investigated for opto-electrical applications, which revealed interesting fluorescence features via photoluminescence (PL) and cathode luminescence (CL). When a 325 nm laser was focused on one end of a single Al4O4C needle, the entire needle was illuminated by the blue emission, which implies that this material exhibits excellent waveguide properties. Interestingly, the thin end exhibited the highest light intensity even though the excited region was located at the thick end. We believe the reason for this observed behaviour is related to the excellent waveguide behaviour as well as to the needle shape, which induces this intriguing blue-light convergence effect. Ab initio calculations demonstrated that the emission light emanates from the interband transition.

  17. Prolonging hypothermic storage (4 C) of bovine embryos with fish antifreeze protein

    PubMed Central

    IDETA, Atsushi; AOYAGI, Yoshito; TSUCHIYA, Kanami; NAKAMURA, Yuuki; HAYAMA, Kou; SHIRASAWA, Atsushi; SAKAGUCHI, Kenichiro; TOMINAGA, Naomi; NISHIMIYA, Yoshiyuki; TSUDA, Sakae

    2014-01-01

    Embryos obtained via superovulation are necessary for mammalian artificial reproduction, and viability is a key determinant of success. Nonfreezing storage at 4 C is possible, but currently used storage solutions can maintain embryo viability for only 24–48 h. Here we found that 10 mg/ml antifreeze protein (AFP) dissolved in culture medium 199 with 20% (v/v) fetal bovine serum and 25 mM HEPES could keep bovine embryos alive for 10 days at 4 C. We used a recombinant AFP isolated from the notched-fin eelpout (Zoarces elongatus Kner). Photomicroscopy indicated that the AFP–embryo interaction was enhanced at 37 C. Embryos pre-warmed with the AFP solution at 37 C for 60 min maintained high viability, whereas those that were not pre-warmed could live no longer than 7 days. Thus, short-term storage of bovine embryos was achieved by a combination of AFP-containing medium and controlled pre-warming. PMID:25311466

  18. La/B(4)C multilayer mirrors with an additional wavelength suppression.

    PubMed

    Naujok, Philipp; Yulin, Sergiy; Bianco, Anna; Mahne, Nicola; Kaiser, Norbert; Tünnermann, Andreas

    2015-02-23

    In this paper, the authors report on La/B(4)C multilayer mirrors designed for an incidence angle of 45° with both maximum reflectivity at a wavelength of 6.7 nm and reflectivity suppression at a wavelength of 20.1 nm. These mirrors were deposited for the EIS-TIMER at the FERMI@Elettra Free Electron Laser. The multilayer structure and optical properties were characterized using grazing incidence X-ray reflectometry with Cu-K(α) radiation and EUV reflectometry in the spectral region of 6.5 - 21.0 nm. An anti-reflective coating designed at the wavelength of 20.1 nm had to be deposited on top of the high reflective La/B(4)C multilayer mirror optimized at a wavelength of 6.7 nm. Measured reflectivities of 53.4% at the wavelength of 6.72 nm and 0.15% at the wavelength of 20.1 nm were simultaneously achieved. It is shown that the reflectivity loss at the wavelength of 6.7 nm due to the utilization of antireflective coating designed at the wavelength of 20.1 nm can be minimized up to 1.0%. PMID:25836465

  19. La/B(4)C multilayer mirrors with an additional wavelength suppression.

    PubMed

    Naujok, Philipp; Yulin, Sergiy; Bianco, Anna; Mahne, Nicola; Kaiser, Norbert; Tünnermann, Andreas

    2015-02-23

    In this paper, the authors report on La/B(4)C multilayer mirrors designed for an incidence angle of 45° with both maximum reflectivity at a wavelength of 6.7 nm and reflectivity suppression at a wavelength of 20.1 nm. These mirrors were deposited for the EIS-TIMER at the FERMI@Elettra Free Electron Laser. The multilayer structure and optical properties were characterized using grazing incidence X-ray reflectometry with Cu-K(α) radiation and EUV reflectometry in the spectral region of 6.5 - 21.0 nm. An anti-reflective coating designed at the wavelength of 20.1 nm had to be deposited on top of the high reflective La/B(4)C multilayer mirror optimized at a wavelength of 6.7 nm. Measured reflectivities of 53.4% at the wavelength of 6.72 nm and 0.15% at the wavelength of 20.1 nm were simultaneously achieved. It is shown that the reflectivity loss at the wavelength of 6.7 nm due to the utilization of antireflective coating designed at the wavelength of 20.1 nm can be minimized up to 1.0%.

  20. OEDGE modeling of the DIII-D double null (CH4)-C-13 puffing experiment

    SciTech Connect

    Elder, J. D.; Wampler, W. R.; McLean, A. G.; Stangeby, P. C.; Allen, S. L.; Bray, B. D.; Brooks, N. H.; Leonard, A. W.; Unterberg, Ezekial A; Watkins, J. G.

    2011-01-01

    Unbalanced double null ELMy H-mode configurations in DIII-D are used to simulate the situation in ITER high triangularity, burning plasma magnetic equilibria, where the second X-point lies close to the top of the vacuum vessel, creating a secondary divertor region at the upper blanket modules. The measured plasma conditions in the outer secondary divertor closely duplicated those projected for ITER. (CH4)-C-13 was injected into the secondary outer divertor to simulate sputtering there. The majority of the C-13 found was in the secondary outer divertor. This material migration pattern is radically different than that observed for main wall (CH4)-C-13 injections into single null configurations where the deposition is primarily at the inner divertor. The implications for tritium codeposition resulting from sputtering at the secondary divertor in ITER are significant since release of tritium from Be co-deposits at the main wall bake temperature for ITER, 240 degrees C, is incomplete. The principal features of the measured C-13 deposition pattern have been replicated by the OEDGE interpretive code.

  1. AGN Spectral Energy Distribution of GLAST Telescope Network Program Object 4C 29.45

    NASA Astrophysics Data System (ADS)

    Adkins, J.; Stefaniak, L.; Rapp, S.; Hinckley, B.; Lacy, M.

    2006-06-01

    The Gamma-Ray Large Area Space Telescope (GLAST) to be launched in 2006 has a proposed observing list that includes AGNs and Polars bright enough to be observed optically by amateurs and students. This observing list is maintained by the GLAST Telescope Network (GTN) and includes a number of objects that have yet to be observed by the Spitzer Space Telescope. Our project observed one of these objects, 4C 29.45, with the Spitzer MIPS and the IRAC instruments and also using ground based telescopes. Observations were made in seven infrared bands with Spitzer. Additional observations made from the ground by students, amateur astronomers, and small college observatories in R,V, and I were nearly simultaneous with the Spitzer observations. We have used this data to construct the Spectral Energy Distribution (SED) of 4C 29.45. We compare these data to models of the dust emission from the torus, sychrotron emission from the radio core, and thermal emission from the accretion disk to determine the relative importance of the different emission mechanisms in this object as a function of wavelength.

  2. Processing and characterization of zeta-Ta4C 3-x: A high toughness tantalum carbide

    NASA Astrophysics Data System (ADS)

    Sygnatowicz, Michael M.

    Tantalum carbides are commonly processed by hot-pressing, canned hot-isostatic-pressing, or spark-plasma sintering because of their high melting temperatures and low diffusivities. This study reports processing of dense ζ-Ta4C 3-x by reaction sintering of a Ta and TaC powder mixture (C/Ta atomic ratio = 0.66). ζ-Ta4C3-x is of interest due to its rhombohedral (trigonal) crystal structure that may be characterized as a polytype with both face-centered-cubic (fcc) and hexagonal-close-packed (hcp) Ta stacking sequences interrupted by stacking faults and missing carbon layers. This structure leads to easy cleaving on the basal planes and high fracture toughness. A key step in processing is the hydrogenation of the Ta powder to produce beta-TaH x, a hard and brittle phase that enables efficient comminution during milling and production of small, equiaxed Ta particles that can be packed to high green density with the TaC powder. Studies of phase evolution by quantitative X-ray diffraction during sintering revealed several intermediate reactions: (a) decomposition of beta-TaHx to Ta, (b) diffusion of C from gamma-TaC to Ta leading to the formation of α-Ta2Cy' with the kinetics described by the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation with an exponent, n = 0.5, and an activation energy of 221 kJ/mole, (c) equilibration of α-Ta2Cy' and gamma-TaC 0.78 phases, and (d) formation of ζ-Ta4C2.56 from the equilibrated α-Ta2C and gamma-TaC0.78 phases with the kinetics characterized by a higher JMAK exponent ( n ≈ 3) and higher activation energy (1089 kJ/mole). The microstructure showed evidence of nucleation and growth of the ζ-Ta4C 2.56 phase in both the α-Ta2C and gamma-TaC0.78 parent phases with distinct difference in the morphology due to the different number of variants of the habit plane. A hot-pressed and hot-isostatic-pressed (HIPed) material (C/Ta atomic ratio = 0.66), having formed 95 w% ζ-phase, attained a fracture toughness of 15.6 +/- 0.5 MPa√m and a

  3. Interfacial properties and electron structure of Al/B4C interface: A first-principles study

    NASA Astrophysics Data System (ADS)

    Xian, Yajiang; Qiu, Ruizhi; Wang, Xin; Zhang, Pengcheng

    2016-09-01

    This research aims at investigating the structural, mechanical and electronic properties of the Al (111)/B4C (0001) interface by first-principles calculations. This model geometry Al (111)/B4C (0001) is chosen because the close-packed planes of Al and B4C have the (111) and (0001) orientation, respectively, and the lattice mismatch is only ∼2.1%. Among four B4C (0001) surfaces with different terminations, our calculation of surface free energies predicted that C-terminated B4C (0001) surface is the most stable one. Relaxed atomic geometries, the work of adhesion and interfacial free energies were calculated for three C-terminated B4C (0001)/Al (111) interfaces with different stacking sequences (top-site, hollow-site, and bridge-site). Results reveal that the relaxed top-site (hollow-site-like) Al/B4C interface has the best adhesion force and also be the most stable. The interfacial electron structure including charge density difference, Bader charge and density of states (DOS) is analyzed to determine the nature of metal/carbide bonding and we find the formation of Alsbnd C bond and possibly the formation of Al4C3 in the interface.

  4. 12 CFR 225.104 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 3 2013-01-01 2013-01-01 false âServicesâ under section 4(c)(1) of Bank... (REGULATION Y) Regulations Financial Holding Companies Interpretations § 225.104 “Services” under section 4(c... payroll, life insurance and budget loan installment account. (2) In the second case, Corporation Y,...

  5. Role of RNA Interference (RNAi) in Dengue Virus Replication and Identification of NS4B as an RNAi Suppressor

    PubMed Central

    Kakumani, Pavan Kumar; Ponia, Sanket Singh; S, Rajgokul K.; Sood, Vikas; Chinnappan, Mahendran; Banerjea, Akhil C.; Medigeshi, Guruprasad R.; Malhotra, Pawan

    2013-01-01

    RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication. PMID:23741001

  6. Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.

    PubMed

    Ermert, David; Weckel, Antonin; Agarwal, Vaibhav; Frick, Inga-Maria; Björck, Lars; Blom, Anna M

    2013-11-01

    Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind the complement inhibitor C4b-binding protein (C4BP). We found a strong correlation between the ability of AP1 and its isogenic mutants lacking protein H to inhibit opsonization with complement C3b and binding of C4BP. C4BP bound to immobilized protein H or AP1 bacteria retained its cofactor activity for degradation of (125)I-C4b. Furthermore, C4b deposited from serum onto AP1 bacterial surfaces was processed into C4c/C4d fragments, which did not occur on strains unable to bind C4BP. Recombinant C4BP mutants, which (i) lack certain CCP domains or (ii) have mutations in single aa as well as (iii) mutants with additional aa between different CCP domains were used to determine that the binding is mainly mediated by a patch of positively charged amino acid residues at the interface of domains CCP1 and CCP2. Using recombinant protein H fragments, we narrowed down the binding site to the N-terminal domain A. With a peptide microarray, we identified one single 18-amino acid-long peptide comprising residues 92-109, which specifically bound C4BP. Biacore was used to determine KD = 6 × 10(-7) M between protein H and a single subunit of C4BP. C4BP binding also correlated with elevated levels of adhesion and invasion to endothelial cells. Taken together, we identified the molecular basis of C4BP-protein H interaction and found that it is not only important for decreased opsonization but also for invasion of endothelial cells by S. pyogenes.

  7. Multifrequency Studies of the Peculiar Quasar 4C +21.35 during the 2010 Flaring Activity

    NASA Astrophysics Data System (ADS)

    Ackermann, M.; Ajello, M.; Allafort, A.; Antolini, E.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Bonamente, E.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caraveo, P. A.; Cavazzuti, E.; Cecchi, C.; Chaves, R. C. G.; Chekhtman, A.; Chiang, J.; Chiaro, G.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Conrad, J.; Cutini, S.; D'Ammando, F.; de Palma, F.; Dermer, C. D.; Silva, E. do Couto e.; Donato, D.; Drell, P. S.; Favuzzi, C.; Finke, J.; Focke, W. B.; Franckowiak, A.; Fukazawa, Y.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Giglietto, N.; Giordano, F.; Giroletti, M.; Godfrey, G.; Grenier, I. A.; Guiriec, S.; Hayashida, M.; Hewitt, J. W.; Horan, D.; Hughes, R. E.; Iafrate, G.; Johnson, A. S.; Knödlseder, J.; Kuss, M.; Lande, J.; Larsson, S.; Latronico, L.; Longo, F.; Loparco, F.; Lovellette, M. N.; Lubrano, P.; Mayer, M.; Mazziotta, M. N.; McEnery, J. E.; Michelson, P. F.; Mizuno, T.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nemmen, R.; Nuss, E.; Ohsugi, T.; Orienti, M.; Orlando, E.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Rainò, S.; Razzano, M.; Reimer, A.; Reimer, O.; Sanchez, D. A.; Schulz, A.; Sgrò, C.; Siskind, E. J.; Spandre, G.; Spinelli, P.; Stawarz, Ł.; Takahashi, H.; Takahashi, T.; Thayer, J. G.; Thayer, J. B.; Thompson, D. J.; Tinivella, M.; Torres, D. F.; Tosti, G.; Troja, E.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vianello, G.; Vitale, V.; Werner, M.; Winer, B. L.; Wood, D. L.; Wood, K. S.; Fermi Large Area Telescope Collaboration; Aleksić, J.; Ansoldi, S.; Antonelli, L. A.; Antoranz, P.; Babic, A.; Bangale, P.; Barres de Almeida, U.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Berger, K.; Bernardini, E.; Biland, A.; Blanch, O.; Bock, R. K.; Bonnefoy, S.; Bonnoli, G.; Borracci, F.; Bretz, T.; Carmona, E.; Carosi, A.; Carreto Fidalgo, D.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Caneva, G.; De Lotto, B.; Delgado Mendez, C.; Doert, M.; Domínguez, A.; Dominis Prester, D.; Dorner, D.; Doro, M.; Einecke, S.; Eisenacher, D.; Elsaesser, D.; Farina, E.; Ferenc, D.; Fonseca, M. V.; Font, L.; Frantzen, K.; Fruck, C.; García López, R. J.; Garczarczyk, M.; Garrido Terrats, D.; Gaug, M.; Giavitto, G.; Godinović, N.; González Muñoz, A.; Gozzini, S. R.; Hadasch, D.; Herrero, A.; Hildebrand, D.; Hose, J.; Hrupec, D.; Idec, W.; Kadenius, V.; Kellermann, H.; Knoetig, M. L.; Kodani, K.; Konno, Y.; Krause, J.; Kubo, H.; Kushida, J.; La Barbera, A.; Lelas, D.; Lewandowska, N.; Lindfors, E.; Lombardi, S.; López, M.; López-Coto, R.; López-Oramas, A.; Lorenz, E.; Lozano, I.; Makariev, M.; Mallot, K.; Maneva, G.; Mankuzhiyil, N.; Mannheim, K.; Maraschi, L.; Marcote, B.; Mariotti, M.; Martínez, M.; Mazin, D.; Menzel, U.; Meucci, M.; Miranda, J. M.; Mirzoyan, R.; Moralejo, A.; Munar-Adrover, P.; Nakajima, D.; Niedzwiecki, A.; Nishijima, K.; Nilsson, K.; Nowak, N.; Orito, R.; Overkemping, A.; Paiano, S.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Paredes-Fortuny, X.; Partini, S.; Persic, M.; Prada, F.; Prada Moroni, P. G.; Prandini, E.; Preziuso, S.; Puljak, I.; Reinthal, R.; Rhode, W.; Ribó, M.; Rico, J.; Rodriguez Garcia, J.; Rügamer, S.; Saggion, A.; Saito, T.; Saito, K.; Salvati, M.; Satalecka, K.; Scalzotto, V.; Scapin, V.; Schultz, C.; Schweizer, T.; Shore, S. N.; Sillanpää, A.; Sitarek, J.; Snidaric, I.; Sobczynska, D.; Spanier, F.; Stamatescu, V.; Stamerra, A.; Steinbring, T.; Storz, J.; Sun, S.; Surić, T.; Takalo, L.; Takami, H.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Thaele, J.; Tibolla, O.; Toyama, T.; Treves, A.; Vogler, P.; Wagner, R. M.; Zandanel, F.; Zanin, R.; MAGIC Collaboration; Aller, M. F.; Angelakis, E.; Blinov, D. A.; Djorgovski, S. G.; Drake, A. J.; Efimova, N. V.; Gurwell, M. A.; Homan, D. C.; Jordan, B.; Kopatskaya, E. N.; Kovalev, Y. Y.; Kurtanidze, O. M.; Lähteenmäki, A.; Larionov, V. M.; Lister, M. L.; Nieppola, E.; Nikolashvili, M. G.; Ros, E.; Savolainen, T.; Sigua, L. A.; Tornikoski, M.

    2014-05-01

    The discovery of rapidly variable Very High Energy (VHE; E > 100 GeV) γ-ray emission from 4C +21.35 (PKS 1222+216) by MAGIC on 2010 June 17, triggered by the high activity detected by the Fermi Large Area Telescope (LAT) in high energy (HE; E > 100 MeV) γ-rays, poses intriguing questions on the location of the γ-ray emitting region in this flat spectrum radio quasar. We present multifrequency data of 4C +21.35 collected from centimeter to VHE during 2010 to investigate the properties of this source and discuss a possible emission model. The first hint of detection at VHE was observed by MAGIC on 2010 May 3, soon after a γ-ray flare detected by Fermi-LAT that peaked on April 29. The same emission mechanism may therefore be responsible for both the HE and VHE emission during the 2010 flaring episodes. Two optical peaks were detected on 2010 April 20 and June 30, close in time but not simultaneous with the two γ-ray peaks, while no clear connection was observed between the X-ray and γ-ray emission. An increasing flux density was observed in radio and mm bands from the beginning of 2009, in accordance with the increasing γ-ray activity observed by Fermi-LAT, and peaking on 2011 January 27 in the mm regime (230 GHz). We model the spectral energy distributions (SEDs) of 4C +21.35 for the two periods of the VHE detection and a quiescent state, using a one-zone model with the emission coming from a very compact region outside the broad line region. The three SEDs can be fit with a combination of synchrotron self-Compton and external Compton emission of seed photons from a dust torus, changing only the electron distribution parameters between the epochs. The fit of the optical/UV part of the spectrum for 2010 April 29 seems to favor an inner disk radius of

  8. On the Merging Cluster Abell 578 and Its Central Radio Galaxy 4C+67.13

    NASA Astrophysics Data System (ADS)

    Hagino, K.; Stawarz, Ł.; Siemiginowska, A.; Cheung, C. C.; Kozieł-Wierzbowska, D.; Szostek, A.; Madejski, G.; Harris, D. E.; Simionescu, A.; Takahashi, T.

    2015-06-01

    Here we analyze radio, optical, and X-ray data for the peculiar cluster Abell 578. This cluster is not fully relaxed and consists of two merging sub-systems. The brightest cluster galaxy (BCG), CGPG 0719.8+6704, is a pair of interacting ellipticals with projected separation ˜10 kpc, the brighter of which hosts the radio source 4C+67.13. The Fanaroff-Riley type-II radio morphology of 4C+67.13 is unusual for central radio galaxies in local Abell clusters. Our new optical spectroscopy revealed that both nuclei of the CGPG 0719.8+6704 pair are active, albeit at low accretion rates corresponding to the Eddington ratio ˜ {{10}-4} (for the estimated black hole masses of ˜ 3× {{10}8} {{M}⊙ } and ˜ {{10}9} {{M}⊙ }). The gathered X-ray (Chandra) data allowed us to confirm and to quantify robustly the previously noted elongation of the gaseous atmosphere in the dominant sub-cluster, as well as a large spatial offset (˜60 kpc projected) between the position of the BCG and the cluster center inferred from the modeling of the X-ray surface brightness distribution. Detailed analysis of the brightness profiles and temperature revealed also that the cluster gas in the vicinity of 4C+67.13 is compressed (by a factor of about ˜1.4) and heated (from ≃ 2.0 keV up to 2.7 keV), consistent with the presence of a weak shock (Mach number ˜1.3) driven by the expanding jet cocoon. This would then require the jet kinetic power of the order of ˜ {{10}45} erg s-1, implying either a very high efficiency of the jet production for the current accretion rate, or a highly modulated jet/accretion activity in the system. Based on service observations made with the WHT operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias.

  9. Multifrequency studies of the peculiar quasar 4C +21.35 during the 2010 flaring activity

    SciTech Connect

    Ackermann, M.; Buehler, R.; Ajello, M.; Allafort, A.; Caliandro, G. A.; Cameron, R. A.; Antolini, E.; Bonamente, E.; Cecchi, C.; Barbiellini, G.; Bastieri, D.; Buson, S.; Bellazzini, R.; Bregeon, J.; Bissaldi, E.; Brigida, M.; Bruel, P.; Cavazzuti, E.; Chaves, R. C. G. E-mail: justin.finke@nrl.navy.mil E-mail: tterzic@uniri.hr [Laboratoire AIM, CEA-IRFU Collaboration: Fermi Large Area Telescope Collaboration; MAGIC Collaboration; and others

    2014-05-10

    The discovery of rapidly variable Very High Energy (VHE; E > 100 GeV) γ-ray emission from 4C +21.35 (PKS 1222+216) by MAGIC on 2010 June 17, triggered by the high activity detected by the Fermi Large Area Telescope (LAT) in high energy (HE; E > 100 MeV) γ-rays, poses intriguing questions on the location of the γ-ray emitting region in this flat spectrum radio quasar. We present multifrequency data of 4C +21.35 collected from centimeter to VHE during 2010 to investigate the properties of this source and discuss a possible emission model. The first hint of detection at VHE was observed by MAGIC on 2010 May 3, soon after a γ-ray flare detected by Fermi-LAT that peaked on April 29. The same emission mechanism may therefore be responsible for both the HE and VHE emission during the 2010 flaring episodes. Two optical peaks were detected on 2010 April 20 and June 30, close in time but not simultaneous with the two γ-ray peaks, while no clear connection was observed between the X-ray and γ-ray emission. An increasing flux density was observed in radio and mm bands from the beginning of 2009, in accordance with the increasing γ-ray activity observed by Fermi-LAT, and peaking on 2011 January 27 in the mm regime (230 GHz). We model the spectral energy distributions (SEDs) of 4C +21.35 for the two periods of the VHE detection and a quiescent state, using a one-zone model with the emission coming from a very compact region outside the broad line region. The three SEDs can be fit with a combination of synchrotron self-Compton and external Compton emission of seed photons from a dust torus, changing only the electron distribution parameters between the epochs. The fit of the optical/UV part of the spectrum for 2010 April 29 seems to favor an inner disk radius of

  10. Geophysical investigation of trench 4, Burial Ground 218-W-4C, 200 west area

    SciTech Connect

    Kiesler, J.P.

    1994-09-01

    This report contains the results of a geophysical investigation conducted to characterize Trench 4, located in Burial Ground 218-W-4C, 200 West Area. Trench 4 is where transuranic (TRU) waste is stored. The primary objective of these geophysical investigations was to determine the outer edges of the trench/modules and select locations for plate-bearing tests. The test locations are to be 5 to 8 ft. beyond the edges of the trench. Secondary objectives include differentiating between the different types of waste containers within a given trench, determining the amount of soil cover over the waste containers, and to locate the module boundaries. Ground-penetrating radar (GPR) and electromagnetic induction (EMI) were the methods selected for this investigation.

  11. Dry Sliding Tribological Studies of AA6061-B4C-Gr Hybrid Composites

    NASA Astrophysics Data System (ADS)

    Monikandan, V. V.; Joseph, M. A.; Rajendrakumar, P. K.

    2016-08-01

    The dry sliding behavior of stir-cast AA6061-10 wt.% B4C composites containing 2.5, 5 and 7.5 wt.% graphite particles was studied as a function of applied load, sliding speed and sliding distance on a pin-on-disk tribotester. The wear rate and friction coefficient increased with increase in applied load and sliding distance. The increase in graphite addition reduced the increase in wear rate and friction coefficient in the sliding speed range 2-2.5 m/s. Scanning electron microscopy of the worn pin revealed a graphite tribolayer, and transmission electron microscopy revealed overlapping deformation bands under 30 N applied load. Upon increasing the applied load to 40 N, welded region with fine crystalline structure was formed due to dynamic recrystallization of AA6061 alloy matrix.

  12. Boron analysis by electron microprobe using MoB4C layered synthetic crystals

    USGS Publications Warehouse

    McGee, J.J.; Slack, J.F.; Herrington, C.R.

    1991-01-01

    Preliminary electron microprobe studies of B distribution in minerals have been carried out using MoB4C-layered synthetic crystals to improve analytical sensitivity for B. Any microprobe measurements of the B contents of minerals using this crystal must include analyses for Cl to assess and correct for the interference of Cl X-rays on the BK?? peak. Microprobe analyses for B can be made routinely in tourmaline and other B-rich minerals, and minor B contents also can be determined in common rock-forming minerals. Incorporation of unusually high B contents in minerals other than borosilicates has been discovered in prograde and retrograde minerals in tourmalinites from the Broken Hill district, Australia, and may reflect high B activities produced during the metamorphism of tourmaline-rich rocks. -from Authors

  13. Dry Sliding Tribological Studies of AA6061-B4C-Gr Hybrid Composites

    NASA Astrophysics Data System (ADS)

    Monikandan, V. V.; Joseph, M. A.; Rajendrakumar, P. K.

    2016-10-01

    The dry sliding behavior of stir-cast AA6061-10 wt.% B4C composites containing 2.5, 5 and 7.5 wt.% graphite particles was studied as a function of applied load, sliding speed and sliding distance on a pin-on-disk tribotester. The wear rate and friction coefficient increased with increase in applied load and sliding distance. The increase in graphite addition reduced the increase in wear rate and friction coefficient in the sliding speed range 2-2.5 m/s. Scanning electron microscopy of the worn pin revealed a graphite tribolayer, and transmission electron microscopy revealed overlapping deformation bands under 30 N applied load. Upon increasing the applied load to 40 N, welded region with fine crystalline structure was formed due to dynamic recrystallization of AA6061 alloy matrix.

  14. BOREAS Level-4c AVHRR-LAC Ten-Day Composite Images: Surface Parameters

    NASA Technical Reports Server (NTRS)

    Cihlar, Josef; Chen, Jing; Huang, Fengting; Nickeson, Jaime; Newcomer, Jeffrey A.; Hall, Forrest G. (Editor)

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the NOAA-11 and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4c data are gridded, 10-day composites of surface parameters produced from sets of single-day images. Temporally, the 10-day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files. Note: Some of the data files on the BOREAS CD-ROMs have been compressed using the Gzip program.

  15. Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation

    PubMed Central

    Carson, Cheryl; Raman, Pichai; Tullai, Jennifer; Xu, Lei; Henault, Martin; Thomas, Emily; Yeola, Sarita; Lao, Jianmin; McPate, Mark; Verkuyl, J. Martin; Marsh, George; Sarber, Jason; Amaral, Adam; Bailey, Scott; Lubicka, Danuta; Pham, Helen; Miranda, Nicolette; Ding, Jian; Tang, Hai-Ming; Ju, Haisong; Tranter, Pamela; Ji, Nan; Krastel, Philipp; Jain, Rishi K.; Schumacher, Andrew M.; Loureiro, Joseph J.; George, Elizabeth; Berellini, Giuliano; Ross, Nathan T.; Bushell, Simon M.; Erdemli, Gül; Solomon, Jonathan M.

    2015-01-01

    Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels. PMID:26098886

  16. Solubility of alkali metal halides in the ionic liquid [C4C1im][OTf].

    PubMed

    Kuzmina, O; Bordes, E; Schmauck, J; Hunt, P A; Hallett, J P; Welton, T

    2016-06-28

    The solubilities of the metal halides LiF, LiCl, LiBr, LiI, NaF, NaCl, NaBr, NaI, KF, KCl, KBr, KI, RbCl, CsCl, CsI, were measured at temperatures ranging from 298.15 to 378.15 K in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4C1im][OTf]). Li(+), Na(+) and K(+) salts with anions matching the ionic liquid have also been investigated to determine how well these cations dissolve in [C4C1im][OTf]. This study compares the influence of metal cation and halide anion on the solubility of salts within this ionic liquid. The highest solubility found was for iodide salts, and the lowest solubility for the three fluoride salts. There is no outstanding difference in the solubility of salts with matching anions in comparison to halide salts. The experimental data were correlated employing several phase equilibria models, including ideal mixtures, van't Hoff, the λh (Buchowski) equation, the modified Apelblat equation, and the non-random two-liquid model (NRTL). It was found that the van't Hoff model gave the best correlation results. On the basis of the experimental data the thermodynamic dissolution parameters (ΔH, ΔS, and ΔG) were determined for the studied systems together with computed gas phase metathesis parameters. Dissolution depends on the energy difference between enthalpies of fusion and dissolution of the solute salt. This demonstrates that overcoming the lattice energy of the solid matrix is the key to the solubility of inorganic salts in ionic liquids. PMID:27264676

  17. Hard X-Ray Detection of the High Redshift Quasar 4C 71.07

    NASA Technical Reports Server (NTRS)

    Malizia, A.; Bassani, L.; Dean, A. J.; McCollough, M. L.; Stephen, J. B.; Zhang, S. N.

    1999-01-01

    BATSE/OSSE observations of the high redshift quasar 4C 71.07 indicate that this is the brightest and furthest AGN so far detected 20 keV. BATSE Earth occultation data have been used to search for emission from 4C 71.07 from nearly 3 years of observation. The mean source flux over the- whole period in the BATSE energy range 20-100 keV is (13.2 +/- 1.06) x 10(exp -11) erg/square cm/s corresponding to a luminosity of 2 x 10(exp 48 erg/s. The BATSE light curve over the 3 years of observations shows several flare-like events, one of which (in January 1996) is associated with an optical flare (R=16.1) but with a delay of 55 days. The OSSE/BATSE spectral analysis indicates that the source is characterized by a flat power spectrum (Gamma is approximately 1.1- 1.3) when in a low state: this spectral form is consistent within errors with the ASCA and ROSAT spectra. This means that the power law observed from 0.1 to 10 keV extends up to at least 1 MeV but steepens soon after to meet EGRET high energy data. BATSE data taken around the January 1996 flare suggests that the spectrum could be steeper when the source is in a bright state. The upsilon-F-upsilon representation of the source is typical of a low frequency peaked/ gamma- ray dominated blazar, with the synchrotron peak in the mm-FIR band and the Compton peak in the MeV band. The BATSE and OSSE spectral data seem to favour a model in which the high energy - flux is due to the sum of the synchrotron self-Compton and the external Compton contributions: this is also supported by the- variability behaviour of the source.

  18. Solubility of alkali metal halides in the ionic liquid [C4C1im][OTf].

    PubMed

    Kuzmina, O; Bordes, E; Schmauck, J; Hunt, P A; Hallett, J P; Welton, T

    2016-06-28

    The solubilities of the metal halides LiF, LiCl, LiBr, LiI, NaF, NaCl, NaBr, NaI, KF, KCl, KBr, KI, RbCl, CsCl, CsI, were measured at temperatures ranging from 298.15 to 378.15 K in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4C1im][OTf]). Li(+), Na(+) and K(+) salts with anions matching the ionic liquid have also been investigated to determine how well these cations dissolve in [C4C1im][OTf]. This study compares the influence of metal cation and halide anion on the solubility of salts within this ionic liquid. The highest solubility found was for iodide salts, and the lowest solubility for the three fluoride salts. There is no outstanding difference in the solubility of salts with matching anions in comparison to halide salts. The experimental data were correlated employing several phase equilibria models, including ideal mixtures, van't Hoff, the λh (Buchowski) equation, the modified Apelblat equation, and the non-random two-liquid model (NRTL). It was found that the van't Hoff model gave the best correlation results. On the basis of the experimental data the thermodynamic dissolution parameters (ΔH, ΔS, and ΔG) were determined for the studied systems together with computed gas phase metathesis parameters. Dissolution depends on the energy difference between enthalpies of fusion and dissolution of the solute salt. This demonstrates that overcoming the lattice energy of the solid matrix is the key to the solubility of inorganic salts in ionic liquids.

  19. Microstructure and Mechanical Properties of Al6061-31vol.% B4C Composites Prepared by Hot Isostatic Pressing

    NASA Astrophysics Data System (ADS)

    Xian, Yajiang; Pang, Xiaoxuan; He, Shixiong; Wang, Wei; Wang, Xin; Zhang, Pengcheng

    2015-10-01

    Fabrication of durable and usable composites with high content of B4C (up to 31vol.%) is quite challenging in several aspects including blending, cold isostatic pressing, and hot isostatic pressing (HIP), and especially the optimal HIP process is essential to achieve the metal matrix composite with desirable properties. The microstructure and mechanical properties of Al6061-31vol.% B4C with different particle sizes were investigated by scanning electron microscopy (SEM) and tensile testing, respectively. SEM analysis and quantitative measurements of the particle distribution reveal that B4C particles were uniformly distributed in the matrix without agglomeration when the HIP treatment temperature was about 580 °C, and x-ray diffraction also identified a dispersion of B4C particles as well as reaction products (AlB2 and Al3BC) in the composites. Microhardness of Al6061-31vol.% B4C composites was improved with B4C particle size, and the tensile strength of all the samples declined with an increase in B4C particle size. The contribution from different strengthening mechanisms was also discussed.

  20. Application of trajectory optimization techniques to upper atmosphere sampling flights using the F4-C Phantom aircraft

    NASA Technical Reports Server (NTRS)

    Hague, D. S.; Merz, A. W.

    1975-01-01

    Altitude potential of an off-the-shelf F4-C aircraft is examined. It is shown that the standard F4-C has a maximum altitude capability in the region from 85000 to 95000 ft, depending on the minimum dynamic pressures deemed acceptable for adequate flight control. By using engine overspeed capability and by making use of prevailing winds in the stratosphere, it is suggested that the maximum altitude achievable by an F4-C should be in the vicinity of 95000 ft for routine flight operation. This altitude is well in excess of the minimum altitudes which must be achieved for monitoring the possible growth of suspected aerosol contaminants.

  1. Specific induction of a functional endogenous D2 short dopamine receptor in GH4C1 cells.

    PubMed

    Allard, S; Lapointe, S; Falardeau, P

    1993-06-15

    In contrast to lactotrophs, tumoral pituitary cells like GH3 and GH4C1 lack expression of dopamine D2short and D2long receptors. In GH4C1 cells, we observed that the expression of only the short isoform of D2 receptor can be induced after transfection with a plasmid which confers resistance to neomycin (pRSVNeo). High levels of fully functional D2short receptor were obtained in GH4C1 following transfection (528fmol/mg protein). Sequence, pharmacology and coupling of the induced-D2 receptor do not show any difference with the cloned rat D2 short receptor.

  2. Report on inspection of compliance with DOE Order 2030.4B at the Savannah River Site

    SciTech Connect

    1997-03-01

    The purpose of this inspection was to evaluate contractor compliance at the Savannah River Site (SRS) with Department of Energy (DOE) Order 2030.4B, {open_quotes}Reporting Fraud, Waste, And Abuse To The Office Of Inspector General.{close_quotes} The specific objective was to determine if the SRS management and operating (M&O) contractors were complying with the requirements in Paragraph 6.c. of DOE Order 2030.4B. These requirements are: (1) annual notification to employees of their duty to report allegations of fraud, waste, abuse, corruption, or mismanagement; (2) display and publish the DOE Office of Inspector General (OIG) Hotline telephone number in common areas of buildings; (3) display and publish the DOE OIG Hotline number in telephone books and newsletters; and (4) notify the OIG cases referred to other law enforcement entities.

  3. Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein.

    PubMed

    Tai, Vincent W-F; Garrido, Dulce; Price, Daniel J; Maynard, Andrew; Pouliot, Jeffrey J; Xiong, Zhiping; Seal, John W; Creech, Katrina L; Kryn, Luz H; Baughman, Todd M; Peat, Andrew J

    2014-05-15

    Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.2nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9nM and 6.1nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's=10.2 and 30.4nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.

  4. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents.

    PubMed

    Nagender, P; Naresh Kumar, R; Malla Reddy, G; Krishna Swaroop, D; Poornachandra, Y; Ganesh Kumar, C; Narsaiah, B

    2016-09-15

    A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule. PMID:27528432

  5. Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity

    PubMed Central

    Qu, Lin; McMullan, Laura K.; Rice, Charles M.

    2001-01-01

    Isolates of bovine viral diarrhea virus (BVDV), the prototype pestivirus, are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. The cp viruses also differ from ncp viruses by the production of viral nonstructural protein NS3. However, the mechanism by which cp viruses induce cytopathic effect in cell culture remains unknown. Here we used a genetic approach to isolate ncp variants that arose from a cp virus at low frequency. A bicistronic BVDV (cp strain NADL) was created that expressed puromycin acetyltransferase as a dominant selectable marker. This bicistronic virus exhibited slightly slower growth kinetics and smaller plaques than NADL but remained cp. A number of independent ncp variants were isolated by puromycin selection. Remarkably, these ncp variants produced NS3 and viral RNA at levels comparable to those of the cp parent. Sequence analyses uncovered no change in NS3, but for all ncp variants a Y2441C substitution at residue 15 of NS4B was found. Introduction of the Y2441C substitution into the NADL or bicistronic cp viruses reconstituted the ncp phenotype. Y2441 is highly conserved among pestiviruses and is located in a region of NS4B predicted to be on the cytosolic side of the endoplasmic reticulum membrane. Other engineered substitutions for Y2441 also affected viral cytopathogenicity and viability, with Y2441V being cp, Y2441A being ncp, and Y2441D rendering the virus unable to replicate. The ncp substitutions for Y2441 resulted in slightly increased levels of NS2-3 relative to NS3. We also showed that NS3, NS4B, and NS5A could be chemically cross-linked in NADL-infected cells, indicating that they are associated as components of a multiprotein complex. Although the mechanism remains to be elucidated, these results demonstrate that mutations in NS4B can attenuate BVDV cytopathogenicity despite NS3 production. PMID:11602707

  6. Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells.

    PubMed

    Saxena, Ashwini; Bachelor, Martha; Park, Yong H; Carreno, Flavia R; Nedungadi, T Prashant; Cunningham, J Thomas

    2014-10-15

    Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 μM) and by a Src kinase inhibitor PP2 (10 μM). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 ± 2.8% n = 5 and ANG II 80.5 ± 2.4% n = 5). This ANG II-induced increase in calcium influx was also blocked by 1 μM losartan and 10 μM PP2 (losartan 26.4 ± 3.8% n = 5 and PP2 19.7 ± 3.9% n = 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway. PMID:25080500

  7. A Flight Investigation of the Spinning of the F4B-2 Biplane with Various Loads and Tail Surfaces

    NASA Technical Reports Server (NTRS)

    Scudder, N F; Seidman, Oscar

    1936-01-01

    A flight investigation of the spinning of the F4B-2 single-seat fighter airplane was made for the purpose of finding modifications that would eliminate dangerous spin tendencies exhibited by this type of airplane in service. The effects on steady spins and on recoveries of changing the loading, enlarging the fin areas, changing the elevator plan form, and raising the horizontal surfaces, were determined.

  8. The complement regulator C4b-binding protein analyzed by molecular modeling, bioinformatics and computer-aided experimental design.

    PubMed

    Villoutreix, B O; Blom, A M; Webb, J; Dahlbäck, B

    1999-05-01

    Molecular modeling and bioinformatics have gained recognition as scientific disciplines of importance in the field of biomedical research. Molecular modeling not only allows to predict the three-dimensional structure of a protein but also helps to define its function. Careful incorporation of the experimental findings in the structural/theoretical data provides means to understand molecular mechanisms for highly complex biological systems. C4b-binding protein (C4BP) is composed of one beta-chain and seven alpha-chains essentially built from three- and eight-complement control protein (CCP) modules, respectively, followed by a non-repeat carboxy-terminal region involved in polymerization of the chains. C4BP is involved in the regulation of the complement system and interacts with many molecules such as C4b, Arp, protein S and heparin. Here, we report experimental and computer data obtained for C4BP. Protein modeling together with site directed mutagenesis indicate that R39, R64 and R66 from the C4BP alpha-chain form a key binding site for heparin, suggesting that this region could be of major importance for interaction with C4b. We also propose that the first CCP of the C4BP beta-chain displays a key hydrophobic surface of major importance for the interaction with the coagulation cofactor protein S. PMID:10408373

  9. Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication.

    PubMed

    van Cleef, Koen W R; Overheul, Gijs J; Thomassen, Michael C; Kaptein, Suzanne J F; Davidson, Andrew D; Jacobs, Michael; Neyts, Johan; van Kuppeveld, Frank J M; van Rij, Ronald P

    2013-08-01

    Dengue virus (DENV) is an important human arthropod-borne virus with a major impact on public health. Nevertheless, a licensed vaccine or specific treatment is still lacking. We therefore screened the NIH Clinical Collection (NCC), a library of drug-like small molecules, for inhibitors of DENV replication using a cell line that contains a stably replicating DENV serotype 2 (DENV2) subgenomic replicon. The most potent DENV inhibitor in the NCC was δ opioid receptor antagonist SDM25N. This compound showed antiviral activity against wild-type DENV2 in both Hela and BHK-21 cells, but not in the C6/36 cell line derived from the mosquito Aedes albopictus. The structurally related compound naltrindole also inhibited DENV replication, albeit less potently. Using a transient subgenomic replicon, we demonstrate that SDM25N restricts genomic RNA replication rather than translation of the viral genome. We identified a single amino acid substitution (F164L) in the NS4B protein that confers resistance to SDM25N. Remarkably, an NS4B amino acid substitution (P104L), which was previously shown to confer resistance to the DENV inhibitor NITD-618, also provided resistance to SDM25N. In conclusion, we have identified a new DENV inhibitor, SDM25N, which restricts genomic RNA replication by - directly or indirectly - targeting the viral NS4B protein. PMID:23735301

  10. Dithiazolo[5,4-b:4',5'-d]phosphole: a highly luminescent electron-accepting building block.

    PubMed

    He, Xiaoming; Woo, Alva Y Y; Borau-Garcia, Javier; Baumgartner, Thomas

    2013-06-01

    A family of highly emissive dithiazolo[5,4-b:4',5'-d]phospholes has been designed and synthesized. The structures of two trivalent P species, as well as their corresponding P oxides, have been confirmed by X-ray crystallography. The parent dithiazolo[5,4-b:4',5'-d]phosphole oxide exhibits strong blue photoluminescence at λem = 442 nm, with an excellent quantum yield efficiency of ϕPL = 0.81. The photophysical properties of these compounds can be easily tuned by extension of the conjugation and modification of the phosphorus center. Compared with the established dithieno[3,2-b:2',3'-d]phosphole system, the incorporation of electronegative nitrogen atoms leads to significantly lowered frontier orbital energy levels, as validated by both electrochemistry and theoretical calculations, thus suggesting that the dithiazolo[5,4-b:4',5'-d]phospholes are valuable, air-stable, n-type conjugated materials. These new building blocks have been further applied to the construction of an extended oligomer with fluorene. Extension of the dithiazolophosphole core with triazole units through click reactions also provides a suitable N,N-chelating moiety for metal binding and a representative molecular species was successfully used as a selective colorimetric and fluorescent sensor for Cu(II) ions.

  11. The GAPS programme with HARPS-N at TNG. VI. The curious case of TrES-4b

    NASA Astrophysics Data System (ADS)

    Sozzetti, A.; Bonomo, A. S.; Biazzo, K.; Mancini, L.; Damasso, M.; Desidera, S.; Gratton, R.; Lanza, A. F.; Poretti, E.; Rainer, M.; Malavolta, L.; Affer, L.; Barbieri, M.; Bedin, L. R.; Boccato, C.; Bonavita, M.; Borsa, F.; Ciceri, S.; Claudi, R. U.; Gandolfi, D.; Giacobbe, P.; Henning, T.; Knapic, C.; Latham, D. W.; Lodato, G.; Maggio, A.; Maldonado, J.; Marzari, F.; Martinez Fiorenzano, A. F.; Micela, G.; Molinari, E.; Mordasini, C.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Pepe, F.; Piotto, G.; Santos, N.; Scandariato, G.; Shkolnik, E.; Southworth, J.

    2015-03-01

    We update the TrES-4 system parameters using high-precision HARPS-N radial-velocity measurements and new photometric light curves. A combined spectroscopic and photometric analysis allows us to determine a spectroscopic orbit with a semi-amplitude K = 51 ± 3 m s-1. The derived mass of TrES-4b is found to be Mp = 0.49 ± 0.04 MJup, significantly lower than previously reported. Combined with the large radius () inferred from our analysis, TrES-4b becomes the transiting hot Jupiter with the second-lowest density known. We discuss several scenarios to explain the puzzling discrepancy in the mass of TrES-4b in the context of the exotic class of highly inflated transiting giant planets. Based on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Fundacion Galileo Galilei of the INAF at the Spanish Observatorio del Roque de los Muchachos of the IAC in the frame of the program Global Architecture of Planetary Systems (GAPS), and with the Zeiss 1.23-m telescope at the German-Spanish Astronomical Center at Calar Alto, Spain. Tables 1 and 3 are available in electronic form at http://www.aanda.org

  12. Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription

    PubMed Central

    Periz, Goran; Lu, Jiayin; Zhang, Tao; Kankel, Mark W.; Jablonski, Angela M.; Kalb, Robert; McCampbell, Alexander; Wang, Jiou

    2015-01-01

    Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B) and lysine-specific demethylase 1 (LSD1), respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy. PMID:25837623

  13. PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization.

    PubMed Central

    Houslay, Miles D; Adams, David R

    2003-01-01

    cAMP is a second messenger that controls many key cellular functions. The only way to inactivate cAMP is to degrade it through the action of cAMP phosphodiesterases (PDEs). PDEs are thus poised to play a key regulatory role. PDE4 cAMP-specific phosphodiesterases appear to have specific functions with selective inhibitors serving as potent anti-inflammatory agents. The recent elucidation of the structure of the PDE4 catalytic unit allows for molecular insight into the mode of catalysis as well as substrate and inhibitor selectivity. The four PDE4 genes encode over 16 isoforms, each of which is characterized by a unique N-terminal region. PDE4 isoforms play a pivotal role in controlling functionally and spatially distinct pools of cAMP by virtue of their unique intracellular targeting. Targeting occurs by association with proteins, such as arrestins, SRC family tyrosyl kinases, A-kinase anchoring proteins ('AKAPs') and receptor for activated C kinase 1 ('RACK1'), and, in the case of isoform PDE4A1, by a specific interaction (TAPAS-1) with phosphatidic acid. PDE4 isoforms are 'designed' to be regulated by extracellular-signal-related protein kinase (ERK), which binds to anchor sites on the PDE4 catalytic domain that it phosphorylates. The upstream conserved region 1 (UCR1) and 2 (UCR2) modules that abut the PDE4 catalytic unit confer regulatory functions by orchestrating the functional outcome of phosphorylation by cAMP-dependent protein kinase ('PKA') and ERK. PDE4 enzymes stand at a crossroads that allows them to integrate various signalling pathways with that of cAMP in spatially distinct compartments. PMID:12444918

  14. Calculation of the store house worker dose in a lost wax foundry using MCNP-4C.

    PubMed

    Alegría, Natalia; Legarda, Fernando; Herranz, Margarita; Idoeta, Raquel

    2005-01-01

    Lost wax casting is an industrial process which permits the transmutation into metal of models made in wax. The wax model is covered with a silicaceous shell of the required thickness and once this shell is built the set is heated and wax melted. Liquid metal is then cast into the shell replacing the wax. When the metal is cool, the shell is broken away in order to recover the metallic piece. In this process zircon sands are used for the preparation of the silicaceous shell. These sands have varying concentrations of natural radionuclides: 238U, 232Th and 235U together with their progenics. The zircon sand is distributed in bags of 50 kg, and 30 bags are on a pallet, weighing 1,500 kg. The pallets with the bags have dimensions 80 cm x 120 cm x 80 cm, and constitute the radiation source in this case. The only pathway of exposure to workers in the store house is external radiation. In this case there is no dust because the bags are closed and covered by plastic, the store house has a good ventilation rate and so radon accumulation is not possible. The workers do not touch with their hands the bags and consequently skin contamination will not take place. In this study all situations of external irradiation to the workers have been considered; transportation of the pallets from vehicle to store house, lifting the pallets to the shelf, resting of the stock on the shelf, getting down the pallets, and carrying the pallets to production area. Using MCNP-4C exposure situations have been simulated, considering that the source has a homogeneous composition, the minimum stock in the store house is constituted by 7 pallets, and the several distances between pallets and workers when they are at work. The photons flux obtained by MCNP-4C is multiplied by the conversion factor of Flux to Kerma for air by conversion factor to Effective Dose by Kerma unit, and by the number of emitted photons. Those conversion factors are obtained of ICRP 74 table 1 and table 17 respectively. This

  15. Thinking Globally, Siting Locally: Renewable Energy and Biodiversity in a 4C World

    NASA Astrophysics Data System (ADS)

    Allison, T.; Frumhoff, P. C.; Root, T.

    2012-12-01

    The continued rise of greenhouse gas emissions and limited progress toward a low-carbon global-energy economy puts increases of global average temperatures on a course to reach 3C - 4C within this century. Such temperature increases are projected to have devastating impacts on biodiversity and ecosystems in the United States, and globally. At an increase of 4C, for example, the Intergovernmental Panel on Climate Change (IPCC) estimates that ~ 50% of recognized species could be committed to extinction. Limiting the magnitude of warming well below these levels will require massive shifts in energy production, including the rapid and large-scale deployment of renewable energy. The National Renewable Energy Laboratory (NREL) estimates that generating 80% of US electricity from renewable energy by 2050 would reduce cumulative US emissions (2011-2050) from the power sector by more than 40 Gt C02e, or 41%, and reduce annual emissions from the US power sector by nearly 81% by 2050. But the expansion of renewable energy at this scale will have impacts on biodiversity and ecosystem function, affecting ~3 % of US land area for siting, transmission and storage. Concerns over impacts to vulnerable species and their habitats are a source of delay in and opposition to renewable energy siting, particularly for wind and concentrated solar. Efforts to expedite renewable energy expansion while protecting biodiversity need to factor in both the direct biodiversity risks of siting and transmission and the benefits of avoided emissions on reducing the global biodiversity risks of high magnitude warming. Toward this end, we describe a combination of research, outreach, and dialogue designed to help policymakers and stakeholders (1) promote efforts to strategically locate renewable energy projects where impacts to species potentially vulnerable to deployment and operation of renewable energy could be avoided or minimized; (2) recognize the inherent uncertainty in characterizing siting

  16. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

    SciTech Connect

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-08-16

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

  17. LAPTM4B is associated with poor prognosis in NSCLC and promotes the NRF2-mediated stress response pathway in lung cancer cells

    PubMed Central

    Maki, Yuho; Fujimoto, Junya; Lang, Wenhua; Xu, Li; Behrens, Carmen; Wistuba, Ignacio I.; Kadara, Humam

    2015-01-01

    We recently demonstrated that lysosomal protein transmembrane 4 beta (LAPTM4B) is elevated in non-small cell lung cancers (NSCLCs) and in the surrounding premalignant airway field of cancerization. In the present study, we sought to begin to understand the relevance of LAPTM4B expression and signaling to NSCLC pathogenesis. In situ hybridization analysis of LAPTM4B transcript in tissue microarrays comprised of 368 NSCLCs demonstrated that LAPTM4B expression was significantly increased in smoker compared to non-smoker lung adenocarcinoma tumors (P < 0.001) and was significantly associated with poor overall survival (P < 0.05) in adenocarcinoma patients. Knockdown of LAPTM4B expression inhibited cell growth, induced cellular apoptosis and decreased cellular autophagy in serum starved lung cancer cells. Expression profiling coupled with pathways analysis revealed decreased activation of the nuclear factor erythroid 2-like 2 (NRF2) stress response pathway following LAPTM4B knockdown. Further analysis demonstrated that LAPTM4B augmented the expression and nuclear translocation of the NRF2 transcription factor following serum deprivation as well as increased the expression of NRF2 target genes such as heme oxygenase 1/HMOX1). Our study points to the relevance of LAPTM4B expression to NSCLC pathogenesis as well as to the probable role of LAPTM4B/NRF2 signaling in promoting lung cancer cell survival. PMID:26343532

  18. Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

    PubMed Central

    Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Shi, Yuzhong

    2016-01-01

    Background The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis. Methods A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I2 > 50%) existed, otherwise the fixed effects model was used. Results Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055). Conclusion This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia. PMID:26756575

  19. Migration behavior of rodent granule neurons in the presence of antibody to the 4C5 antigen.

    PubMed

    Yfanti, E; Nagata, I; Patsavoudi, E

    1998-10-01

    We have reported the production of monoclonal antibody 4C5, which recognizes a cell surface antigen, the 4C5 antigen, involved in granule cell migration processes. In the present study, we investigated in a more precise manner the role of the 4C5 antigen in the different types of granule cell migrations that take place during cerebellar development. When cerebellar explant cultures derived from 10-day-old rats were performed for 2 days in the presence of monoclonal antibody 4C5, vertical granule cell migration, occurring in the presence of glia, was not significantly inhibited. In contrast, when monoclonal antibody 4C5 was included in the medium of microexplant cultures derived from 4-day-old mice and maintained for 4 days in vitro, granule cell migrations that occurred both parallel and perpendicular to the neurite bundles that were free of glia were inhibited. Moreover, a stronger inhibitory effect of the antibody was observed on migration perpendicular to the neurite bundles compared with the parallel type of migration. Our results indicate that the 4C5 antigen differentially affects the different developmental stages and types of granule cell migration during rodent cerebellar development. PMID:9751168

  20. Intermittent Jet Activity in the Radio Galaxy 4C29.30?

    SciTech Connect

    Jamrozy, M.; Konar, C.; Saikia, D.J.; Stawarz, L.; Mack, K.-H.; Siemiginowska, A.; /Harvard-Smithsonian Ctr. Astrophys.

    2007-04-02

    We present radio observations at frequencies ranging from 240 to 8460 MHz of the radio galaxy 4C29.30 (J0840+2949) using the Giant Metrewave Radio Telescope (GMRT), the Very Large Array (VLA) and the Effelsberg telescope. We report the existence of weak extended emission with an angular size of {approx} 520 arcsec (639 kpc) within which a compact edge-brightened double-lobed source with a size of 29 arcsec (36 kpc) is embedded. We determine the spectrum of the inner double from 240 to 8460 MHz and show that it has a single power-law spectrum with a spectral index is {approx} 0.8. Its spectral age is estimated to be 33 Myr. The extended diffuse emission has a steep spectrum with a spectral index of {approx} 1.3 and a break frequency 240 MHz. The spectral age is {approx}>200 Myr, suggesting that the extended diffuse emission is due to an earlier cycle of activity. We reanalyze archival x-ray data from Chandra and suggest that the x-ray emission from the hotspots consists of a mixture of nonthermal and thermal components, the latter being possibly due to gas which is shock heated by the jets from the host galaxy.

  1. Performance of the MTR core with MOX fuel using the MCNP4C2 code.

    PubMed

    Shaaban, Ismail; Albarhoum, Mohamad

    2016-08-01

    The MCNP4C2 code was used to simulate the MTR-22 MW research reactor and perform the neutronic analysis for a new fuel namely: a MOX (U3O8&PuO2) fuel dispersed in an Al matrix for One Neutronic Trap (ONT) and Three Neutronic Traps (TNTs) in its core. Its new characteristics were compared to its original characteristics based on the U3O8-Al fuel. Experimental data for the neutronic parameters including criticality relative to the MTR-22 MW reactor for the original U3O8-Al fuel at nominal power were used to validate the calculated values and were found acceptable. The achieved results seem to confirm that the use of MOX fuel in the MTR-22 MW will not degrade the safe operational conditions of the reactor. In addition, the use of MOX fuel in the MTR-22 MW core leads to reduce the uranium fuel enrichment with (235)U and the amount of loaded (235)U in the core by about 34.84% and 15.21% for the ONT and TNTs cases, respectively. PMID:27213809

  2. a New Method for Neutron Capture Therapy (nct) and Related Simulation by MCNP4C Code

    NASA Astrophysics Data System (ADS)

    Shirazi, Mousavi; Alireza, Seyed; Ali, Taheri

    2010-01-01

    Neutron capture therapy (NCT) is enumerated as one of the most important methods for treatment of some strong maladies among cancers in medical science thus is unavoidable controlling and protecting instances in use of this science. Among of treatment instances of this maladies with use of nuclear medical science is use of neutron therapy that is one of the most important and effective methods in treatment of cancers. But whereas fast neutrons have too destroyer effects and also sake of protection against additional absorbed energy (absorbed dose) by tissue during neutron therapy and also naught damaging to rest of healthy tissues, should be measured absorbed energy by tissue accurately, because destroyer effects of fast neutrons is almost quintuple more than gamma photons. In this article for neutron therapy act of male's liver has been simulated a system by the Monte Carlo method (MCNP4C code) and also with use of analytical method, thus absorbed dose by this tissue has been obtained for sources with different energies accurately and has been compared results of this two methods together.

  3. Music 4C, a multi-voiced synthesis program with instruments defined in C

    NASA Astrophysics Data System (ADS)

    Beauchamp, James W.

    2003-04-01

    Music 4C is a program which runs under Unix (including Linux) and provides a means for the synthesis of arbitrary signals as defined by the C code. The program is actually a loose translation of an earlier program, Music 4BF [H. S. Howe, Jr., Electronic Music Synthesis (Norton, 1975)]. A set of instrument definitions are driven by a numerical score which consists of a series of ``events.'' Each event gives an instrument name, start time and duration, and a number of parameters (e.g., pitch) which describe the event. Each instrument definition consists of event parameters, performance variables, initializations, and a synthesis algorithmic code. Thus, the synthetic signal, no matter how complex, is precisely defined. Moreover, the resulting sounds can be overlaid in any arbitrary pattern. The program serves as a mixer of algorithmically produced sounds or recorded sounds taken from sample files or synthesized from spectrum files. A score file can be entered by hand, generated from a program, translated from a MIDI file, or generated from an alpha-numeric score using an auxiliary program, Notepro. Output sample files are in wav, snd, or aiff format. The program is provided in the C source code for download.

  4. REVERSIBLE HYDROGEN STORAGE IN A LiBH{sub 4}-C{sub 60} NANOCOMPOSITE

    SciTech Connect

    Teprovich, J.; Zidan, R.; Peters, B.; Wheeler, J.

    2013-08-06

    Reversible hydrogen storage in a LiBH{sub 4}:C{sub 60} nanocomposite (70:30 wt. %) synthesized by solvent-assisted mixing has been demonstrated. During the solvent-assisted mixing and nanocomposite formation, a chemical reaction occurs in which the C{sub 60} cages are significantly modified by polymerization as well as by hydrogenation (fullerane formation) in the presence of LiBH{sub 4}. We have determined that two distinct hydrogen desorption events are observed upon rehydrogenation of the material, which are attributed to the reversible formation of a fullerane (C{sub 60}H{sub x}) as well as a LiBH4 species. This system is unique in that the carbon species (C{sub 60}) actively participates in the hydrogen storage process which differs from the common practice of melt infiltration of high surface area carbon materials with LiBH{sub 4} (nanoconfinment effect). This nanocomposite demonstrated good reversible hydrogen storage properties as well as the ability to absorb hydrogen under mild conditions (pressures as low as 10 bar H{sub 2} or temperatures as low as 150°C). The nanocomposite was characterized by TGA-RGA, DSC, XRD, LDI-TOF-MS, FTIR, 1H NMR, and APPI MS.

  5. Performance of the MTR core with MOX fuel using the MCNP4C2 code.

    PubMed

    Shaaban, Ismail; Albarhoum, Mohamad

    2016-08-01

    The MCNP4C2 code was used to simulate the MTR-22 MW research reactor and perform the neutronic analysis for a new fuel namely: a MOX (U3O8&PuO2) fuel dispersed in an Al matrix for One Neutronic Trap (ONT) and Three Neutronic Traps (TNTs) in its core. Its new characteristics were compared to its original characteristics based on the U3O8-Al fuel. Experimental data for the neutronic parameters including criticality relative to the MTR-22 MW reactor for the original U3O8-Al fuel at nominal power were used to validate the calculated values and were found acceptable. The achieved results seem to confirm that the use of MOX fuel in the MTR-22 MW will not degrade the safe operational conditions of the reactor. In addition, the use of MOX fuel in the MTR-22 MW core leads to reduce the uranium fuel enrichment with (235)U and the amount of loaded (235)U in the core by about 34.84% and 15.21% for the ONT and TNTs cases, respectively.

  6. Imaging of the Field of 4C41.17 Below the Lyman Limit

    NASA Technical Reports Server (NTRS)

    Lacy, Mark; Rawlings, Steve

    1997-01-01

    Imaging of zeta greater than or equal to 3.4 radio galaxy fields below the Lyman continuum wavelength allows companion galaxies to be identified on the basis of red colors across the wavelength of redshifted Ly(alpha) and very red colors across the redshifted Lyman continuum. These arise due to a combination of absorption by intervening Ly(alpha) forest and Lyman-limit systems, and intrinsic Lyman-limit breaks in the galaxy spectral energy distribution caused by an Hi screen or breaks in stellar spectra. As a pilot study, we have imaged the field of the zeta = 3.8 radio galaxy 4C41.17 in U, V and R with the Auxiliary Port of the WHT. We find a number of potential companion galaxies, which require confirmation via spectroscopy or narrow-band imaging. The Lyman-limit in the spectrum of the radio galaxy itself and its implications for the origin of the UV flux is also discussed.

  7. Allelic Variation and Differential Expression of the mSIN3A Histone Deacetylase Complex Gene Arid4b Promote Mammary Tumor Growth and Metastasis

    PubMed Central

    Winter, Scott F.; Lukes, Luanne; Walker, Renard C.; Welch, Danny R.; Hunter, Kent W.

    2012-01-01

    Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT–rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA–mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer. PMID:22693453

  8. Douglas OA-4A Dolphin

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Douglas OA-4A Dolphin: This twin-engine Douglas OA-4A Dolphin was unusual in comparison with other OA-4s in that it employed a nose wheel instead of a tail wheel during its NACA testing at Langley. Here is is seen in the NACA hangar in September 1938.

  9. Channel catfish, Ictalurus punctatus, chemokine receptor CXCR4 cDNA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chemokine receptor CXCR4, a member of the G protein-coupled receptor superfamily, binds selectively CXCL12. This protein plays many important roles in immunological as well as pathophysiological functions. In this communication, we identified and characterized the channel catfish CXCR4 transcript....

  10. The peculiar radio galaxy 4C 35.06: a case for recurrent AGN activity?

    NASA Astrophysics Data System (ADS)

    Shulevski, A.; Morganti, R.; Barthel, P. D.; Murgia, M.; van Weeren, R. J.; White, G. J.; Brüggen, M.; Kunert-Bajraszewska, M.; Jamrozy, M.; Best, P. N.; Röttgering, H. J. A.; Chyzy, K. T.; de Gasperin, F.; Bîrzan, L.; Brunetti, G.; Brienza, M.; Rafferty, D. A.; Anderson, J.; Beck, R.; Deller, A.; Zarka, P.; Schwarz, D.; Mahony, E.; Orrú, E.; Bell, M. E.; Bentum, M. J.; Bernardi, G.; Bonafede, A.; Breitling, F.; Broderick, J. W.; Butcher, H. R.; Carbone, D.; Ciardi, B.; de Geus, E.; Duscha, S.; Eislöffel, J.; Engels, D.; Falcke, H.; Fallows, R. A.; Fender, R.; Ferrari, C.; Frieswijk, W.; Garrett, M. A.; Grießmeier, J.; Gunst, A. W.; Heald, G.; Hoeft, M.; Hörandel, J.; Horneffer, A.; van der Horst, A. J.; Intema, H.; Juette, E.; Karastergiou, A.; Kondratiev, V. I.; Kramer, M.; Kuniyoshi, M.; Kuper, G.; Maat, P.; Mann, G.; McFadden, R.; McKay-Bukowski, D.; McKean, J. P.; Meulman, H.; Mulcahy, D. D.; Munk, H.; Norden, M. J.; Paas, H.; Pandey-Pommier, M.; Pizzo, R.; Polatidis, A. G.; Reich, W.; Rowlinson, A.; Scaife, A. M. M.; Serylak, M.; Sluman, J.; Smirnov, O.; Steinmetz, M.; Swinbank, J.; Tagger, M.; Tang, Y.; Tasse, C.; Thoudam, S.; Toribio, M. C.; Vermeulen, R.; Vocks, C.; Wijers, R. A. M. J.; Wise, M. W.; Wucknitz, O.

    2015-07-01

    Using observations obtained with the LOw Fequency ARray (LOFAR), the Westerbork Synthesis Radio Telescope (WSRT) and archival Very Large Array (VLA) data, we have traced the radio emission to large scales in the complex source 4C 35.06 located in the core of the galaxy cluster Abell 407. At higher spatial resolution (~ 4″), the source was known to have two inner radio lobes spanning 31 kpc and a diffuse, low-brightness extension running parallel to them, offset by about 11 kpc (in projection). At 62 MHz, we detect the radio emission of this structure extending out to 210 kpc. At 1.4 GHz and intermediate spatial resolution (~ 30″), the structure appears to have a helical morphology. We have derived the characteristics of the radio spectral index across the source. We show that the source morphology is most likely the result of at least two episodes of AGN activity separated by a dormant period of around 35 Myr. The outermost regions of radio emission have a steep spectral index (α< - 1), indicative of old plasma. We connect the spectral index properties of the resolved source structure with the integrated fluxdensity spectral index of 4C 35.06 and suggest an explanation for its unusual integrated flux density spectral shape (a moderately steep power law with no discernible spectral break), possibly providing a proxy for future studies of more distant radio sources through inferring their detailed spectral index properties and activity history from their integrated spectral indices. The AGN is hosted by one of the galaxies located in the cluster core of Abell 407. We propose that it is intermittently active as it moves in the dense environment in the cluster core. In this scenario, the AGN turned on sometime in the past, and has produced the helical pattern of emission, possibly a sign of jet precession/merger during that episode of activity. Using LOFAR, we can trace the relic plasma from that episode of activity out to greater distances from the core than ever

  11. Mechanism for amorphization of boron carbide B{sub 4}C under uniaxial compression

    SciTech Connect

    Aryal, Sitaram; Rulis, Paul; Ching, W. Y.

    2011-11-01

    Boron carbide undergoes an amorphization transition under high-velocity impacts, causing it to suffer a catastrophic loss in strength. The failure mechanism is not clear and this limits the ways to improve its resistance to impact. To help uncover the failure mechanism, we used ab initio methods to carry out large-scale uniaxial compression simulations on two polytypes of stoichiometric boron carbide (B{sub 4}C), B{sub 11}C-CBC, and B{sub 12}-CCC, where B{sub 11}C or B{sub 12} is the 12-atom icosahedron and CBC or CCC is the three-atom chain. The simulations were performed on large supercells of 180 atoms. Our results indicate that the B{sub 11}C-CBC (B{sub 12}-CCC) polytype becomes amorphous at a uniaxial strain s = 0.23 (0.22) and with a maximum stress of 168 (151) GPa. In both cases, the amorphous state is the consequence of structural collapse associated with the bending of the three-atom chain. Careful analysis of the structures after amorphization shows that the B{sub 11}C and B{sub 12} icosahedra are highly distorted but still identifiable. Calculations of the elastic coefficients (C{sub ij}) at different uniaxial strains indicate that both polytypes may collapse under a much smaller shear strain (stress) than the uniaxial strain (stress). On the other hand, separate simulations of both models under hydrostatic compression up to a pressure of 180 GPa show no signs of amorphization, in agreement with experimental observation. The amorphized nature of both models is confirmed by detailed analysis of the evolution of the radial pair distribution function, total density of states, and distribution of effective charges on atoms. The electronic structure and bonding of the boron carbide structures before and after amorphization are calculated to further elucidate the mechanism of amorphization and to help form the proper rationalization of experimental observations.

  12. The warm absorber in the radio-loud quasar 4C +74.26

    NASA Astrophysics Data System (ADS)

    Di Gesu, L.; Costantini, E.

    2016-10-01

    Outflows of photoionized gas are commonly detected in the X-ray spectra of Seyfert 1 galaxies. However, the evidence for this phenomenon in broad line radio galaxies, which are analogous to Seyfert 1 galaxies in the radio-loud regime, has so far been scarce. Here, we present the analysis of the X-ray absorption in the radio-loud quasar 4C +74.26. With the aim of characterizing the kinetic and the ionization conditions of the absorbing material, we fitted jointly the XMM-Newton Reflection Grating Spectrometer (RGS) and the Chandra High Energy Transmission Grating Spectrometer (HETGS) spectra, which were taken 4 months apart. The intrinsic continuum flux did not vary significantly during this time lapse. The spectrum shows the absorption signatures (e.g., Fe-UTA, O vii, and Ne vii-Ne x) of a photoionized gas outflow (NH ~ 3.5 × 1021 cm-2, log ξ ~ 2.6, vout ~ 3600 km s-1) located at the redshift of source. We estimate that the gas is located outside the broad line region but within the boundaries of the putative torus. This ionized absorber is consistent with the X-ray counterpart of a polar scattering outflow reported in the optical band for this source. The kinetic luminosity carried by the outflow is insufficient to produce a significant feedback is this quasar. Finally, we show that the heavy soft X-ray absorption that was noticed in the past for this source arises mostly in the Galactic interstellar medium.

  13. 4C code analysis of thermal-hydraulic transients in the KSTAR PF1 superconducting coil

    NASA Astrophysics Data System (ADS)

    Savoldi Richard, L.; Bonifetto, R.; Chu, Y.; Kholia, A.; Park, S. H.; Lee, H. J.; Zanino, R.

    2013-01-01

    The KSTAR tokamak, in operation since 2008 at the National Fusion Research Institute in Korea, is equipped with a full superconducting magnet system including the central solenoid (CS), which is made of four symmetric pairs of coils PF1L/U-PF4L/U. Each of the CS coils is pancake wound using Nb3Sn cable-in-conduit conductors with a square Incoloy jacket. The coils are cooled with supercritical He in forced circulation at nominal 4.5 K and 5.5 bar inlet conditions. During different test campaigns the measured temperature increase due to AC losses turned out to be higher than expected, which motivates the present study. The 4C code, already validated against and applied to different types of thermal-hydraulic transients in different superconducting coils, is applied here to the thermal-hydraulic analysis of a full set of trapezoidal current pulses in the PF1 coils, with different ramp rates. We find the value of the coupling time constant nτ that best fits, at each current ramp rate, the temperature increase up to the end of the heating at the coil outlet. The agreement between computed results and the whole set of measured data, including temperatures, pressures and mass flow rates, is then shown to be very good both at the inlet and at the outlet of the coil. The nτ values needed to explain the experimental results decrease at increasing current ramp rates, consistently with the results found in the literature.

  14. Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility

    PubMed Central

    Lin, Chien-Yu; Chen, Chun-Yu; Yu, Chih-Hsiang; Yu, I-Shing; Lin, Shu-Rung; Wu, June-Tai; Lin, Ying-Hung; Kuo, Pao-Lin; Wu, Jui-Ching; Lin, Shu-Wha

    2016-01-01

    In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4bΔ/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis. PMID:26832838

  15. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  16. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  17. 15 CFR 744.9 - Restrictions on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... reexports of cameras controlled by ECCN 6A003.b.4.b. 744.9 Section 744.9 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF... on certain exports and reexports of cameras controlled by ECCN 6A003.b.4.b. (a) General...

  18. Evolution of the local superconducting density of states in ErRh4B4 close to the ferromagnetic transition.

    PubMed

    Crespo, V; Rodrigo, J G; Suderow, H; Vieira, S; Hinks, D G; Schuller, I K

    2009-06-12

    We present local tunneling spectroscopy experiments in the superconducting and ferromagnetic phases of the reentrant superconductor ErRh4B4. The tunneling conductance curves jump from showing normal to superconducting features within a few mK close to the ferromagnetic transition temperature, with a clear hysteretic behavior. Within the ferromagnetic phase, we do not detect any superconducting correlations. Within the superconducting phase we find a peculiar V-shaped density of states at low energies, which is produced by the magnetically modulated phase that coexists with superconductivity just before ferromagnetism sets in. PMID:19658962

  19. Thermo-optical properties of 1H[3,4-b] quinoline films used in electroluminescent devices

    NASA Astrophysics Data System (ADS)

    Jaglarz, Janusz; Kępińska, Mirosława; Sanetra, Jerzy

    2014-06-01

    Electroluminescence cells with H[3,4-b] quinoline layers are promising devices for a blue light emitting EL diode. This work measured the optical reflectance as a function of temperature in copolymers PAQ layers deposited on Si crystalline substrate. Using the extended Cauchy dispersion model of the film refractive index we determined the thermo-optical coefficients for quinoline layers in the temperature range of 76-333 K from combined ellipsometric and spectrofotometric studies. The obtained values of thermo-optical coefficients of thin PAQ film, were negative and ranged in 5-10 × 10-4 [1/K].

  20. Dithieno[3,4-b:3',4'-d]thiophene-annelated antiaromatic planar cyclooctatetraene with olefinic protons.

    PubMed

    Aita, Kazunari; Ohmae, Takeshi; Takase, Masayoshi; Nomura, Kotohiro; Kimura, Hideaki; Nishinaga, Tohru

    2013-07-19

    The design and synthesis of a new planar cyclooctatetraene (COT) with protons directly connected to the COT ring was attained by monoannelation with dithieno[3,4-b:3',4'-d]thiophene. The planar structure of the COT core was unambiguously confirmed by X-ray crystallography. The magnetic antiaromaticity of the COT core was found to be higher than that of the previously synthesized planar COTs with olefinic protons, according to the results of (1)H NMR and absorption spectra as well as NICS calculations.

  1. 6-(Azaindol-2-yl)pyridine-3-sulfonamides as potent and selective inhibitors targeting hepatitis C virus NS4B.

    PubMed

    Chen, Guangming; Ren, Hongyu; Zhang, Nanjing; Lennox, William; Turpoff, Anthony; Paget, Steven; Li, Chunshi; Almstead, Neil; Njoroge, F George; Gu, Zhengxian; Graci, Jason; Jung, Stephen P; Colacino, Joseph; Lahser, Fred; Zhao, Xin; Weetall, Marla; Nomeir, Amin; Karp, Gary M

    2015-02-15

    A structure-activity relationship investigation of various 6-(azaindol-2-yl)pyridine-3-sulfonamides using the HCV replicon cell culture assay led to the identification of a potent series of 7-azaindoles that target the hepatitis C virus NS4B. Compound 2ac, identified via further optimization of the series, has excellent potency against the HCV 1b replicon with an EC50 of 2nM and a selectivity index of >5000 with respect to cellular GAPDH RNA. Compound 2ac also has excellent oral plasma exposure levels in rats, dogs and monkeys and has a favorable liver to plasma distribution profile in rats. PMID:25613678

  2. Farnesylated and methylated KRAS4b: high yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions.

    PubMed

    Gillette, William K; Esposito, Dominic; Abreu Blanco, Maria; Alexander, Patrick; Bindu, Lakshman; Bittner, Cammi; Chertov, Oleg; Frank, Peter H; Grose, Carissa; Jones, Jane E; Meng, Zhaojing; Perkins, Shelley; Van, Que; Ghirlando, Rodolfo; Fivash, Matthew; Nissley, Dwight V; McCormick, Frank; Holderfield, Matthew; Stephen, Andrew G

    2015-11-02

    Prenylated proteins play key roles in several human diseases including cancer, atherosclerosis and Alzheimer's disease. KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed by farnesylation, proteolytic cleavage and carboxymethylation at the C-terminus. Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not accurately replicate the mature KRAS protein found in mammalian cells and the protein yield is typically low. We describe a protocol that yields 5-10 mg/L highly purified, farnesylated, and methylated KRAS4b from insect cells. Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEδ.

  3. Facile synthesis of Fe3O4@C hollow nanospheres and their application in polluted water treatment

    NASA Astrophysics Data System (ADS)

    Zhang, Yuanguang; Xu, Shihao; Xia, Hongyu; Zheng, Fangcai

    2016-11-01

    Nanostructured carbon-based materials, such as carbon nanotube arrays have shown respectable removal ability for heavy metal ions and organic dyes in aqueous solution. Although the carbon-based materials exhibited excellent removal ability, the separation of them from the aqueous solution is difficult and time-consuming. Here we demonstrated a novel and facile route for the large-scale fabrication of Fe3O4@C hollow nanospheres, with using ferrocene as a single reagent and SiO2 as a template. The as-prepared Fe3O4@C hollow nanospheres exhibited adsorption ability for heavy metal ions and organic dyes from aqueous solution, and can be easily separated by an external magnet. When the as-prepared Fe3O4@C hollow nanospheres were mixed with the aqueous solution of Hg2+ within 15 min, the removal efficiency was 90.3%. The as-prepared Fe3O4@C hollow nanospheres were also exhibited a high adsorption capacity (100%) as the adsorbent for methylene blue (MB). In addition, the as-prepared Fe3O4@C hollow nanospheres can be used as the recyclable sorbent for water treatment via a simple magnetic separation.

  4. Preparation of LiCoPO 4/C nanocomposite cathode of lithium batteries with high rate performance

    NASA Astrophysics Data System (ADS)

    Doan, The Nam Long; Taniguchi, Izumi

    LiCoPO 4/C nanocomposites could be successfully prepared by a combination of spray pyrolysis and wet ball-milling followed by heat treatment. X-ray diffraction analysis confirmed that the LiCoPO 4/C nanocomposites were well crystallized in an orthorhombic structure with Pmna space group. Scanning electron microscopy and transmission electron microscopy with equipped energy dispersive spectroscopy verified that the LiCoPO 4/C nanocomposites were the agglomerates of LiCoPO 4 primary particles with a geometric mean diameter of 87 nm, and the carbon was well distributed on the surface of the agglomerates. The LiCoPO 4/C nanocomposites were used as cathode active materials for lithium batteries, and the electrochemical tests were carried out for the cell Li|1 M LiPF 6 in EC:DMC = 1:1|LiCoPO 4/C at various charge-discharge rates. The cells delivered first discharge capacities of 142 and 109 mAh g -1 at 0.05 and 20 C, respectively. Furthermore, the discharge capacity after 40 cycles corresponded to 87% of initial one at 0.1 C rate. The excellent rate capability of the cells is mainly due to the well distributed carbon on the LiCoPO 4 agglomerates, and a much smaller lithium ion diffusion distance in the electrode.

  5. High-performance, nanostructure LiMnPO4/C composites synthesized via one-step solid state reaction

    NASA Astrophysics Data System (ADS)

    Zheng, Jugong; Ni, Liang; Lu, Yanwen; Qin, Cancan; Liu, Panxing; Wu, Tongfu; Tang, Yuefeng; Chen, Yanfeng

    2015-05-01

    LiMnPO4 is proposed as more promising cathode material as LiFePO4, while poor electronic conductivity and Jahn-Teller effects during charge/discharge processes hinder the electrochemical performance. To overcome these problems, one-step solid state reaction method is developed to synthesize LiMnPO4/C composites, which is with nanostructure, high crystallinity and good carbon coating. Manganese oxide sources and calcination temperature are investigated as factors for preparing high-performance LiMnPO4/C for Li-ion batteries. The results show that the LiMnPO4/C composites prepared with mixed manganese oxide deliver a superior initial capacity of 153 mAh g-1 at 0.05 C and high rate performance with discharge capacities of 123 mAh g-1 at 1 C and 103 mAh g-1 at 2 C. And the LiMnPO4/C composites synthesized at 600 °C can retain 94% of the initial capacity after 200 cycles at 1 C, revealing a stable cycling stability. Therefore, one-step solid state reaction brings to light the synthesis of high performance LiMnPO4/C cathode materials and is suitable for large scale production.

  6. Intracellular membrane association of the N-terminal domain of classical swine fever virus NS4B determines viral genome replication and virulence.

    PubMed

    Tamura, Tomokazu; Ruggli, Nicolas; Nagashima, Naofumi; Okamatsu, Masatoshi; Igarashi, Manabu; Mine, Junki; Hofmann, Martin A; Liniger, Matthias; Summerfield, Artur; Kida, Hiroshi; Sakoda, Yoshihiro

    2015-09-01

    Classical swine fever virus (CSFV) causes a highly contagious disease in pigs that can range from a severe haemorrhagic fever to a nearly unapparent disease, depending on the virulence of the virus strain. Little is known about the viral molecular determinants of CSFV virulence. The nonstructural protein NS4B is essential for viral replication. However, the roles of CSFV NS4B in viral genome replication and pathogenesis have not yet been elucidated. NS4B of the GPE-  vaccine strain and of the highly virulent Eystrup strain differ by a total of seven amino acid residues, two of which are located in the predicted trans-membrane domains of NS4B and were described previously to relate to virulence, and five residues clustering in the N-terminal part. In the present study, we examined the potential role of these five amino acids in modulating genome replication and determining pathogenicity in pigs. A chimeric low virulent GPE- -derived virus carrying the complete Eystrup NS4B showed enhanced pathogenicity in pigs. The in vitro replication efficiency of the NS4B chimeric GPE-  replicon was significantly higher than that of the replicon carrying only the two Eystrup-specific amino acids in NS4B. In silico and in vitro data suggest that the N-terminal part of NS4B forms an amphipathic α-helix structure. The N-terminal NS4B with these five amino acid residues is associated with the intracellular membranes. Taken together, this is the first gain-of-function study showing that the N-terminal domain of NS4B can determine CSFV genome replication in cell culture and viral pathogenicity in pigs. PMID:26018962

  7. Identification of Substituted Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

    PubMed Central

    2013-01-01

    A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NFκB activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NFκB and type I interferon associated cytokines, IL-6 and interferon γ-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators. PMID:23656327

  8. The Phosphatase PP4c Controls Spindle Orientation to Maintain Proliferative Symmetric Divisions in the Developing Neocortex

    PubMed Central

    Xie, Yunli; Jüschke, Christoph; Esk, Christopher; Hirotsune, Shinji; Knoblich, Juergen A.

    2013-01-01

    Summary In the developing neocortex, progenitor cells expand through symmetric division before they generate cortical neurons through multiple rounds of asymmetric cell division. Here, we show that the orientation of the mitotic spindle plays a crucial role in regulating the transition between those two division modes. We demonstrate that the protein phosphatase PP4c regulates spindle orientation in early cortical progenitor cells. Upon removing PP4c, mitotic spindles fail to orient in parallel to the neuroepithelial surface and progenitors divide with random orientation. As a result, their divisions become asymmetric and neurogenesis starts prematurely. Biochemical and genetic experiments show that PP4c acts by dephosphorylating the microtubule binding protein Ndel1, thereby enabling complex formation with Lis1 to form a functional spindle orientation complex. Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division. PMID:23830831

  9. Influenza A Virus-Induced Degradation of Eukaryotic Translation Initiation Factor 4B Contributes to Viral Replication by Suppressing IFITM3 Protein Expression

    PubMed Central

    Wang, Song; Chi, Xiaojuan; Wei, Haitao; Chen, Yuhai; Chen, Zhilong; Huang, Shile

    2014-01-01

    ABSTRACT Although alteration in host cellular translation machinery occurs in virus-infected cells, the role of such alteration and the precise pathogenic processes are not well understood. Influenza A virus (IAV) infection shuts off host cell gene expression at transcriptional and translational levels. Here, we found that the protein level of eukaryotic translation initiation factor 4B (eIF4B), an integral component of the translation initiation apparatus, was dramatically reduced in A549 cells as well as in the lung, spleen, and thymus of mice infected with IAV. The decrease in eIF4B level was attributed to lysosomal degradation of eIF4B, which was induced by viral NS1 protein. Silencing eIF4B expression in A549 cells significantly promoted IAV replication, and conversely, overexpression of eIF4B markedly inhibited the viral replication. Importantly, we observed that eIF4B knockdown transgenic mice were more susceptible to IAV infection, exhibiting faster weight loss, shorter survival time, and more-severe organ damage. Furthermore, we demonstrated that eIF4B regulated the expression of interferon-induced transmembrane protein 3 (IFITM3), a critical protein involved in immune defense against a variety of RNA viruses, including influenza virus. Taken together, our findings reveal that eIF4B plays an important role in host defense against IAV infection at least by regulating the expression of IFITM3, which restricts viral entry and thereby blocks early stages of viral production. These data also indicate that influenza virus has evolved a strategy to overcome host innate immunity by downregulating eIF4B protein. IMPORTANCE Influenza A virus (IAV) infection stimulates the host innate immune system, in part, by inducing interferons (IFNs). Secreted IFNs activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, leading to elevated transcription of a large group of IFN-stimulated genes that have antiviral function. To circumvent

  10. Quantum deformations of D = 4 Euclidean, Lorentz, Kleinian and quaternionic o⋆ (4) symmetries in unified o (4 ; C) setting

    NASA Astrophysics Data System (ADS)

    Borowiec, A.; Lukierski, J.; Tolstoy, V. N.

    2016-03-01

    We employ new calculational technique and present complete list of classical r-matrices for D = 4 complex homogeneous orthogonal Lie algebra o (4 ; C), the rotational symmetry of four-dimensional complex space-time. Further applying reality conditions we obtain the classical r-matrices for all possible real forms of o (4 ; C): Euclidean o (4), Lorentz o (3 , 1), Kleinian o (2 , 2) and quaternionic o⋆ (4) Lie algebras. For o (3 , 1) we get known four classical D = 4 Lorentz r-matrices, but for other real Lie algebras (Euclidean, Kleinian, quaternionic) we provide new results and mention some applications.

  11. Evidence of quinonoid structures in the vibrational spectra of thiophene based conducting polymers: Poly(thiophene), poly(thieno[3,4-b]benzene), and poly(thieno[3,4-b]pyrazine)

    NASA Astrophysics Data System (ADS)

    Cuff, Lilee; Kertesz, Miklos

    1997-04-01

    By combining vibrational spectra and ab initio calculations, we obtained a consistent description of the IR and nonresonant Raman spectra, including intensities, of four thiophene based polymers—undoped and heavily doped poly(thiophene) (PTh), undoped poly(thieno[3,4-b]benzene) (PITN), and poly(thieno[3,4-b]pyrazine) (PThP) for the first time. Predicted spectra for poly(thiophene) agree with experiment very well. Based on the calculated force constants and Badger's rule, we also estimated the average inter-ring bond lengths of undoped and doped PTh to be 1.47 and 1.42 Å, respectively. The latter leads to an estimated 33% quinonoid character on average for heavily doped PTh. The average inter-ring bond lengths of undoped PITN and PThP, that are consistent with their vibrational spectra, are estimated to be 1.41, and 1.42 Å, respectively. These values showed that undoped PITN and PThP have quinonoid character close to that of heavily doped PTh. Further, we also estimated that, upon doping the average bond lengths of PTh changed by -0.01, 0.11, and -0.05 Å for intra-ring Cβ-Cβ, Cα-Cβ, and inter-ring bonds, respectively. These bond length changes are significantly different from those of Hartree-Fock-type calculations, reflecting significant correlation contributions and are also in conflict with earlier empirical fits of the vibrational spectrum of the highly doped phase of PTh. However, our results are more in line with the generally accepted picture of an aromatic to quinonoid "transition" of the doping process. Furthermore, the counterintuitive downward frequency shifts in the vibrational spectra of PTh upon doping can be explained by the structural change from an essentially aromatic to a partially quinonoid form.

  12. PDE4B mediates local feedback regulation of β₁-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes.

    PubMed

    Mika, Delphine; Richter, Wito; Westenbroek, Ruth E; Catterall, William A; Conti, Marco

    2014-03-01

    Multiple cAMP phosphodiesterase (PDE) isoforms play divergent roles in cardiac homeostasis but the molecular basis for their non-redundant function remains poorly understood. Here, we report a novel role for the PDE4B isoform in β-adrenergic (βAR) signaling in the heart. Genetic ablation of PDE4B disrupted βAR-induced cAMP transients, as measured by FRET sensors, at the sarcolemma but not in the bulk cytosol of cardiomyocytes. This effect was further restricted to a subsarcolemmal compartment because PDE4B regulates β1AR-, but not β2AR- or PGE2-induced responses. The spatially restricted function of PDE4B was confirmed by its selective effects on PKA-mediated phosphorylation patterns. PDE4B limited the PKA-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca(2+) channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. β1AR- but not β2AR-ligation induced PKA-dependent activation of PDE4B and interruption of this negative feedback with PKA inhibitors increased sarcolemmal cAMP. Thus, PDE4B mediates a crucial PKA-dependent feedback that controls β1AR-dependent cAMP signals in a restricted subsarcolemmal domain. Disruption of this feedback augments local cAMP/PKA signals, leading to an increased intracellular Ca(2+) level and contraction rate.

  13. Rab4b controls an early endosome sorting event by interacting with the γ-subunit of the clathrin adaptor complex 1.

    PubMed

    Perrin, Laura; Laura, Perrin; Lacas-Gervais, Sandra; Sandra, Lacas-Gervais; Gilleron, Jérôme; Jérôme, Gilleron; Ceppo, Franck; Franck, Ceppo; Prodon, François; François, Prodon; Benmerah, Alexandre; Alexandre, Benmerah; Tanti, Jean-François; Jean-François, Tanti; Cormont, Mireille; Mireille, Cormont

    2013-11-01

    The endocytic pathway is essential for cell homeostasis and numerous small Rab GTPases are involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated, although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis or adaptive immunity. Here, we show that Rab4b is required for early endosome sorting of transferrin receptors (TfRs) to the recycling endosomes, and we identified the AP1γ subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosome sorting. We show that internalised transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in the absence of Rab4b, whereas it is rapidly recycled back to the plasma membrane. By contrast, overexpression of Rab4b leads to the accumulation of internalised Tf within AP-1- and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except for TfR and require AP1γ for their formation. Furthermore, the targeted overexpression of the Rab4b-binding domain of AP1γ to early endosome upon its fusion with FYVE domains inhibited the interaction between Rab4b and endogenous AP1γ, and perturbed Tf traffic. We thus proposed that the interaction between early endocytic Rab4b and AP1γ could allow the budding of clathrin-coated vesicles for subsequent traffic to recycling endosomes. The data also uncover a novel type of endosomes, characterised by low abundance of either early or recycling endocytic markers, which could potentially be generated in cell types that naturally express high level of Rab4b.

  14. 75 FR 34983 - Order (1) Pursuant to Section 4(c) of the Commodity Exchange Act, Permitting the Kansas City...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... proscribing fraud and manipulation. See Reg. Sec. 35.2. \\6\\ See 58 FR 5587 (Jan. 22, 1993). Section 4(c) of...\\ See 74 FR 58608 (Nov. 13, 2009). The Commission received three comment letters.\\18\\ All three letters... of Trade Clearing Corporation To Clear Over-the-Counter Wheat Calendar Swaps and (2) Pursuant...

  15. Complete Genome Sequence of Spiroplasma turonicum Tab4cT, a Bacterium Isolated from Horse Flies (Haematopota sp.).

    PubMed

    Lo, Wen-Sui; Gasparich, Gail E; Kuo, Chih-Horng

    2016-09-22

    Spiroplasma turonicum Tab4c(T) was isolated from a horse fly (Haematopota sp.; probably Haematopota pluvialis) collected at Champchevrier, Indre-et-Loire, Touraine, France, in 1991. Here, we report the complete genome sequence of this bacterium to facilitate the investigation of its biology and the comparative genomics among Spiroplasma spp.

  16. 12 CFR 225.109 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false âServicesâ under section 4(c)(1) of Bank Holding Company Act. 225.109 Section 225.109 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM BANK HOLDING COMPANIES AND CHANGE IN BANK CONTROL (REGULATION...

  17. Neutron irradiation tests on B4C/epoxy composite for neutron shielding application and the parameters assay

    NASA Astrophysics Data System (ADS)

    Adeli, Ruhollah; Shirmardi, Seyed Pezhman; Ahmadi, Seyed Javad

    2016-10-01

    In this investigation, epoxy resin with a low viscosity amine-based curing agent was chosen as matrix and additives were added to epoxy resin using low speed stirring with ultrasonic waves approach. The chemical stability of resin during fabrication of composites was studied with Fourier transform infrared spectroscopy (FTIR). The effect of B4C particle size (20 and 150 μm) on neutron shielding was investigated. Besides, in order to develop the high performance composites, the effect of ATH (flame retardant) and WO3 powders (for shielding from against gamma rays) on neutron shielding property is considered. The neutron experiments were based on foil activation analysis in thermal column of Tehran Research Reactor (TRR). According to experimental data, required shield thickness (B4C, 150 μm, 3 wt%) for 80% absorption of neutron fluence was calculated about 9.8 mm. Consequently, data show thermal neutron absorption is dependent also on the size of the boron compound filler and show a significant enhancement in shielding performance when using smaller particle size of B4C filler. Furthermore, data obviously show that the neutron attenuation coefficient of reinforced composites increases to 0.345 cm-1 for B4C (20 μm, 5 wt%)/ Epoxy composite shield. As clearly data indicate, adding WO3 and ATH additive had a significant influence on the thermal neutron attenuation property and hybrid shield shows an enhancement of more than 60% in shielding performance.

  18. Ethanol production from D-lactic acid by lactic acid-assimilating Saccharomyces cerevisiae NAM34-4C.

    PubMed

    Wakamatsu, Makoto; Tani, Tatsunori; Taguchi, Hisataka; Matsuoka, Masayoshi; Kida, Kenji; Akamatsu, Takashi

    2013-07-01

    The lactic acid-assimilating yeast Saccharomyces cerevisiae NAM34-4C grew rapidly in minimal D-lactate medium (pH 3.5) at 35°C, compared with minimal L-lactate medium. A laboratory strain, S. cerevisiae S288C, did not grow in either medium at pH 3.5. Strain NAM34-4C produced remarkably high levels of ethanol in YPDL medium at pH 3.5, but not at pH 5.5, when D-lactate was provided as the carbon source. Optimal cultivation conditions for ethanol production from D-lactate by strain NAM34-4C were as follows: shaking speed, 60 rpm; initial pH, 3.0; cultivation temperature, 35°C; yeast extract, 5 g/L; peptone, 10 g/L; and D-lactate, 30 g/L. Under these conditions, strain NAM34-4C produced 2.7 g/L ethanol, which is 18% of the theoretical maximal yield (0.51 3 initial D-lactate concentration).

  19. Resonant soft x-ray reflectivity of Me/B(4)C multilayers near the boron K edge.

    PubMed

    Ksenzov, Dmitriy; Schlemper, Christoph; Pietsch, Ullrich

    2010-09-01

    Energy dependence of the optical constants of boron carbide in the short period Ru/B(4)C and Mo/B(4)C multilayers (MLs) are evaluated from complete reflectivity scans across the boron K edge using the energy-resolved photon-in-photon-out method. Differences between the refractive indices of the B(4)Cmaterial inside and close to the surface are obtained from the peak profile of the first order ML Bragg peak and the reflection profile near the critical angle of total external reflection close to the surface. Where a Mo/B(4)C ML with narrow barrier layers appears as a homogeneous ML at all energies, a Ru/B(4)C ML exhibits another chemical nature of boron at the surface compared to the bulk. From evaluation of the critical angle of total external reflection in the energy range between 184 and 186eV, we found an enriched concentration of metallic boron inside the Ru-rich layer at the surface, which is not visible in other energy ranges.

  20. 12 CFR 225.137 - Acquisitions of shares pursuant to section 4(c)(6) of the Bank Holding Company Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Acquisitions of shares pursuant to section 4(c... CONTROL (REGULATION Y) Regulations Financial Holding Companies Interpretations § 225.137 Acquisitions of... believes that, even apart from this Interpretation, this language preserves the authority of the Board...

  1. 12 CFR 225.104 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 3 2012-01-01 2012-01-01 false âServicesâ under section 4(c)(1) of Bank... GOVERNORS OF THE FEDERAL RESERVE SYSTEM BANK HOLDING COMPANIES AND CHANGE IN BANK CONTROL (REGULATION Y... and budget loan installment account. (2) In the second case, Corporation Y, a nonbanking subsidiary...

  2. 12 CFR 225.109 - “Services” under section 4(c)(1) of Bank Holding Company Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false âServicesâ under section 4(c)(1) of Bank... GOVERNORS OF THE FEDERAL RESERVE SYSTEM BANK HOLDING COMPANIES AND CHANGE IN BANK CONTROL (REGULATION Y...., Senate Report 1095, part 2, p. 3) makes it evident that Congress had in mind the exemption of...

  3. Learning Electrical Circuits: The Effects of the 4C-ID Instructional Approach in the Acquisition and Transfer of Knowledge

    ERIC Educational Resources Information Center

    Melo, Mário; Miranda, Guilhermina Lobato

    2015-01-01

    This study was designed to investigate the effects of two instructional approaches (4C-ID versus conventional) on learners' knowledge-acquisition and learning transfer of the electrical circuits content in Physics. Participants were 129 9th graders from a secondary school in Lisbon, M = 14.3 years, SD = 0.54. The participants were divided in two…

  4. Complete Genome Sequence of Spiroplasma turonicum Tab4cT, a Bacterium Isolated from Horse Flies (Haematopota sp.).

    PubMed

    Lo, Wen-Sui; Gasparich, Gail E; Kuo, Chih-Horng

    2016-01-01

    Spiroplasma turonicum Tab4c(T) was isolated from a horse fly (Haematopota sp.; probably Haematopota pluvialis) collected at Champchevrier, Indre-et-Loire, Touraine, France, in 1991. Here, we report the complete genome sequence of this bacterium to facilitate the investigation of its biology and the comparative genomics among Spiroplasma spp. PMID:27660788

  5. Additive synthesis with DIASS-M4C on Argonne National Laboratory`s IBM POWERparallel System (SP)

    SciTech Connect

    Kaper, H.; Ralley, D.; Restrepo, J.; Tiepei, S.

    1995-12-31

    DIASS-M4C, a digital additive instrument was implemented on the Argonne National Laboratory`s IBM POWER parallel System (SP). This paper discusses the need for a massively parallel supercomputer and shows how the code was parallelized. The resulting sounds and the degree of control the user can have justify the effort and the use of such a large computer.

  6. Complete Genome Sequence of Spiroplasma turonicum Tab4cT, a Bacterium Isolated from Horse Flies (Haematopota sp.)

    PubMed Central

    Lo, Wen-Sui; Gasparich, Gail E.

    2016-01-01

    Spiroplasma turonicum Tab4cT was isolated from a horse fly (Haematopota sp.; probably Haematopota pluvialis) collected at Champchevrier, Indre-et-Loire, Touraine, France, in 1991. Here, we report the complete genome sequence of this bacterium to facilitate the investigation of its biology and the comparative genomics among Spiroplasma spp. PMID:27660788

  7. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.

    PubMed

    Buffalo, Cosmo Z; Bahn-Suh, Adrian J; Hirakis, Sophia P; Biswas, Tapan; Amaro, Rommie E; Nizet, Victor; Ghosh, Partho

    2016-01-01

    No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently ∼90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant 'reading head' in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M-C4BP interaction, and also inform a path towards vaccine design. PMID:27595425

  8. Magnetic properties and glass formability of Fe61Co10Zr5W4B20 bulk metallic glassy alloy

    NASA Astrophysics Data System (ADS)

    Pawlik, P.; Davies, H. A.; Gibbs, M. R. J.

    2003-10-01

    Amorphous melt spun ribbon samples of Fe61Co10Zr5W4B20 alloy of various thicknesses up to ˜350 μm and suction cast 1 mm diameter rod and 2, 3, and 4 mm outside diameter tube samples of the same alloy were produced. The experimental results for the rod samples indicate a relatively high saturation polarization μ0Ms=0.8 T and a Curie temperature TC=615 K, as well as a very low coercive field Hc=1.4±0.5 A/m with high anisotropy that lowers the permeability of the samples. Thermal analysis by differential scanning calorimetry carried out on ribbon and rod samples revealed a large supercooled liquid region ΔTx of ˜60 K for this alloy.

  9. Spectral properties of 1H-pyrazolo[3,4-b]quinoline substituted with N,N-diethylamine moiety

    NASA Astrophysics Data System (ADS)

    Kolbus, Anna; Grabka, Danuta; Danel, Andrzej; Szary, Karol

    2016-07-01

    Photophysical properties of 6-N,N-diethyl-3-methyl-1-phenyl-1H-pyrazol[3,4-b]quinoline (DEPQ), a potential material for electroluminescent applications, were investigated. The absorption and fluorescence spectra and fluorescence lifetimes were recorded in a great number of solvents with different polarity. The red shifts in absorption and fluorescence maxima with the solvent's polarity were observed. Different trends in values of quantum yield for non-polar and polar solvents suggest two different deactivation ways of the excited state, depending on solvent polarity. DEPQ in non-polar solvents emits from locally excited states while deactivation DEPQ in polar solvents indicates charge transfer (CT) fluorescence. Several electro-optical parameters were also calculated.

  10. Anillin-dependent organization of septin filaments promotes intercellular bridge elongation and Chmp4B targeting to the abscission site.

    PubMed

    Renshaw, Matthew J; Liu, Jinghe; Lavoie, Brigitte D; Wilde, Andrew

    2014-01-01

    The final step of cytokinesis is abscission when the intercellular bridge (ICB) linking the two new daughter cells is broken. Correct construction of the ICB is crucial for the assembly of factors involved in abscission, a failure in which results in aneuploidy. Using live imaging and subdiffraction microscopy, we identify new anillin-septin cytoskeleton-dependent stages in ICB formation and maturation. We show that after the formation of an initial ICB, septin filaments drive ICB elongation during which tubules containing anillin-septin rings are extruded from the ICB. Septins then generate sites of further constriction within the mature ICB from which they are subsequently removed. The action of the anillin-septin complex during ICB maturation also primes the ICB for the future assembly of the ESCRT III component Chmp4B at the abscission site. These studies suggest that the sequential action of distinct contractile machineries coordinates the formation of the abscission site and the successful completion of cytokinesis.

  11. Discovery of Spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as Potent NOP and Opioid Receptor Agonists.

    PubMed

    Schunk, Stefan; Linz, Klaus; Frormann, Sven; Hinze, Claudia; Oberbörsch, Stefan; Sundermann, Bernd; Zemolka, Saskia; Englberger, Werner; Germann, Tieno; Christoph, Thomas; Kögel, Babette-Y; Schröder, Wolfgang; Harlfinger, Stephanie; Saunders, Derek; Kless, Achim; Schick, Hans; Sonnenschein, Helmut

    2014-08-14

    We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors. PMID:25147602

  12. Photocatalytic degradation of Chicago Sky Blue 6B and Benzopurpurin 4B using titanium dioxide thin film.

    PubMed

    Mohammed, Abdul K; McKenzie, Katrina T

    2005-01-01

    Aqueous solutions of azo dyes undergo degradation to form harmless intermediates and colorless products following irradiation by visible light in the presence of titanium dioxide thin films. The dyes that were studied in this work are: Chicago Sky Blue 6B and Benzopurpurin 4B. Results obtained indicated that complete mineralization of the dyes took place under the experimental conditions. There was an increase in conductivity after the complete mineralization experiments possibly indicating the formation of ions such as NO3- and SO4(2-). Chemical oxygen demand (COD) measurements show a decrease in organic matter for both dyes following complete degradation. The effect of how changing experimental conditions such as pH, temperature and starting concentrations of dyes affected the rate of dye degradation was measured. There was an increase in the rate of disappearance of the dye color at lower pH. High concentrations of dye solutions required long degradation time.

  13. A Conserved Gammaherpesvirus Cyclin Specifically Bypasses Host p18INK4c To Promote Reactivation from Latency

    PubMed Central

    Williams, Lisa M.; Niemeyer, Brian F.; Franklin, David S.; Clambey, Eric T.

    2015-01-01

    ABSTRACT Gammaherpesviruses (GHVs) carry homologs of cellular genes, including those encoding a viral cyclin that promotes reactivation from latent infection. The viral cyclin has reduced sensitivity to host cyclin-dependent kinase inhibitors in vitro; however, the in vivo significance of this is unclear. Here, we tested the genetic requirement for the viral cyclin in mice that lack the host inhibitors p27Kip1 and p18INK4c, two cyclin-dependent kinase inhibitors known to be important in regulating B cell proliferation and differentiation. While the viral cyclin was essential for reactivation in wild-type mice, strikingly, it was dispensable for reactivation in mice lacking p27Kip1 and p18INK4c. Further analysis revealed that genetic ablation of only p18INK4c alleviated the requirement for the viral cyclin for reactivation from latency. p18INK4c regulated reactivation in a dose-dependent manner so that the viral cyclin was dispensable in p18INK4c heterozygous mice. Finally, treatment of wild-type cells with the cytokine BAFF, a known attenuator of p18INK4c function in B lymphocytes, was also able to bypass the requirement for the viral cyclin in reactivation. These data show that the gammaherpesvirus viral cyclin functions specifically to bypass the cyclin-dependent kinase inhibitor p18INK4c, revealing an unanticipated specificity between a GHV cyclin and a single cyclin-dependent kinase inhibitor. IMPORTANCE The gammaherpesviruses (GHVs) cause lifelong infection and can cause chronic inflammatory diseases and cancer, especially in immunosuppressed individuals. Many GHVs encode a conserved viral cyclin that is required for infection and disease. While a common property of the viral cyclins is that they resist inhibition by normal cellular mechanisms, it remains unclear how important it is that the GHVs resist this inhibition. We used a mouse GHV that either contained or lacked a viral cyclin to test whether the viral cyclin lost importance when these inhibitory

  14. Poly(thieno[3,4-b]thiophene)-poly(styrene sulfonate): a low band gap, water dispersible conjugated polymer.

    PubMed

    Lee, Byoungchul; Seshadri, Venkataramanan; Sotzing, Gregory A

    2005-11-01

    Herein we report the oxidative chemical polymerization of thieno[3,4-b]thiophene (T34bT) using several different oxidants including ferric sulfate, ammonium persulfate, and hydrogen peroxide in the presence of poly(styrenesulfonic acid) in water and properties of the resulting poly(thieno[3,4-b]thiophene)-poly(styrenesulfonic acid) (PT34bT-PSS) dispersion. The PT34bT-PSS is rendered a colloidal dispersion in water with a particle size diameter ranging between 180 and 220 nm depending on the oxidant used for polymerization. PT34bT-PSS films have band gaps of ca. 1 eV (1260 nm) as determined by the onset of the pi to pi transition from the vis-NIR spectrum with absorption maxima ranging from 1.4 eV (912 nm) to 1.7 eV (724 nm). The neutral and oxidized forms of PT34bT-PSS prepared from ferric sulfate dispersed in water were blue and lime green, respectively, whereas the neutral and oxidized forms of PT34bT-PSS prepared from ammonium persulfate and hydrogen peroxide were blue and blue-green, respectively. Spectral properties of the PT34bT-PSS dispersion can be tuned by the combination of oxidants. PT34bT-PSS films showed ca. 100% cation dominant ion transport behavior as determined by electrochemical gravimetry with each charge-discharge cycle and the doping level of the polymer was calculated to be 26%. Electrical conductivities for these polymers were found to be dependent on chemical oxidants used and varied from 10(-2) to 10(-4) S/cm. PMID:16262354

  15. Donor Splice-Site Mutation in CUL4B is Likely Cause of X-Linked Intellectual Disability

    PubMed Central

    Londin, Eric R.; Adijanto, Jeffrey; Philp, Nancy; Novelli, Antonio; Vitale, Emilia; Perria, Chiara; Serra, Gigliola; Alesi, Viola; Surrey, Saul; Fortina, Paolo

    2015-01-01

    X-linked intellectual disability is the most common form of cognitive disability in males. Syndromic intellectual disability encompasses cognitive deficits with other medical and behavioral manifestations. Recently, a large family with a novel form of syndromic X-linked intellectual disability was characterized. Eight of 24 members of the family are male and had cognitive dysfunction, short stature, aphasia, skeletal abnormalities, and minor anomalies. To identify the causative gene(s), we performed exome sequencing in three affected boys, both parents, and an unaffected sister. We identified a haplotype consisting of eight variants located in cis within the linkage region that segregated with affected members in the family. Of these variants, two were novel. The first was at the splice-donor site of intron 7 (c.974+1G>T) in the cullin-RING ubiquitin ligase (E3) gene, CUL4B. This variant is predicted to result in failure to splice and remove intron 7 from the primary transcript. The second variant mapped to the 3′-UTR region of the KAISO gene (c.1127T>G). Sanger sequencing validated the variants in these relatives as well as in three affected males and five carriers. The KAISO gene variant was predicted to create a binding site for the microRNAs miR-4999 and miR-4774; however, luciferase expression assays failed to validate increased targeting of these miRNAs to the variant 3′-UTR. This SNP may affect 3′-UTR structure leading to decreased mRNA stability. Our results suggest that the intellectual disability phenotype in this family is caused by aberrant splicing and removal of intron 7 from CUL4B gene primary transcript. PMID:24898194

  16. Study of multi-carbide B4C-SiC/(Al, Si) reaction infiltrated composites by SEM with EBSD

    NASA Astrophysics Data System (ADS)

    Almeida, B. A.; Ferro, M. C.; Ravanan, A.; Grave, P. M. F.; Wu, H.-Y.; Gao, M.-X.; Pan, Y.; Oliveira, F. J.; Lopes, A. B.; Vieira, J. M.

    2014-03-01

    In the definition of conceptual developments and design of new materials with singular or unique properties, characterisation takes a key role in clarifying the relationships of composition, properties and processing that define the new material. B4C has a rare combination of properties that makes it suitable for a wide range of applications in engineering: high refractoriness, thermal stability, high hardness and abrasion resistance coupled to low density. However, the low self-diffusion coefficient of B4C limits full densification by sintering. A way to overturn this constraint is by using an alloy, for example Al-Si, forming composites with B4C. Multi-carbide B4C-SiC/(Al, Si) composites were produced by the reactive melt infiltration technique at 1200 - 1350 °C with up to 1 hour of isothermal temperature holds. Pressed preforms made from C-containing B4C were spontaneously infiltrated with Al-Si alloys of composition varying from 25 to 50 wt% Si. The present study involves the characterisation of the microstructure and crystalline phases in the alloys and in the composites by X-ray diffraction and SEM/EDS with EBSD. Electron backscatter diffraction is used in detail to look for segregation and spatial distribution of Si and Al containing phases during solidification of the metallic infiltrate inside the channels of the ceramic matrix when the composite cools down to the eutectic temperature (577 °C). It complements elemental maps of the SEM/EDS. The production of a flat surface by polishing is intrinsically difficult and the problems inherent to the preparation of EBSD qualified finishing in polished samples of such type of composites are further discussed.

  17. Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome.

    PubMed

    Chong, Chan Eng; Lim, Kue Peng; Gan, Chai Phei; Marsh, Christina A; Zain, Rosnah Binti; Abraham, Mannil Thomas; Prime, Stephen S; Teo, Soo-Hwang; Silvio Gutkind, J; Patel, Vyomesh; Cheong, Sok Ching

    2012-08-01

    MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC. PMID:22459352

  18. Stringent Regulation of Complement Lectin Pathway C3/C5 Convertase By C4b-Binding Protein (C4bp)

    PubMed Central

    Rawal, Nenoo; Rajagopalan, Rema; Salvi, Veena P.

    2009-01-01

    The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (EMan) was examined. While the C4BP concentration for inhibiting 50% (IC50) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05 nM), ∼3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81 nM) and EMan (42.66 nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000-431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79 ± 0.60) when the C4b density on EMan was increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a ∼7 to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions. PMID:19660812

  19. Cullin 4B is recruited to tristetraprolin-containing messenger ribonucleoproteins and regulates TNF-α mRNA polysome loading.

    PubMed

    Pfeiffer, Jason R; Brooks, Seth A

    2012-02-15

    TNF-α is a central mediator of inflammation and critical for host response to infection and injury. TNF-α biosynthesis is controlled by transcriptional and posttranscriptional mechanisms allowing for rapid, transient production. Tristetraprolin (TTP) is an AU-rich element binding protein that regulates the stability of the TNF-α mRNA. Using a screen to identify TTP-interacting proteins, we identified Cullin 4B (Cul4B), a scaffolding component of the Cullin ring finger ligase family of ubiquitin E3 ligases. Short hairpin RNA knockdown of Cul4B results in a significant reduction in TNF-α protein and mRNA in LPS-stimulated mouse macrophage RAW264.7 cells as well as a reduction in TTP protein. TNF-α message t(1/2) was reduced from 69 to 33 min in LPS-stimulated cells. TNF-3' untranslated region luciferase assays utilizing wild-type and mutant TTP-AA (S52A, S178A) indicate that TTP function is enhanced in Cul4B short hairpin RNA cells. Importantly, the fold induction of TNF-α mRNA polysome loading in response to LPS stimulation is reduced by Cul4B knockdown. Cul4B is present on the polysomes and colocalizes with TTP to exosomes and processing bodies, which are sites of mRNA decay. We conclude that Cul4B licenses the TTP-containing TNF-α messenger ribonucleoprotein for loading onto polysomes, and reduction of Cul4B expression shunts the messenger ribonucleoproteins into the degradative pathway.

  20. Interferon-dependent engagement of eukaryotic initiation factor 4B via S6 kinase (S6K)- and ribosomal protein S6K-mediated signals.

    PubMed

    Kroczynska, Barbara; Kaur, Surinder; Katsoulidis, Efstratios; Majchrzak-Kita, Beata; Sassano, Antonella; Kozma, Sara C; Fish, Eleanor N; Platanias, Leonidas C

    2009-05-01

    Although the roles of Jak-Stat pathways in type I and II interferon (IFN)-dependent transcriptional regulation are well established, the precise mechanisms of mRNA translation for IFN-sensitive genes remain to be defined. We examined the effects of IFNs on the phosphorylation/activation of eukaryotic translation initiation factor 4B (eIF4B). Our data show that eIF4B is phosphorylated on Ser422 during treatment of sensitive cells with alpha IFN (IFN-alpha) or IFN-gamma. Such phosphorylation is regulated, in a cell type-specific manner, by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) and results in enhanced interaction of the protein with eIF3A (p170/eIF3A) and increased associated ATPase activity. Our data also demonstrate that IFN-inducible eIF4B activity and IFN-stimulated gene 15 protein (ISG15) or IFN-gamma-inducible chemokine CXCL-10 protein expression are diminished in S6k1/S6k2 double-knockout mouse embryonic fibroblasts. In addition, IFN-alpha-inducible ISG15 protein expression is blocked by eIF4B or eIF3A knockdown, establishing a requirement for these proteins in mRNA translation/protein expression by IFNs. Importantly, the generation of IFN-dependent growth inhibitory effects on primitive leukemic progenitors is dependent on activation of the S6K/eIF4B or RSK/eIF4B pathway. Taken together, our findings establish critical roles for S6K and RSK in the induction of IFN-dependent biological effects and define a key regulatory role for eIF4B as a common mediator and integrator of IFN-generated signals from these kinases. PMID:19289497

  1. CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+ homeostasis and motility.

    PubMed

    Aravindan, Rolands G; Fomin, Victor P; Naik, Ulhas P; Modelski, Mark J; Naik, Meghna U; Galileo, Deni S; Duncan, Randall L; Martin-Deleon, Patricia A

    2012-08-01

    Deletion of the highly conserved gene for the major Ca(2+) efflux pump, Plasma membrane calcium/calmodulin-dependent ATPase 4b (Pmca4b), in the mouse leads to loss of progressive and hyperactivated sperm motility and infertility. Here we first demonstrate that compared to wild-type (WT), Junctional adhesion molecule-A (Jam-A) null sperm, previously shown to have motility defects and an abnormal mitochondrial phenotype reminiscent of that seen in Pmca4b nulls, exhibit reduced (P < 0.001) ATP levels, significantly (P < 0.001) greater cytosolic Ca(2+) concentration ([Ca(2+) ](c)) and ∼10-fold higher mitochondrial sequestration, indicating Ca(2+) overload. Investigating the mechanism involved, we used co-immunoprecipitation studies to show that CASK (Ca(2+) /calmodulin-dependent serine kinase), identified for the first time on the sperm flagellum where it co-localizes with both PMCA4b and JAM-A on the proximal principal piece, acts as a common interacting partner of both. Importantly, CASK binds alternatively and non-synergistically with each of these molecules via its single PDZ (PDS-95/Dlg/ZO-1) domain to either inhibit or promote efflux. In the absence of CASK-JAM-A interaction in Jam-A null sperm, CASK-PMCA4b interaction is increased, resulting in inhibition of PMCA4b's enzymatic activity, consequent Ca(2+) accumulation, and a ∼6-fold over-expression of constitutively ATP-utilizing CASK, compared to WT. Thus, CASK negatively regulates PMCA4b by directly binding to it and JAM-A positively regulates it indirectly through CASK. The decreased motility is likely due to the collateral net deficit in ATP observed in nulls. Our data indicate that Ca(2+) homeostasis in sperm is maintained by the relative ratios of CASK-PMCA4b and CASK-JAM-A interactions.

  2. Enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome P450 4B1: applications for prodrug-activating gene therapy.

    PubMed

    Steffens, S; Frank, S; Fischer, U; Heuser, C; Meyer, K L; Dobberstein, K U; Rainov, N G; Kramm, C M

    2000-05-01

    To monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (EGFP) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (HSV-tk) and rabbit cytochrome P450 4B1 (cyp4b1). Expression of the resulting fusion proteins, TK-EGFP and 4B1-EGFP, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. Ganciclovir and 4-ipomeanol sensitivity was comparable with that achieved with the native HSV-TK and CYP4B1 proteins. As shown by fluorescence microscopy, TK-EGFP was expressed predominantly intranuclearly, whereas 4B1-EGFP was detectable in the cytoplasm, thereby displaying the orthotopic subcellular distribution of the corresponding native enzymes. The fluorescence intensity correlated well with the corresponding prodrug sensitivity, as shown by fluorescence-activated cell sorter analysis. EGFP expression was also used for the selection of stably HSV-tk-transduced cells by flow cytometric cell sorting. Resulting cell populations showed a homogeneity of fluorescence intensity similar to single-cell clones after antibiotic selection. In conclusion, tk-egfp and 4b1-egfp fusion genes are valuable tools for monitoring prodrug-activating gene therapy in living cells. EGFP fusion genes/proteins provide a simple and reproducible means for the detection, selection, and characterization of cells expressing enzyme genes for prodrug activation.

  3. LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation

    PubMed Central

    Tan, Xiaojun; Sun, Yue; Thapa, Narendra; Liao, Yihan; Hedman, Andrew C; Anderson, Richard A

    2015-01-01

    Lysosomal degradation is essential for the termination of EGF-stimulated EGF receptor (EGFR) signaling. This requires EGFR sorting to the intraluminal vesicles (ILVs) of multi-vesicular endosomes (MVEs). Cytosolic proteins including the ESCRT machineries are key regulators of EGFR intraluminal sorting, but roles for endosomal transmembrane proteins in receptor sorting are poorly defined. Here, we show that LAPTM4B, an endosomal transmembrane oncoprotein, inhibits EGF-induced EGFR intraluminal sorting and lysosomal degradation, leading to enhanced and prolonged EGFR signaling. LAPTM4B blocks EGFR sorting by promoting ubiquitination of Hrs (an ESCRT-0 subunit), which inhibits the Hrs association with ubiquitinated EGFR. This is counteracted by the endosomal PIP kinase, PIPKIγi5, which directly binds LAPTM4B and neutralizes the inhibitory function of LAPTM4B in EGFR sorting by generating PtdIns(4,5)P2 and recruiting SNX5. PtdIns(4,5)P2 and SNX5 function together to protect Hrs from ubiquitination, thereby promoting EGFR intraluminal sorting. These results reveal an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2 signaling, and the ESCRT complex and define a mechanism by which the oncoprotein LAPTM4B can transform cells and promote tumor progression. PMID:25588945

  4. Molecular Basis for the Association of Human E4B U Box Ubiquitin Ligase with E2-Conjugating Enzymes UbcH5c and Ubc4

    SciTech Connect

    Benirschke, Robert C.; Thompson, James R.; Nominé, Yves; Wasielewski, Emeric; Juranić, Nenad; Macura, Slobodan; Hatakeyama, Shigetsugu; Nakayama, Keiichi I.; Botuyan, Maria Victoria; Mer, Georges

    2010-09-07

    Human E4B, also called UFD2a, is a U box-containing protein that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is thought to participate in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. The U box domain is an anchor site for E2 ubiquitin-conjugating enzymes, but little is known of the binding mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U box free and bound to UbcH5c and Ubc4 E2s. Whereas previously characterized U box domains are homodimeric, we show that E4B U box is a monomer stabilized by a network of hydrogen bonds identified from scalar coupling measurements. These structural studies, complemented by calorimetry- and NMR-based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B U box and provide a molecular basis to understand how the ubiquitylation machinery involving E4B assembles.

  5. The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice

    SciTech Connect

    Plowman, Sarah J.; Arends, Mark J.; Brownstein, David G.; Luo Feijun; Devenney, Paul S.; Rose, Lorraine; Ritchie, Ann-Marie; Berry, Rachel L.; Harrison, David J.; Hooper, Martin L.; Patek, Charles E. . E-mail: Charles.Patek@ed.ac.uk

    2006-01-01

    Ras proteins function as molecular switches in signal transduction pathways, and, here, we examined the effects of the K-ras4A and 4B splice variants on cell function by comparing wild-type embryonic stem (ES) cells with K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} (exon 4A knock-out) ES cells which express K-ras4B only and K-ras {sup -/-} (exons 1-3 knock-out) ES cells which express neither splice variant, and intestinal epithelium from wild-type and K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} mice. RT-qPCR analysis found that K-ras4B expression was reduced in K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells but unaffected in small intestine. K-Ras deficiency did not affect ES cell growth, and K-Ras4A deficiency did not affect intestinal epithelial proliferation. K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} and K-ras {sup -/-} ES cells showed a reduced capacity for differentiation following LIF withdrawal, and K-ras {sup -/-} cells were least differentiated. K-Ras4A deficiency inhibited etoposide-induced apoptosis in ES cells and intestinal epithelial cells. However, K-ras {sup tm{delta}}{sup 4A/tm{delta}}{sup 4A} ES cells were more resistant to etoposide-induced apoptosis than K-ras {sup -/-} cells. The results indicate that (1) K-Ras4A promotes apoptosis while K-Ras4B inhibits it, and (2) K-Ras4B, and possibly K-Ras4A, promotes differentiation. The findings raise the possibility that alteration of the K-Ras4A/4B isoform ratio modulates tumorigenesis by differentially affecting stem cell survival and/or differentiation. However, K-Ras4A deficiency did not affect life expectancy or spontaneous overall tumor incidence in aging mice.

  6. C/EBPβ-LAP*/LAP Expression Is Mediated by RSK/eIF4B-Dependent Signalling and Boosted by Increased Protein Stability in Models of Monocytic Differentiation

    PubMed Central

    Christmann, Martin; Friesenhagen, Judith; Westphal, Andreas; Pietsch, Daniel; Brand, Korbinian

    2015-01-01

    The transcription factor C/EBPβ plays a key role in monocytic differentiation and inflammation. Its small isoform LIP is associated with proliferation at early premonocytic developmental stages and regulated via mTOR-dependent signalling. During later stages of (pre)monocytic differentiation there is a considerable increase in the large C/EBPβ isoforms LAP*/LAP which inhibit proliferation thus supporting terminal differentiation. Here, we showed in different models of monocytic differentiation that this dramatic increase in the LAP*/LAP protein and LAP/LIP ratio was accompanied by an only modest/retarded mRNA increase suggesting an important role for (post)translational mechanisms. We found that LAP*/LAP formation was induced via MEK/RSK-dependent cascades, whereas mTOR/S6K1 were not involved. Remarkably, LAP*/LAP expression was dependent on phosphorylated eIF4B, an acceleratory protein of RNA helicase eIF4A. PKR inhibition reduced the expression of eIF4B and C/EBPβ in an eIF2α-independent manner. Furthermore, under our conditions a marked stabilisation of LAP*/LAP protein occurred, accompanied by reduced chymotrypsin-like proteasome/calpain activities and increased calpastatin levels. Our study elucidates new signalling pathways inducing LAP*/LAP expression and indicates new alternative PKR functions in monocytes. The switch from mTOR- to RSK-mediated signalling to orchestrate eIF4B-dependent LAP*/LAP translation, accompanied by increased protein stability but only small mRNA changes, may be a prototypical example for the regulation of protein expression during selected processes of differentiation/proliferation. PMID:26646662

  7. Interaction of ultrashort x-ray pulses with B{sub 4}C, SiC, and Si

    SciTech Connect

    Bergh, M.; Timneanu, N.; Hau-Riege, S. P.; Scott, H. A.

    2008-02-15

    The interaction of 32.5 and 6 nm ultrashort x-ray pulses with the solid materials B{sub 4}C, SiC, and Si is simulated with a nonlocal thermodynamic equilibrium radiation transfer code. We study the ionization dynamics as a function of depth in the material and modifications of the opacity during irradiation, and estimate the crater depth. Furthermore, we compare the estimated crater depth with experimental data, for fluences up to 2.2 J/cm{sup 2}. Our results show that, at 32.5 nm irradiation, the opacity changes by less than a factor of 2 for B{sub 4}C and Si and by a factor of 3 for SiC, for fluences up to 200 J/cm{sup 2}. At a laser wavelength of 6 nm, the model predicts a dramatic decrease in opacity due to the weak inverse bremsstrahlung, increasing the crater depth for high fluences.

  8. Surface Nb-ALLOYING on 0.4C-13Cr Stainless Steel: Microstructure and Tribological Behavior

    NASA Astrophysics Data System (ADS)

    Yu, Shengwang; You, Kai; Liu, Xiaozhen; Zhang, Yihui; Wang, Zhenxia; Liu, Xiaoping

    2016-02-01

    0.4C-13Cr stainless steel was alloyed with niobium using double glow plasma surface alloying and tribological properties of Nb-alloyed steel such as hardness, friction and wear were measured. Effects of the alloying temperature on microstructure and the tribological behavior of the alloyed steel were investigated compared with untreated steel. Formation mechanisms of Nb-alloyed layers and increased wear resistance were also studied. The result shows that after surface Nb-alloying treatment, the 0.4C-13Cr steel exhibits a diffusion adhesion at the alloyed layer/substrate interface and improved tribological property. The friction coefficient of Nb-alloyed steel is decreased by about 0.3-0.45 and the wear rate after Nb-alloying is only 2-5% of untreated steel.

  9. Normal-incidence Sb/B{sub 4}C multilayer mirrors for the 80 A < {lambda} < 120 A wavelength range

    SciTech Connect

    Vishnyakov, E A; Voronov, D L; Gullikson, E M; Kondratenko, V V; Kopylets, I A; Luginin, M S; Pirozhkov, A S; Ragozin, Evgenii N; Shatokhin, A N

    2013-07-31

    Periodic and aperiodic Sb/B4C multilayer structures have been theoretically calculated and synthesised for the first time for the application in soft X-ray optics in the 80 A < {lambda} < 120 A range. The reflection spectra of the periodic multilayer mirrors are measured using synchrotron radiation and laser plasma-generated radiation. The experimental spectra are theoretically interpreted with the inclusion of transition layers and substrate roughness. The density of antimony layers is supposedly {rho}{sub (Sb)} = 6.0 g cm{sup -3}, and the thickness of transition layers (if any) in the Sb/B4C multilayer structures does not exceed 10 A. A peak reflectivity of 19 % is attained at a wavelength of 85 A. An aperiodic mirror optimised for maximum uniform reflectivity in the 100 - 120 A range is tested employing the laser plasma radiation source. (x-ray optics)

  10. Fabrication and thermal shock resistance of HfB2-SiC composite with B4C additives

    NASA Astrophysics Data System (ADS)

    Weng, L.; Han, W.; Hong, Ch.

    2011-12-01

    A HfB2 based ceramic matrix composite containing 20 vol.% SiC particles with 2 vol.% B4C as sintering additives was fabricated by hot-pressed sintering. The microstructure and properties, especially the thermal shock resistance of the composite were investigated. Results showed that the addition of B4C improved the powder sinterability and led to obtaining nearly full dense composite. The flexural strength and fracture toughness of the composite were 771 MPa and 7.06 MPam1/2, respectively. The thermal shock resistance tests indicated that the residual strength decreased significantly when the thermal shock temperature difference was higher than 600 °C. The large number of microcracks on the sample surface was the main reason for the catastrophic failure.

  11. Translocation of PKG1α acts on TRPV4-C1 heteromeric channels to inhibit endothelial Ca2+ entry

    PubMed Central

    Zhang, Peng; Mao, Ai-qin; Sun, Chun-yuan; Zhang, Xiao-dong; Pan, Qiong-xi; Yang, Dan-tong; Jin, Jian; Tang, Chun-lei; Yang, Zhen-yu; Yao, Xiao-qiang; Lu, Xiao-jie; Ma, Xin

    2016-01-01

    Aim: TRPV4-C1 heteromeric channels contribute to store-operated Ca2+ entry in vascular endothelial cells. However, the negative regulation of these channels is not fully understood. This study was conducted to investigate the inhibitory effect of PKG1α on TRPV4-C1 heteromeric channels. Methods: Immuno-fluorescence resonance energy transfer (FRET) was used to explore the spatial proximity of PKG1α and TRPC1. Phosphorylation of endogenous TRPC1 was tested by phosphorylation assay. [Ca2+]i transients and cation current in MAECs were assessed with Fura-2 fluorescence and whole-cell recording, respectively. In addition, rat mesenteric arteries segments were prepared, and vascular relaxation was examined with wire myography. Results: In immuno-FRET experiments, after exposure of these cells to 8-Br-cGMP, more PKG1α was observed in the plasma membrane, and PKG1α and TRPC1 were observed to be in closer proximity. TAT-TRPC1S172 and TAT-TRPC1T313 peptide fragments, which contain the PKG targeted residues Ser172 and Thr313, respectively, were introduced into isolated endothelial cells to abrogate the translocation of PKG1α. Furthermore, a phosphorylation assay demonstrated that PKG directly phosphorylates TRPC1 at Ser172 and Thr313 in endothelial cells. In addition, PKG activator 8-Br-cGMP markedly reduced the magnitude of the 4αPDD-induced and 11,12-EET-induced [Ca2+]i transients, the cation current and vascular relaxation. Conclusion: This study uncovers a novel mechanism by which PKG negatively regulates endothelial heteromeric TRPV4-C1 channels through increasing the spatial proximity of TRPV4-C1 to PKG1α via translocation and through phosphorylating Ser172 and Thr313 of TRPC1. PMID:27397542

  12. Non-ejection cervical spine fracture due to defensive aerial combat maneuvering in an RF-4C: a case report.

    PubMed

    Schall, D G

    1983-12-01

    An unusual case report is presented describing an incident in which an RF-4C instructor pilot fractured three cervical vertebrae after impacting the rear canopy top during a negative G defensive maneuver. The pilot subsequently developed an incomplete tetraparesis later in flight and the aircraft had to be recovered by the front seat pilot. No similar cases have ever been reported to the USAF Safety Center or described in the aviation literature. PMID:6661124

  13. Volumetric Properties of the Mixture Tetrachloromethane CCl4 + C8H16 Cyclooctane (VMSD1211, LB3564_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Tetrachloromethane CCl4 + C8H16 Cyclooctane (VMSD1211, LB3564_V)' providing data from direct low-pressure dilatometric measurement of molar excess volume at variable mole fraction and constant temperature.

  14. Heat of Mixing and Solution of Tetrachloromethane CCl4 + C8H16 Cyclooctane (HMSD1111, LB4087_H)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Heat of Mixing and Solution of Tetrachloromethane CCl4 + C8H16 Cyclooctane (HMSD1111, LB4087_H)' providing data from direct low-pressure calorimetric measurement of molar excess enthalpy at variable mole fraction and constant temperature.

  15. Formation mechanism of LiFePO 4/C composite powders investigated by X-ray absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Kuei-Feng; Hu, Shao-Kang; Chen, Chinh-Hsiang; Cheng, Ming-Yao; Tsay, Sun-Yuan; Chou, Tse-Chuan; Sheu, Hwo-Shuenn; Lee, Jyh-Fu; Hwang, Bing-Joe

    The local structure and oxidation states for both the precursors and the LiFePO 4/C composite powders were investigated by X-ray absorption spectroscopy (XAS) to provide a deep insight into their formation mechanism. It was found that the local structure and oxidation states of the precursors and the synthesized LiFePO 4/C powders as well as the electrochemical properties of the synthesized powders were strongly influenced by the R ratio (R: molar ratio of citric acid to total metal ions). The oxidation states of iron ions of the precursors for R = 1 and 0.75 consist mainly of Fe(II) and traces of Fe(III). However, the oxidation state of iron ions of the precursor for R = 0.5 comprises mainly of Fe(III). The oxidation state of iron ions of all the synthesized powders is Fe(II). The structure of the precursors and the synthesized powders for R = 1 and 0.75 is more ordering than that for R = 0.5. It is in good agreement with the observation of the cation mixing obtained from the Riteveld analysis of the XRD data. The better the electrochemical performance is, the more ordering the structure or the less the cation mixing. However, the effect of the R values on the carbon content is also essential for the electrochemical properties of the synthesized LiFePO 4/C composite powders. Increasing the carbon content leads to the increase in the electronic conductivity but impedes the Li + ion diffusion of the composite materials. Consequently, the powders synthesized at the optimal R ratio of 0.75 exhibited the highest initial capacity, about 150 mAh g -1 when cycled at 1/40 C rate at room temperature. The structural scheme of the precursors and the synthesized powders and the formation mechanism of the LiFePO 4/C composite powders are also addressed in this work.

  16. First-principles study of configurational disorder in B4C using a superatom-special quasirandom structure method

    NASA Astrophysics Data System (ADS)

    Ektarawong, A.; Simak, S. I.; Hultman, L.; Birch, J.; Alling, B.

    2014-07-01

    Configurationally disordered crystalline boron carbide, with the composition B4C, is studied using first-principles calculations. We investigate both dilute and high concentrations of carbon-boron substitutional defects. For the latter purpose, we suggest a superatom's picture of the complex structure and combine it with a special quasirandom structure approach for disorder. In this way, we model a random distribution of high concentrations of the identified low-energy defects: (1) bipolar defects and (2) rotation of icosahedral carbon among the three polar-up sites. Additionally, the substitutional disorder of the icosahedral carbon at all six polar sites, as previously discussed in the literature, is also considered. Two configurational phase transitions from the ordered to the disordered configurations are predicted to take place upon an increase in temperature using a mean-field approximation for the entropy. The first transition, at 870 K, induces substitutional disorder of the icosahedral carbon atoms among the three polar-up sites; meanwhile the second transition, at 2325 K, reveals the random substitution of the icosahedral carbon atoms at all six polar sites coexisting with bipolar defects. Already the first transition removes the monoclinic distortion existing in the ordered ground-state configuration and restore the rhombohedral system (R3m). The restoration of inversion symmetry yielding the full rhombohedral symmetry (R3¯m ) on average, corresponding to what is reported in the literature, is achieved after the second transition. Investigating the effects of high pressure on the configurational stability of the disordered B4C phases reveals a tendency to stabilize the ordered ground-state configuration as the configurationally ordering/disordering transition temperature increases with pressure exerted on B4C. The electronic density of states, obtained from the disordered phases, indicates a sensitivity of the band gap to the degree of configurational

  17. Effects of Nb-doped on the structure and electrochemical performance of LiFePO{sub 4}/C composites

    SciTech Connect

    Ma, Zhipeng; Shao, Guangjie; Wang, Guiling; Zhang, Ying; Du, Jianping

    2014-02-15

    The olivine-type niobium doping Li{sub 1−x}Nb{sub x}FePO{sub 4}/C (x=0, 0.005, 0.010, 0.015, 0.025) cathode materials were synthesized via a two-step ball milling solid state reaction. The effects of Nb doping were charactered by X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), galvanostatic intermittent titration technique (GITT), cyclic voltammetry (CV), electrochemical impedance spectra (EIS) and galvanostatic charge–discharge. It is found that Nb doping enlarges the interplanar distance of crystal plane parallel to [0 1 0] direction in LiFePO{sub 4}. In other words, it widens the one dimensional diffusion channels of Li{sup +} along the [0 1 0] direction. Electrochemical test results indicate that the Li{sub 0.99}Nb{sub 0.01}FePO{sub 4}/C composite exhibits the best electrochemical performance with initial special discharge capacity of 139.3 mA h g{sup −1} at 1 C rate. The present synthesis route is promising in making the solid state reaction method more practical for preparation of the LiFePO{sub 4} material. - Graphical abstract: The proper amount of Nb doping widens the one dimensional diffusion channels of Li{sup +} along the [0 1 0] direction. Display Omitted - Highlights: • The Nb doping LiFePO{sub 4}/C is prepared by a facile two-step ball milling solid state reaction. • The sample possesses the better high-rate performance. • The tap density of Li{sub 0.99}Nb{sub 0.01}FePO{sub 4}/C sample is 1.76 g cm{sup −3}.

  18. 75 FR 34429 - Petition of Hard Eight Futures, LLC for Exemptive Relief, Pursuant to Section 4(c) of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ..., pursuant to Section 4(c) of the Act, from Section 2(a)(1)(C)(iv) of the Act and 17 CFR Part 30 Appendix D... Commodity Exchange Act, From Section 2(a)(1)(C)(iv) of the Commodity Exchange Act and Appendix D to Part 30... Eight Futures Petition for Exemption from Section 2(a)(1)(C)(iv) of the Act and Appendix D to Part 30...

  19. Explosive Indentation Study of B4C-TiAlx Composites Fabricated by the Dipping Exothermic Reaction Process

    NASA Astrophysics Data System (ADS)

    Kim, Jong Ho; Ansari, Haris Masood; Kim, Haneul; Kim, Do Kyung; Chang, Soon Nam

    The aim of this study is to fabricate a high volume fraction B4C-reinforced intermetallic matrix composite by the dipping exothermic reaction process and investigate the shock impact damage response of composites by explosive indentation experiment. It has been shown that the final microstructure of the dipping exothermic reaction process-fabricated composite can be tailored by treatment of the constituent powders and post heat treatment. The hardness and impact damage resistance of the fabricated composites were evaluated.

  20. One-step fabricated Fe3O4@C core-shell composites for dye removal: Kinetics, equilibrium and thermodynamics

    NASA Astrophysics Data System (ADS)

    Qu, Lingling; Han, Tingting; Luo, Zhijun; Liu, Cancan; Mei, Yan; Zhu, Ting

    2015-03-01

    B-Fe3O4@C core-shell composites were synthesized via one-pot hydrothermal carbonization (HTC) process and used as an adsorbent for the removal of methylene blue (MB) from aqueous solution. By using sodium borate as the catalyst, the hydrothermal carbonization process of B-Fe3O4@C core-shell composites was optimized and a higher surface area was obtained. The adsorbent was characterized by XRD, Raman spectra, SEM, TEM and N2 adsorption/desorption isotherms. We studied the dye adsorption process at different conditions and analyzed the data by employing the Langmuir and Freundlich models, and the equilibrium data fitted well with both models. Kinetic analyses were conducted by using the Lagergren pseudo-first-order and pseudo-second-order model and the results showed that the adsorption process was more consistent with the pseudo-second-order kinetics. To better understand the dye adsorption process from the thermodynamics perspective, we also calculated ΔHο, ΔSο, ΔGο and Ea, the results suggesting that the MB adsorption process was physisorption endothermic process, and spontaneous at room temperature. The as-synthesized B-Fe3O4@C showing high magnetic sensitivity provides a facile and efficient way to recycle from aqueous solution.

  1. Characterization of a phage-like pyocin from the plant growth-promoting rhizobacterium Pseudomonas fluorescens SF4c.

    PubMed

    Fischer, Sonia; Godino, Agustina; Quesada, José Miguel; Cordero, Paula; Jofré, Edgardo; Mori, Gladys; Espinosa-Urgel, Manuel

    2012-06-01

    R-type and F-type pyocins are high-molecular-mass bacteriocins produced by Pseudomonas aeruginosa that resemble bacteriophage tails. They contain no head structures and no DNA, and are used as defence systems. In this report, we show that Pseudomonas fluorescens SF4c, a strain isolated from the wheat rhizosphere, produces a high-molecular-mass bacteriocin which inhibits the growth of closely related bacteria. A mutant deficient in production of this antimicrobial compound was obtained by transposon mutagenesis. Sequence analysis revealed that the transposon had disrupted a gene that we have named ptm, since it is homologous to that encoding phage tape-measure protein in P. fluorescens Pf0-1, a gene belonging to a prophage similar to phage-like pyocin from P. aeruginosa PAO1. In addition, we have identified genes from the SF4c pyocin cluster that encode a lytic system and regulatory genes. We constructed a non-polar ptm mutant of P. fluorescens SF4c. Heterologous complementation of this mutation restored the production of bacteriocin. Real-time PCR was used to analyse the expression of pyocin under different stress conditions. Bacteriocin was upregulated by mitomycin C, UV light and hydrogen peroxide, and was downregulated by saline stress. This report constitutes, to our knowledge, the first genetic characterization of a phage tail-like bacteriocin in a rhizosphere Pseudomonas strain.

  2. High-performance LiFePO4/C electrode with polytetrafluoroethylene as an aqueous-based binder

    NASA Astrophysics Data System (ADS)

    Gao, Shiyan; Su, Yuefeng; Bao, Liying; Li, Ning; Chen, Lai; Zheng, Yu; Tian, Jun; Li, Jian; Chen, Shi; Wu, Feng

    2015-12-01

    An environmental-friendly and low-cost polymer, polytetrafluoroethylene (PTFE) has been applied as an aqueous-based binder for the fabrication of LiFePO4/C electrode. The electrode with PTFE has been compared to the electrode with the conventional binder, polyvinylidene fluoride (PVDF) via Rheology test, X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and electrochemical tests. The Rheology test indicates that the viscosity of the slurry prepared with PTFE as a binder is better than that prepared with PVDF. The electrochemical measurements demonstrate that the electrode with PTFE binder displays a higher discharge capacity of 161.1 mAh g-1 compared to the electrode with PVDF binder, which shows a discharge capacity of 150.7 mAh g-1. The EIS analysis indicates the LiFePO4/C electrode with PTFE binder shows a higher ionic conductivity and a smaller increasing in charge transfer rate compared to the LiFePO4/C electrode with PVDF binder. In addition, the electrodes applying the aqueous-based binder have been optimized by controlling the moisture content in the electrodes. The electrochemical enhancement of these electrodes can be achieved by controlling the vacuum drying temperature and time during the preparation of the electrodes.

  3. Effect of heat treatment temperature on superconducting performance of B 4C added MgB 2/Nb conductors

    NASA Astrophysics Data System (ADS)

    Viljamaa, J.; Kario, A.; Dobročka, E.; Reissner, M.; Kulich, M.; Kováč, P.; Häßler, W.

    2012-02-01

    A previously observed enhancing effect of addition of 10 wt.% of B 4C on critical current density ( Jc) dependence on magnetic flux density ( B) in MgB 2 superconductors is examined here in more detail. Nb sheathed in situ MgB 2 monofilamentary Powder-in-Tube (PIT) samples are prepared with the 10 wt.% addition of boron carbide. The samples are heat treated at different temperatures, namely at 650, 700, 750, and 800 °C for 30 min. The phases and lattice parameters of the samples are studied using X-ray Diffraction (XRD). The amount of B 4C does not decrease from the initial amount with increasing heat treatment temperature ( Tht) but instead increases. This indicates that some of the Mg from the precursor reacts with the Nb sheath. Magnetic Jc( B) characteristics are obtained at several temperatures in external B in a Vibrating Sample Magnetometer (VSM). The magnetic and transport Jc( B) results disagree with each other which can be explained by unsuitability of Nb as the sheath with higher Tht. From these results, also pinning force densities ( Fp) are calculated. No effect on pinning mechanism of B 4C added samples is observed by the heat treatment conditions. Resistance dependencies on temperature are also measured in a Physical Properties Measurement System (PPMS). Mg deficiency with high Tht is supported by these measurements.

  4. Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells.

    PubMed

    Fujii, Setsuko; Nishikawa-Torikai, Satomi; Futatsugi, Yoko; Toyooka, Yayoi; Yamane, Mariko; Ohtsuka, Satoshi; Niwa, Hitoshi

    2015-01-01

    Nuclear receptor subfamily 0, group B, member 1 (Nr0b1, also known as Dax1) is regarded as an important component of the transcription factor network that governs pluripotency in mouse embryonic stem (ES) cells. Here we generated inducible knockout ES cells for Nr0b1 using the Cre-loxP system and analyzed its precise function. We succeeded in establishing the Nr0b1-null ES cells and confirmed their pluripotency by showing their contribution to chimeric embryos. However, they proliferated slowly with over-expression of 2-cell stage specific transcripts including Zscan4c, which is known to be involved in telomere elongation in ES cells. We revealed that over-expression of Zscan4c prevents normal self-renewal by inducing arrest at G2 phase followed by cell death and that Nr0b1 directly represses the Zscan4c promoter. These data indicated that Nr0b1 is not essential to maintain pluripotency but is involved in the proper activation of 2-cell specific transcripts for self-renewal. PMID:25772165

  5. Determination of High-Resolution 3D Chromatin Organization Using Circular Chromosome Conformation Capture (4C-seq).

    PubMed

    Matelot, Mélody; Noordermeer, Daan

    2016-01-01

    3D chromatin organization is essential for many aspects of transcriptional regulation. Circular Chromosome Conformation Capture followed by Illumina sequencing (4C-seq) is among the most powerful techniques to determine 3D chromatin organization. 4C-seq, like other modifications of the original 3C technique, uses the principle of "proximity ligation" to identify and quantify ten thousands of genomic interactions at a kilobase scale in a single experiment for predefined loci in the genome.In this chapter we focus on the experimental steps in the 4C-seq protocol, providing detailed descriptions on the preparation of cells, the construction of the circularized 3C library and the generation of the Illumina high throughput sequencing library. This protocol is particularly suited for the use of mammalian tissue samples, but can be used with minimal changes on circulating cells and cell lines from other sources as well. In the final section of this chapter, we provide a brief overview of data analysis approaches, accompanied by links to publicly available analysis tools. PMID:27659989

  6. Solvothermal synthesis and electrochemical performance in super-capacitors of Co3O4/C flower-like nanostructures

    NASA Astrophysics Data System (ADS)

    Jiang, Jinhui; Shi, Weidong; Song, Shuyan; Hao, Qingli; Fan, Weiqiang; Xia, Xifeng; Zhang, Xian; Wang, Qian; liu, Chunbo; Yan, Dan

    2014-02-01

    Novel three dimensional (3D) Co3O4/C flower-like nanostructures are synthesized via a facile solvothermal strategy. The samples are characterized by XRD, XPS, FT-IR, Raman, TG, SEM and HRTEM. The results show that the 3D flower-like nanostructures are consisted of numerous 2D nanosheets with the thickness of about 20 nm. The pseudocapacitive behaviors of Co3O4/C and bare Co3O4 flower-like nanostructures are investigated by cyclic voltammograms, galvanostatic charge-discharge and electrochemical impedance spectroscopy test. The results reveal that the Co3O4/C delivers a large specific capacitance of as high as 865 F g-1 and 330 F g-1 at 1 mV s-1 and 0.5 A g-1, according to CV and galvanostatic test, respectively; while the bare Co3O4 has a poor electrochemical performance, which exhibits specific capacitance of 131.7 F g-1 and 46.1 F g-1 at the same condition. The excellent electrochemical performance is attributed to the carbon present on the Co3O4 and the morphology, which possesses large surface area, unique flower-like nanostructures and low equivalent series resistance.

  7. Pepper pathogenesis-related protein 4c is a plasma membrane-localized cysteine protease inhibitor that is required for plant cell death and defense signaling.

    PubMed

    Kim, Nak Hyun; Hwang, Byung Kook

    2015-01-01

    Xanthomonas campestris pv. vesicatoria (Xcv) type III effector AvrBsT triggers programmed cell death (PCD) and activates the hypersensitive response (HR) in plants. Here, we isolated and identified the plasma membrane localized pathogenesis-related (PR) protein 4c gene (CaPR4c) from pepper (Capsicum annuum) leaves undergoing AvrBsT-triggered HR cell death. CaPR4c encodes a protein with a signal peptide and a Barwin domain. Recombinant CaPR4c protein expressed in Escherichia coli exhibited cysteine protease-inhibitor activity and ribonuclease (RNase) activity. Subcellular localization analyses revealed that CaPR4c localized to the plasma membrane in plant cells. CaPR4c expression was rapidly and specifically induced by avirulent Xcv (avrBsT) infection. Transient expression of CaPR4c caused HR cell death in pepper leaves, which was accompanied by enhanced accumulation of H2 O2 and significant induction of some defense-response genes. Deletion of the signal peptide from CaPR4c abolished the induction of HR cell death, indicating a requirement for plasma membrane localization of CaPR4c for HR cell death. CaPR4c silencing in pepper disrupted both basal and AvrBsT-triggered resistance responses, and enabled Xcv proliferation in infected leaves. H2 O2 accumulation, cell-death induction, and defense-response gene expression were distinctly reduced in CaPR4c-silenced pepper. CaPR4c overexpression in transgenic Arabidopsis plants conferred greater resistance against infection by Pseudomonas syringae pv. tomato and Hyaloperonospora arabidopsidis. These results collectively suggest that CaPR4c plays an important role in plant cell death and defense signaling.

  8. Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection.

    PubMed

    Ngampasutadol, Jutamas; Ram, Sanjay; Blom, Anna M; Jarva, Hanna; Jerse, Ann E; Lien, Egil; Goguen, Jon; Gulati, Sunita; Rice, Peter A

    2005-11-22

    Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind the classical pathway of complement down-regulatory protein C4b-binding protein (C4bp) to evade killing by human complement. Strains of N. gonorrhoeae that resisted killing by human serum complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee infection. Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates.

  9. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system?

    PubMed

    Blom, Anna M; Villoutreix, Bruno O; Dahlbäck, Björn

    2004-04-01

    The complement system constitutes an important component of the defence against foreign organisms, functioning both in innate and adaptive immune systems. It is potentially harmful also to the own organism and is therefore tightly regulated by a number of membrane-bound and soluble factors. C4b-binding protein (C4BP) is a potent circulating soluble inhibitor of the classical and lectin pathways of complement. In recent years, the relationships between the structure of C4BP and its functions have been elucidated using a combination of computer-based molecular analysis and recombinant DNA technologies. Moreover, two novel functions have recently been ascribed to C4BP. One is the ability of C4BP to localize complement regulatory activity to the surface of apoptotic cells via its interaction with the membrane-binding vitamin K-dependent protein S. The other is the ability of C4BP to act as a survival factor for B cells due to an interaction with CD40. The complement regulatory activity of C4BP is not only beneficial because it is also explored by pathogens such as Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes, Escherichia coli K1, and Candida albicans, that bind C4BP to their surfaces. This contributes to the serum resistance and the pathogenicity of these bacteria. In this review, the structural requirements and functional importance of the interactions between C4BP and its various ligands are discussed.

  10. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-08-02

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  11. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-01-01

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  12. Sharp green electroluminescence from 1H-pyrazolo[3,4-b]quinoline-based light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Tao, Y. T.; Balasubramaniam, E.; Danel, A.; Jarosz, B.; Tomasik, P.

    2000-09-01

    A multilayer organic light-emitting diode was fabricated using a fluorescent compound {6-N,N-diethylamino-1-methyl-3-phenyl-1H-pyrazolo[3,4-b]quinoline} (PAQ-NEt2) doped into the hole-transporting layer of NPB {4,4'-bis[N-(1-naphthyl-1-)-N-phenyl-amino]-biphenyl}, with the TPBI {2,2',2″-(1,3,5-phenylene)tris[1-phenyl-1H-benzimidazole]} as an electrontransporting material. At 16% PAQ-NEt2 doping concentration, the device gave a sharp, bright, and efficient green electroluminescence (EL) peaked at around 530 nm. The full width at half maximum of the EL is 60 nm, which is 60% of the green emission from typical NPB/AlQ [where AlQ=tris(8-hydroxyquinoline) aluminum] device. For the same concentration, a maximum luminance of 37 000 cd/m2 was obtained at 10.0 V and the maximum power, luminescence, and external quantum efficiencies were obtained 4.2 lm/W, 6.0 cd/A, and 1.6%, respectively, at 5.0 V.

  13. Purification of beef-heart cytochrome c oxidase by hydrophobic interaction chromatography on octyl-Sepharose CL-4B.

    PubMed

    Rosén, S

    1978-04-12

    1. Hydrophobic interaction chromatography on Octyl-Sepharose CL-4B is used as a new and simple method for the preparation of large amounts of beef-heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). 2. The method involves only one cycle of (NH4)2SO4 fractionation before the material is applied to the column. After washing with 10% cholate and 1.5% Tween 80, elution of the enzyme is accomplished with 1% Triton X-100. 3. The enzyme so prepared contains about 10 nmol heme alpha/mg protein and about 0.2% phospholipid. 4. Characterization of the enzyme has been made with optical and EPR spectroscopy and polyacrylamide gel electrophoresis. The preparation appears by these criteria to be at least as good as other purified enzyme preparations. 5. The turnover rate at infinite cytochrome c concentration in 0.1 M sodium phosphate buffer and 0.5% Tween 80 at pH 6.1 is 80 s-1 per functional unit of the enzyme. A more than three-fold activation could be obtained by the addition of phosphatidylcholine at neutral pH.

  14. Heterodyne coherent detection of WDM PDM-QPSK signals with spectral efficiency of 4b/s/Hz.

    PubMed

    Li, Xinying; Dong, Ze; Yu, Jianjun; Yu, Jianguo; Chi, Nan

    2013-04-01

    We experimentally demonstrate heterodyne coherent detection of 8 × 112-Gb/s ultra-density wavelength-division-multiplexing (WDM) polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) signal after 1120-km single-mode fiber-28 (SMF-28) transmission. The spectral efficiency (SE) is 4b/s/Hz. It is the first time to realize WDM signal transmission with high SE by adopting heterodyne coherent detection. At the heterodyne coherent receiver, intermediate frequency (IF) down conversion is realized in digital frequency domain after analog-to-digital conversion. A digital post filter and 1-bit maximum likelihood sequence estimation (MLSE) adopted after carrier phase estimation (CPE) in the conventional digital-signal-processing (DSP) process is used to suppress the enhanced noise and crosstalk as well as overcome the filtering effects. The bit-error ratio (BER) for all channels is under the forward-error-correction (FEC) limit of 3.8 × 10(-3) after 1120-km SMF-28 transmission.

  15. Heterodyne detection and transmission of 60-Gbaud PDM-QPSK signal with SE of 4b/s/Hz.

    PubMed

    Li, Xinying; Xiao, Jiangnan; Yu, Jianjun

    2014-04-21

    We experimentally demonstrate 8 × 240-Gb/s super-Nyquist wavelength-division-multiplexing (WDM) polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) signal transmission on a 50-GHz grid with a net spectral efficiency (SE) of 4b/s/Hz adopting hardware-efficient simplified heterodyne detection. 9-ary quadrature-amplitude-modulation-like (9QAM-like) processing based on multi-modulus blind equalization (MMBE) is adopted to reduce analog-to-digital converter (ADC) bandwidth requirement and improve receiver sensitivity. The transmission distance at the soft-decision forward-error-correction (SD-FEC) threshold of 2 × 10(-2) is 2 × 420 km based on digital post filtering while largely extended to over 5 × 420 km based on 9QAM-like processing, which well illustrates 9QAM-like processing is more efficient for heterodyne coherent WDM system. Moreover, only two ADC channels are needed for simplified heterodyne detection of one 60-Gbaud PDM-QPSK WDM channel, and thus only one commercial oscilloscope (OSC) with two input ports can work well for each WDM channel.

  16. Ammonia Inhibition of Plasmid pRmeGR4a Conjugal Transfer between Rhizobium meliloti Strains

    PubMed Central

    Herrera-Cervera, J. A.; Olivares, J.; Sanjuan, J.

    1996-01-01

    We have examined nutritional factors influencing conjugal transfer of the two nonsymbiotic large plasmids, pRmeGR4a and pRmeGR4b, of Rhizobium meliloti GR4. To monitor transfer, each plasmid was tagged with a different antibiotic resistance marker. Transfer of plasmid pRmeGR4b was dependent upon the presence of plasmid pRmeGR4a on the same donor cell. Transconjugants for pRmeGR4b were obtained at frequencies 5-to 10-fold higher than transconjugants carrying both plasmids, indicating that mobilization of pRmeGR4b by pRmeGR4a probably occurred in trans. Conjugal transfer of the tagged plasmids between R. meliloti strains was tested on minimal medium supplemented with single amino acids, nitrate, or ammonium as the single nitrogen source. A higher number of transconjugants was obtained when glutamate was the only nitrogen source, whereas conjugation was virtually undetectable on ammonium. No relationship was found between donor or recipient growth rate and plasmid transfer rate on a given nitrogen source. Furthermore, in media containing both glutamate and ammonium as nitrogen sources, transfer was reduced almost 100-fold compared with that in media containing glutamate alone. Inhibition was readily detected at 2.5 mM or higher concentrations of either ammonium chloride or ammonium sulfate and appeared to be specific for exogenously supplied ammonium. Inhibition of conjugal transfer between R. meliloti strains by ammonium was only observed for rhizobial plasmids, not for a heterologous plasmid such as RP4. Apparently, ammonium did not affect the plasmid-encoded transfer machinery, as it had no influence on rhizobial plasmid transfer from R. meliloti to Agrobacterium tumefaciens. The effect of ammonium seemed to take place on R. meliloti recipient cells, thereby reducing the efficiency of plasmid conjugation, probably by affecting mating pair formation or stabilization. PMID:16535284

  17. A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine responses in human monocytic and macrophage cells

    PubMed Central

    Xie, Guorui; Luo, Huanle; Tian, Bing; Mann, Brian; Bao, Xiaoyong; McBride, Jere; Tesh, Robert; Barrett, Alan D; Wang, Tian

    2015-01-01

    Previous studies have shown that an attenuated West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant induces stronger innate and adaptive immune responses than wild-type WNV in mice, which has important applications to vaccine development. To investigate the mechanism of immunogenicity, we characterized WNV NS4B-P38G mutant infection in two human cell lines--THP-1 cells and THP-1 macrophages. Although the NS4B-P38G mutant produced more viral RNA than the parental WNV NY99 in both cell types, there was no detectable infectious virus in the supernatant of either cell type. Nonetheless, the attenuated mutant boosted higher innate cytokine responses than virulent parental WNV NY99 in these cells. The NS4B-P38G mutant infection of THP-1 cells led to more diverse and robust innate cytokine responses than that seen in THP-1 macrophages, which were mediated by toll-like receptor (TLR)7 and retinoic acid-inducible gene 1(RIG-I) signaling pathways. Overall, these results suggest that a defective viral life cycle during NS4B-P38G mutant infection in human monocytic and macrophage cells leads to more potent cell intrinsic innate cytokine responses. PMID:25562791

  18. MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B.

    PubMed

    Li, Lei; Ma, Hui-Qiang

    2015-08-01

    There is increasing evidence to suggest that microRNAs (miRNAs; miRs) are involved in the development of oral squamous cell carcinoma (OSCC). miR-216a has been identified as being involved in tumorigenesis, however, the mechanisms of miR-216a in various types of cancer, either as a tumor suppressor or as an oncogenic miRNA, and the specific regulatory role of miR-216a in OSCC remain to be elucidated. The present study demonstrated that the expression of miR-216a was significantly reduced in OSCC tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, colony formation, migration and invasion of the OSCC cells. In addition, eukaryotic translation initiation factor 4B (EIF4B) was identified as a direct target of miR-216a, which was observed to be upregulated in the OSCC tissues. Furthermore, overexpression of EIF4B significantly attenuated the antitumor effect of miR-216a, and a negative correlation was observed between miR-216a and EIF4B in the OSCC tissues. Taken together, these findings indicated that miR-216a has a suppressive role in OSCC cells by directly targeting EIF4B, and may function as a potential prognostic biomarker and novel therapeutic target.

  19. Optimized human CYP4B1 in combination with the alkylator prodrug 4-ipomeanol serves as a novel suicide gene system for adoptive T-cell therapies.

    PubMed

    Roellecke, K; Virts, E L; Einholz, R; Edson, K Z; Altvater, B; Rossig, C; von Laer, D; Scheckenbach, K; Wagenmann, M; Reinhardt, D; Kramm, C M; Rettie, A E; Wiek, C; Hanenberg, H

    2016-07-01

    Engineering autologous or allogeneic T cells to express a suicide gene can control potential toxicity in adoptive T-cell therapies. We recently reported the development of a novel human suicide gene system that is based on an orphan human cytochrome P450 enzyme, CYP4B1, and the naturally occurring alkylator prodrug 4-ipomeanol. The goal of this study was to systematically develop a clinically applicable self-inactivating lentiviral vector for efficient co-expression of CYP4B1 as an ER-located protein with two distinct types of cell surface proteins, either MACS selection genes for donor lymphocyte infusions after allogeneic stem cell transplantation or chimeric antigen receptors for retargeting primary T cells. The U3 region of the myeloproliferative sarcoma virus in combination with the T2A site was found to drive high-level expression of our CYP4B1 mutant with truncated CD34 or CD271 as MACS suitable selection markers. This lentiviral vector backbone was also well suited for co-expression of CYP4B1 with a codon-optimized CD19 chimeric antigen receptor (CAR) construct. Finally, 4-ipomeanol efficiently induced apoptosis in primary T cells that co-express mutant CYP4B1 and the divergently located MACS selection and CAR genes. In conclusion, we here developed a clinically suited lentiviral vector that supports high-level co-expression of cell surface proteins with a potent novel human suicide gene. PMID:27092941

  20. Farnesylated and methylated KRAS4b: high yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions

    PubMed Central

    Gillette, William K.; Esposito, Dominic; Abreu Blanco, Maria; Alexander, Patrick; Bindu, Lakshman; Bittner, Cammi; Chertov, Oleg; Frank, Peter H.; Grose, Carissa; Jones, Jane E.; Meng, Zhaojing; Perkins, Shelley; Van, Que; Ghirlando, Rodolfo; Fivash, Matthew; Nissley, Dwight V.; McCormick, Frank; Holderfield, Matthew; Stephen, Andrew G.

    2015-01-01

    Prenylated proteins play key roles in several human diseases including cancer, atherosclerosis and Alzheimer’s disease. KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed by farnesylation, proteolytic cleavage and carboxymethylation at the C-terminus. Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not accurately replicate the mature KRAS protein found in mammalian cells and the protein yield is typically low. We describe a protocol that yields 5–10 mg/L highly purified, farnesylated, and methylated KRAS4b from insect cells. Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEδ. PMID:26522388

  1. Synthesis of Fe3O4@C core-shell nanorings and their enhanced electrochemical performance for lithium-ion batteries.

    PubMed

    Wang, Lili; Liang, Jianwen; Zhu, Yongchun; Mei, Tao; Zhang, Xing; Yang, Qing; Qian, Yitai

    2013-05-01

    Fe3O4@C core-shell nanorings (R-Fe3O4@C) were fabricated by a synchronous reduction and carbon deposition process. As the anodes for lithium-ion batteries, these R-Fe3O4@C exhibit a high capacity, excellent cycling stability and good rate performance. This ring-shaped core-shell nanostructure design may pave the way to enhance electrochemical performances of electrode materials.

  2. Mechanical Properties and Strengthening Mechanisms of Al-15 Pct B4C Composites with Sc and Zr at Elevated Temperatures

    NASA Astrophysics Data System (ADS)

    Qin, Jian; Zhang, Zhan; Chen, X.-Grant

    2016-09-01

    The mechanical properties at ambient and elevated temperatures of two Al-15 vol pct B4C composites, S40 with 0.4 wt pct Sc and SZ40 with 0.4 wt pct Sc and 0.24 wt pct Zr, are investigated during long-term thermal annealing. The presence of large B4C particles in the microscale has a moderate but stable strengthening effect on Al-B4C composites at ambient and elevated temperatures, while the precipitation of nanoscale Al3Sc and Al3(Sc, Zr) in the composite matrix provides a predominate contribution to the composite strength, which is varied by tested temperatures. The Al3Sc precipitates in S40 remain coarsening resistant at 523 K (250 °C), whereas the Al3(Sc, Zr) precipitates in SZ40 are thermally stable at 573 K (300 °C) over 2000 hours of annealing. At higher annealing temperatures (573 K (300 °C) for S40 and 623 K (350 °C) for SZ40), both Al3Sc and Al3(Sc, Zr) precipitates become coarsening with prolonged annealing time. The yield strength of S40 and SZ40 at ambient temperature decreases with the increasing precipitate size, which can be explained by the classical precipitate shearing and Orowan bypass mechanisms. At elevated temperatures [523 K to 623 K (250 °C to 350 °C)], considerably lower yield stresses are observed compared to those at ambient temperature, which invokes a dislocation climb mechanism. The predicted yield strengths at elevated temperatures by the combination of dislocation climb and Orowan models are in good agreement with the experimental data.

  3. Excellent temperature performance of spherical LiFePO4/C composites modified with composite carbon and metal oxides.

    PubMed

    Zhang, Bao; Zeng, Tao; Zhang, Jiafeng; Peng, Chunli; Zheng, Junchao; Chen, Guomin

    2014-01-01

    Nanosized spherical LiFePO4/C composite was synthesized from nanosized spherical FePO4 ·2H2O, Li2C2O4, aluminum oxide, titanium oxide, oxalic acid, and sucrose by binary sintering process. The phases and morphologies of LiFePO4/C were characterized using SEM, TEM, CV, EIS, EDS, and EDX as well as charging and discharging measurements. The results showed that the as-prepared LiFePO4/C composite with good conductive webs from nanosized spherical FePO4 ·2H2O exhibits excellent electrochemical performances, delivering an initial discharge capacity of 161.7 mAh·g(-1) at a 0.1 C rate, 152.4 mAh·g(-1) at a 1 C rate and 131.7 mAh·g(-1) at a 5 C rate, and the capacity retention of 99.1%, 98.7%, and 95.8%, respectively, after 50 cycles. Meanwhile, the high and low temperature performance is excellent for 18650 battery, maintaining capacity retention of 101.7%, 95.0%, 88.3%, and 79.3% at 55°C, 0°C, -10°C, and -20°C by comparison withthat of room temperature (25°C) at the 0.5 C rate over a voltage range of 2.2 V to 3.6 V, respectively.

  4. Deposition and characterization of B4C/CeO2 multilayers at 6.x nm extreme ultraviolet wavelengths

    NASA Astrophysics Data System (ADS)

    Sertsu, M. G.; Giglia, A.; Brose, S.; Park, D.; Wang, Z. S.; Mayer, J.; Juschkin, L.; Nicolosi, P.

    2016-03-01

    New multilayers of boron carbide/cerium dioxide (B4C/CeO2) combination on silicon (Si) substrate are manufactured to represent reflective-optics candidates for future lithography at 6.x nm wavelength. This is one of only a few attempts to make multilayers of this kind. Combination of several innovative experiments enables detailed study of optical properties, structural properties, and interface profiles of the multilayers in order to open up a room for further optimization of the manufacturing process. The interface profile is visualized by high-angle annular dark-field imaging which provides highly sensitive contrast to atomic number. Synchrotron based at-wavelength extreme ultraviolet (EUV) reflectance measurements near the boron (B) absorption edge allow derivation of optical parameters with high sensitivity to local atom interactions. X-ray reflectivity measurements at Cu-Kalpha (8 keV ) determine the period of multilayers with high in-depth resolution. By combining these measurements and choosing robust nonlinear curve fitting algorithms, accuracy of the results has been significantly improved. It also enables a comprehensive characterization of multilayers. Interface diffusion is determined to be a major cause for the low reflectivity performance. Optical constants of B4C and CeO2 layers are derived in EUV wavelengths. Besides, optical properties and asymmetric thicknesses of inter-diffusion layers (interlayers) in EUV wavelengths near the boron edge are determined. Finally, ideal reflectivity of the B4C/CeO2 combination is calculated by using optical constants derived from the proposed measurements in order to evaluate the potentiality of the design.

  5. Excellent Temperature Performance of Spherical LiFePO4/C Composites Modified with Composite Carbon and Metal Oxides

    PubMed Central

    Zhang, Bao; Zeng, Tao; Zhang, Jiafeng; Peng, Chunli; Zheng, Junchao; Chen, Guomin

    2014-01-01

    Nanosized spherical LiFePO4/C composite was synthesized from nanosized spherical FePO4·2H2O, Li2C2O4, aluminum oxide, titanium oxide, oxalic acid, and sucrose by binary sintering process. The phases and morphologies of LiFePO4/C were characterized using SEM, TEM, CV, EIS, EDS, and EDX as well as charging and discharging measurements. The results showed that the as-prepared LiFePO4/C composite with good conductive webs from nanosized spherical FePO4·2H2O exhibits excellent electrochemical performances, delivering an initial discharge capacity of 161.7 mAh·g−1 at a 0.1 C rate, 152.4 mAh·g−1 at a 1 C rate and 131.7 mAh·g−1 at a 5 C rate, and the capacity retention of 99.1%, 98.7%, and 95.8%, respectively, after 50 cycles. Meanwhile, the high and low temperature performance is excellent for 18650 battery, maintaining capacity retention of 101.7%, 95.0%, 88.3%, and 79.3% at 55°C, 0°C, −10°C, and −20°C by comparison withthat of room temperature (25°C) at the 0.5 C rate over a voltage range of 2.2 V to 3.6 V, respectively. PMID:24526888

  6. Reactions of ethynyl radicals - Rate constants with CH4, C2H6, and C2D6

    NASA Technical Reports Server (NTRS)

    Laufer, A. H.

    1981-01-01

    An experiment to measure ethynyl radical reactivity with other simple molecules is described. Flash photolysis of CF3C2H, a C2H precursor, was kinetically and spectroscopically analyzed for C2H reactions with CH4, C2H6, and C2D6 and rate constants for the abstraction reaction at room temperature were determined. The experimental apparatus is described, and the acetylene feedstock purification procedures are outlined. Rate constants are provided, and additional examination of the effects of added helium showed no alterations over the pressure range 20-700 torr.

  7. Atomic structure of icosahedral B4C boron carbide from a first principles analysis of NMR spectra.

    PubMed

    Mauri, F; Vast, N; Pickard, C J

    2001-08-20

    Density functional theory is demonstrated to reproduce the 13C and 11B NMR chemical shifts of icosahedral boron carbides with sufficient accuracy to extract previously unresolved structural information from experimental NMR spectra. B4C can be viewed as an arrangement of 3-atom linear chains and 12-atom icosahedra. According to our results, all the chains have a CBC structure. Most of the icosahedra have a B11C structure with the C atom placed in a polar site, and a few percent have a B (12) structure or a B10C2 structure with the two C atoms placed in two antipodal polar sites.

  8. PROCESSING, MICROSTRUCTURE AND MECHANICAL PROPERTY CORRELATION IN Al-B4C SURFACE COMPOSITE PRODUCED VIA FRICTION STIR PROCESSING

    SciTech Connect

    Komarasamy, Mageshwari; Mishra, Rajiv S.; Baumann, John A.; Grant, Glenn J.; Hovanski, Yuri

    2013-01-29

    Friction stir processing (FSP) was employed to prepare surface composites (SC) composed of B4C particles in 5024 Al matrix. The processing parameters, such as hole pattern and geometry,and the number of FSP passes, were optimized to obtain uniform powder distribution. The micrographs revealed a homogeneous distribution of the particles with good interfacial bonding. The hardness of the composite was uniform across the processed region which again indicates the uniformity of powder distribution. The modulus of the surface composite was measured using strain gage and showed a significant improvement. This improvement in modulus lies in the load sharing capability from the soft matrix to the hard particles.

  9. Volumetric Properties of the Mixture Tetrachloroethene C2Cl4 + C14H30 Tetradecane (VMSD1212, LB3196_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Tetrachloroethene C2Cl4 + C14H30 Tetradecane (VMSD1212, LB3196_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  10. Volumetric Properties of the Mixture Tetrachloroethene C2Cl4 + C14H30 Tetradecane (VMSD1111, LB3200_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume B 'Binary Liquid Systems of Nonelectrolytes II' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Tetrachloroethene C2Cl4 + C14H30 Tetradecane (VMSD1111, LB3200_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  11. Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones.

    PubMed

    Arvieux, J; Yssel, H; Colomb, M G

    1988-10-01

    The effect of complement fragments C3b and C4b, on the triggering of antigen-specific human T-cell clones by Epstein-Barr virus-transformed human lymphoblastoid B cells (LCL) when these fragments are covalently coupled to the antigen tetanus toxin (TT) is described. TT was chemically cross-linked to purified C3b [(TT-C3b)n], C4b [(TT-C4b)n] or bovine serum albumin [(TT-BSA)n] as a control. T-cell activation was quantified by tritiated thymidine incorporation and 51Cr release. (TT-C3b)n and (TT-C4b)n induced proliferative responses comparable to (TT-BSA)n but at 18-25 and 4-6 lower concentrations, respectively. This enhancing effect required the covalent cross-linking of the complement fragments to the antigen and involved intracellular processing of the latter by LCL. Antigen presentation was similarly enhanced when measuring the cytotoxic activity of a helper T-cell clone against LCL previously pulsed with (TT-C3b)n or (TT-C4b)n compared with (TT-BSA)n. Binding studies, carried out on LCL using TT radiolabelled with 125I before cross-linking, indicated that (TT-C3b)n and (TT-C4b)n gave three- to four-fold more binding than (TT-BSA)n. Addition of antibodies against CR1 and CR2 or proteolytic removal of these complement receptors with trypsin inhibited by about 60% the enhancing effect of TT-bound C3b and C4b in both binding and functional assays. These results indicate that binding of C3b or C4b to antigen enhances antigen-specific proliferative and cytotoxic responses of T cells by targeting opsonized antigen onto complement receptors CR1 and CR2 of LCL. The putative significance of these findings in terms of regulation of immune responses by complement is discussed.

  12. Instability due to a two recirculation pump trip in a BWR using RAMONA-4B computer code with 3D neutron kinetics

    SciTech Connect

    Cheng, H.S.; Rohatgi, U.S.

    1993-06-01

    An investigation was made of the potential for thermal-hydraulic instabilities coupled to neutronic feedback in a BWR due to a two recirculation pump trip event using the RAMONA-4B computer code with 3D neutron kinetics. It is concluded that a high-power (100%) and low-flow (75%) initial condition would most likely lead to in-phase density wave oscillations after the tripping of both recirculation pumps, and that RAMONA-4B is capable of predicting such thermal-hydraulic instabilities coupled to neutronic feedback in BWR and in SBWR.

  13. Synthesis of new 9-glycosyl-4,9-dihydropyrano [3,4-b]indole-1(3H)-ones as antibacterial agents.

    PubMed

    Kassab, Shaymaa E; Hegazy, Gehan H; Eid, Nahed M; Amin, Kamelia M; El-Gendy, Adel A

    2011-11-01

    A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. α-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains.

  14. An analysis of the deformation approach to calculation of the life of hydrogen impregnated 1Kh16N4B steel in low-cycle fatigue

    SciTech Connect

    Litvin, V.V.; Anan'evskii, V.A.; Mints, A.I.

    1986-01-01

    This paper presents the results of experimental investigations and an analysis of the applicability of the deformation approach for calculation of the life of 1Kh16N4B steel in low-cycle fatigue. Hydrogen impregnation was done with use of cathodic polarization in a special cell with a polarization current density of 35 mA/cm/sup 2/ for 60 min. The test results are presented, and it can be seen that the influence of hydrogen absorption significantly changes the life of 1Kh16N4B steel, but the Coffin-Kavomoto criterion does not give satisfactory results.

  15. Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones.

    PubMed

    Arvieux, J; Yssel, H; Colomb, M G

    1988-10-01

    The effect of complement fragments C3b and C4b, on the triggering of antigen-specific human T-cell clones by Epstein-Barr virus-transformed human lymphoblastoid B cells (LCL) when these fragments are covalently coupled to the antigen tetanus toxin (TT) is described. TT was chemically cross-linked to purified C3b [(TT-C3b)n], C4b [(TT-C4b)n] or bovine serum albumin [(TT-BSA)n] as a control. T-cell activation was quantified by tritiated thymidine incorporation and 51Cr release. (TT-C3b)n and (TT-C4b)n induced proliferative responses comparable to (TT-BSA)n but at 18-25 and 4-6 lower concentrations, respectively. This enhancing effect required the covalent cross-linking of the complement fragments to the antigen and involved intracellular processing of the latter by LCL. Antigen presentation was similarly enhanced when measuring the cytotoxic activity of a helper T-cell clone against LCL previously pulsed with (TT-C3b)n or (TT-C4b)n compared with (TT-BSA)n. Binding studies, carried out on LCL using TT radiolabelled with 125I before cross-linking, indicated that (TT-C3b)n and (TT-C4b)n gave three- to four-fold more binding than (TT-BSA)n. Addition of antibodies against CR1 and CR2 or proteolytic removal of these complement receptors with trypsin inhibited by about 60% the enhancing effect of TT-bound C3b and C4b in both binding and functional assays. These results indicate that binding of C3b or C4b to antigen enhances antigen-specific proliferative and cytotoxic responses of T cells by targeting opsonized antigen onto complement receptors CR1 and CR2 of LCL. The putative significance of these findings in terms of regulation of immune responses by complement is discussed. PMID:2973431

  16. Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats

    SciTech Connect

    Chen, Xiang-Qi; Chen, Liang-Long Fan, Lin; Fang, Jun; Chen, Zhao-Yang; Li, Wei-Wei

    2014-04-25

    Highlights: • BFGF exists only in the cytoplasm of live cells. • BFGF cannot be secreted into the extracellular space to promote cell growth. • We combine the secretion-promoting signal peptide of FGF4. • We successfully modified BMSCs with the fused genes of FGF4-bFGF. • We promoted the therapeutic effects of transplanted BMSCs in myocardial infarction. - Abstract: The aim of this study was to investigate whether the modification of bone marrow-derived mesenchymal stem cells (BMSCs) with the fused FGF4 (fibroblast growth factor 4)-bFGF (basic fibroblast growth factor) gene could improve the expression and secretion of BFGF, and increase the efficacies in repairing infarcted myocardium. We used In-Fusion technique to construct recombinant lentiviral vectors containing the individual gene of bFGF, enhanced green fluorescent protein (EGFP), or genes of FGF4-bFGF and EGFP, and then transfected these lentiviruses into rat BMSCs. We conducted an in vitro experiment to compare the secretion of bFGF in BMSCs infected by these lentiviruses and also examined their therapeutic effects in the treatment of myocardial infraction in a rodent study. Sixty rats were tested in the following five conditions: Group-SHAM received only sham operation as controls; Group-AMI received only injection of placebo PBS buffer; Group-BMSC, Group-bFGF and Group-FGF4-bFGF received implantation of BMSCs with empty lentivirus, bFGF lentivirus, and FGF4-bFGF lentivirus, respectively. Our results found out that the transplanted FGF4-bFGF BMSCs had the highest survival rate, and also the highest myocardial expression of bFGF and microvascular density as evidenced by Western blotting and immunohistochemistry, respectively. As compared to other groups, the Group-FGF4-BFGF rats had the lowest myocardial fibrotic fraction, and the highest left ventricular ejection fraction. These results suggest that the modification of BMSCs with the FGF4-bFGF fused gene can not only increase the expression of

  17. Sequence analysis, characterization and mRNA distribution of channel catfish (Ictalurus punctatus Rafinesque, 1818) chemokine (C-X-C motif) receptor 4 (CXCR4) cDNA.

    PubMed

    Yeh, Hung-Yueh; Klesius, Phillip H

    2010-04-15

    Chemokine receptor CXCR4, a member of the G protein-coupled receptor superfamily, binds selectively CXCL12. This protein plays many important roles in immunological as well as pathophysiological functions. In this study, we identified and characterized the channel catfish CXCR4 transcript. The full-length nucleic acid sequence of channel catfish CXCR4 cDNA comprised of 1994 nucleotides, including an open reading frame, which appears to encode a putative peptide of 357 amino acid residues with a calculated molecular mass of 40.1kDa. By comparison with the human counterpart, the channel catfish CXCR4 peptide can be divided into domains, including seven transmembrane domains, four cytoplasmic domains, and four extracellular domains. The CXCR4 transcript was detected in spleen, anterior kidney, liver, intestine, skin and gill of all catfish examined in this study. Because four CXCL of channel catfish have been identified, the result provides valuable information for further exploring the channel catfish chemokine signalling pathways and their roles in immune responses to infection. PMID:19853928

  18. Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice

    PubMed Central

    Yang, Li-Ping; Jiang, Fang-Jie; Wu, Gui-Sheng; Deng, Ke; Wen, Meng; Zhou, Xiaoju; Hong, Xuechuan; Zhu, Michael X.; Luo, Huai-Rong

    2015-01-01

    Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research. PMID:26317356

  19. Apolipoprotein E/C1/C4/C2 gene cluster diversity in two native Andean populations: Aymaras and Quechuas.

    PubMed

    Gayà-Vidal, Magdalena; Athanasiadis, Georgios; Carreras-Torres, Robert; Via, Marc; Esteban, Esther; Villena, Mercedes; Vasquez, René; Dugoujon, Jean-Michel; Moral, Pedro

    2012-07-01

    The APOE/C1/C4/C2 gene cluster presents high relevance in lipid metabolism and, therefore, has important epidemiological implications. Here, we study for the first time the variation patterns of 25 polymorphisms (10 short tandem repeats, STRs, and 15 single nucleotide polymorphismas, SNPs) in two native Andean samples from Bolivia (45 Aymaras and 45 Quechuas) as well as one European sample (n = 41) as external reference. We estimated diversity parameters, linkage disequilibrium patterns, population structure, and possible selective effects. In general, diversity was low and could be partly attributed to selection (probably due to its physiological importance), since the APOE/C1/C4/C2 region was highly conserved compared to the flanking genes in both Bolivians and Europeans. Moreover, the lower gene diversity in Bolivians compared to Europeans for some markers might indicate different demographic histories. Regarding the APOE isoforms, in addition to ɛ3 (94%) and ɛ4 (5%), isoform ɛ2 (1%) was also detected in Bolivians. In relation to previous hypotheses, our results support that genetic drift or founder effects rather than selection for increased cholesterol absorption are the main factors that have shaped the distribution of APOE isoforms observed in South America. PMID:22681517

  20. What is the mechanism of the OSO ring formation in sulfur tetroxide (SO4(C2v)) molecule?

    NASA Astrophysics Data System (ADS)

    Goodarzi, Moein; Vahedpour, Morteza; Solimannejad, Mohammad

    2012-06-01

    The mechanism of SO2 + O2 and O + SO3(D3h) reactions have been investigated at the MP2/6-31 + G(d) and CCSD(T)/cc-pV(Q + d)Z//MP2 levels on the triplet and singlet PESs. Although, no stable collision complexes have been found for the SO2 + O2(3∑g-), O(3P) + SO3(D3h) and O(1D) + SO3(D3h) reactions, 1IN(O2S-O2) has been considered on the singlet PES for the SO2 + O2(1Δg) reaction. The results show that there are no favorable paths for the OSO ring formation of SO4(C2v) in the atmospheric reactions of the SO2 + O2(3∑g-), SO2 + O2(1Δg) and O(3P) + SO3(D3h) while, the O(1D) + SO3(D3h) reaction can be suitable for the SO4(C2v) formation on the singlet PES.

  1. Stability and normal incidence reflectivity of W/B4C multilayer mirror near the boron K absorption edge.

    PubMed

    Rao, P N; Rai, S K; Nayak, M; Lodha, G S

    2013-09-01

    A multilayer structure consisting of alternate layers of W and B4C has been deposited using a magnetron sputtering system. The structure of the as-deposited and vacuum-annealed W/B4C multilayer sample has been characterized using grazing incidence x-ray reflectivity, grazing incidence diffraction, and the normal incidence reflectivity has been measured using synchrotron radiation. A two-layer model consisting of tungsten and boron carbide is presented. The multilayer structure was found to be stable after 800°C annealing. Grazing incidence x-ray diffraction measurements suggested that W is polycrystalline with small grain size. No signature of tungsten carbide or tungsten boride formation could be observed during the annealing treatments. A near normal incidence soft x-ray reflectivity (SXRR) of ~8.3% was obtained at 6.8 nm wavelength. A little drop (~1%) in SXRR after 800°C annealing suggested that there were no compositional changes within the layers during the annealing treatments.

  2. Thermal and stress studies of normal incidence Mo/B4C multilayers for a 6.7 nm wavelength.

    PubMed

    Barthelmess, Miriam; Bajt, Saša

    2011-04-10

    Wavelength, reflectance, and stress stability of Mo/B(4)C multilayers were studied as a function of postdeposition annealing up to 900 °C. These multilayers are of interest as normal incidence coatings for wavelengths above the boron K-absorption edge. Mo/B(4)C multilayers deposited at low sputtering pressure have high compressive stress. Zero stress can be achieved at 360 °C-370 °C, but annealing at <200 °C is sufficient to reduce stress by ∼40%. This stress relaxation is accompanied with a multilayer period expansion of ∼0.02 nm and a <0.5% decrease in normal incidence reflectivity. The multilayer period remains stable up to ∼600 °C, while intrinsic stress changes from compressive to tensile. A four-layer model with amorphous molybdenum and boron carbide layers separated by amorphous layers of molybdenum borides (Mo(x)B(y)) is presented. These interlayers are present already in the as-deposited state and continue to grow with increasing temperature. Their presence lowers the optical contrast and the achievable reflectivity. However, they also increase multilayer thermal stability. At temperatures >600 °C, a noticeable decrease in reflectivity associated with the phase transition from amorphous to crystalline molybdenum boride is observed. This is accompanied with an increase in interface and surface roughness and a change in stress as a function of temperature.

  3. Neutron reflectometry on highly absorbing films and its application to 10B4C-based neutron detectors

    PubMed Central

    Piscitelli, F.; Khaplanov, A.; Devishvili, A.; Schmidt, S.; Höglund, C.; Birch, J.; Dennison, A. J. C.; Gutfreund, P.; Hall-Wilton, R.; Van Esch, P.

    2016-01-01

    Neutron reflectometry is a powerful tool used for studies of surfaces and interfaces. The absorption in the typical studied materials is neglected and this technique is limited only to the reflectivity measurement. For strongly absorbing nuclei, the absorption can be directly measured by using the neutron-induced fluorescence technique which exploits the prompt particle emission of absorbing isotopes. This technique is emerging from soft matter and biology where highly absorbing nuclei, in very small quantities, are used as a label for buried layers. Nowadays, the importance of absorbing layers is rapidly increasing, partially because of their application in neutron detection; a field that has become more active also due to the 3He-shortage. We extend the neutron-induced fluorescence technique to the study of layers of highly absorbing materials, in particular 10B4C. The theory of neutron reflectometry is a commonly studied topic; however, when a strong absorption is present the subtle relationship between the reflection and the absorption of neutrons is not widely known. The theory for a general stack of absorbing layers has been developed and compared to measurements. We also report on the requirements that a 10B4C layer must fulfil in order to be employed as a converter in neutron detection. PMID:26997902

  4. Optical and structural characterization of CeO2/B4C multilayers near boron K-edge energy

    NASA Astrophysics Data System (ADS)

    Sertsu, M. G.; Giglia, A.; Brose, S.; Comisso, A.; Wang, Z. S.; Juschkin, L.; Nicolosi, P.

    2015-05-01

    A search for novel materials for making multilayers of high reflectivity has been driven by the vigorous demand towards miniaturizing photonics. A typical consumer of high performance multilayers (MLs) is the extreme ultraviolet lithography (EUVL) based on the 13.5 nm laser produced plasma (LPP) source. To sustain "Moore's law" and print fine features below 10 nm on integrated circuits (IC), source of radiation for the EUVL has to shift towards even shorter wavelengths where 6.x nm wavelength seems to be immediate successor. However, the 6.x nm EUV lithography needs MLs of reflectivity performance above 70 % to support high volume manufacturing (HVM). It is clear that more work is required particularly on the development of MLs with high reflectance, stable to thermal heat and sufficient lifetime. In this work new MLs of B4C/CeO2 are deposited, analyzed and characterized for the first time. Combinations of X-ray reflectometry (XRR) and EUV reflectance measurements near resonance edge of boron are analyzed to derive structural and optical parameters of MLs. ML coatings of B4C/CeO2 MLs have shown similar reflectance performance with the leading candidate MLs around 6.x nm wavelength. Analysis shows that interlayer diffusion is a major reason for low reflectivity performance. Cross-sectional scanning electron microscopy (SEM) images of the MLs have proved formation of interlayer diffusion.

  5. Synthesis and Photophysical Studies of Thiadiazole[3,4-c]pyridine Copolymer Based Organic Field-Effect Transistors.

    PubMed

    Bathula, Chinna; Lee, Sang Kyu; Kalode, Pranav; Badgujar, Sachin; Belavagi, Ningaraddi S; Khazi, Imtiyaz Ahmed M; Kang, Youngjong

    2016-05-01

    A novel thiadiazolo[3,4-c]pyridine] based donor-acceptor (D-A) copolymer, poly[4,8-bis(triisopropylsilylethynyl)benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-[4,7-bis(4-(2-ethylhexyl)thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-c]pyridine] (PTBDTPT), containing triisopropylsilylethynyl(TIPS)benzo[1,2-b:4,5-b']dithiophene as a donor is synthesized by Stille polymerization reaction. All the important photo physical prerequisites for organic field-effect transistor (OFET) application such as strong and broad optical absorption, thermal stability, and compatible HOMO-LUMO levels can be accomplished and combined on one macromolecule. Optical band gap of the polymer was found to be 1.61 eV as calculated from its film onset absorption edge. The hole mobility of bottom gate OFET using the synthesized polymer as an active channel is found to be 1.92 X 10(-2) cm V(-1) s(-1) with the On/Off ratio of 25. The photophysical study suggests that PTBDTPT is promising candidate for future large area organic electronic applications.

  6. Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions

    PubMed Central

    Jiang, Tingting; Raviram, Ramya; Snetkova, Valentina; Rocha, Pedro P.; Proudhon, Charlotte; Badri, Sana; Bonneau, Richard; Skok, Jane A.; Kluger, Yuval

    2016-01-01

    Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiEκ, 3′Eκ and Edκ, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings. PMID:27439714

  7. Induced overexpression of OCT4A in human embryonic stem cells increases cloning efficiency.

    PubMed

    Tsai, Steven C; Chang, David F; Hong, Chang-Mu; Xia, Ping; Senadheera, Dinithi; Trump, Lisa; Mishra, Suparna; Lutzko, Carolyn

    2014-06-15

    Our knowledge of the molecular mechanisms underlying human embryonic stem cell (hESC) self-renewal and differentiation is incomplete. The level of octamer-binding transcription factor 4 (Oct4), a critical regulator of pluripotency, is precisely controlled in mouse embryonic stem cells. However, studies of human OCT4 are often confounded by the presence of three isoforms and six expressed pseudogenes, which has complicated the interpretation of results. Using an inducible lentiviral overexpression and knockdown system to manipulate OCT4A above or below physiological levels, we specifically examine the functional role of the OCT4A isoform in hESC. (We also designed and generated a comparable series of vectors, which were not functional, for the overexpression and knockdown of OCT4B.) We show that specific knockdown of OCT4A results in hESC differentiation, as indicated by morphology changes, cell surface antigen expression, and upregulation of ectodermal genes. In contrast, inducible overexpression of OCT4A in hESC leads to a transient instability of the hESC phenotype, as indicated by changes in morphology, cell surface antigen expression, and transcriptional profile, that returns to baseline within 5 days. Interestingly, sustained expression of OCT4A past 5 days enhances hESC cloning efficiency, suggesting that higher levels of OCT4A can support self-renewal. Overall, our results indicate that high levels of OCT4A increase hESC cloning efficiency and do not induce differentiation (whereas OCT4B expression cannot be induced in hESC), highlighting the importance of isoform-specific studies in a stable and inducible expression system for human OCT4. Additionally, we demonstrate the utility of an efficient method for conditional gene expression in hESC.

  8. Draft Genome Sequences of Pseudomonas fluorescens Strains SF39a and SF4c, Potential Plant Growth Promotion and Biocontrol Agents

    PubMed Central

    Ly, Lindsey K.; Underwood, Grace E.; McCully, Lucy M.; Bitzer, Adam S.; Godino, Agustina; Bucci, Vanni; Brigham, Christopher J.; Príncipe, Analía; Fischer, Sonia E.

    2015-01-01

    Pseudomonas fluorescens SF4c and SF39a, strains isolated from wheat rhizosphere, have potential applications in plant growth promotion and biocontrol of fungal diseases of crop plants. We report the draft genome sequences of SF4c and SF39a with estimated sizes of 6.5 Mb and 5.9 Mb, respectively. PMID:25814613

  9. Draft Genome Sequences of Pseudomonas fluorescens Strains SF39a and SF4c, Potential Plant Growth Promotion and Biocontrol Agents.

    PubMed

    Ly, Lindsey K; Underwood, Grace E; McCully, Lucy M; Bitzer, Adam S; Godino, Agustina; Bucci, Vanni; Brigham, Christopher J; Príncipe, Analía; Fischer, Sonia E; Silby, Mark W

    2015-03-26

    Pseudomonas fluorescens SF4c and SF39a, strains isolated from wheat rhizosphere, have potential applications in plant growth promotion and biocontrol of fungal diseases of crop plants. We report the draft genome sequences of SF4c and SF39a with estimated sizes of 6.5 Mb and 5.9 Mb, respectively.

  10. Comparative assessment of an Og4C3 ELISA and an ICT filariasis test: a study of Myanmar migrants in Thailand.

    PubMed

    Nuchprayoon, Surang; Porksakorn, Chantima; Junpee, Alisa; Sanprasert, Vivornpun; Poovorawan, Yong

    2003-12-01

    Detection of circulating filarial antigen has now emerged as an alternative method for the diagnosis of bancroftian filariasis. We compared two antigen detection assays, an Og4C3 ELISA and an ICT (immunochromatography) Filariasis test, for the diagnosis of Wuchereria bancrofti infections in migrant Myanmar workers in Tak province, Western Thailand. A total of 337 Myanmars participated in this study. The microfilarial rate was 3.3%. The Og4C3 ELISA could detect 19.1% of bancroftian filariasis while the ICT test detected 12.7%. Both antigen assays could detect all microfilaremics. The Og4C3 ELISA detected 14.8% of amicrofilaremics while the ICT test identified 8.1%. Those who were positive for the ICT test were also positive by the Og4C3 ELISA. Those Og4C3 positive cases, that were ICT negative (ICT-ve/Og4C3+ve) had statistically significant (p < 0.05, unpaired t-test) lower Og4C3 antigen levels (409.5 units, range 117-2,389) than those that were ICT positive (ICT+ve/Og4C3+ve) (5,252.0 units, range 130-28,062). Our results emphasize the problem of bancroftian filariasis in Myanmar migrants working in Thailand. Close monitoring and control of this disease in Myanmar migrants are of public health importance. Antigen detection systems are promising tools for the surveillance of bancroftian filariasis. PMID:15198343

  11. A comparison study on the densification behavior and mechanical properties of gelcast vs conventionally formed B{sub 4}C sintered conventionally and by microwaves

    SciTech Connect

    Menchhofer, P.A.; Kiggans, J.O.; Morrow, M.S.; Schechter, D.E.

    1996-06-01

    The utilization of microwave energy for reaching high temperatures necessary to densify B{sub 4}C powder is compared with conventional means of sintering by evaluating the mechanical properties after densification. Microwave energy has been shown to be an effective means for achieving high sintered densities, even though temperatures of {approximately} 2,250 C are required. In this study, green preforms of B{sub 4}C specimens were sintered by both conventional and microwave heating. This study also utilized an advanced forming method called ``Gelcasting`` developed at ORNL. Gelcasting is a fluid forming process whereby high solids suspensions of powders containing dissolved monomers are cast into a mold, then polymerized or ``gelled`` in situ. This investigation compares microstructures and mechanical properties of both Gelcast B{sub 4}C and ``conventionally`` die-pressed B{sub 4}C. The microstructures and final mechanical properties of B{sub 4}C specimens are discussed.

  12. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    PubMed

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  13. Complete Genome Sequences of Two Listeria monocytogenes Serovars, 1/2a and 4b, Isolated from Dairy Products in Brazil

    PubMed Central

    Campos, Fabrício Souza; Mariot, Roberta Fogliatto; Prichula, Janira; de Moura, Tiane Martin; Frazzon, Ana Paula Guedes

    2015-01-01

    Listeria monocytogenes is the foodborne pathogen responsible for a bacterial infection called listeriosis. Here, we present the whole-genome sequences of two L. monocytogenes serovars, 1/2a and 4b, which are considered the most prevalent in food processing plants and listeriosis outbreaks, respectively. PMID:26679596

  14. PARAQUAT TOLERANCE3 Is an E3 Ligase That Switches off Activated Oxidative Response by Targeting Histone-Modifying PROTEIN METHYLTRANSFERASE4b

    PubMed Central

    Du, Jin; Zhao, Tao-Lan; Wang, Peng-Fei; Zhao, Ping-Xia; Xie, Qi; Cao, Xiao-Feng; Xiang, Cheng-Bin

    2016-01-01

    Oxidative stress is unavoidable for aerobic organisms. When abiotic and biotic stresses are encountered, oxidative damage could occur in cells. To avoid this damage, defense mechanisms must be timely and efficiently modulated. While the response to oxidative stress has been extensively studied in plants, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutant paraquat tolerance3, we identified the genetic locus PARAQUAT TOLERANCE3 (PQT3) as a major negative regulator of oxidative stress tolerance. PQT3, encoding an E3 ubiquitin ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b upregulates the expression of APX1 and GPX1, encoding two key enzymes against oxidative stress. On the other hand, PRMT4b is recognized by PQT3 for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress and found that histone modification by PRMT4b at APX1 and GPX1 loci plays an important role in oxidative stress tolerance. PMID:27676073

  15. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    PubMed

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

  16. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

    PubMed

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.

  17. Synergistic effects of sodium chloride, Glucose, and temperature on biofilm formation by Listeria monocytogenes serotype 1/2a and 4b strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biofilm formation by Listeria monocytogenes is generally associated with its persistence in the food processing environment. Serotype 1/2a strains make up more than 50% of the total isolates recovered from food and environment, while serotype 4b strains are most often associated with major outbreaks...

  18. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome

    PubMed Central

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-01-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome. PMID:24781758

  19. Identification of a novel SBF2 frameshift mutation in charcot-marie-tooth disease type 4B2 using whole-exome sequencing.

    PubMed

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-10-01

    Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient's condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases. PMID:25462154

  20. Flaviviral NS4b, chameleon and jack‐in‐the‐box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention

    PubMed Central

    Zmurko, Joanna; Dallmeier, Kai

    2015-01-01

    Summary Dengue virus and other flaviviruses such as the yellow fever, West Nile, and Japanese encephalitis viruses are emerging vector‐borne human pathogens that affect annually more than 100 million individuals and that may cause debilitating and potentially fatal hemorrhagic and encephalitic diseases. Currently, there are no specific antiviral drugs for the treatment of flavivirus‐associated disease. A better understanding of the flavivirus–host interactions during the different events of the flaviviral life cycle may be essential when developing novel antiviral strategies. The flaviviral non‐structural protein 4b (NS4b) appears to play an important role in flaviviral replication by facilitating the formation of the viral replication complexes and in counteracting innate immune responses such as the following: (i) type I IFN signaling; (ii) RNA interference; (iii) formation of stress granules; and (iv) the unfolded protein response. Intriguingly, NS4b has recently been shown to constitute an excellent target for the selective inhibition of flavivirus replication. We here review the current knowledge on NS4b. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:25828437

  1. Draft Genome Sequences of Listeria monocytogenes Serotype 4b Strains 944 and 2993 and Serotype 1/2c Strains 198 and 2932

    PubMed Central

    Casey, Aidan; Fox, Edward M.; Leong, Dara; Gahan, Cormac G. M.; Jordan, Kieran

    2016-01-01

    Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis among humans and animals. The draft genome sequences of L. monocytogenes serotype 4b strains 944 and 2993 and serotype 1/2c strains 198 and 2932 are reported here. PMID:27257200

  2. Identification of A Novel SBF2 Frameshift Mutation in Charcot–Marie–Tooth Disease Type 4B2 Using Whole-exome Sequencing

    PubMed Central

    Chen, Meiyan; Wu, Jing; Liang, Ning; Tang, Lihui; Chen, Yanhua; Chen, Huishuang; Wei, Wei; Wei, Tianying; Huang, Hui; Yi, Xin; Qi, Ming

    2014-01-01

    Charcot–Marie–Tooth disease type 4B2 with early-onset glaucoma (CMT4B2, OMIM 604563) is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient’s condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG (P.Gly1524Glufs∗42), was revealed in the CMT4B2-related gene SBF2 (also known as MTMR13, MIM 607697), and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases. PMID:25462154

  3. A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways.

    PubMed

    Xie, Guorui; Welte, Thomas; Wang, Jia; Whiteman, Melissa C; Wicker, Jason A; Saxena, Vandana; Cong, Yingzi; Barrett, Alan D T; Wang, Tian

    2013-08-28

    Prior work shows that an attenuated West Nile virus (WNV), the nonstructural (NS)4B-P38G mutant infection in mice induced strong immune responses and protected host from subsequent lethal wild-type WNV infection. Here, we investigated NS4B-P38G mutant infection in myeloid differentiation factor 88-deficient (MyD88(-/-)) and Toll-like receptor 7-deficient (TLR7(-/-)) mice and found they had enhanced susceptibility compared to wild-type mice. Both groups had lower WNV-specific IgM response and reduced effector T cell functions. Dendritic cells (DCs) also exhibited a reduced maturation and impaired antigen-presenting functions compared to wild-type DCs. Moreover, infection with NS4B-P38G mutant in TLR7(-/-) and MyD88(-/-) mice provided full and partial protection respectively from subsequent challenge with lethal wild-type WNV. There were reduced T cell responses in MyD88(-/-) and interleukin-1 receptor deficient (IL-1R(-/-)) mice during secondary challenge with wild-type WNV. In contrast, TLR7(-/-) mice displayed normal T cell functions. Collectively, these results suggest that TLR7-dependent MyD88 signaling is required for T cell priming during NS4B-P38G mutant infection, whereas the TLR7-independent MyD88 signaling pathways are involved in memory T cell development, which may contribute to host protection during secondary challenge with wild-type WNV. PMID:23845800

  4. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis Cases in the United States from 2003 to 2008

    PubMed Central

    Ward, Todd J.; Graves, Lewis M.; Tarr, Cheryl L.; Siletzky, Robin M.; Kathariou, Sophia

    2014-01-01

    Listeria monocytogenes can cause severe food-borne disease (listeriosis). Numerous outbreaks have involved three serotype 4b epidemic clones (ECs): ECI, ECII, and ECIa. However, little is known about the population structure of L. monocytogenes serotype 4b from sporadic listeriosis in the United States, even though most cases of human listeriosis are in fact sporadic. Here we analyzed 136 serotype 4b isolates from sporadic cases in the United States, 2003 to 2008, utilizing multiple tools including multilocus genotyping, pulsed-field gel electrophoresis, and sequence analysis of the inlAB locus. ECI, ECII, and ECIa were frequently encountered (32, 17, and 7%, respectively). However, annually 30 to 68% of isolates were outside these ECs, and several novel clonal groups were identified. An estimated 33 and 17% of the isolates, mostly among the ECs, were resistant to cadmium and arsenic, respectively, but resistance to benzalkonium chloride was uncommon (3%) among the sporadic isolates. The frequency of clonal groups fluctuated within the 6-year study period, without consistent trends. However, on several occasions, temporal clusters of isolates with indistinguishable genotypes were detected, suggesting the possibility of hidden multistate outbreaks. Our analysis suggests a complex population structure of serotype 4b L. monocytogenes from sporadic disease, with important contributions by ECs and several novel clonal groups. Continuous monitoring will be needed to assess long-term trends in clonality patterns and population structure of L. monocytogenes from sporadic listeriosis. PMID:24705322

  5. Synthesis and Characterization of New Iron Phosphatooxalates: [( - 5H 14N 2] [Fe 4(C 2O 4) 3(HPO 4) 2(H 2O) 2] and [( - 5H 14N 2] [Fe 4(C 2O 4) 3(HPO 4) 2

    NASA Astrophysics Data System (ADS)

    Chang, Wen-Jung; Lin, Hsiu-Mei; Lii, Kwang-Hwa

    2001-02-01

    Two new organically templated iron(II) phosphatooxalates, [(S)-C5H14N2] [Fe4(C2O4)3(HPO4)2(H2O)2] (1) and [(S)-C5H14 N2] [Fe4(C2O4)3(HPO4)2] (2), have been synthesized under hydrothermal conditions and characterized by single-crystal X-ray diffraction and Mössbauer spectroscopy. Crystal data are as follows: compound 1, triclinic, P1 (No. 1), a=7.6999(4) Å, b=7.9542(4) Å, c=9.8262(5) Å, α=74.8444(7)°, β=81.7716(8)°, γ=85.4075(8)°, V=574.34(8) Å3, Z=1, and R1=0.0255; compound 2, monoclinic, P21 (No. 4), a=7.5943(8) Å, b=7.8172(8) Å, c=18.318(2) Å, β=99.111(2)°, V=1073.8(3) Å3, Z=2, and R1=0.0281. The structure of 1 consists of dimers of edge-sharing FeO6 octahedra that are linked by phosphate and oxalate groups to generate a three-dimensional framework with intersecting tunnels parallel to the [100] and [010] directions. Diprotonated (S)-2-methylpiperazinium cations are located at the intersections of these tunnels. Compound 1 crystallizes as a minor product when a racemic mixture of 2-methylpiperazine is used in the synthesis, and can be prepared as a major product with a small amount of 2 if optically pure (S)-2-methylpiperzine is used. The structure of 2 is similar to that of 1 except that the coordination around the iron centers in the dimer are square pyramidal and octahedral. The two compounds are the first 3-dimensional phosphatooxalates containing a chiral amine.

  6. Structure, growth and properties of a novel polar material, KSr{sub 4}B{sub 3}O{sub 9}

    SciTech Connect

    Zhao, Wenwu; Pan, Shilie; Wang, Yongjiang; Yang, Zhihua; Wang, Xian; Han, Jian

    2012-11-15

    A novel polar material, KSr{sub 4}B{sub 3}O{sub 9}, has been obtained by the high temperature solution method for the first time. It crystallizes in the polar space group Ama2. The material exhibits a three-dimensional structure consisting of interconnecting KO{sub 10} groups, SrO{sub x} (x=8, 9) units and isolated BO{sub 3} triangles. DSC/TG curve shows that KSr{sub 4}B{sub 3}O{sub 9} melts incongruently. The calculated band structures and the density of states of KSr{sub 4}B{sub 3}O{sub 9} suggest that its direct gap is 3.897 eV. The absorption spectrum indicates the absorption edge of KSr{sub 4}B{sub 3}O{sub 9} is about 302 nm. It produces SHG intensity about as large as that of KH{sub 2}PO{sub 4} (KDP) and is phase matchable. - Graphical abstract: Viewed along the c-axis, B(2)O{sub 3} triangles and B(3)O{sub 3} triangles are parallel with the (0 1 0) face and opposite to each other. However, all the B(1)O{sub 3} triangles have the same direction along the c-axis. So the main SHG efficiency of the compound comes from B(1)O{sub 3} triangles according to the anion group theory. Highlights: Black-Right-Pointing-Pointer A polar material, KSr{sub 4}B{sub 3}O{sub 9}, has been obtained by high temperature solution method. Black-Right-Pointing-Pointer The material consists of KO{sub 10} units, SrO{sub x}(x=8, 9) units and isolated BO{sub 3} units. Black-Right-Pointing-Pointer KSr{sub 4}B{sub 3}O{sub 9} produces SHG intensity as large as that of KDP and is phase matchable. Black-Right-Pointing-Pointer The absorption edge of KSr{sub 4}B{sub 3}O{sub 9} is about 302 nm.

  7. On Parametrization of the Linear GL(4,C) and Unitary SU(4) Groups in Terms of Dirac Matrices

    NASA Astrophysics Data System (ADS)

    Red'Kov, Victor M.; Bogush, Andrei A.; Tokarevskaya, Natalia G.

    2008-02-01

    Parametrization of 4 × 4-matrices G of the complex linear group GL(4,C) in terms of four complex 4-vector parameters (k,m,n,l) is investigated. Additional restrictions separating some subgroups of GL(4,C) are given explicitly. In the given parametrization, the problem of inverting any 4 × 4 matrix G is solved. Expression for determinant of any matrix G is found: det G = F(k,m,n,l). Unitarity conditions G+ = G-1 have been formulated in the form of non-linear cubic algebraic equations including complex conjugation. Several simplest solutions of these unitarity equations have been found: three 2-parametric subgroups G1, G2, G3 - each of subgroups consists of two commuting Abelian unitary groups; 4-parametric unitary subgroup consis! ting of a product of a 3-parametric group isomorphic SU(2) and 1-parametric Abelian group. The Dirac basis of generators Λk, being of Gell-Mann type, substantially differs from the basis λi used in the literature on SU(4) group, formulas relating them are found - they permit to separate SU(3) subgroup in SU(4). Special way to list 15 Dirac generators of GL(4,C) can be used {Λk} = {μiÅνjÅ(μiVνj = KÅL ÅM )}, which permit to factorize SU(4) transformations according to S = eiaμ eibνeikKeilLeimM, where two first factors commute with each other and are isomorphic to SU(2) group, the three last ones are 3-parametric groups, each of them consisting of three Abelian commuting unitary subgroups. Besides, the structure of fifteen Dirac matrices Λk permits to separate twenty 3-parametric subgroups in SU(4) isomorphic to SU(2); those subgroups might be used as bigger elementary blocks in constructing of a general transformation SU(4). It is shown how one can specify the present approach for the pseudounitary group SU(2,2) and SU(3,1).

  8. Downregulation of HO-1 promoted apoptosis induced by decitabine via increasing p15INK4B promoter demethylation in myelodysplastic syndrome.

    PubMed

    Ma, D; Fang, Q; Wang, P; Gao, R; Sun, J; Li, Y; Hu, X Y; Wang, J S

    2015-04-01

    Decitabine, which reverses hypermethylation of the p15(INK4B) gene in vitro, has been used to relieve cytopenias and blast excess in over 50% of patients with high-risk myelodysplastic syndrome (MDS). In this study, heme oxygenase-1 (HO-1) was overexpressed in MDS cell line SKM-1, which was closely related to resistance to decitabine-induced apoptosis. We aimed to further investigate the role of HO-1 in apoptosis induced by low-dose decitabine in SKM-1 cells. Upregulation of HO-1 by transfecting it into SKM-1 cells with lentivirus vector promoted cell proliferation and protected them against apoptosis. In contrast, downregulation of HO-1 enhanced decitabine-induced apoptosis but reduced accumulation of the S phase in cell cycle. To explore the mechanism, the expressions of cell cycle-related proteins were detected after the cells were treated by decitabine in each group. p15(INK4B) and CDK4 were overexpressed in SKM-1 cells in which HO-1 was inhibited, and the expression-depending apoptosis was related to the caspase-3 pathway. Even though HO-1 was silenced, the apoptotic rate never increased as the caspase-3 pathway was blocked. It is well known that p15(INK4B) dominantly regulates the S phase of the cell cycle. p15(INK4B) was herein demethylated more evidently in the group of SKM-1 cells in which HO-1 was downregulated, as well as in the mononuclear cells of patients suffering from MDS. In the case of poor prognosis, the mRNA level of HO-1 was raised. In conclusion, overexpression of HO-1 indicated resistance to demethylation of p15(INK4B) induced by decitabine.

  9. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

    PubMed Central

    Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

    2016-01-01

    Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP–GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID:26902995

  10. Organometallic 3-(1H-Benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines as Potential Anticancer Agents

    PubMed Central

    2011-01-01

    Six organometallic complexes of the general formula [MIICl(η6-p-cymene)(L)]Cl, where M = Ru (11a, 12a, 13a) or Os (11b, 12b, 13b) and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1–L3) have been synthesized. The latter are known as potential cyclin-dependent kinase (Cdk) inhibitors. All compounds have been comprehensively characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, UV–vis spectroscopy, ESI mass spectrometry, and X-ray crystallography (11b and 12b). The multistep synthesis of 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1–L3), which was reported by other researchers, has been modified by us essentially (e.g., the synthesis of 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (3) via 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine (2); the synthesis of 1-methoxymethyl-2,3-diaminobenzene (5) by avoiding the use of unstable 2,3-diaminobenzyl alcohol; and the activation of 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acids (1, 3) through the use of an inexpensive coupling reagent, N,N′-carbonyldiimidazole (CDI)). Stabilization of the 7b tautomer of methoxymethyl-substituted L3 by coordination to a metal(II) center, as well as the NMR spectroscopic characterization of two tautomers 7b-L3 and 4b′-L3 in a metal-free state are described. Structure–activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells, as well as Cdk inhibitory activity, are also reported. PMID:22032295

  11. Cytotoxicity of the Bacillus thuringiensis Cry4B toxin is mediated by the cadherin receptor BT-R₃ of Anopheles gambiae.

    PubMed

    Ibrahim, Mohamed A; Griko, Natalya B; Bulla, Lee A

    2013-07-01

    We demonstrate for the first time the selective cytotoxicity of Bacillus thuringiensis subsp. israelensis Cry4B toxin mediated by BT-R₃ using a cell-based system, which employs High Five insect cells stably expressing BT-R₃. Discovery and validation of BT-R₃ as the Cry4B receptor was accomplished using a web-based computational pipeline platform that facilitates high-throughput insecticidal target identification utilizing the Anopheles gambiae genome. Once the Cry4B toxin binds to the BT-R₃ receptor, a cell death pathway is manifested by sequential cytological changes that include membrane blebbing, cell swelling and lysis. Cry4B toxin associates with cell membrane in both oligomeric and monomeric forms. Monomeric toxin binds specifically to BT-R₃ whereas oligomer interacts with cell membrane non-specifically. Cytotoxicity and cell death are the direct result of binding of toxin monomer to BT-R₃. The oligomeric form of Cry4B toxin is not involved in cell death. Both the location of the toxin-binding region within BT-R₃ and its structural motif are critical to the binding affinity and specificity of the toxin. The toxin-binding region of BT-R₃ appears to be located in EC11, the most membrane proximal EC module within the extracellular domain. It is characterized by the presence of two highly conserved amino acid sequences within their N- and C-termini that flank EC11. These sequences represent signature motifs that mark the toxin-binding function in BT-R₃. The two sequences form two adjacent β-strands within the β-barrel of EC11, the positioning of which is a hallmark of all Cry toxin receptors thus far reported.

  12. Porous LiFePO4/C microspheres as high-power cathode materials for lithium ion batteries.

    PubMed

    Sun, Bing; Wang, Ying; Wang, Bei; Kim, Hyun-Soo; Kim, Woo-Seong; Wang, Guoxiu

    2013-05-01

    Porous LiFePO4/C microspheres were synthesized by a novel hydrothermal reaction combined with high-temperature calcinations. The morphology of the prepared material was investigated by field-emission scanning electron microscopy. Porous microspheres with diameters around 1-3 microm were obtained, which consisting of primary LiFePO4 nanoparticles. The electrochemical performances of the as-prepared LiFePO4 microspheres were evaluated by cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge-discharge cycling. The carbon coated LiFePO4 microspheres showed lower polarization, higher rate capability, and better cycling stability than that of pristine LiFePO4 microspheres, indicating the potential application as the cathode material for high-power lithium ion batteries.

  13. Enhancement of thermal neutron attenuation of nano-B4C, -BN dispersed neutron shielding polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Kim, Jaewoo; Lee, Byung-Chul; Uhm, Young Rang; Miller, William H.

    2014-10-01

    Nano-sized boron carbide (B4C) and boron nitride (BN) powder were prepared using ball milling. Micro- and milled nano-powders were melt blended with high density polyethylene (HDPE) using a polymer mixer followed by hot pressing to fabricate sheet composites. The tensile and flexural strengths of HDPE nanocomposites were ∼20% higher than their micro counterparts, while those for latter decreased compared to neat HDPE. Thermal neutrons attenuation of the prepared HDPE nanocomposites was evaluated using a monochromatic ∼0.025 eV neutron beam. Thermal neutron attenuation of the HDPE nanocomposites was greatly enhanced compared to their micro counterparts at the same B-10 areal densities. Monte Carlo n-Particles (MCNP) simulations based on the lattice structure modeling also shows the similar filler size dependent thermal neutron absorption.

  14. Acquisition of Multicomponent-4C Seismic Data from Unconventional Marine Reservoirs to Improve Exploration and Risk Attenuation in Reservoir Characterization

    NASA Astrophysics Data System (ADS)

    Aluka, I. J.

    2013-12-01

    The move to explore for commercial oil and gas from unconventional reservoirs such as shale/mudstone and tight gas sand reservoirs is having serious technical challenges. Multicomponent- 4C seismic data acquisition in marine settings will go a long way to assist oil and gas companies to discover unconventional resources with significant commercial value in the marine environments. Multicomponent technology has been proved to be effective in exploration and reservoir characterization and risk reduction. The technology provides enhanced strata images by reflecting independent subsurfaces, direct lithofacies and hydrocarbon indication compared to only conventional P-wave seismic stratigraphy. Multi component seismic data can be acquired in the marine settings by utilizing energy from towed air-gun arrays, and 4-component ocean bottom sensor (4-C OBS) packages deployed on the seafloor. Because the S waves do not travel through liquids, the sensors have to be deployed on the seafloor. The 4-component ocean bottom sensor comprises of a hydrophone, a gimbaled 3-component geophone as opposed to ungimbaled 3-component geophone. This gimbaled 3-component geophone is continually rotated by gravity to make sure that the moving-coil elements are placed in the crossline horizontal, and vertical, inline horizontal directions. Two or more vessels are used in marine multicompnent data acquisition. One vessel is a source vessel and the others are connected to the seafloor cable and record the 4-C seismic data. Every receiver on the seafloor is composed of a single 4-C sensor package, which is stationary during data recording. P-wave data are combination of particle-velocity wavefield recorded by the vertical geophone and pressure wavefield recorded by the hydrophone. The inline and crossline horizontal geophones record the particle-velocity data which are used to generate the upgoing reflected SV wavefield arriving at the seafloor. The downgoing P wavefield at non normal angles of

  15. Promotion of triplex formation by 3'-amino-2'-O,4'-C-methylene bridged nucleic acid modification.

    PubMed

    Sasaki, Kiyomi; Rahman, S M Abdur; Sato, Norihiro; Obika, Satoshi; Imanishi, Takeshi; Torigoe, Hidetaka

    2009-01-01

    We examined the effect of 3'-amino-2'-O,4'-C-methylene bridged nucleic acid (3'-amino-2',4'-BNA) backbone modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The melting temperature of the pyrimidine motif triplex at pH 6.8 with 3'-amino-2',4'-BNA modified TFO was significantly higher than that observed with unmodified TFO. The 3'-amino-2',4'-BNA modification of TFO increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the 3'-amino-2',4'-BNA modification of TFO could be a key chemical modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo. PMID:19749309

  16. Improved battery performance using Pd nanoparticles synthesized on the surface of LiFePO4/C by ultrasound irradiation

    NASA Astrophysics Data System (ADS)

    Saliman, Muhammad Ali; Okawa, Hirokazu; Takai, Misaki; Ono, Yuki; Kato, Takahiro; Sugawara, Katsuyasu; Sato, Mineo

    2016-07-01

    LiFePO4 has been attracting interest as a cathode material for Li-ion batteries due to its high energy density, low cost, and eco-friendliness. The electrochemical performance of LiFePO4 is limited because it exhibits low Li-ion diffusivity and low electronic conductivity. Numerous solutions have been considered, such as carbon coating, which is widely known to improve the electronic conductivity of LiFePO4. The deposition of metal nanoparticles (NPs) on the surface of carbon-coated LiFePO4 further enhances the electronic conductivity. In this study, we deposited Pd NPs onto the surface of LiFePO4/C and investigated the resulting electrochemical performance. Sonochemical synthesis was used to prepare the metal NPs; the procedure did not require any surfactants and the reaction was rapid.

  17. Synthesis of B4C-Nano TiB2 Composite Powder by Sol-Gel Method

    NASA Astrophysics Data System (ADS)

    Baharvandi, H. R.; Talebzadeh, N.; Ehsani, N.; Aghand, F.

    2009-04-01

    Production of (B4C-nano TiB2) composite powder by chemical method was evaluated in this study. Starting materials were boron carbide, carbon, and titanium (IV) iso propoxide (TTIP). Water was used as a hydrolyser agent. TTIP was hydrolyzed with water and, consequently, amorphous Ti(OH)4 was formed. Heat-treatment of Ti(OH)4 at 100 and 850 °C led to the production of TiO2 and TiB2 phases, respectively. The effect of heat-treatment time and temperature on the phase transformation and size of the produced nano powder were investigated. The produced nano powder was characterized by XRD, SEM, and DTA. It was found that heat-treatment time and temperature have significant effects on the amount and size of the produced TiB2 powder. The data also reveal that the minimum temperature for TiB2 formation is 650 °C.

  18. Novel Octahydropyrrolo[3,4-c]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate.

    PubMed

    Letavic, Michael A; Bonaventure, Pascal; Carruthers, Nicholas I; Dugovic, Christine; Koudriakova, Tatiana; Lord, Brian; Lovenberg, Timothy W; Ly, Kiev S; Mani, Neelakandha S; Nepomuceno, Diane; Pippel, Daniel J; Rizzolio, Michele; Shelton, Jonathan E; Shah, Chandra R; Shireman, Brock T; Young, Lana K; Yun, Sujin

    2015-07-23

    The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent and selective orexin-2 antagonists is described. Optimization of physicochemical and DMPK properties led to the discovery of compounds with tissue distribution and duration of action suitable for evaluation in the treatment of primary insomnia. These selective orexin-2 antagonists are proven to promote sleep in rats, and this work ultimately led to the identification of a compound that progressed into human clinical trials for the treatment of primary insomnia. The synthesis, SAR, and optimization of the pharmacokinetic properties of this series of compounds as well as the identification of the clinical candidate, JNJ-42847922 (34), are described herein.

  19. Ballistic Impact Behavior of Nacre-Like Laminated Composites Consisting of B4C Tablets and Polyurea Matrix

    NASA Astrophysics Data System (ADS)

    Grujicic, M.; Snipes, J. S.; Ramaswami, S.

    2016-03-01

    A nacre-like composite armor consisting of B4C tablets and polyurea matrix is modeled, and its ballistic impact behavior and penetration resistance (under a normal and a 15°-oblique impact by a solid right circular cylindrical projectile) were analyzed using a series of transient, nonlinear dynamic, finite-element analyses. Nacre is a biological material constituting the innermost layer of the shells of gastropods and bivalves. It consists of polygonal tablets of aragonite, tessellated to form individual layers and having the adjacent layers as well as the tablets within a layer bonded by a biopolymer. Due to its highly complex hierarchical microstructure, nacre possesses an outstanding combination of mechanical properties, the properties which are far superior to the ones that are predicted using the homogenization techniques such as the rule of mixtures. The results of the transient nonlinear dynamic analysis pertaining to the ballistic impact response and the penetration resistance of the modeled nacre-like armor are compared with their counterparts for the B4C single-block armor having an identical areal density. Furthermore, the effect of various nacre microstructural features (e.g., surface profiling, micron-scale asperities, mineral bridges between the overlapping tablets lying in adjacent layers) on the ballistic penetration resistance of the nacre-like composite armor is investigated in order to identify an optimal nacre-like composite-armor architecture having the largest penetration resistance. The results obtained clearly show that a nacre-like armor possesses a superior penetration resistance relative to its monolithic counterpart, and that the nacre microstructural features considered play a critical role in the armor penetration resistance.

  20. CLEC4C p.K210del variant causes impaired cell surface transport in plasmacytoid dendritic cells of amyotrophic lateral sclerosis

    PubMed Central

    Choi, Won Jun; Oh, Ki-Wook; Noh, Min-Young; Kwon, Min-Soo; Nahm, Minyeop; Kim, Namshin

    2016-01-01

    The type II C-type lectin CLEC4C is a transmembrane protein selectively expressed on plasmacytoid dendritic cells (PDCs). Although its mechanism of action remains unclear, triggering of the extracellular C-terminal C-type carbohydrate recognition region of CLEC4C regulates the secretion of proinflammatory cytokines and type I IFNs in PDCs. Applying whole-exome sequencing in a patient with juvenile amyotrophic lateral sclerosis (ALS) and both healthy parents, we identified a de novo CLEC4C variant (c.629_631delAGA; p.Lys210del). In this study, we report that the deletion of a lysine residue at the extracellular region of CLEC4C yields a C-terminal dilysine motif that results in endoplasmic reticulum (ER) retention of the protein in transfected HeLa and Jurkat T lymphoma cell models. As a consequence, a decrease in the surface expression of CLEC4C and the ER localization of the mutant construct were observed. Furthermore, depletion of the cell surface CLEC4C level was also observed in the patient PDCs, further suggesting that the variant p.Lys210del CLEC4C may contribute to juvenile ALS susceptibility. PMID:26943047

  1. A study of radiolytic stability of 25,27-bis(2-propyloxy) calix[4]-26,28-crown-6 (iPR-C[4]C-6)

    SciTech Connect

    Jianchen, Wang; Chongli, Song

    2008-07-01

    The radiolytic stability of 25,27-bis(2-propyloxy)calix[4] arene -26,28-crown-6 (iPr-C[4]C-6) was studied. {sup 60}co was used as a radiation source. Its dose rate was 437 Gy/min., and the total absorbed dose of the iPr-C[4]C-6 was from 10{sup 4} to 10{sup 6} Gy. The iPr-C[4]C-6 solid and 0.025 mol/L iPr-C[4]C-6/n-octanol which were pre-equilibrated with 0.01 mol/L and 3 mol/L nitric acid, respectively, were given different doses, and their extraction performance was researched. Their degradation mechanism was investigated by mass spectrometry (MS) and infrared spectroscopy (IR). The results show that radiolytic stability of the iPr-C[4]C-6 solid and 0.025 mol/L iPr-C[4]C-6/n-octanol are good when their absorbed dose is less than 10{sup 6} Gy. The extracting system of iPr-C[4]C-6/n-octanol is promising for separating cesium from high-level liquid waste(HLLW)

  2. A new structure type of RE{sub 4}B{sub 4}O{sub 11}F{sub 2}: High-pressure synthesis and crystal structure of La{sub 4}B{sub 4}O{sub 11}F{sub 2}

    SciTech Connect

    Haberer, Almut; Kaindl, Reinhard; Oeckler, Oliver; Huppertz, Hubert

    2010-09-15

    The first lanthanum fluoride borate La{sub 4}B{sub 4}O{sub 11}F{sub 2} was obtained in a Walker-type multianvil apparatus at 6 GPa and 1300 {sup o}C. La{sub 4}B{sub 4}O{sub 11}F{sub 2} crystallizes in the monoclinic space group P2{sub 1}/c with the lattice parameters a=778.1(2) pm, b=3573.3(7) pm, c=765.7(2) pm, {beta}=113.92(3){sup o} (Z=8), and represents a new structure type in the class of compounds with the composition RE{sub 4}B{sub 4}O{sub 11}F{sub 2}. The crystal structure contains BO{sub 4}-tetrahedra interconnected with two BO{sub 3}-groups via common vertices, B{sub 2}O{sub 5}-pyroborate units, and isolated BO{sub 3}-groups. The structure shows a wave-like modulation along the b-axis. The crystal structure and properties of La{sub 4}B{sub 4}O{sub 11}F{sub 2} are discussed and compared to Gd{sub 4}B{sub 4}O{sub 11}F{sub 2}. - Graphical abstract: A new structure type of RE{sub 4}B{sub 4}O{sub 11}F{sub 2}: high-pressure synthesis and crystal structure of La{sub 4}B{sub 4}O{sub 11}F{sub 2}.

  3. Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm.

    PubMed

    Al-Dossary, Amal A; Strehler, Emanuel E; Martin-Deleon, Patricia A

    2013-01-01

    PMCA4, a membrane protein, is the major Ca(2+) efflux pump in murine sperm where its deletion leads to a severe loss of hyperactivated motility and to male infertility. We have previously shown that the PMCA4b splice variant interacts with CASK (Ca(2+/)CaM-dependent serine kinase) in regulating sperm Ca(2+). More recently we detected that PMCA4a isoform, in addition to its presence in testis, is secreted in the epididymal luminal fluid and transferred to sperm. Here we show that Pmca4 mRNA is expressed in both the 4a and 4b variants in the vagina, uterus, and oviduct. Immunofluorescence reveals that PMCA4a is similarly expressed and is elevated during estrus, appearing in the glandular and luminal epithelia. Western analysis detected PMCA4a in all tissues and in the luminal fluids (LF) of the vagina (VLF), uterus (ULF), and the oviduct (OLF) collected during estrus. It was ~9- and 4-fold higher in OLF than in VLF and ULF, and only marginally present in LF collected at metestrus/diestrus. Fractionation of the LF collected at estrus, via ultracentrifugation, revealed that 100% of the PMCA4a resides in the vesicular fraction of the ULF and OLF. Transmission electron microscopy (TEM) revealed that OLF vesicles have an exosomal orientation (with the cytoplasmic-side inward), a size range of 25-100 nm, with the characteristic CD9 biomarker. Thus, we dubbed these vesicles "oviductosomes", to which PMCA4a was immunolocalized. Incubation of caudal sperm in the combined LF or exosomes resulted in up to a ~3-fold increase of sperm PMCA4a, as detected by flow cytometry, indicating in vitro uptake. Our results are consistent with the increased requirement of Ca(2+) efflux in the oviduct. They show for the first time the presence of oviductal exosomes and highlight their role, along with uterosomes and vaginal exosomes, in post-testicular sperm acquisition of PMCA4a which is essential for hyperactivated motility and fertility. PMID:24244642

  4. Effect of the content of B4C on microstructural evolution and wear behaviors of the laser-clad coatings fabricated on Ti6Al4V

    NASA Astrophysics Data System (ADS)

    Bai, L. L.; Li, J.; Chen, J. L.; Song, R.; Shao, J. Z.; Qu, C. C.

    2016-01-01

    TiNi/Ti2Ni-based composite coatings reinforced by TiC and TiB2 were produced on Ti6Al4V by laser cladding the mixture of a Ni-based alloy and different contents of B4C (0 wt%, 5 wt%, 15 wt%, and 25 wt%). The macromorphologies and microstructures of the coatings were examined through optical microscopy, X-ray diffractometry, scanning electron microscopy, and energy dispersive spectrometry. The microhardness, fracture toughness, and wear behaviors of the coatings were also investigated by using a microhardness tester and an ultra-functional wear testing machine. Results showed that the coatings were mainly composed of TiNi/Ti2Ni and TiC/TiB2 as the matrix and reinforcement particles, respectively. The phase constituents of the coatings were not influenced by addition of different contents of B4C. The microstructure of the reinforcements in the coatings presented the following evolution: hypereutectic consisting of blocky (TiC+TiB2)e eutectic and primary TiCp cellular dendrites (0 wt% B4C), mixture of hypereutectic and willow-shaped (TiB2+TiC)p pseudoeutectic (5 wt% B4C), and pseudoeutectic (15 and 25 wt% B4C). With increasing B4C content, the volume fraction and size of the pseudoeutectic structures as well as the average microhardness of the coatings (850, 889, 969, and 1002 HV0.2) were increased. By contrast, the average fracture toughness of the coatings was gradually decreased (4.47, 4.21, 4.06, and 3.85 Mpa m1/2) along with their wear volumes (0 wt%, 5 wt%, and 15 wt% B4C). The increase in B4C content to 25 wt% did not further reduce wear loss. The wear mechanism transformed from micro-cutting (0 wt% B4C) into a combination of micro-cutting and brittle debonding (5 wt% B4C) and finally led to brittle debonding (15 wt% and 25 wt% B4C). Coatings with suitable contents of B4C (less than 15 wt%) showed excellent comprehensive mechanical properties.

  5. Discovery of 2-(4-sulfonamidophenyl)-indole 3-carboxamides as potent and selective inhibitors with broad hepatitis C virus genotype activity targeting HCV NS4B.

    PubMed

    Zhang, Nanjing; Turpoff, Anthony; Zhang, Xiaoyan; Huang, Song; Liu, Yalei; Almstead, Neil; Njoroge, F George; Gu, Zhengxian; Graci, Jason; Jung, Stephen P; Pichardo, John; Colacino, Joseph; Lahser, Fred; Ingravallo, Paul; Weetall, Marla; Nomeir, Amin; Karp, Gary M

    2016-01-15

    A novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides was identified and optimized for activity against the HCV genotype 1b replicon resulting in compounds with potent and selective activity. Further evaluation of this series demonstrated potent activity across HCV genotypes 1a, 2a and 3a. Compound 4z had reduced activity against HCV genotype 1b replicons containing single mutations in the NS4B coding sequence (F98C and V105M) indicating that NS4B is the target. This novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides serves as a promising starting point for a pan-genotype HCV discovery program.

  6. Quantitative Measurement of the Proportions of High-Order Harmonics for the 4B7B Soft-X-Ray Source at Beijing Synchrotron Radiation Facility

    NASA Astrophysics Data System (ADS)

    Zhu, Tuo; Shang, Wanli; Zhang, Wenhai; Yang, Jiamin; Xiong, Gang; Zhao, Yang; Kuang, Longyu; Zhao, Yidong; Zheng, Lei; Cui, Mingqi; Tang, Kun; Ma, Chenyan

    2013-12-01

    A transmission grating coupled with an X-ray charge coupled device (CCD) is used to quantitatively measure the proportion of high-order harmonics of the soft-X-ray source of beam line 4B7B. The results show that the monochromatic X-ray has third-order and second-order harmonics. The proportion of second-order harmonic of 4B7B is less than 9.0% and the third-order harmonic is below 0.7% when no suppressing method is applied. When suppression methods are used, the proportion of second-order harmonic is less than 1.7% and the third-order harmonic is ignorable.

  7. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  8. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  9. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  10. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  11. 15 CFR 4a.3 - Classification levels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Classification levels. 4a.3 Section 4a.3 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.3 Classification levels. Information...

  12. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  13. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  14. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  15. 15 CFR 4a.4 - Classification authority.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Classification authority. 4a.4 Section 4a.4 Commerce and Foreign Trade Office of the Secretary of Commerce CLASSIFICATION, DECLASSIFICATION, AND PUBLIC AVAILABILITY OF NATIONAL SECURITY INFORMATION § 4a.4 Classification authority. Authority...

  16. Influence of B4C to TTIP Molar Ratio on Synthesis of Nano Titanium Diboride Powders via Sol-Gel Method

    NASA Astrophysics Data System (ADS)

    Sinaei Pour Fard, Hamed; Baharvandi, Hamidreza; Abdizadeh, Hossein

    Titanium diboride (TiB2) has attracted great interests for its excellent mechanical properties, chemical resistance and good thermal and electrical conductivities. So it is widely applied as cutting tool composites, wear resistant parts, metal melting crucibles and electrode materials. This paper presents synthesis of nano titanium diboride powders via sol-gel method using a mixture of TTIP and B4C as precursors. In the hydrolysis step, B4C to TTIP molar ratio varied from 1.3 to 2.5. Solution samples stirred well and after aging and drying process, they were heat treated in an argon atmosphere. X-ray diffraction (XRD) patterns and Scanning electron microscopy (SEM) analysis showed that the percentage of synthesized TiB2 increased gradually as the molar ratio of B4C to TTIP reached to 2.3, afterward increasing the B4C to TTIP molar ratio caused decreasing of titanium diboride percentage.

  17. Effect of the B4C content on the structure and thermal expansion coefficient of the Al-5% Cu alloy-based metal-matrix composite material

    NASA Astrophysics Data System (ADS)

    Pozdniakov, A. V.; Lotfy, A.; Qadir, A.; Zolotorevskiy, V. S.

    2016-08-01

    The Al-5% Cu alloy-based metal-matrix composite materials reinforced with 5-μm B4C particles have been produced using mechanical mixing-in method. A process of addition of the B4C particles into the melt has been developed. A homogeneous distribution of the B4C reinforcing particles in the metal-matrix composite matrix was obtained. Using X-ray diffraction analysis, the formation of Al3BC and AlB2 phases has been revealed at the interphase matrix/particle boundary, which indicates a good interaction in the phases. With increasing B4C content in the matrix alloy, an insignificant increase in the porosity (from 1 to 3.1%) occurs. The average linear thermal-expansion coefficient is reduced from 24.5 to 22.6 × 10-6 K-1 in the temperature range of 20-100°C.

  18. Synthesis of a new boron carbonitride with a B4C-like structure from the thermolysis of N-alkylated borazines.

    PubMed

    Brydson, Rik; Daniels, Howard; Fox, Mark A; Greatrex, Robert; Workman, Christopher

    2002-04-01

    Thermolysis of N-trialkyl borazines at 500 degrees C produces homogeneous, amorphous boron carbonitride phases, whose compositions are dependent upon the borazine substituent, and whose structures are similar to that of icosahedral boron carbide, B4C.

  19. Enhanced PDE4B expression augments LPS-inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease.

    PubMed

    Gobejishvili, Leila; Barve, Shirish; Joshi-Barve, Swati; McClain, Craig

    2008-10-01

    Increased plasma and hepatic TNF-alpha expression is well documented in patients with alcoholic hepatitis and is implicated in the pathogenesis of alcoholic liver disease. We have previously shown that monocytes from patients with alcoholic hepatitis show increased constitutive and LPS-induced NF-kappaB activation and TNF-alpha production. Our recent studies showed that chronic ethanol exposure significantly decreased cellular cAMP levels in both LPS-stimulated and unstimulated monocytes and Kupffer cells, leading to an increase in LPS-inducible TNF-alpha production by affecting NF-kappaB activation and induction of TNF mRNA expression. Accordingly, the mechanisms underlying this ethanol-induced decrease in cellular cAMP leading to an increase in TNF expression were examined in monocytes/macrophages. In this study, chronic ethanol exposure was observed to significantly increase LPS-inducible expression of cAMP-specific phosphodiesterase (PDE)4B that degrades cellular cAMP. Increased PDE4B expression was associated with enhanced NF-kappaB activation and transcriptional activity and subsequent priming of monocytes/macrophages leading to enhanced LPS-inducible TNF-alpha production. Selective inhibition of PDE4 by rolipram abrogated LPS-mediated TNF-alpha expression at both protein and mRNA levels in control and ethanol-treated cells. Notably, PDE4 inhibition did not affect LPS-inducible NF-kappaB activation but significantly decreased NF-kappaB transcriptional activity. These findings strongly support the pathogenic role of PDE4B in the ethanol-mediated priming of monocytes/macrophages and increased LPS-inducible TNF production and the subsequent development of alcoholic liver disease (ALD). Since enhanced TNF expression plays a significant role in the evolution of clinical and experimental ALD, its downregulation via selective PDE4B inhibitors could constitute a novel therapeutic approach in the treatment of ALD. PMID:18687753

  20. Oral Administration of the Pimelic Diphenylamide HDAC Inhibitor HDACi 4b Is Unsuitable for Chronic Inhibition of HDAC Activity in the CNS In Vivo

    PubMed Central

    Beconi, Maria; Aziz, Omar; Matthews, Kim; Moumné, Lara; O’Connell, Catherine; Yates, Dawn; Clifton, Steven; Pett, Hannah; Vann, Julie; Crowley, Lynsey; Haughan, Alan F.; Smith, Donna L.; Woodman, Ben; Bates, Gillian P.; Brookfield, Fred; Bürli, Roland W.; McAllister, George; Dominguez, Celia; Munoz-Sanjuan, Ignacio; Beaumont, Vahri

    2012-01-01

    Histone deacetylase (HDAC) inhibitors have received considerable attention as potential therapeutics for a variety of cancers and neurological disorders. Recent publications on a class of pimelic diphenylamide HDAC inhibitors have highlighted their promise in the treatment of the neurodegenerative diseases Friedreich’s ataxia and Huntington’s disease, based on efficacy in cell and mouse models. These studies’ authors have proposed that the unique action of these compounds compared to hydroxamic acid-based HDAC inhibitors results from their unusual slow-on/slow-off kinetics of binding, preferentially to HDAC3, resulting in a distinctive pharmacological profile and reduced toxicity. Here, we evaluate the HDAC subtype selectivity, cellular activity, absorption, distribution, metabolism and excretion (ADME) properties, as well as the central pharmacodynamic profile of one such compound, HDACi 4b, previously described to show efficacy in vivo in the R6/2 mouse model of Huntington’s disease. Based on our data reported here, we conclude that while the in vitro selectivity and binding mode are largely in agreement with previous reports, the physicochemical properties, metabolic and p-glycoprotein (Pgp) substrate liability of HDACi 4b render this compound suboptimal to investigate central Class I HDAC inhibition in vivo in mouse per oral administration. A drug administration regimen using HDACi 4b dissolved in drinking water was used in the previous proof of concept study, casting doubt on the validation of CNS HDAC3 inhibition as a target for the treatment of Huntington’s disease. We highlight physicochemical stability and metabolic issues with 4b that are likely intrinsic liabilities of the benzamide chemotype in general. PMID:22973455