Sample records for xa27 confers enhanced

  1. The rice XA21 ectodomain fused to the Arabidopsis EFR cytoplasmic domain confers resistance to Xanthomonas oryzae pv. oryzae.

    PubMed

    Thomas, Nicholas C; Oksenberg, Nir; Liu, Furong; Caddell, Daniel; Nalyvayko, Alina; Nguyen, Yen; Schwessinger, Benjamin; Ronald, Pamela C

    2018-01-01

    Rice ( Oryza sativa ) plants expressing the XA21 cell-surface receptor kinase are resistant to Xanthomonas oryzae pv. oryzae (Xoo) infection. We previously demonstrated that expressing a chimeric protein containing the ELONGATION FACTOR Tu RECEPTOR (EFR) ectodomain and the XA21 endodomain (EFR:XA21) in rice does not confer robust resistance to Xoo . To test if the XA21 ectodomain is required for Xoo resistance, we produced transgenic rice lines expressing a chimeric protein consisting of the XA21 ectodomain and EFR endodomain (XA21:EFR) and inoculated these lines with Xoo . We also tested if the XA21:EFR rice plants respond to a synthetic sulfated 21 amino acid derivative (RaxX21-sY) of the activator of XA21-mediated immunity, RaxX. We found that five independently transformed XA21:EFR rice lines displayed resistance to Xoo as measured by lesion length analysis, and showed that five lines share characteristic markers of the XA21 defense response (generation of reactive oxygen species and defense response gene expression) after treatment with RaxX21-sY. Our results indicate that expression of the XA21:EFR chimeric receptor in rice confers resistance to Xoo . These results suggest that the endodomain of the EFR and XA21 immune receptors are interchangeable and the XA21 ectodomain is the key determinant conferring robust resistance to Xoo .

  2. XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

    PubMed

    Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

    2015-02-01

    The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE)-associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113 amino acid protein that shares 50% identity with the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23 but differs in promoter region by lacking the TALE binding element (EBE) for AvrXa23. XA23 can trigger a strong hypersensitive response in rice, tobacco, and tomato. Our results provide the first evidence that plant genomes have an executor R gene family of which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in the pathogen. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  3. XA23 is an executor R protein and confers broad-spectrum disease resistance in rice.

    PubMed

    Wang, Chunlian; Zhang, Xiaoping; Fan, Yinglun; Gao, Ying; Zhu, Qinlong; Zheng, Chongke; Qin, Tengfei; Li, Yanqiang; Che, Jinying; Zhang, Mingwei; Yang, Bing; Liu, Yaoguang; Zhao, Kaijun

    2014-11-09

    The majority of plant disease resistance (R) genes encode proteins that share common structural features. However, the transcription activator-like effector (TALE) associated executor type R genes show no considerable sequence homology to any known R genes. We adopted a map-based cloning approach and TALE-based technology to isolate and characterize Xa23, a new executor R gene derived from the wild rice (Oryza rufipogon) that confers an extremely broad spectrum of resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23 encodes a 113-amino acid protein that shares 50% identity to the known executor R protein XA10. The predicted transmembrane helices in XA23 also overlap with those of XA10. Unlike Xa10, however, Xa23 transcription is specifically activated by AvrXa23, a TALE present in all examined Xoo field isolates. Moreover, the susceptible xa23 allele has an identical open reading frame of Xa23, but differs in promoter region by lacking the TALE binding-element (EBE) for AvrXa23. XA23 can trigger strong hypersensitive response in rice, tobacco and tomato. Our results provide the first evidence that plant genomes have an executor R gene family in which members execute their function and spectrum of disease resistance by recognizing the cognate TALEs in pathogen. © The Author 2014. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.

  4. Induction of Xa10-like Genes in Rice Cultivar Nipponbare Confers Disease Resistance to Rice Bacterial Blight.

    PubMed

    Wang, Jun; Tian, Dongsheng; Gu, Keyu; Yang, Xiaobei; Wang, Lanlan; Zeng, Xuan; Yin, Zhongchao

    2017-06-01

    Bacterial blight of rice, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive bacterial diseases throughout the major rice-growing regions in the world. The rice disease resistance (R) gene Xa10 confers race-specific disease resistance to X. oryzae pv. oryzae strains that deliver the corresponding transcription activator-like (TAL) effector AvrXa10. Upon bacterial infection, AvrXa10 binds specifically to the effector binding element in the promoter of the R gene and activates its expression. Xa10 encodes an executor R protein that triggers hypersensitive response and activates disease resistance. 'Nipponbare' rice carries two Xa10-like genes in its genome, of which one is the susceptible allele of the Xa23 gene, a Xa10-like TAL effector-dependent executor R gene isolated recently from 'CBB23' rice. However, the function of the two Xa10-like genes in disease resistance to X. oryzae pv. oryzae strains has not been investigated. Here, we designated the two Xa10-like genes as Xa10-Ni and Xa23-Ni and characterized their function for disease resistance to rice bacterial blight. Both Xa10-Ni and Xa23-Ni provided disease resistance to X. oryzae pv. oryzae strains that deliver the matching artificially designed TAL effectors (dTALE). Transgenic rice plants containing Xa10-Ni and Xa23-Ni under the Xa10 promoter provided specific disease resistance to X. oryzae pv. oryzae strains that deliver AvrXa10. Xa10-Ni and Xa23-Ni knock-out mutants abolished dTALE-dependent disease resistance to X. oryzae pv. oryzae. Heterologous expression of Xa10-Ni and Xa23-Ni in Nicotiana benthamiana triggered cell death. The 19-amino-acid residues at the N-terminal regions of XA10 or XA10-Ni are dispensable for their function in inducing cell death in N. benthamiana and the C-terminal regions of XA10, XA10-Ni, and XA23-Ni are interchangeable among each other without affecting their function. Like XA10, both XA10-Ni and XA23-Ni locate to the endoplasmic reticulum (ER) membrane

  5. An XA21-Associated Kinase (OsSERK2) Regulates Immunity Mediated by the XA21 and XA3 Immune Receptors

    PubMed Central

    Chen, Xuewei; Zuo, Shimin; Schwessinger, Benjamin; Chern, Mawsheng; Canlas, Patrick E.; Ruan, Deling; Zhou, Xiaogang; Wang, Jing; Daudi, Arsalan; Petzold, Christopher J.; Heazlewood, Joshua L.; Ronald, Pamela C.

    2014-01-01

    The rice XA21 immune receptor kinase and the structurally related XA3 receptor confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast two-hybrid system in a kinase activity-dependent manner. OsSERK2 undergoes bidirectional transphosphorylation with XA21 in vitro and forms a constitutive complex with XA21 in vivo. These results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function. Taken together, our findings suggest that the mechanism of OsSERK2-meditated regulation of rice XA21, XA3, and FLS2 differs from that of AtSERK3/BAK1-mediated regulation of Arabidopsis FLS2 and EFR. PMID:24482436

  6. Transgenic expression of the rice Xa21 pattern-recognition receptor in banana (Musa sp.) confers resistance to Xanthomonas campestris pv. musacearum.

    PubMed

    Tripathi, Jaindra N; Lorenzen, Jim; Bahar, Ofir; Ronald, Pamela; Tripathi, Leena

    2014-08-01

    Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum (Xcm), is the most devastating disease of banana in east and central Africa. The spread of BXW threatens the livelihood of millions of African farmers who depend on banana for food security and income. There are no commercial chemicals, biocontrol agents or resistant cultivars available to control BXW. Here, we take advantage of the robust resistance conferred by the rice pattern-recognition receptor (PRR), XA21, to the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). We identified a set of genes required for activation of Xa21-mediated immunity (rax) that were conserved in both Xoo and Xcm. Based on the conservation, we hypothesized that intergeneric transfer of Xa21 would confer resistance to Xcm. We evaluated 25 transgenic lines of the banana cultivar 'Gonja manjaya' (AAB) using a rapid bioassay and 12 transgenic lines in the glasshouse for resistance against Xcm. About 50% of the transgenic lines showed complete resistance to Xcm in both assays. In contrast, all of the nontransgenic control plants showed severe symptoms that progressed to complete wilting. These results indicate that the constitutive expression of the rice Xa21 gene in banana results in enhanced resistance against Xcm. Furthermore, this work demonstrates the feasibility of PRR gene transfer between monocotyledonous species and provides a valuable new tool for controlling the BXW pandemic of banana, a staple food for 100 million people in east Africa. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  7. Transgenic expression of the rice Xa21 pattern recognition receptor in banana (Musa sp.) confers resistance to Xanthomonas campestris pv. musacearum

    PubMed Central

    Tripathi, Jaindra Nath; Lorenzen, Jim; Bahar, Ofir; Ronald, Pamela; Tripathi, Leena

    2014-01-01

    Summary Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum (Xcm), is the most devastating disease of banana in east and central Africa. The spread of BXW threatens the livelihood of millions of African farmers who depend on banana for food security and income. There are no commercial chemicals, bio-control agents or resistant cultivars available to control BXW. Here we take advantage of the robust resistance conferred by the rice pattern recognition receptor (PRR), XA21, to the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). We identified a set of genes required for activation of Xa21 mediated immunity (rax) that were conserved in both Xoo and Xcm. Based on the conservation, we hypothesized that intergeneric transfer of Xa21 would confer resistance to Xcm. We evaluated 25 transgenic lines of the banana cultivar ‘Gonja manjaya’ (AAB) using a rapid bioassay and 12 transgenic plants in the glass house for resistance against Xcm. About fifty percent of the transgenic lines showed complete resistance to Xcm in both assays. In contrast, all of the non-transgenic control plants showed severe symptoms that progressed to complete wilting. These results indicate that the constitutive expression of the rice Xa21 gene in banana results in enhanced resistance against Xcm. Furthermore this work demonstrates the feasibility of PRR gene transfer between monocotyledonous species and provides a valuable new tool for controlling the BXW pandemic of banana, a staple food for 100 million people in east Africa. PMID:24612254

  8. Silencing of the Rice Gene LRR1 Compromises Rice Xa21 Transcript Accumulation and XA21-Mediated Immunity.

    PubMed

    Caddell, Daniel F; Park, Chang-Jin; Thomas, Nicholas C; Canlas, Patrick E; Ronald, Pamela C

    2017-12-01

    The rice immune receptor XA21 confers resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. We previously demonstrated that an auxilin-like protein, XA21 BINDING PROTEIN 21 (XB21), positively regulates resistance to Xoo. To further investigate the function of XB21, we performed a yeast two-hybrid screen. We identified 22 unique XB21 interacting proteins, including LEUCINE-RICH REPEAT PROTEIN 1 (LRR1), which we selected for further analysis. Silencing of LRR1 in the XA21 genetic background (XA21-LRR1Ri) compromises resistance to Xoo compared with control XA21 plants. XA21-LRR1Ri plants have reduced Xa21 transcript levels and reduced expression of genes that serve as markers of XA21-mediated activation. Overexpression of LRR1 is insufficient to alter resistance to Xoo in rice lines lacking XA21. Taken together, our results indicate that LRR1 is required for wild-type Xa21 transcript expression and XA21-mediated immunity.

  9. Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

    PubMed

    Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

    2013-08-01

    Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

  10. Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae.

    PubMed

    Park, Chang-Jin; Wei, Tong; Sharma, Rita; Ronald, Pamela C

    2017-12-01

    The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differential expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in 'cell death' and 'vesicle-mediated transport'. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling 'vesicle-mediated transport' in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.

  11. Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Chang-Jin; Wei, Tong; Sharma, Rita

    The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differentialmore » expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in ‘cell death’ and ‘vesicle-mediated transport’. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling ‘vesicle-mediated transport’ in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.« less

  12. Overexpression of Rice Auxilin-Like Protein, XB21, Induces Necrotic Lesions, up-Regulates Endocytosis-Related Genes, and Confers Enhanced Resistance to Xanthomonas oryzae pv. oryzae

    DOE PAGES

    Park, Chang-Jin; Wei, Tong; Sharma, Rita; ...

    2017-06-02

    The rice immune receptor XA21 confers resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo). To elucidate the mechanism of XA21-mediated immunity, we previously performed a yeast two-hybrid screening for XA21 interactors and identified XA21 binding protein 21 (XB21). Here, we report that XB21 is an auxilin-like protein predicted to function in clathrin-mediated endocytosis. We demonstrate an XA21/XB21 in vivo interaction using co-immunoprecipitation in rice. Overexpression of XB21 in rice variety Kitaake and a Kitaake transgenic line expressing XA21 confers a necrotic lesion phenotype and enhances resistance to Xoo. RNA sequencing reveals that XB21 overexpression results in the differentialmore » expression of 8735 genes (4939 genes up- and 3846 genes down-regulated) (≥2-folds, FDR ≤0.01). The up-regulated genes include those predicted to be involved in ‘cell death’ and ‘vesicle-mediated transport’. These results indicate that XB21 plays a role in the plant immune response and in regulation of cell death. The up-regulation of genes controlling ‘vesicle-mediated transport’ in XB21 overexpression lines is consistent with a functional role for XB21 as an auxilin.« less

  13. XA21-specific induction of stress-related genes following Xanthomonas infection of detached rice leaves.

    PubMed

    Thomas, Nicholas C; Schwessinger, Benjamin; Liu, Furong; Chen, Huamin; Wei, Tong; Nguyen, Yen P; Shaker, Isaac W F; Ronald, Pamela C

    2016-01-01

    The rice XA21 receptor kinase confers robust resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae ( Xoo ). We developed a detached leaf infection assay to quickly and reliably measure activation of the XA21-mediated immune response using genetic markers. We used RNA sequencing of elf18 treated EFR:XA21:GFP plants to identify candidate genes that could serve as markers for XA21 activation. From this analysis, we identified eight genes that are up-regulated in both in elf18 treated EFR:XA21:GFP rice leaves and Xoo infected XA21 rice leaves. These results provide a rapid and reliable method to assess bacterial-rice interactions.

  14. Promoter variants of Xa23 alleles affect bacterial blight resistance and evolutionary pattern

    PubMed Central

    Xu, Feifei; Tang, Yongchao; Gao, Ying

    2017-01-01

    Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most important bacterial disease in rice (Oryza sativa L.). Our previous studies have revealed that the bacterial blight resistance gene Xa23 from wild rice O. rufipogon Griff. confers the broadest-spectrum resistance against all the naturally occurring Xoo races. As a novel executor R gene, Xa23 is transcriptionally activated by the bacterial avirulence (Avr) protein AvrXa23 via binding to a 28-bp DNA element (EBEAvrXa23) in the promoter region. So far, the evolutionary mechanism of Xa23 remains to be illustrated. Here, a rice germplasm collection of 97 accessions, including 29 rice cultivars (indica and japonica) and 68 wild relatives, was used to analyze the evolution, phylogeographic relationship and association of Xa23 alleles with bacterial blight resistance. All the ~ 473 bp DNA fragments consisting of promoter and coding regions of Xa23 alleles in the germplasm accessions were PCR-amplified and sequenced, and nine single nucleotide polymorphisms (SNPs) were detected in the promoter regions (~131 bp sequence upstream from the start codon ATG) of Xa23/xa23 alleles while only two SNPs were found in the coding regions. The SNPs in the promoter regions formed 5 haplotypes (Pro-A, B, C, D, E) which showed no significant difference in geographic distribution among these 97 rice accessions. However, haplotype association analysis indicated that Pro-A is the most favored haplotype for bacterial blight resistance. Moreover, SNP changes among the 5 haplotypes mostly located in the EBE/ebe regions (EBEAvrXa23 and corresponding ebes located in promoters of xa23 alleles), confirming that the EBE region is the key factor to confer bacterial blight resistance by altering gene expression. Polymorphism analysis and neutral test implied that Xa23 had undergone a bottleneck effect, and selection process of Xa23 was not detected in cultivated rice. In addition, the Xa23 coding region was found highly

  15. Promoter variants of Xa23 alleles affect bacterial blight resistance and evolutionary pattern.

    PubMed

    Cui, Hua; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Zhao, Kaijun

    2017-01-01

    Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most important bacterial disease in rice (Oryza sativa L.). Our previous studies have revealed that the bacterial blight resistance gene Xa23 from wild rice O. rufipogon Griff. confers the broadest-spectrum resistance against all the naturally occurring Xoo races. As a novel executor R gene, Xa23 is transcriptionally activated by the bacterial avirulence (Avr) protein AvrXa23 via binding to a 28-bp DNA element (EBEAvrXa23) in the promoter region. So far, the evolutionary mechanism of Xa23 remains to be illustrated. Here, a rice germplasm collection of 97 accessions, including 29 rice cultivars (indica and japonica) and 68 wild relatives, was used to analyze the evolution, phylogeographic relationship and association of Xa23 alleles with bacterial blight resistance. All the ~ 473 bp DNA fragments consisting of promoter and coding regions of Xa23 alleles in the germplasm accessions were PCR-amplified and sequenced, and nine single nucleotide polymorphisms (SNPs) were detected in the promoter regions (~131 bp sequence upstream from the start codon ATG) of Xa23/xa23 alleles while only two SNPs were found in the coding regions. The SNPs in the promoter regions formed 5 haplotypes (Pro-A, B, C, D, E) which showed no significant difference in geographic distribution among these 97 rice accessions. However, haplotype association analysis indicated that Pro-A is the most favored haplotype for bacterial blight resistance. Moreover, SNP changes among the 5 haplotypes mostly located in the EBE/ebe regions (EBEAvrXa23 and corresponding ebes located in promoters of xa23 alleles), confirming that the EBE region is the key factor to confer bacterial blight resistance by altering gene expression. Polymorphism analysis and neutral test implied that Xa23 had undergone a bottleneck effect, and selection process of Xa23 was not detected in cultivated rice. In addition, the Xa23 coding region was found highly

  16. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae

    DOE PAGES

    Wei, Tong; Chen, Tsung-Chi; Ho, Yuen Ting; ...

    2016-10-05

    Background: The rice receptor kinase XA21 confers robust resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae( Xoo). We previously reported that XA21 is cleaved in transgenic plants overexpressing XA21 with a GFP tag ( Ubi-XA21-GFP) and that the released C-terminal domain is localized to the nucleus. XA21 carries a predicted nuclear localization sequence (NLS) that directs the C-terminal domain to the nucleus in transient assays, whereas alanine substitutions in the NLS disrupt the nuclear localization. Methods: To determine if the predicted NLS is required for XA21-mediated immunity in planta, we generated transgenic plants overexpressing an XA21 variant carrying themore » NLS with the same alanine substitutions ( Ubi-XA21nls-GFP). Results: Ubi- XA21nls-GFP plants displayed slightly longer lesion lengths, higher Xoo bacterial populations after inoculation and lower levels of reactive oxygen species production compared with the Ubi- XA21-GFP control plants. However, the Ubi- XA21nls-GFP plants express lower levels of protein than that observed in Ubi- XA21-GFP. Discussion: These results demonstrate that the predicted NLS is not required for XA21-mediated immunity.« less

  17. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae.

    PubMed

    Wei, Tong; Chen, Tsung-Chi; Ho, Yuen Ting; Ronald, Pamela C

    2016-01-01

    The rice receptor kinase XA21 confers robust resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae ( Xoo ). We previously reported that XA21 is cleaved in transgenic plants overexpressing XA21 with a GFP tag ( Ubi -XA21-GFP) and that the released C-terminal domain is localized to the nucleus. XA21 carries a predicted nuclear localization sequence (NLS) that directs the C-terminal domain to the nucleus in transient assays, whereas alanine substitutions in the NLS disrupt the nuclear localization. To determine if the predicted NLS is required for XA21-mediated immunity in planta , we generated transgenic plants overexpressing an XA21 variant carrying the NLS with the same alanine substitutions ( Ubi -XA21nls-GFP). Ubi- XA21nls-GFP plants displayed slightly longer lesion lengths, higher Xoo bacterial populations after inoculation and lower levels of reactive oxygen species production compared with the Ubi- XA21-GFP control plants. However, the Ubi- XA21nls-GFP plants express lower levels of protein than that observed in Ubi- XA21-GFP. These results demonstrate that the predicted NLS is not required for XA21-mediated immunity.

  18. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wei, Tong; Chen, Tsung-Chi; Ho, Yuen Ting

    Background: The rice receptor kinase XA21 confers robust resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae( Xoo). We previously reported that XA21 is cleaved in transgenic plants overexpressing XA21 with a GFP tag ( Ubi-XA21-GFP) and that the released C-terminal domain is localized to the nucleus. XA21 carries a predicted nuclear localization sequence (NLS) that directs the C-terminal domain to the nucleus in transient assays, whereas alanine substitutions in the NLS disrupt the nuclear localization. Methods: To determine if the predicted NLS is required for XA21-mediated immunity in planta, we generated transgenic plants overexpressing an XA21 variant carrying themore » NLS with the same alanine substitutions ( Ubi-XA21nls-GFP). Results: Ubi- XA21nls-GFP plants displayed slightly longer lesion lengths, higher Xoo bacterial populations after inoculation and lower levels of reactive oxygen species production compared with the Ubi- XA21-GFP control plants. However, the Ubi- XA21nls-GFP plants express lower levels of protein than that observed in Ubi- XA21-GFP. Discussion: These results demonstrate that the predicted NLS is not required for XA21-mediated immunity.« less

  19. Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21.

    PubMed

    Ellur, Ranjith K; Khanna, Apurva; S, Gopala Krishnan; Bhowmick, Prolay K; Vinod, K K; Nagarajan, M; Mondal, Kalyan K; Singh, Nagendra K; Singh, Kuldeep; Prabhu, Kumble Vinod; Singh, Ashok K

    2016-07-11

    Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India's forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region.

  20. Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21

    PubMed Central

    Ellur, Ranjith K.; Khanna, Apurva; S, Gopala Krishnan.; Bhowmick, Prolay K.; Vinod, K. K.; Nagarajan, M.; Mondal, Kalyan K.; Singh, Nagendra K.; Singh, Kuldeep; Prabhu, Kumble Vinod; Singh, Ashok K.

    2016-01-01

    Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India’s forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region. PMID:27403778

  1. The Xanthomonas oryzae pv. oryzae PhoPQ Two-Component System Is Required for AvrXA21 Activity, hrpG Expression, and Virulence▿ †

    PubMed Central

    Lee, Sang-Won; Jeong, Kyu-Sik; Han, Sang-Wook; Lee, Seung-Eun; Phee, Bong-Kwan; Hahn, Tae-Ryong; Ronald, Pamela

    2008-01-01

    The rice pathogen recognition receptor, XA21, confers resistance to Xanthomonas oryzae pv. oryzae strains producing the type one system-secreted molecule, AvrXA21. X. oryzae pv. oryzae requires a regulatory two-component system (TCS) called RaxRH to regulate expression of eight rax (required for AvrXA21 activity) genes and to sense population cell density. To identify other key components in this critical regulatory circuit, we assayed proteins expressed in a raxR gene knockout strain. This survey led to the identification of the phoP gene encoding a response regulator that is up-regulated in the raxR knockout strain. Next we generated a phoP knockout strain and found it to be impaired in X. oryzae pv. oryzae virulence and no longer able to activate the response regulator HrpG (hypersensitive reaction and pathogenicity G) in response to low levels of Ca2+. The impaired virulence of the phoP knockout strain can be partially complemented by constitutive expression of hrpG, indicating that PhoP controls a key aspect of X. oryzae pv. oryzae virulence through regulation of hrpG. A gene encoding the cognate putative histidine protein kinase, phoQ, was also isolated. Growth curve analysis revealed that AvrXA21 activity is impaired in a phoQ knockout strain as reflected by enhanced growth of this strain in rice lines carrying XA21. These results suggest that the X. oryzae pv. oryzae PhoPQ TCS functions in virulence and in the production of AvrXA21 in partnership with RaxRH. PMID:18203830

  2. The Use of a Dexamethasone-inducible System to Synchronize Xa21 Expression to Study Rice Immunity.

    PubMed

    Caddell, Daniel F; Wei, Tong; Park, Chang-Jin; Ronald, Pamela C

    2015-05-05

    Inducible gene expression systems offer researchers the opportunity to synchronize target gene expression at particular developmental stages and in particular tissues. The glucocorticoid receptor (GR), a vertebrate steroid receptor, has been well adopted for this purpose in plants. To generate steroid-inducible plants, a construct of GAL4-binding domain-VP16 activation domain-GR fusion (GVG) with the target gene under the control of upstream activation sequence (UAS) has been developed and extensively used in plant research. Immune receptors perceive conserved molecular patterns secreted by pathogens and initiate robust immune responses. The rice immune receptor, XA21 , recognizes a molecular pattern highly conserved in all sequenced genomes of Xanthomonas , and confers robust resistance to X. oryzae pv. oryzae ( Xoo ). However, identifying genes downstream of XA21 has been hindered because of the restrained lesion and thus limited defense response region in the plants expressing Xa21 . Inducible expression allows for a synchronized immune response across a large amount of rice tissue, well suited for studying XA21-mediated immunity by genome-wide approaches such as transcriptomics and proteomics. In this protocol, we describe the use of this GVG system to synchronize Xa21 expression.

  3. The Use of a Dexamethasone-inducible System to Synchronize Xa21 Expression to Study Rice Immunity

    PubMed Central

    Caddell, Daniel F.; Wei, Tong; Park, Chang-Jin; Ronald, Pamela C.

    2016-01-01

    Inducible gene expression systems offer researchers the opportunity to synchronize target gene expression at particular developmental stages and in particular tissues. The glucocorticoid receptor (GR), a vertebrate steroid receptor, has been well adopted for this purpose in plants. To generate steroid-inducible plants, a construct of GAL4-binding domain-VP16 activation domain-GR fusion (GVG) with the target gene under the control of upstream activation sequence (UAS) has been developed and extensively used in plant research. Immune receptors perceive conserved molecular patterns secreted by pathogens and initiate robust immune responses. The rice immune receptor, XA21, recognizes a molecular pattern highly conserved in all sequenced genomes of Xanthomonas, and confers robust resistance to X. oryzae pv. oryzae (Xoo). However, identifying genes downstream of XA21 has been hindered because of the restrained lesion and thus limited defense response region in the plants expressing Xa21. Inducible expression allows for a synchronized immune response across a large amount of rice tissue, well suited for studying XA21-mediated immunity by genome-wide approaches such as transcriptomics and proteomics. In this protocol, we describe the use of this GVG system to synchronize Xa21 expression. PMID:27525297

  4. The cytochrome complex SoxXA of Paracoccus pantotrophus is produced in Escherichia coli and functional in the reconstituted sulfur-oxidizing enzyme system.

    PubMed

    Rother, Dagmar; Friedrich, Cornelius G

    2002-07-29

    The heterodimeric c-type cytochrome complex SoxXA of Paracoccus pantotrophus was produced in Escherichia coli. The soxX and soxA genes, separated by two genes in the sox gene cluster of P. pantotrophus, were fused with ribosome binding sites optimal for E. coli and combined to give soxXA in pRD133.27. The cytochrome complex SoxXA was produced in E. coli M15 containing pRD133.27, pREP4 encoding the Lac repressor and plasmid pEC86, carrying essential cytochrome c maturation genes. SoxX and SoxA were formed in a ratio of about 2.5:1. SoxA appeared to be unstable when not complexed with SoxX. The cytochrome complex SoxXA, purified to homogeneity from periplasmic extracts of E. coli M15 (pRD133.27, pREP4, pEC86), exhibited identical biochemical and biophysical properties as compared to SoxXA of P. pantotrophus. Moreover, this cytochrome complex was shown to be equally catalytically active with respect to rates and reactivity with different sulfur substrates in the reconstituted sulfur-oxidizing enzyme system using homogeneous Sox-proteins of P. pantotrophus. Homogeneous SoxX was catalytically inactive.

  5. Enhanced resistance to citrus canker in transgenic mandarin expressing Xa21 from rice.

    PubMed

    Omar, Ahmad A; Murata, Mayara M; El-Shamy, Hesham A; Graham, James H; Grosser, Jude W

    2018-04-01

    Genetic engineering approaches offer an alternative method to the conventional breeding of Citrus sp. 'W. Murcott' mandarin (a hybrid of 'Murcott' and an unknown pollen parent) is one of the most commercially important cultivars grown in many regions around the world. Transformation of 'W. Murcott' mandarin was achieved by direct DNA uptake using a protoplast transformation system. DNA construct (pAO3), encoding Green Fluorescent Protein (GFP) and the cDNA of Xa21, a Xanthomonas resistance gene from rice, was used to transform protoplasts of 'W. Murcott' mandarin. Following citrus protoplast culture and regeneration, transformed micro calli were microscopically designated via GFP expression, physically isolated from non-transformed tissue, and cultured on somatic embryogenesis induction medium. More than 150 transgenic embryos were recovered and from them, ten transgenic lines were regenerated and cultured on rooting medium for shoot elongation. Transgenic shoots were micrografted and established in the greenhouse with 3-5 replicates per line. The insertion of Xa21 and GFP was confirmed by PCR and southern blot analysis. GFP expression was verified by fluorescence microscopy and western blot analysis revealed expression of Xa21 although it was variable among transgenic lines, as shown by RT-qPCR. Transgenic plants challenged with the citrus canker pathogen by syringe inoculation showed a reduction in lesion number and bacterial populations within lesions compared to non-transgenic control plants. Transgenic 'W. Murcott' mandarin lines with improved canker resistance via protoplast transformation from embryogenic callus with the Xa21 gene from rice are being evaluated under field conditions to validate the level of resistance.

  6. RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature.

    PubMed

    Cohen, Stephen P; Liu, Hongxia; Argueso, Cristiana T; Pereira, Andy; Vera Cruz, Casiana; Verdier, Valerie; Leach, Jan E

    2017-01-01

    Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61) containing Xa7, a bacterial blight disease resistance (R) gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant hormone abscisic

  7. RNA-Seq analysis reveals insight into enhanced rice Xa7-mediated bacterial blight resistance at high temperature

    PubMed Central

    Argueso, Cristiana T.; Pereira, Andy; Vera Cruz, Casiana; Verdier, Valerie

    2017-01-01

    Plant disease is a major challenge to agriculture worldwide, and it is exacerbated by abiotic environmental factors. During some plant-pathogen interactions, heat stress allows pathogens to overcome host resistance, a phenomenon which could severely impact crop productivity considering the global warming trends associated with climate change. Despite the importance of this phenomenon, little is known about the underlying molecular mechanisms. To better understand host plant responses during simultaneous heat and pathogen stress, we conducted a transcriptomics experiment for rice plants (cultivar IRBB61) containing Xa7, a bacterial blight disease resistance (R) gene, that were infected with Xanthomonas oryzae, the bacterial blight pathogen of rice, during high temperature stress. Xa7-mediated resistance is unusual relative to resistance mediated by other R genes in that it functions better at high temperatures. Using RNA-Seq technology, we identified 8,499 differentially expressed genes as temperature responsive in rice cultivar IRBB61 experiencing susceptible and resistant interactions across three time points. Notably, genes in the plant hormone abscisic acid biosynthesis and response pathways were up-regulated by high temperature in both mock-treated plants and plants experiencing a susceptible interaction and were suppressed by high temperature in plants exhibiting Xa7-mediated resistance. Genes responsive to salicylic acid, an important plant hormone for disease resistance, were down-regulated by high temperature during both the susceptible and resistant interactions, suggesting that enhanced Xa7-mediated resistance at high temperature is not dependent on salicylic acid signaling. A DNA sequence motif similar to known abscisic acid-responsive cis-regulatory elements was identified in the promoter region upstream of genes up-regulated in susceptible but down-regulated in resistant interactions. The results of our study suggest that the plant hormone abscisic

  8. Clinical Scenarios for Discordant Anti-Xa

    PubMed Central

    Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

  9. How useful is determination of anti-factor Xa activity to guide bridging therapy with enoxaparin? A pilot study.

    PubMed

    Hammerstingl, Christoph; Omran, Heyder; Tripp, Christian; Poetzsch, Bernd

    2009-02-01

    Low-molecular-weight heparins (LMWH) are commonly used as peri-procedural bridging anticoagulants. The usefulness of measurement of anti-factor Xa activity (anti-Xa) to guide bridging therapy with LMWH is unknown. It was the objective of this study to determine levels of anti-Xa during standard bridging therapy with enoxaparin, and to examine predictors for residual anti-Xa. Consecutive patients receiving enoxaparin at a dosage of 1 mg/kg body weight/12 hours for temporary interruption of phenprocoumon were prospectively enrolled to the study. Blood-samples were obtained 14 hours after LMWH-application immediately pre- procedurally. Procedural details, clinical and demographic data were collected and subsequently analyzed. Seventy patients were included (age 75.2 +/- 10.8 years, Cr Cl 55.7 +/- 21.7ml/min, body mass index [BMI] 27.1 +/- 4.9). LMWH- therapy was for a mean of 4.2 +/- 1.6 days; overall anti-Xa was 0.58 +/- 0.32 U/ml. In 37 (52.8%) of patients anti-Xa was > or U/ml, including 10 (14.3%) patients with anti-Xa > 1U/ml. Linear regression analysis of single variables and logistic multivariable regression analysis failed to prove a correlation between anti-Xa and single or combined factors. No major bleeding, no thromboembolism and four (5.7%) minor haemorrhages were observed. When bridging OAC with therapeutic doses of enoxaparin a high percentage of patients undergo interventions with high residual anti-Xa. The levels of anti-Xa vary largely and are independent of single or combined clinical variables. Since the anti-Xa-related outcome of patients receiving bridging therapy with LMWH is not investigated, no firm recommendation on the usefulness of monitoring of anti-Xa can be given at this stage.

  10. Gene silencing using the recessive rice bacterial blight resistance gene xa13 as a new paradigm in plant breeding.

    PubMed

    Li, Changyan; Wei, Jing; Lin, Yongjun; Chen, Hao

    2012-05-01

    Resistant germplasm resources are valuable for developing resistant varieties in agricultural production. However, recessive resistance genes are usually overlooked in hybrid breeding. Compared with dominant traits, however, they may confer resistance to different pathogenic races or pest biotypes with different mechanisms of action. The recessive rice bacterial blight resistance gene xa13, also involved in pollen development, has been cloned and its resistance mechanism has been recently characterized. This report describes the conversion of bacterial blight resistance mediated by the recessive xa13 gene into a dominant trait to facilitate its use in a breeding program. This was achieved by knockdown of the corresponding dominant allele Xa13 in transgenic rice using recently developed artificial microRNA technology. Tissue-specific promoters were used to exclude most of the expression of artificial microRNA in the anther to ensure that Xa13 functioned normally during pollen development. A battery of highly bacterial blight resistant transgenic plants with normal seed setting rates were acquired, indicating that highly specific gene silencing had been achieved. Our success with xa13 provides a paradigm that can be adapted to other recessive resistance genes.

  11. Factor Xa Inhibitor Suppresses the Release of Phosphorylated HSP27 from Collagen-Stimulated Human Platelets: Inhibition of HSP27 Phosphorylation via p44/p42 MAP Kinase

    PubMed Central

    Tsujimoto, Masanori; Kuroyanagi, Gen; Matsushima-Nishiwaki, Rie; Kito, Yuko; Enomoto, Yukiko; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Tokuda, Haruhiko; Kozawa, Osamu; Iwama, Toru

    2016-01-01

    Selective inhibitors of factor Xa (FXa) are widely recognized as useful therapeutic tools for stroke prevention in non-valvular atrial fibrillation or venous thrombosis. Thrombin, which is rapidly generated from pro-thrombin through the activation of factor X to FXa, acts as a potent activator of human platelets. Thus, the reduction of thrombin generation by FXa inhibitor eventually causes a suppressive effect on platelet aggregation. However, little is known whether FXa inhibitors directly affect the function of human platelets. We have previously reported that collagen induces the phosphorylation of heat shock protein 27 (HSP27), a low-molecular weight heat shock protein via Rac-dependent activation of p44/p42 mitogen-activated protein (MAP) kinase in human platelets, eventually resulting in the release of HSP27. In the present study, we investigated the direct effect of FXa inhibitor on the collagen-induced human platelet activation. Rivaroxaban as well as edoxaban significantly reduced the collagen-induced phosphorylation of both HSP27 and p44/p42 MAP kinase without affecting the platelet aggregation. Rivaroxaban significantly inhibited the release of phosphorylated HSP27 from collagen-stimulated platelets but not the secretion of platelet derived growth factor-AB. In patients administrated with rivaroxaban, the collagen-induced levels of phosphorylated HSP27 were markedly diminished after 2 days of administration, which failed to affect the platelet aggregation. These results strongly suggest that FXa inhibitor reduces the collagen-stimulated release of phosphorylated HSP27 from human platelets due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase. PMID:26867010

  12. Factor Xa Inhibitor Suppresses the Release of Phosphorylated HSP27 from Collagen-Stimulated Human Platelets: Inhibition of HSP27 Phosphorylation via p44/p42 MAP Kinase.

    PubMed

    Tsujimoto, Masanori; Kuroyanagi, Gen; Matsushima-Nishiwaki, Rie; Kito, Yuko; Enomoto, Yukiko; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Tokuda, Haruhiko; Kozawa, Osamu; Iwama, Toru

    2016-01-01

    Selective inhibitors of factor Xa (FXa) are widely recognized as useful therapeutic tools for stroke prevention in non-valvular atrial fibrillation or venous thrombosis. Thrombin, which is rapidly generated from pro-thrombin through the activation of factor X to FXa, acts as a potent activator of human platelets. Thus, the reduction of thrombin generation by FXa inhibitor eventually causes a suppressive effect on platelet aggregation. However, little is known whether FXa inhibitors directly affect the function of human platelets. We have previously reported that collagen induces the phosphorylation of heat shock protein 27 (HSP27), a low-molecular weight heat shock protein via Rac-dependent activation of p44/p42 mitogen-activated protein (MAP) kinase in human platelets, eventually resulting in the release of HSP27. In the present study, we investigated the direct effect of FXa inhibitor on the collagen-induced human platelet activation. Rivaroxaban as well as edoxaban significantly reduced the collagen-induced phosphorylation of both HSP27 and p44/p42 MAP kinase without affecting the platelet aggregation. Rivaroxaban significantly inhibited the release of phosphorylated HSP27 from collagen-stimulated platelets but not the secretion of platelet derived growth factor-AB. In patients administrated with rivaroxaban, the collagen-induced levels of phosphorylated HSP27 were markedly diminished after 2 days of administration, which failed to affect the platelet aggregation. These results strongly suggest that FXa inhibitor reduces the collagen-stimulated release of phosphorylated HSP27 from human platelets due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.

  13. The rice immune receptor XA21 recognizes a tyrosine-sulfated protein from a Gram-negative bacterium.

    PubMed

    Pruitt, Rory N; Schwessinger, Benjamin; Joe, Anna; Thomas, Nicholas; Liu, Furong; Albert, Markus; Robinson, Michelle R; Chan, Leanne Jade G; Luu, Dee Dee; Chen, Huamin; Bahar, Ofir; Daudi, Arsalan; De Vleesschauwer, David; Caddell, Daniel; Zhang, Weiguo; Zhao, Xiuxiang; Li, Xiang; Heazlewood, Joshua L; Ruan, Deling; Majumder, Dipali; Chern, Mawsheng; Kalbacher, Hubert; Midha, Samriti; Patil, Prabhu B; Sonti, Ramesh V; Petzold, Christopher J; Liu, Chang C; Brodbelt, Jennifer S; Felix, Georg; Ronald, Pamela C

    2015-07-01

    Surveillance of the extracellular environment by immune receptors is of central importance to eukaryotic survival. The rice receptor kinase XA21, which confers robust resistance to most strains of the Gram-negative bacterium Xanthomonas oryzae pv. oryzae (Xoo), is representative of a large class of cell surface immune receptors in plants and animals. We report the identification of a previously undescribed Xoo protein, called RaxX, which is required for activation of XA21-mediated immunity. Xoo strains that lack RaxX, or carry mutations in the single RaxX tyrosine residue (Y41), are able to evade XA21-mediated immunity. Y41 of RaxX is sulfated by the prokaryotic tyrosine sulfotransferase RaxST. Sulfated, but not nonsulfated, RaxX triggers hallmarks of the plant immune response in an XA21-dependent manner. A sulfated, 21-amino acid synthetic RaxX peptide (RaxX21-sY) is sufficient for this activity. Xoo field isolates that overcome XA21-mediated immunity encode an alternate raxX allele, suggesting that coevolutionary interactions between host and pathogen contribute to RaxX diversification. RaxX is highly conserved in many plant pathogenic Xanthomonas species. The new insights gained from the discovery and characterization of the sulfated protein, RaxX, can be applied to the development of resistant crop varieties and therapeutic reagents that have the potential to block microbial infection of both plants and animals.

  14. The rice immune receptor XA21 recognizes a tyrosine-sulfated protein from a Gram-negative bacterium

    PubMed Central

    Pruitt, Rory N.; Schwessinger, Benjamin; Joe, Anna; Thomas, Nicholas; Liu, Furong; Albert, Markus; Robinson, Michelle R.; Chan, Leanne Jade G.; Luu, Dee Dee; Chen, Huamin; Bahar, Ofir; Daudi, Arsalan; De Vleesschauwer, David; Caddell, Daniel; Zhang, Weiguo; Zhao, Xiuxiang; Li, Xiang; Heazlewood, Joshua L.; Ruan, Deling; Majumder, Dipali; Chern, Mawsheng; Kalbacher, Hubert; Midha, Samriti; Patil, Prabhu B.; Sonti, Ramesh V.; Petzold, Christopher J.; Liu, Chang C.; Brodbelt, Jennifer S.; Felix, Georg; Ronald, Pamela C.

    2015-01-01

    Surveillance of the extracellular environment by immune receptors is of central importance to eukaryotic survival. The rice receptor kinase XA21, which confers robust resistance to most strains of the Gram-negative bacterium Xanthomonas oryzae pv. oryzae (Xoo), is representative of a large class of cell surface immune receptors in plants and animals. We report the identification of a previously undescribed Xoo protein, called RaxX, which is required for activation of XA21-mediated immunity. Xoo strains that lack RaxX, or carry mutations in the single RaxX tyrosine residue (Y41), are able to evade XA21-mediated immunity. Y41 of RaxX is sulfated by the prokaryotic tyrosine sulfotransferase RaxST. Sulfated, but not nonsulfated, RaxX triggers hallmarks of the plant immune response in an XA21-dependent manner. A sulfated, 21–amino acid synthetic RaxX peptide (RaxX21-sY) is sufficient for this activity. Xoo field isolates that overcome XA21-mediated immunity encode an alternate raxX allele, suggesting that coevolutionary interactions between host and pathogen contribute to RaxX diversification. RaxX is highly conserved in many plant pathogenic Xanthomonas species. The new insights gained from the discovery and characterization of the sulfated protein, RaxX, can be applied to the development of resistant crop varieties and therapeutic reagents that have the potential to block microbial infection of both plants and animals. PMID:26601222

  15. Kinetic characterization of factor Xa binding using a quenched fluorescent substrate based on the reactive site of factor Xa inhibitor from Bauhinia ungulata seeds.

    PubMed

    Oliva, M L V; Andrade, S A; Juliano, M A; Sallai, R C; Torquato, R J; Sampaio, M U; Pott, V J; Sampaio, C A M

    2003-07-01

    The specific Kunitz Bauhinia ungulata factor Xa inhibitor (BuXI) and the Bauhinia variegata trypsin inhibitor (BvTI) blocked the activity of trypsin, chymotrypsin, plasmin, plasma kallikrein and factor XIIa, and factor Xa inhibition was achieved only by BuXI (K(i) 14 nM). BuXI and BvTI are highly homologous (70%). The major differences are the methionine residues at BuXI reactive site, which are involved in the inhibition, since the oxidized protein no longer inhibits factor Xa but maintains the trypsin inhibition. Quenched fluorescent substrates based on the reactive site sequence of the inhibitors were synthesized and the kinetic parameters of the hydrolysis were determined using factor Xa and trypsin. The catalytic efficiency k(cat)/K(m) 4.3 x 10(7) M(-1)sec(>-1) for Abz-VMIAALPRTMFIQ-EDDnp (lead peptide) hydrolysis by factor Xa was 10(4)-fold higher than that of Boc-Ile-Glu-Gly-Arg-AMC, widely used as factor Xa substrate. Lengthening of the substrate changed its susceptibility to factor Xa hydrolysis. Both methionine residues in the substrate influence the binding to factor Xa. Serine replacement of threonine (P(1)') decreases the catalytic efficiency by four orders of magnitude. Factor Xa did not hydrolyze the substrate containing the reactive site sequence of BvTI, that inhibits trypsin inhibitor but not factor Xa. Abz-VMIAALPRTMFIQ-EDDnp prolonged both the prothrombin time and the activated partial thromboplastin time, and the other modified substrates used in this experiment altered blood-clotting assays.

  16. Comparative Transcriptome Profiling of Rice Near-Isogenic Line Carrying Xa23 under Infection of Xanthomonas oryzae pv. oryzae.

    PubMed

    Tariq, Rezwan; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Ji, Zhiyuan; Zhao, Kaijun

    2018-03-02

    Bacterial blight, caused by Xanthomonas oryzae pv. oryzae ( Xoo ), is an overwhelming disease in rice-growing regions worldwide. Our previous studies revealed that the executor R gene Xa23 confers broad-spectrum disease resistance to all naturally occurring biotypes of Xoo . In this study, comparative transcriptomic profiling of two near-isogenic lines (NILs), CBB23 (harboring Xa23 ) and JG30 (without Xa23 ), before and after infection of the Xoo strain, PXO99 A , was done by RNA sequencing, to identify genes associated with the resistance. After high throughput sequencing, 1645 differentially expressed genes (DEGs) were identified between CBB23 and JG30 at different time points. Gene Ontlogy (GO) analysis categorized the DEGs into biological process, molecular function, and cellular component. KEGG analysis categorized the DEGs into different pathways, and phenylpropanoid biosynthesis was the most prominent pathway, followed by biosynthesis of plant hormones, flavonoid biosynthesis, and glycolysis/gluconeogenesis. Further analysis led to the identification of differentially expressed transcription factors (TFs) and different kinase responsive genes in CBB23, than that in JG30. Besides TFs and kinase responsive genes, DEGs related to ethylene, jasmonic acid, and secondary metabolites were also identified in both genotypes after PXO99 A infection. The data of DEGs are a precious resource for further clarifying the network of Xa23 -mediated resistance.

  17. Comparative Transcriptome Profiling of Rice Near-Isogenic Line Carrying Xa23 under Infection of Xanthomonas oryzae pv. oryzae

    PubMed Central

    Tariq, Rezwan; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Ji, Zhiyuan; Zhao, Kaijun

    2018-01-01

    Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is an overwhelming disease in rice-growing regions worldwide. Our previous studies revealed that the executor R gene Xa23 confers broad-spectrum disease resistance to all naturally occurring biotypes of Xoo. In this study, comparative transcriptomic profiling of two near-isogenic lines (NILs), CBB23 (harboring Xa23) and JG30 (without Xa23), before and after infection of the Xoo strain, PXO99A, was done by RNA sequencing, to identify genes associated with the resistance. After high throughput sequencing, 1645 differentially expressed genes (DEGs) were identified between CBB23 and JG30 at different time points. Gene Ontlogy (GO) analysis categorized the DEGs into biological process, molecular function, and cellular component. KEGG analysis categorized the DEGs into different pathways, and phenylpropanoid biosynthesis was the most prominent pathway, followed by biosynthesis of plant hormones, flavonoid biosynthesis, and glycolysis/gluconeogenesis. Further analysis led to the identification of differentially expressed transcription factors (TFs) and different kinase responsive genes in CBB23, than that in JG30. Besides TFs and kinase responsive genes, DEGs related to ethylene, jasmonic acid, and secondary metabolites were also identified in both genotypes after PXO99A infection. The data of DEGs are a precious resource for further clarifying the network of Xa23-mediated resistance. PMID:29498672

  18. Novel factor Xa inhibitors: a patent review.

    PubMed

    de Candia, Modesto; Lopopolo, Gianfranco; Altomare, Cosimo

    2009-11-01

    New oral anticoagulants with favorable safety profiles and fixed doses are required for the management of thromboembolism and stroke prevention in patients with atrial fibrillation. Among them, fXa inhibitors (the so-called xabans) are attractive options that can overcome limitations (e.g., bleeding) of the current oral antithrombotic therapy. The rational design of small-molecule direct fXa inhibitors, whose importance is testified by the growing number of publications and patents recently registered, has been fully supported by the X-ray crystallography of enzyme-ligand complexes. Pubmed, SciFinder Scholar, ISI web of knowledge(SM), http://ep.espacenet.com/ and Google websites were used as the main sources for literature retrieving, and > 100 patents filed between 2006 and April 2009, reviewed and discussed herein, highlight the variety among the P1 and P4 moieties on suitable scaffolds. The replacement of the benzamidine P1 moiety, which characterizes the first generation, with less basic bioisosteric or nonpolar neutral P1 groups led to the disclosure of numerous fXa inhibitors with high potency, selectivity and oral bioavailability. Novel selective fXa inhibitors with stable pharmacokinetics, better therapeutic windows and ease-of-use than the existing anticoagulants are currently under advanced stage clinical trials. Available data from Phase II and Phase III studies reflect the drive towards fXa inhibitors as potentially more effective and safer antithrombotic drugs. Their development is expected to address two major needs for anticoagulation, namely safety and ease-of-use, and to significantly affect the anticoagulant market.

  19. Designer TAL effectors induce disease susceptibility and resistance to Xanthomonas oryzae pv. oryzae in rice.

    PubMed

    Li, Ting; Huang, Sheng; Zhou, Junhui; Yang, Bing

    2013-05-01

    TAL (transcription activator-like) effectors from Xanthomonas bacteria activate the cognate host genes, leading to disease susceptibility or resistance dependent on the genetic context of host target genes. The modular nature and DNA recognition code of TAL effectors enable custom-engineering of designer TAL effectors (dTALE) for gene activation. However, the feasibility of dTALEs as transcription activators for gene functional analysis has not been demonstrated. Here, we report the use of dTALEs, as expressed and delivered by the pathogenic Xanthomonas oryzae pv. oryzae (Xoo), in revealing the new function of two previously identified disease-related genes and the potential of one developmental gene for disease susceptibility in rice/Xoo interactions. The dTALE gene dTALE-xa27, designed to target the susceptible allele of the resistance gene Xa27, elicited a resistant reaction in the otherwise susceptible rice cultivar IR24. Four dTALE genes were made to induce the four annotated Xa27 homologous genes in rice cultivar Nipponbare, but none of the four induced Xa27-like genes conferred resistance to the dTALE-containing Xoo strains. A dTALE gene was also generated to activate the recessive resistance gene xa13, an allele of the disease-susceptibility gene Os8N3 (also named Xa13 or OsSWEET11, a member of sucrose efflux transporter SWEET gene family). The induction of xa13 by the dTALE rendered the resistant rice IRBB13 (xa13/xa13) susceptible to Xoo. Finally, OsSWEET12, an as-yet uncharacterized SWEET gene with no corresponding naturally occurring TAL effector identified, conferred susceptibility to the Xoo strains expressing the corresponding dTALE genes. Our results demonstrate that dTALEs can be delivered through the bacterial secretion system to activate genes of interest for functional analysis in plants.

  20. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.

    PubMed

    Lu, Genmin; DeGuzman, Francis R; Hollenbach, Stanley J; Karbarz, Mark J; Abe, Keith; Lee, Gail; Luan, Peng; Hutchaleelaha, Athiwat; Inagaki, Mayuko; Conley, Pamela B; Phillips, David R; Sinha, Uma

    2013-04-01

    Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non-protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors.

  1. Fast rotation of a subkilometer-sized near-Earth object 2011 XA{sub 3}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Urakawa, Seitaro; Ohtsuka, Katsuhito; Abe, Shinsuke

    2014-05-01

    We present light curve observations and their multiband photometry for near-Earth object (NEO) 2011 XA{sub 3}. The light curve has shown a periodicity of 0.0304 ± 0.0003 days (= 43.8 ± 0.4 minutes). The fast rotation shows that 2011 XA{sub 3} is in a state of tension (i.e., a monolithic asteroid) and cannot be held together by self-gravitation. Moreover, the multiband photometric analysis indicates that the taxonomic class of 2011 XA{sub 3} is S-complex, or V-type. Its estimated effective diameter is 225 ± 97 m (S-complex) and 166 ± 63 m (V-type), respectively. Therefore, 2011 XA{sub 3} is a candidatemore » for the second-largest, fast-rotating, monolithic asteroid. Moreover, the orbital parameters of 2011 XA{sub 3} are apparently similar to those of NEO (3200) Phaethon, but F/B-type. We computed the orbital evolutions of 2011 XA{sub 3} and Phaethon. However, the results of the computation and distinct taxonomy indicate that neither of the asteroids is of common origin.« less

  2. Antithrombotic effects of factor Xa inhibition with DU-176b: Phase-I study of an oral, direct factor Xa inhibitor using an ex-vivo flow chamber.

    PubMed

    Zafar, Mohammad Urooj; Vorchheimer, David A; Gaztanaga, Juan; Velez, Mauricio; Yadegar, Daniel; Moreno, Pedro R; Kunitada, Satoshi; Pagan, Juan; Fuster, Valentin; Badimon, Juan J

    2007-10-01

    Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.

  3. Potent arterial antithrombotic effect of direct factor-Xa inhibition with ZK-807834 administered to coronary artery disease patients.

    PubMed

    Zafar, M Urooj; Farkouh, Michael E; Osende, Julio; Shimbo, Daichi; Palencia, Stella; Crook, Julia; Leadley, Robert; Fuster, Valentin; Chesebro, James H

    2007-03-01

    It was the objective of this study to evaluate the anti-thrombotic potency of direct factor-Xa inhibition with ZK-807834 in stable coronary patients, using an ex-vivo model of arterial thrombus formation. Tissue factor pathway is important in atherothrombosis. Direct factor-Xa blockade may more potently reduce thrombosis and prevent coronary events. Badimon Perfusion Chamber 5-minute quantitative studies have shown 40-55% arterial thrombus reduction with abciximab, 23% with clopidogrel, but none with heparin. Coronary patients (n = 18, 59 +/- 9 years, 55% males) were blindly randomized to four groups receiving 24-hour infusion of a low, medium or high dose of direct factor- Xa inhibitor ZK-807834, or placebo. Arterial thrombus formation was measured in Badimon Chamber at baseline, end-of-infusion [EoI], and four hours and eight hours after EoI, and factor-X activity, prothrombin time [PT] ratio and plasma drug levels were measured simultaneously. For the low-, medium- and high-dose ZK-807834 groups, mean percent-reduction in thrombus size from baseline to EoI were 29%, 34% and 68%, respectively (p < 0.001), and at 8-h post EoI were 11%, 19% and 27%, respectively (p < 0.01). Mean PT-ratio prolongation showed a strong linear relationship (Pearson's r = 0.93) with ZK-807834 plasma concentration. Mean percent-reduction in factor-X activity from baseline was 13%, 42% and 58%, respectively. Placebo had no effect on thrombus size or factor-X activity. In conclusion, direct factor-Xa inhibition with ZK-807834 markedly reduces ex-vivo arterial thrombus formation and factor-X activity in a dose-dependent manner. Plasma levels of ZK-807834 show a strong linear correlation with PT ratio. This direct factor-Xa inhibitor may reduce the need for additional potent glycoprotein IIbIIIa inhibition.

  4. Measuring Anti–Factor Xa Activity to Monitor Low-Molecular-Weight Heparin in Obesity: A Critical Review

    PubMed Central

    Egan, Gregory; Ensom, Mary H H

    2015-01-01

    Background: The choice of whether to monitor anti–factor Xa (anti-Xa) activity in patients who are obese and who are receiving low-molecular-weight heparin (LMWH) therapy is controversial. To the authors’ knowledge, no systematic review of monitoring of anti-Xa activity in such patients has been published to date. Objective: To systematically ascertain the utility of monitoring anti-Xa concentrations for LMWH therapy in obese patients. Data Sources: MEDLINE (1946 to September 2014), the Cochrane Database of Systematic Reviews, Embase (1974 to September 2014), PubMed (1947 to September 2014), International Pharmaceutical Abstracts (1970 to September 2014), and Scopus were searched using the terms obesity, morbid obesity, thrombosis, venous thrombosis, embolism, venous thromboembolism, pulmonary embolism, low-molecular weight heparin, enoxaparin, dalteparin, tinzaparin, anti-factor Xa, anti-factor Xa monitoring, anti-factor Xa activity, and anti-factor Xa assay. The reference lists of retrieved articles were also reviewed. Study Selection and Data Extraction: English-language studies describing obese patients treated with LMWH or reporting anti-Xa activity were reviewed using a 9-step decision-making algorithm to determine whether monitoring of LMWH therapy by means of anti-Xa activity in obesity is warranted. Studies published in abstract form were excluded. Data Synthesis: The analysis showed that anti-Xa concentrations are not strongly associated with thrombosis or hemorrhage. In clinical studies of LMWH for thromboprophylaxis in bariatric surgery, orthopedic surgery, general surgery, and medical patients, and for treatment of venous thrombo embolism and acute coronary syndrome, anti-Xa activity can be predicted from dose of LMWH and total body weight; no difference in clinical outcome was found between obese and non-obese participants. Conclusions: Routinely determining anti-Xa concentrations in obese patients to monitor the clinical effectiveness of LMWH is

  5. Population structure and its effect on haplotype diversity and linkage disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).

    PubMed Central

    Garris, Amanda J; McCouch, Susan R; Kresovich, Stephen

    2003-01-01

    To assess the usefulness of linkage disequilibrium mapping in an autogamous, domesticated species, we have characterized linkage disequilibrium in the candidate region for xa5, a recessive gene conferring race-specific resistance to bacterial blight in rice. This trait and locus have good mapping information, a tractable phenotype, and available sequence data, but no cloned gene. We sampled 13 short segments from the 70-kb candidate region in 114 accessions of Oryza sativa. Five additional segments were sequenced from the adjacent 45-kb region in resistant accessions to estimate the distance at which linkage disequilibrium decays. The data show significant linkage disequilibrium between sites 100 kb apart. The presence of the xa5 resistant reaction in two ecotypes and in accessions with different haplotypes in the candidate region may indicate multiple origins or genetic heterogeneity for resistance. In addition, genetic differentiation between ecotypes emphasizes the need for controlling for population structure in the design of linkage disequilibrium studies in rice. PMID:14573486

  6. A comparative approach expands the protein-protein interaction node of the immune receptor XA21 in wheat and rice

    PubMed Central

    Yang, Baoju; Ruan, Randy; Cantu, Dario; Wang, Xiaodong; Ji, Wanquan; Ronald, Pamela C; Dubcovsky, Jorge

    2016-01-01

    The rice (Oryza sativa) OsXA21 receptor kinase is a well-studied immune receptor that initiates a signal transduction pathway leading to resistance to Xanthomonas oryzae pv. oryzae. Two homologs of OsXA21 were identified in wheat (Triticum aestivum): TaXA21-like1 located in a syntenic region with OsXA21, and TaXA21-like2 located in a non-syntenic region. Proteins encoded by these two wheat genes interact with four wheat orthologs of known OsXA21 interactors. In this study, we screened a wheat yeast-two-hybrid (Y2H) library using the cytosolic portion of TaXA21-like1 as bait to identify additional interactors. Using full-length T. aestivum and T. monococcum proteins and Y2H assays we identified three novel TaXA21-like1 interactors (TaARG, TaPR2, TmSKL1) plus one previously known in rice (TaSGT1). An additional full-length wheat protein (TaCIPK14) interacted with TaXA21-like2 and OsXA21 but not with TaXA21-like1. The interactions of TaXA21-like1 with TmSKL1 and TaSGT1 were also observed in rice protoplasts using bimolecular fluorescence complementation (BiFC) assays. We then cloned the rice homologs of the novel wheat interactors and confirmed that they all interact with OsXA21. This last result suggests that inter-specific comparative interactome analyses can be used not only to transfer known interactions from rice to wheat, but also to identify novel interactions in rice. PMID:23957671

  7. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    PubMed

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis.

    PubMed

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-06-30

    11 randomised controlled trials of 27,945 participants. Three studies tested oral DTIs (two dabigatran and one ximelagatran), while eight tested oral factor Xa inhibitors (four rivaroxaban, two apixaban and two edoxaban). We deemed all included studies to be of high methodological quality and low risk of bias. The quality of the evidence was graded as high as the outcomes were direct and effect estimates were consistent and precise, as reflected in the narrow CIs around the ORs. Meta-analysis of three studies (7596 participants) comparing oral DTIs with standard anticoagulation groups showed no difference in the rate of recurrent VTE (OR 1.09; 95% CI 0.80 to 1.49), recurrent DVT (OR 1.08; 95% CI 0.74 to 1.58), fatal PE (OR 1.00; 95% CI 0.27 to 3.70), non-fatal PE (OR 1.12; 95% CI 0.66 to 1.90) or all-cause mortality (OR 0.82; 95% CI 0.60 to 1.13). However, oral DTIs were associated with reduced bleeding (OR 0.68; 95% CI 0.47 to 0.98). Meta-analysis of eight studies (16,356 participants) comparing oral factor Xa inhibitors with standard anticoagulation demonstrated a similar rate of recurrent VTE between the two treatments (OR 0.89; 95% CI 0.73 to 1.07). Oral factor Xa inhibitors were associated with a lower rate of recurrent DVT (OR 0.75; 95% CI 0.57 to 0.98). However, this was a weak association, heavily dependent on one study. The rate of fatal (OR 1.20; 95% CI 0.71 to 2.03), non-fatal PE (OR 0.94; 95% CI 0.68 to 1.28) and all-cause mortality (OR 0.90; 95% CI 0.65 to 1.23) was similar between the two treatment groups. Oral factor Xa inhibitors were also associated with reduced bleeding (OR 0.57; 95% CI 0.43 to 0.76). None of the included studies measured post-thrombotic syndrome or health-related quality of life. NOACs such as DTIs and factor Xa inhibitors may be an effective and safe alternative to conventional anticoagulation treatment for acute DVT.

  9. A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma.

    PubMed

    Zhang, Yurong; Tao, Xuemei; Jin, Guangzhi; Jin, Haojie; Wang, Ning; Hu, Fangyuan; Luo, Qin; Shu, Huiqun; Zhao, Fangyu; Yao, Ming; Fang, Jingyuan; Cong, Wenming; Qin, Wenxin; Wang, Cun

    2016-01-01

    Heat shock protein 27 (Hsp27) is an ATP-independent molecular chaperone and confers survival advantages and resistance to cancer cells under stress conditions. The effects and molecular mechanisms of Hsp27 in HCC invasion and metastasis are still unclear. In this study, hepatocellular carcinoma (HCC) tissue array (n = 167) was used to investigate the expression and prognostic relevance of Hsp27 in HCC patients. HCC patients with high expression of Hsp27 exhibited poor prognosis. Overexpression of Hsp27 led to the forced invasion of HCC cells, whereas silencing Hsp27 attenuated invasion and metastasis of HCC cells in vitro and in vivo. We revealed that Hsp27 activated Akt signaling, which in turn promoted MMP2 and ITGA7 expression and HCC metastasis. We further observed that targeting Hsp27 using OGX-427 obviously suppressed HCC metastasis in two metastatic models. These findings indicate that Hsp27 is a useful predictive factor for prognosis of HCC and it facilitates HCC metastasis through Akt signaling. Targeting Hsp27 with OGX-427 may represent an attractive therapeutic option for suppressing HCC metastasis.

  10. 27th International Conference on CADCAM, Robotics and Factories of the Future 2014

    NASA Astrophysics Data System (ADS)

    Karamanoglu, Mehmet; Yang, Xin-She; Zivanovic, Aleksandar; Smith, Martin; Loureiro, Rui

    2014-07-01

    It is a great pleasure to welcome you to the 27th International Conference on CADCAM, Robotics and Factories of the Future, sponsored by the International Society for Productivity Enhancement, Middlesex University, Festo Limited GB, National Instruments UK & Ireland, the Sector Skills Council for Science, Engineering and Manufacturing Technologies and our proceedings publisher Institute of Physics Publications. This is the second time Middlesex University has played host to this longstanding international conference, last time being the 12th edition in 1996. The subject content of the conference remains current, focusing on cutting edge developments in research. The conference themes this year are divided into seven themes, Product Development and Sustainability, Modelling and Simulation, Automation, Robotics and Handling Systems, Advanced Quality Systems Tools and Quality Management, Human Aspects in Engineering Activities, Emerging Scenarios in Engineering Education and Training, and Emerging Technologies in Factories of the Future. The conference is organised into seven sessions running in parallel over three days, providing a platform to speakers from 16 different countries. The programme also features four eminent keynote speakers and a hands-on workshop organised by National Instruments. Organising an event such as this would not be possible without the help of many colleagues. I am grateful to the members of the Organising Committee, the International Scientific Committee, our sponsors and all those colleagues who helped in the review of many abstracts and consequently full papers. This required meticulous attention to detail and strict adherence to very tight deadlines. However large or small a conference is, the effort required to make the local arrangements work for all is not insignificant. The conference organisers acknowledge the particular efforts of Miss Mita Vaghi in providing her expertise in event management and her diligent support and Anete

  11. ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP4 and ICP0

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lengyel, Joy; Strain, Anna K.; Perkins, Keith D.

    2006-09-01

    It was previously shown that herpes simplex virus type 1 (HSV-1) is sensitive to leptomycin B (LMB), an inhibitor of nuclear export factor CRM1, and that a single methionine to threonine change at residue 50 (M50T) of viral immediate-early (IE) protein ICP27 can confer LMB resistance. In this work, we show that deletion of residues 21-63 from ICP27 can also confer LMB resistance. We further show that neither the M50T mutation nor the presence of LMB affects the nuclear shuttling activity of ICP27, suggesting that another function of ICP27 determines LMB resistance. A possible clue to this function emerged whenmore » it was discovered that LMB treatment of HSV-1-infected cells dramatically enhances the cytoplasmic accumulation of two other IE proteins, ICP0 and ICP4. This effect is completely dependent on ICP27 and is reversed in cells infected with LMB-resistant mutants. Moreover, LMB-resistant mutations in ICP27 enhance the nuclear localization of ICP0 and ICP4 even in the absence of LMB, and this effect can be discerned in transfected cells. Thus, the same amino (N)-terminal region of ICP27 that determines sensitivity to LMB also enhances ICP27's previously documented ability to promote the cytoplasmic accumulation of ICP4 and ICP0. We speculate that ICP27's effects on ICP4 and ICP0 may contribute to HSV-1 LMB sensitivity.« less

  12. A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma

    PubMed Central

    Zhang, Yurong; Tao, Xuemei; Jin, Guangzhi; Jin, Haojie; Wang, Ning; Hu, Fangyuan; Luo, Qin; Shu, Huiqun; Zhao, Fangyu; Yao, Ming; Fang, Jingyuan; Cong, Wenming; Qin, Wenxin; Wang, Cun

    2016-01-01

    Heat shock protein 27 (Hsp27) is an ATP-independent molecular chaperone and confers survival advantages and resistance to cancer cells under stress conditions. The effects and molecular mechanisms of Hsp27 in HCC invasion and metastasis are still unclear. In this study, hepatocellular carcinoma (HCC) tissue array (n = 167) was used to investigate the expression and prognostic relevance of Hsp27 in HCC patients. HCC patients with high expression of Hsp27 exhibited poor prognosis. Overexpression of Hsp27 led to the forced invasion of HCC cells, whereas silencing Hsp27 attenuated invasion and metastasis of HCC cells in vitro and in vivo. We revealed that Hsp27 activated Akt signaling, which in turn promoted MMP2 and ITGA7 expression and HCC metastasis. We further observed that targeting Hsp27 using OGX-427 obviously suppressed HCC metastasis in two metastatic models. These findings indicate that Hsp27 is a useful predictive factor for prognosis of HCC and it facilitates HCC metastasis through Akt signaling. Targeting Hsp27 with OGX-427 may represent an attractive therapeutic option for suppressing HCC metastasis. PMID:26941848

  13. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

    PubMed

    Bruins Slot, Karsten Mh; Berge, Eivind

    2018-03-06

    warfarin (OR 0.47, 95% CI 0.40 to 0.56), with low, non-statistically significant heterogeneity (I 2 = 27%).Treatment with a factor Xa inhibitor also significantly reduced the number of all-cause deaths compared with warfarin (OR 0.89, 95% 0.83 to 0.95; 10 studies; 65,624 participants; moderate-quality evidence). Treatment with factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in people with AF. The absolute effect of factor Xa inhibitors compared with warfarin treatment was, however, rather small. Factor Xa inhibitors also reduced the number of ICHs, all-cause deaths and major bleedings compared with warfarin, although the evidence for a reduction in the latter is less robust.

  14. Materials Testing on the DC-X and DC-XA

    NASA Technical Reports Server (NTRS)

    Smith, Dane; Carroll, Carol; Marschall, Jochen; Pallix, Joan

    1997-01-01

    Flight testing of thermal protection materials has been carried out over a two year period on the base heat shield of the Delta Clipper (DC-X and DC-XA), as well on a body flap. The purpose was to use the vehicle as a test bed for materials and more efficient repair or maintenance processes which would be potentially useful for application on new entry vehicles (i.e., X-33, RLV, planetary probes), as well as on the existing space shuttle orbiters. Panels containing Thermal Protection Systems (TPS) and/or structural materials were constructed either at NASA Ames Research Center or at McDonnell Douglas Aerospace (MDA) and attached between two of the four thrusters in the base heat shield of the DC-X or DC-XA. Three different panels were flown on DC-X flights 6, 7, and 8. A total of 7 panels were flown on DC-XA flights 1, 2, and 3. The panels constructed at Ames contained a variety of ceramic TPS including flexible blankets, tiles with high emissivity coatings, lightweight ceramic ablators and other ceramic composites. The MDS test panels consisted primarily of a variety of metallic composites. This report focuses on the ceramic TPS test results.

  15. END 2015: International Conference on Education and New Developments. Conference Proceedings (Porto, Portugal, June 27-29, 2015)

    ERIC Educational Resources Information Center

    Carmo, Mafalda, Ed.

    2015-01-01

    We are delighted to welcome you to the International Conference on Education and New Developments 2015-END 2015, taking place in Porto, Portugal, from 27 to 29 of June. Education, in our contemporary world, is a right since we are born. Every experience has a formative effect on the constitution of the human being, in the way one thinks, feels and…

  16. DOUGLAS XA3D-1 #413 AIRPLANE.

    NASA Image and Video Library

    1955-07-27

    DOUGLAS XA3D-1 #413 AIRPLANE MOUNTED IN THE NACA AMES RESEARCH CENTER'S 40X80_FOOT SUBSONIC WIND TUNNEL Testing the boundary layer control of the A3D in the 40 x 80 wind tunnel. Boundary layer control was added to increase the lift of the wing for take off from an aircraft carrier.

  17. DOUGLAS XA3D-1 #413 AIRPLANE.

    NASA Image and Video Library

    1955-07-27

    DOUGLAS XA3D-1 #413 AIRPLANE MOUNTED IN THE NACA AMES RESEARCH CENTER'S 40X80_FOOT SUBSONIC WIND TUNNEL sweptback wing Testing the wing boundary layer control of the A3D in the 40 x 80 wind tunnel. Boundary layer control was added to increase the lift of the wing for aircraft carrier take off and landing.

  18. Enhanced Condensation of R-113 on a Small Bundle of Horizontal Tubes

    DTIC Science & Technology

    1991-12-01

    Anthony J. l lcaley, Ch an )epartment of Mechanic’ Engineering ABSTRACT Condensation of R-113 was studied using an evaporator/condenser test platform. The...IF 7825 FOR I=1 TO Npair5 7830 ENTER @File;Xa,Ya 7835 S×=Sx+Xa 7840 Sy=Sy+Ya 7845 5x2=Sx2+XaŖ 7850 Sxy-Sxy+Xa*Ya 7855 X=(Xa-Xmin)*Sfx 7860 Y-(Ya-Ymin...9th Int. Heat Transfer Conf., Vol. 3, pp. 15-20, 1990. 33. Fujii, T., Wang, W. Ch ., Koyama, Sh. and Y. Shimizu, Heat Transfer Enhancement for Gravity

  19. EPRI-DOE Conference on Environmentally-Enhanced Hydropower Turbines: Technical Papers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hogan, T.

    2011-12-01

    The EPRI-DOE Conference on Environmentally-Enhanced Hydropower Turbines was a component of a larger project. The goal of the overall project was to conduct the final developmental engineering required to advance the commercialization of the Alden turbine. As part of this effort, the conference provided a venue to disseminate information on the status of the Alden turbine technology as well as the status of other advanced turbines and research on environmentally-friendly hydropower turbines. The conference was also a product of a federal Memorandum of Understanding among DOE, USBR, and USACE to share technical information on hydropower. The conference was held inmore » Washington, DC on May 19 and 20, 2011 and welcomed over 100 attendees. The Conference Organizing Committee included the federal agencies with a vested interest in hydropower in the U.S. The Committee collaboratively assembled this conference, including topics from each facet of the environmentally-friendly conventional hydropower research community. The conference was successful in illustrating the readiness of environmentally-enhanced hydropower technologies. Furthermore, the topics presented illustrated the need for additional deployment and field testing of these technologies in an effort to promote the growth of environmentally sustainable hydropower in the U.S. and around the world.« less

  20. Influence of apixaban on antifactor Xa levels in a patient with acute kidney injury.

    PubMed

    Wendte, Jodi; Voss, Glenn; VanOverschelde, Beau

    2016-04-15

    The case of a patient requiring conversion from apixaban to heparin in the setting of acute kidney injury is reported. A 70-year-old man was initiated on apixaban 5 mg twice daily for new-onset, nonvalvular atrial fibrillation with a CHA2DS2-VASc score of 4, indicating a high risk of stroke. Soon after starting apixaban, he experienced pulmonary edema with pneumonia requiring hospitalization. During the course of hospitalization, the patient developed acute kidney injury requiring hemodialysis, and apixaban was stopped due to concerns about altered pharmacokinetics and impaired drug elimination in this setting. A heparin infusion was started 36 hours after the last dose of apixaban was administered. Antifactor Xa levels were monitored consistent with the hospital's standard practice protocols. The initial and repeat antifactor Xa concentrations were elevated (1.8-4.4 IU/mL) for up 72 hours after stopping the heparin infusion. Given the suspected interference of apixaban with standard antifactor Xa level monitoring, the heparin protocol was modified to reflect drip-rate adjustments based on activated partial thromboplastin times (aPTTs). The hospital protocol for heparin infusions was reinstituted on hospital day 7, with dosage adjustments based on antifactor Xa levels. The patient remained on a continuous heparin infusion for atrial fibrillation for the remainder of his hospitalization without complications or bleeding events. A 70-year-old man with new-onset nonvalvular atrial fibrillation and receiving apixaban discontinued this therapy and was given heparin instead due to acute kidney injury. His heparin dosage was successfully adjusted based on antifactor Xa levels and aPPTs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. 3D/3D registration of coronary CTA and biplane XA reconstructions for improved image guidance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dibildox, Gerardo, E-mail: g.dibildox@erasmusmc.nl; Baka, Nora; Walsum, Theo van

    2014-09-15

    Purpose: The authors aim to improve image guidance during percutaneous coronary interventions of chronic total occlusions (CTO) by providing information obtained from computed tomography angiography (CTA) to the cardiac interventionist. To this end, the authors investigate a method to register a 3D CTA model to biplane reconstructions. Methods: The authors developed a method for registering preoperative coronary CTA with intraoperative biplane x-ray angiography (XA) images via 3D models of the coronary arteries. The models are extracted from the CTA and biplane XA images, and are temporally aligned based on CTA reconstruction phase and XA ECG signals. Rigid spatial alignment ismore » achieved with a robust probabilistic point set registration approach using Gaussian mixture models (GMMs). This approach is extended by including orientation in the Gaussian mixtures and by weighting bifurcation points. The method is evaluated on retrospectively acquired coronary CTA datasets of 23 CTO patients for which biplane XA images are available. Results: The Gaussian mixture model approach achieved a median registration accuracy of 1.7 mm. The extended GMM approach including orientation was not significantly different (P > 0.1) but did improve robustness with regards to the initialization of the 3D models. Conclusions: The authors demonstrated that the GMM approach can effectively be applied to register CTA to biplane XA images for the purpose of improving image guidance in percutaneous coronary interventions.« less

  2. Revisiting the X:A signal that specifies Caenorhabditis elegans sexual fate.

    PubMed

    Gladden, John M; Farboud, Behnom; Meyer, Barbara J

    2007-11-01

    In Caenorhabditis elegans, sex is determined by the opposing actions of X-signal elements (XSEs) and autosomal signal elements (ASEs), which communicate the ratio of X chromosomes to sets of autosomes (X:A signal). This study delves more deeply into the mechanism by which XSEs transmit X chromosome dose. We determined the relative contributions of individual XSEs to the X:A signal and showed the order of XSE strength to be sex-1 > sex-2 > fox-1 > ceh-39 >/= region 1 XSE. sex-1 exerts a more potent influence on sex determination and dosage compensation than any other XSE by functioning in two separate capacities in the pathway: sex-1 acts upstream as an XSE to repress xol-1 and downstream as an activator of hermaphrodite development and dosage compensation. Furthermore, the process of dosage compensation affects expression of the very XSEs that control it; XSEs become fully dosage compensated once sex is determined. The X:A signal is then equivalent between XO and XX animals, causing sexual differentiation to be controlled by genes downstream of xol-1 in the sex-determination pathway. Prior to the onset of dosage compensation, the difference in XSE expression between XX and XO embryos appears to be greater than twofold, making X chromosome counting a robust process.

  3. The White House Conference on Handicapped Individuals: Volume II. Final Report. Part A. May 23-27, 1977.

    ERIC Educational Resources Information Center

    1977

    The three-part final report documents recommendations and resolutions and summarizes the work of more than 700 delegates to the White House Conference on Handicapped Individuals, May 23-27, 1977, in Washington, D.C. It is emphasized that the primary purpose of the conference was to give persons with mental and/or physical disabilities an…

  4. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence

    PubMed Central

    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R.; Kehn-Hall, Kylene; Omichinski, James G.

    2015-01-01

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH. PMID:25918396

  5. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

    PubMed

    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

    2015-05-12

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

  6. Addition of transcription activator-like effector binding sites to a pathogen strain-specific rice bacterial blight resistance gene makes it effective against additional strains and against bacterial leaf streak.

    PubMed

    Hummel, Aaron W; Doyle, Erin L; Bogdanove, Adam J

    2012-09-01

    Xanthomonas transcription activator-like (TAL) effectors promote disease in plants by binding to and activating host susceptibility genes. Plants counter with TAL effector-activated executor resistance genes, which cause host cell death and block disease progression. We asked whether the functional specificity of an executor gene could be broadened by adding different TAL effector binding elements (EBEs) to it. We added six EBEs to the rice Xa27 gene, which confers resistance to strains of the bacterial blight pathogen Xanthomonas oryzae pv. oryzae (Xoo) that deliver the TAL effector AvrXa27. The EBEs correspond to three other effectors from Xoo strain PXO99(A) and three from strain BLS256 of the bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc). Stable integration into rice produced healthy lines exhibiting gene activation by each TAL effector, and resistance to PXO99(A) , a PXO99(A) derivative lacking AvrXa27, and BLS256, as well as two other Xoo and 10 Xoc strains virulent toward wildtype Xa27 plants. Transcripts initiated primarily at a common site. Sequences in the EBEs were found to occur nonrandomly in rice promoters, suggesting an overlap with endogenous regulatory sequences. Thus, executor gene specificity can be broadened by adding EBEs, but caution is warranted because of the possible coincident introduction of endogenous regulatory elements. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  7. Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds.

    PubMed

    Oliva, M L; Andrade, S A; Batista, I F; Sampaio, M U; Juliano, M; Fritz, H; Auerswald, E A; Sampaio, C A

    1999-12-01

    Kunitz type Bauhinia ungulata factor Xa inhibitor (BuXI) was purified from B. ungulata seeds. BuXI inactivates factor Xa and human plasma kallikrein (HuPK) with Ki values of 18.4 and 6.9 nM, respectively. However, Bauhinia variegata trypsin inhibitor (BvTI) which is 70% homologous to BuXI does not inhibit factor Xa and is less efficient on HuPK (Ki = 80 nM). The comparison between BuXI and BvTI reactive site structure indicates differences at Met59, Thr66 and Met67 residues. The hydrolysis rate of quenched fluorescence peptide substrates based on BuXI reactive site sequence, Abz-VMIAALPRTMFIQ-EDDnp (leading peptide), by HuPK and porcine pancreatic kallikrein (PoPK) is low, but hydrolysis is enhanced with Abz-VMIAALPRTMQ-EDDnp, derived from the leading peptide shortened by removing the dipeptide Phe-Ileu from the C-terminal portion, for HuPK (Km = 0.68 microM, k(cat)/Km = 1.3 x 10(6) M(-1) s(-1)), and the shorter substrate Abz-LPRTMQ-EDDnp is better for PoPK (Km = 0.66 microM, k(cat)/Km = 2.2 x 10(3) M(-1) s(-1)). The contribution of substrate methionine residues to HuPK and PoPK hydrolysis differs from that observed with factor Xa. The determined Km and k(cat) values suggest that the substrates interact with kallikreins the same as an enzyme and inhibitor interacts to form complexes.

  8. Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

    PubMed

    Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

  9. Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.

    PubMed

    Henshaw, Daryl S; Turner, James D; Forest, Daniel J; Thompson, Garrett R; Weller, Robert S

    Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available.

  10. Anticoagulation by factor Xa inhibitors.

    PubMed

    Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

    2010-08-01

    Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

  11. Characterization and expression analysis of two cDNAs encoding Xa1 and oxysterol binding proteins in sorghum (Sorghum bicolor)

    USDA-ARS?s Scientific Manuscript database

    Using suppression subtractive hybridization (SSH) and subsequent microarray analysis, expression profiles of sorghum genes responsive to greenbug phloem-feeding were obtained and identified. Among the profiles, two cDNAs designated to MM73 and MM95 were identified to encode Xa1 (Xa1) and oxysterol ...

  12. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

    PubMed

    Bruins Slot, Karsten M H; Berge, Eivind

    2013-08-08

    Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1950 to April 2013) and EMBASE (1980 to April 2013). In an effort to identify further published, unpublished and ongoing trials we searched trials registers and Google Scholar (July 2012). We also screened reference lists and contacted pharmaceutical companies, authors and sponsors of relevant published trials. Randomised controlled trials that directly compared the effects of long-term treatment (more than four weeks) with factor Xa inhibitors and VKAs for the prevention of cerebral and systemic embolism in patients with AF. We included patients with and without a previous stroke or TIA. The primary efficacy outcome was the composite endpoint of all strokes and other systemic embolic events. Two authors independently assessed trial quality and the risk of bias, and extracted data. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. However, in the case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects and performed a pre-specified sensitivity analysis excluding any fully open-label studies. We included data from 42,084 participants randomised into

  13. Farmingdale State College Teaching of Psychology: Ideas and Innovations. Proceedings of the Annual Conference (27th, Tarrytown, New York, April 5-6, 2013)

    ERIC Educational Resources Information Center

    Gonder, Jennifer, Ed.; Howell-Carter, Marya, Ed.; Anderson, Jessica, Ed.

    2013-01-01

    Included herein is the conference proceedings of the 27th Annual Conference on the Teaching of Psychology: Ideas and Innovations, sponsored by the Psychology Department of the State University of New York at Farmingdale. The conference theme for 2013 was: The Science of Learning. The Conference featured a keynote address by Victor Benassi, Ph.D.…

  14. The pepper Bs4C proteins are localized to the endoplasmic reticulum (ER) membrane and confer disease resistance to bacterial blight in transgenic rice.

    PubMed

    Wang, Jun; Zeng, Xuan; Tian, Dongsheng; Yang, Xiaobei; Wang, Lanlan; Yin, Zhongchao

    2018-03-30

    Transcription activator-like effector (TALE)-dependent dominant disease resistance (R) genes in plants, also referred to as executor R genes, are induced on infection by phytopathogenic bacteria of the genus Xanthomonas harbouring the corresponding TALE genes. Unlike the traditional R proteins, the executor R proteins do not determine the resistance specificity and may function broadly in different plant species. The executor R gene Bs4C-R in the resistant genotype PI 235047 of the pepper species Capsicum pubescens (CpBs4C-R) confers disease resistance to Xanthomonas campestris pv. vesicatoria (Xcv) harbouring the TALE genes avrBsP/avrBs4. In this study, the synthetic genes of CpBs4C-R and two other Bs4C-like genes, the susceptible allele in the genotype PI585270 of C. pubescens (CpBs4C-S) and the CaBs4C-R homologue gene in the cultivar 'CM334' of Capsicum annum (CaBs4C), were characterized in tobacco (Nicotiana benthamiana) and rice (Oryza sativa). The Bs4C genes induced cell death in N. benthamiana. The functional Bs4C-eCFP fusion proteins were localized to the endoplasmic reticulum (ER) membrane in the leaf epidermal cells of N. benthamiana. The Xa10 promoter-Bs4C fusion genes in transgenic rice conferred strain-specific disease resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight in rice, and were specifically induced by the Xa10-incompatible Xoo strain PXO99 A (pHM1avrXa10). The results indicate that the Bs4C proteins from pepper species function broadly in rice and the Bs4C protein-mediated cell death from the ER is conserved between dicotyledonous and monocotyledonous plants, which can be utilized to engineer novel and enhanced disease resistance in heterologous plants. © 2018 TEMASEK LIFE SCIENCES LABORATORY. MOLECULAR PLANT PATHOLOGY © 2018 JOHN WILEY & SONS LTD.

  15. Nucleic acid molecules conferring enhanced ethanol tolerance and microorganisms having enhanced tolerance to ethanol

    DOEpatents

    Brown, Steven; Guss, Adam; Yang, Shihui; Karpinets, Tatiana; Lynd, Lee; Shao, Xiongjun

    2014-01-14

    The present invention provides isolated nucleic acid molecules which encode a mutant acetaldehyde-CoA/alcohol dehydrogenase or mutant alcohol dehydrogenase and confer enhanced tolerance to ethanol. The invention also provides related expression vectors, genetically engineered microorganisms having enhanced tolerance to ethanol, as well as methods of making and using such genetically modified microorganisms for production of biofuels based on fermentation of biomass materials.

  16. Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.

    2007-07-15

    Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we show that coagulation factor (F)Xa drives tumor cells of epithelial origin, but not endothelial cells or monocytes, into apoptosis, whereas it even enhances fibroblast survival. FXa signals through the protease activated receptor (PAR)-1 to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This activation is associated with phosphorylation of the transcription factor CREB, and in tumor cells withmore » up-regulation of the BH3-only pro-apoptotic protein Bim, leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim, ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa-induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond its role in blood coagulation, FXa plays a key role in cellular processes in which Bim is the central player in determining cell survival.« less

  17. Functional assembly of intrinsic coagulation proteases on monocytes and platelets. Comparison between cofactor activities induced by thrombin and factor Xa

    PubMed Central

    1992-01-01

    Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of factor VIII to VIIIa. In the present studies, autocatalytic regulatory pathways operating on monocyte and platelet membranes were investigated by comparing the cofactor function of thrombin-activated factor VIII to that of factor Xa-activated factor VIII. Reciprocal functional titrations with purified human factor VIII and factor IXa were performed at fixed concentrations of human monocytes, CaCl2, factor X, and either factor IXa or factor VIII. Factor VIII was preactivated with either thrombin or factor Xa, and reactions were initiated by addition of factor X. Rates of factor X activation were measured using chromogenic substrate specific for factor Xa. The K1/2 values, i.e., concentration of factor VIIIa at which rates were half maximal, were 0.96 nM with thrombin- activated factor VIII and 1.1 nM with factor Xa-activated factor VIII. These values are close to factor VIII concentration in plasma. The Vsat, i.e., rates at saturating concentrations of factor VIII, were 33.3 and 13.6 nM factor Xa/min, respectively. The K1/2 and Vsat values obtained in titrations with factor IXa were not significantly different from those obtained with factor VIII. In titrations with factor X, the values of Michaelis-Menten coefficients (Km) were 31.7 nM with thrombin- activated factor VIII, and 14.2 nM with factor Xa-activated factor VIII. Maximal rates were 23.4 and 4.9 nM factor Xa/min, respectively. The apparent catalytic efficiency was similar with either form of factor VIIIa. Kinetic profiles obtained with platelets as a source of membrane were comparable to those obtained with monocytes

  18. Nontraumatic spinal subdural hematoma complicating direct factor Xa inhibitor treatment (rivaroxaban): a challenging management.

    PubMed

    Dargazanli, Cyril; Lonjon, Nicolas; Gras-Combe, Guillaume

    2016-05-01

    We report on a 72-year-old male patient who developed a nontraumatic spinal subdural hematoma (SSDH) during rivaroxaban therapy, a relatively new orally administered direct factor Xa inhibitor. The patient sustained a sudden onset of interscapular pain, followed by gait impairment and paraplegia. Magnetic resonance imaging (MRI) of the spine demonstrated SSDH from T6 to T8. Laboratory tests revealed a high rivaroxaban level, associated with a major hemorrhagic risk. Surgery was, therefore, performed the following morning, after normalization of coagulation parameters. Determining the time of safe surgery remains challenging when hemorrhagic complications happen with direct factor Xa inhibitor, especially when neurological prognosis is engaged. Spinal subdural hematoma has not previously been reported following rivaroxaban therapy.

  19. Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

    PubMed

    Turpie, Alexander G G

    2003-11-15

    The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy.

  20. Threshold Concepts: From Personal Practice to Communities of Practice. Proceedings of the National Academy's Sixth Annual Conference and the Fourth Biennial Threshold Concepts Conference [E-publication] (Dublin, Ireland, June 27-29, 2012)

    ERIC Educational Resources Information Center

    O'Mahony, Catherine, Ed.; Buchanan, Avril, Ed.; O'Rourke, Mary, Ed.; Higgs, Bettie, Ed.

    2014-01-01

    The 6th Annual Conference of the National Academy for the Integration of Research, Teaching and Learning (NAIRTL) and the 4th Biennial Threshold Concepts Conference was held at Trinity College Dublin, Ireland, on June 27-29, 2012. The NAIRTL is a collaborative initiative between University College Cork, Cork Institute of Technology, National…

  1. Research in Medical Education: Proceedings of the Annual Conference (38th, Washington, DC, October 25-27, 1999).

    ERIC Educational Resources Information Center

    Anderson, M. Brownell, Ed.

    1999-01-01

    The Proceedings of the 38th Annual Conference on Research in Medical Education (Washington, DC, October 25-27, 1999) contain 43 research papers on innovative curricula, diagnostic reasoning, student evaluations of faculty, practicing physicians, prediction, licensing examinations, admissions, faculty development, managed care, technology-enhanced…

  2. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy

    PubMed Central

    Musiani, Daniele; Konda, John David; Pavan, Simona; Torchiaro, Erica; Sassi, Francesco; Noghero, Alessio; Erriquez, Jessica; Perera, Timothy; Olivero, Martina; Di Renzo, Maria Flavia

    2014-01-01

    The tyrosine kinase encoded by the MET oncogene is activated by gene mutation or amplification in tumors, which in most instances maintain addiction, i.e., dependency, to MET activation. This makes MET an attractive candidate for targeted therapies. Here we show that, in 3/3 MET-addicted human gastric cancer cell lines, MET kinase inhibition resulted in a 3- to 4-fold increased expression of the antiapoptotic small heat-shock protein of 27 kDa (HSP27, HSPB1). HSP27 increase depended on the inhibition of the MEK/ERK pathway and on heat-shock factor 1 (HSF1) and hypoxia-inducible factor-1α (HIF-1α) regulation. Importantly, HSP27-silenced MET-addicted cells underwent 2- and 3-fold more apoptosis following MET inhibition in vitro and in vivo, respectively. Likewise, in human cancer cells susceptible to epidermal growth factor receptor (EGFR) inhibition, EGFR inhibitors induced HSP27 expression and were strengthened by HSP27 suppression. In control cell lines that were not affected by drugs targeting MET or EGFR, these drugs did not induce HSP27 increase. Therefore, in cancer therapies targeting the MET pathway, the induction of HSP27 might limit the efficacy of anti-MET agents. As HSP27 increase also impairs the effectiveness of EGFR inhibitors and is known to protect cells from chemotherapeutics, the induction of HSP27 by targeted agents might strongly affect the success of combination treatments.—Musiani, D., Konda, J. D., Pavan, S., Torchiaro, E., Sassi, F., Noghero, A., Erriquez, J., Perera, T., Olivero, M., Di Renzo, M. F. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy. PMID:24903273

  3. Clinical impact of major bleeding in patients with venous thromboembolism treated with factor Xa inhibitors or vitamin K antagonists. An individual patient data meta-analysis.

    PubMed

    Bleker, Suzanne M; Brekelmans, Marjolein P A; Eerenberg, Elise S; Cohen, Alexander T; Middeldorp, Saskia; Raskob, Gary; Büller, Harry R

    2017-10-05

    Factor Xa (fXa)-inhibitors are as effective and safer than vitamin-K-antagonists (VKA) in the treatment of venous thromboembolism (VTE). We previously classified the severity of clinical presentation and course of all major bleeding events from the EINSTEIN, AMPLIFY and HOKUSAI-VTE trials separately. The current aim was to combine these findings in order to increase precision, assess a class effect and analyse presentation and course for different types of bleeding, i. e. intracranial, gastro-intestinal, and other. We classified the clinical presentation and course of all major bleeding events using pre-defined criteria. Both classifications comprised four categories; one being the mildest, and four the most severe. Odds ratios (OR) were calculated for all events classified as category three or four between fXa-inhibitors and VKA recipients. Also, ORs were computed for different types of bleeding. Major bleeding occurred in 111 fXa-inhibitor recipients and in 187 LMWH/VKA recipients. The clinical presentation was classified as category three or four in 35 % and 48 % of the major bleeds in fXa inhibitor and VKA recipients, respectively (OR 0.59, 95 % CI 0.36-0.97). For intracranial, gastro-intestinal and other bleeding a trend towards a less severe presentation was observed for patients treated with fXa inhibitors. Clinical course was classified as severe in 22 % of the fXa inhibitor and 25 % of the VKA associated bleeds (OR 0.83, 95 % CI 0.47-1.46). In conclusion, FXa inhibitor associated major bleeding events had a significantly less severe presentation and a similar course compared to VKA. This finding was consistent for different types of bleeding.

  4. Unfractionated heparin activity measured by anti-factor Xa levels is associated with the need for extracorporeal membrane oxygenation circuit/membrane oxygenator change: a retrospective pediatric study.

    PubMed

    Irby, Katherine; Swearingen, Christopher; Byrnes, Jonathan; Bryant, Joshua; Prodhan, Parthak; Fiser, Richard

    2014-05-01

    Investigate whether anti-Factor Xa levels are associated with the need for change of circuit/membrane oxygenator secondary to thrombus formation in pediatric patients. Retrospective single institution study. Retrospective record review of 62 pediatric patients supported with extracorporeal membrane oxygenation from 2009 to 2011. Data on standard demographic characteristics, indications for extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, activated clotting time measurements, anti-Factor Xa measurements, and heparin infusion rate were collected. Generalized linear models were used to associate anti-Factor Xa concentrations and need for change of either entire circuit/membrane oxygenator secondary to thrombus formation. Sixty-two patients met study inclusion criteria. No-circuit change was required in 45 of 62 patients. Of 62 patients, 17 required change of circuit/membrane oxygenator due to thrombus formation. Multivariate analysis of daily anti-Factor Xa measurements throughout duration of extracorporeal membrane oxygenation support estimated a mean anti-Factor Xa concentration of 0.20 IU/mL (95% CI, 0.16, 0.24) in no-complete-circuit group that was significantly higher than the estimated concentration of 0.13 IU/mL (95% CI, 0.12, 0.14) in complete-circuit group (p = 0.001). A 0.01 IU/mL decrease in anti-Factor Xa increased odds of need for circuit/membrane oxygenator change by 5% (odds ratio = 1.105; 95% CI, 1.00, 1.10; p = 0.044). Based on the observed anti-Factor Xa concentrations, complete-circuit group had 41% increased odds for requiring circuit/membrane oxygenator change compared with no-complete-circuit group (odds ratio = 1.41; 95% CI, 1.01, 1.96; p = 0.044). Mean daily activated clotting time measurement (p = 0.192) was not different between groups, but mean daily heparin infusion rate (p < 0.001) was significantly different between the two groups. Higher anti-Factor Xa concentrations were associated with freedom from

  5. Reading in Early Childhood Education; Proceedings of the York College Reading Conference (1st, Jamaica, New York, April 27, 1974). DICTA No. II.

    ERIC Educational Resources Information Center

    Seittelman, Elizabeth E., Ed.

    This booklet provides abstracts of the proceedings of a conference on reading conducted on 27 April 1974 by the Department of Teacher Preparation of York College of the City University of New York. The following conference presentations are discussed: "Reading Readiness--What Do I Believe?" (Lilyan Peters), "Preschool as a Language Laboratory"…

  6. Phosphomimics destabilize Hsp27 oligomeric assemblies and enhance chaperone activity.

    PubMed

    Jovcevski, Blagojce; Kelly, Megan A; Rote, Anthea P; Berg, Tracey; Gastall, Heidi Y; Benesch, Justin L P; Aquilina, J Andrew; Ecroyd, Heath

    2015-02-19

    Serine phosphorylation of the mammalian small heat-shock protein Hsp27 at residues 15, 78, and 82 is thought to regulate its structure and chaperone function; however, the site-specific impact has not been established. We used mass spectrometry to assess the combinatorial effect of mutations that mimic phosphorylation upon the oligomeric state of Hsp27. Comprehensive dimerization yielded a relatively uncrowded spectrum, composed solely of even-sized oligomers. Modification at one or two serines decreased the average oligomeric size, while the triple mutant was predominantly a dimer. These changes were reflected in a greater propensity for oligomers to dissociate upon increased modification. The ability of Hsp27 to prevent amorphous or fibrillar aggregation of target proteins was enhanced and correlated with the amount of dissociated species present. We propose that, in vivo, phosphorylation promotes oligomer dissociation, thereby enhancing chaperone activity. Our data support a model in which dimers are the chaperone-active component of Hsp27. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 75 FR 2552 - NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening Notice is hereby given by the National Institutes of Health (NIH) of the ``NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening'' to be held...

  8. Enhanced LPS-induced activation of IL-27 signalling in sarcoidosis.

    PubMed

    Ringkowski, Sabine; Loke, Joshua; Huang, Shuying; Ahmadzai, Hasib; Herth, Felix J F; Thomas, Paul S; Herbert, Cristan

    2016-08-01

    Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects. Protein and mRNA (in PBMC) levels for IL-27 and IL-35 (IL27, EBI3, IL12A subunits) as well as IL-27 receptor (IL6ST and IL27RA subunits) were assessed spontaneously and following direct (LPS) and indirect (anti-CD3/28 activation beads) macrophage stimulation using RT- PCR, ELISA and flow cytometry. Following stimulation with LPS, PBMC of patients with sarcoidosis displayed significantly enhanced expression of IL27 and EBI3 mRNA (p = 0.020 and p = 0.037 respectively) compared to PBMCs from healthy controls. There was also significantly enhanced production of IL-27 by PBMC from patients with sarcoidosis compared to healthy controls in response to LPS stimulation (p = 0.027). IL6ST mRNA and IL6ST protein were significantly lower in patients with sarcoidosis (mRNA p = 0.0002; MFI p = 0.0015) whilst IL27RA protein levels were significantly higher in patients with sarcoidosis compared to healthy controls (MFI p < 0.0001). Plasma IL-35 protein levels did not differ between control and sarcoidosis subjects (p = 0.23). These results suggest there may be exaggerated activation of IL-27 signalling in response to LPS in sarcoidosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. L2₁ and XA Ordering Competition in Hafnium-Based Full-Heusler Alloys Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb).

    PubMed

    Wang, Xiaotian; Cheng, Zhenxiang; Wang, Wenhong

    2017-10-20

    For theoretical designing of full-Heusler based spintroinc materials, people have long believed in the so-called Site Preference Rule (SPR). Very recently, according to the SPR, there are several studies on XA-type Hafnium-based Heusler alloys X₂YZ, i.e., Hf₂VAl, Hf₂CoZ (Z = Ga, In) and Hf₂CrZ (Z = Al, Ga, In). In this work, a series of Hf₂-based Heusler alloys, Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb), were selected as targets to study the site preferences of their atoms by first-principle calculations. It has been found that all of them are likely to exhibit the L2₁-type structure instead of the XA one. Furthermore, we reveal that the high values of spin-polarization of XA-type Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb) alloys have dropped dramatically when they form the L2₁-type structure. Also, we prove that the electronic, magnetic, and physics nature of these alloys are quite different, depending on the L2₁-type or XA-type structures.

  10. 10th international conference on high-occupancy vehicle systems : conference proceedings

    DOT National Transportation Integrated Search

    2001-08-01

    This report documents the proceedings from the 10th International High-Occupancy Vehicle (HOV) Systems Conference held in Dallas, Texas on August 27-30, 2000. The Conference was sponsored by the Transportation Research Board (TRB), in cooperation wit...

  11. 40 CFR 27.19 - Prehearing conferences.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... conference at a reasonable time in advance of the hearing. (c) The presiding officer may use prehearing... and of proposed exhibits; (8) Discovery; (9) The time and place for the hearing; and (10) Such other matters as may tend to expedite the fair and just disposition of the proceedings. (d) The presiding...

  12. 40 CFR 27.19 - Prehearing conferences.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... conference at a reasonable time in advance of the hearing. (c) The presiding officer may use prehearing... and of proposed exhibits; (8) Discovery; (9) The time and place for the hearing; and (10) Such other matters as may tend to expedite the fair and just disposition of the proceedings. (d) The presiding...

  13. Proceedings of the 27th International Group for the Psychology of Mathematics Education Conference Held Jointly with the 25th PME-NA Conference (Honolulu, Hawaii, July 13-18, 2003). Volume 4

    ERIC Educational Resources Information Center

    Pateman, Neil A., Ed; Dougherty, Barbara J., Ed.; Zilliox, Joseph T., Ed.

    2003-01-01

    This volume of the 27th International Group for the Psychology of Mathematics Education Conference includes the following research reports: (1) Improving Decimal Number Conception by Transfer from Fractions to Decimals (Irita Peled and Juhaina Awawdy Shahbari); (2) The Development of Student Teachers' Efficacy Beliefs in Mathematics during…

  14. Proceedings of the 27th International Group for the Psychology of Mathematics Education Conference Held Jointly with the 25th PME-NA Conference (Honolulu, Hawaii, July 13-18, 2003). Volume 1

    ERIC Educational Resources Information Center

    Pateman, Neil A., Ed; Dougherty, Barbara J., Ed.; Zilliox, Joseph T., Ed.

    2003-01-01

    This volume of the 27th International Group for the Psychology of Mathematics Education Conference presents papers from: plenary panels; research forums; working sessions; discussion groups; short oral communications; and poster sessions from the meeting. Plenary lectures included: (1) Studying and Capturing the Complexity of Practice: The Case of…

  15. Proceedings of the 27th International Group for the Psychology of Mathematics Education Conference Held Jointly with the 25th PME-NA Conference (Honolulu, Hawaii, July 13-18, 2003). Volume 2

    ERIC Educational Resources Information Center

    Pateman, Neil A., Ed.; Dougherty, Barbara J., Ed.; Zilliox, Joseph T., Ed.

    2003-01-01

    This volume of the 27th International Group for the Psychology of Mathematics Education Conference presents the following research reports: (1) Text Talk, Body Talk, Table Talk: A Design of Ratio and Proportion as Classroom Parallel Events (Dor Abrahamson); (2) Generalizing the Context and Generalising the Calculation (Janet Ainley); (3) Interview…

  16. Proceedings of the 27th International Group for the Psychology of Mathematics Education Conference Held Jointly with the 25th PME-NA Conference (Honolulu, Hawaii, July 13-18, 2003). Volume 3

    ERIC Educational Resources Information Center

    Pateman, Neil A., Ed; Dougherty, Barbara J., Ed.; Zilliox, Joseph T., Ed.

    2003-01-01

    This volume of the 27th International Group for the Psychology of Mathematics Education Conference includes the following research reports: (1) The Affective Views of Primary School Children (Peter Grootenboer); (2) Theoretical Model of Analysis of Rate Problems in Algebra (Jose Guzman, Nadine Bednarz and Fernando Hitt); (3) Locating Fractions on…

  17. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of pulmonary embolism.

    PubMed

    Robertson, Lindsay; Kesteven, Patrick; McCaslin, James E

    2015-12-04

    Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes

  18. Reproducibility of the anti-Factor Xa and anti-Factor IIa assays applied to enoxaparin solution.

    PubMed

    Martinez, Céline; Savadogo, Adama; Agut, Christophe; Anger, Pascal

    2013-01-01

    Enoxaparin is a widely used subcutaneously administered antithrombotic agent comprising a complex mixture of glycosaminoglycan chains. Owing to this complexity, its antithrombotic potency cannot be defined by physicochemical methods and is therefore evaluated using an enzymatic assay of anti-Xa and anti-IIa activity. Maintaining consistent anti-Xa activity in the final medicinal product allows physicians to ensure administration of the appropriate dosage to their patients. Bioassays are usually complex and display poorer reproducibility than physicochemical tests such as HPLC assays. Here, we describe the implementation of a common robotic platform and standard release potency testing procedures for enoxaparin sodium injection (Lovenox, Sanofi, Paris, France) products at seven quality control sites within Sanofi. Qualification and analytical procedures, as well as data handling, were optimized and harmonized to improve assay reproducibility. An inter-laboratory study was performed in routine-release conditions. The coefficients of variation for repeatability and reproducibility in assessments of anti-Xa activity were 1.0% and 1.2%, respectively. The tolerance interval in reproducibility precision conditions, expressed as percentage potency, was 96.8-103.2% of the drug product target of 10,000 IU/ml, comparing favorably with the United States of America Pharmacopeia specification (90-110%). The maximum difference between assays in two different laboratories is expected to be 4.1%. The reproducibility characteristics of anti-IIa activity assessments were found to be similar. These results demonstrate the effectiveness of the standardization process established and allow for further improvements to quality control in Lovenox manufacture. This process guarantees closeness between actual and target potencies, as exemplified by the results of release assays obtained during a three-year period. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Chemoenzymatic Synthesis of Heparin Oligosaccharides with both Anti-factor Xa and Anti-factor IIa Activities*

    PubMed Central

    Xu, Yongmei; Pempe, Elizabeth H.; Liu, Jian

    2012-01-01

    Heparan sulfate (HS) and heparin are highly sulfated polysaccharides. Heparin is a commonly used anticoagulant drug that inhibits the activities of factors Xa and IIa (also known as thrombin) to prevent blood clot formation. Here, we report the synthesis of a series of size-defined oligosaccharides to probe the minimum size requirement for an oligosaccharide with anti-IIa activity. The synthesis was completed by a chemoenzymatic approach involving glycosyltransferases, HS sulfotransferases, and C5-epimerase. We demonstrate the ability to synthesize highly purified N-sulfo-oligosaccharides having up to 21 saccharide residues. The results from anti-Xa and anti-IIa activity measurements revealed that an oligosaccharide longer than 19 saccharide residues is necessary to display anti-IIa activity. The oligosaccharides also exhibit low binding toward platelet factor 4, raising the possibility of preparing a synthetic heparin with a reduced effect of heparin-induced thrombocytopenia. The results from this study demonstrate the ability to synthesize large HS oligosaccharides and provide a unique tool to probe the structure and function relationships of HS that require the use of large HS fragments. PMID:22773834

  20. Acoustic Emission Monitoring of the DC-XA Composite Liquid Hydrogen Tank During Structural Testing

    NASA Technical Reports Server (NTRS)

    Wilkerson, C.

    1996-01-01

    The results of acoustic emission (AE) monitoring of the DC-XA composite liquid hydrogen tank are presented in this report. The tank was subjected to pressurization, tensile, and compressive loads at ambient temperatures and also while full of liquid nitrogen. The tank was also pressurized with liquid hydrogen. AE was used to monitor the tank for signs of structural defects developing during the test.

  1. International conference on "Photosynthesis Research for Sustainability-2014: in honor of Vladimir A. Shuvalov", held on June 2-7, 2014, in Pushchino, Russia.

    PubMed

    Allakhverdiev, Suleyman I; Tomo, Tatsuya; Govindjee

    2014-12-01

    In this article, we provide a News Report on an international conference "Photosynthesis Research for Sustainability-2014" that was held in honor of Vladimir A. Shuvalov at the Biological Research Center of the Russian Academy of Sciences, in Pushchino, Russia, during June 2-7, 2014 (http://photosynthesis2014.cellreg.org/). We begin this report with a short description of Vladimir A. Shuvalov, the honored scientist. We then provide some information on the conference, and the program. A special feature of this conference was awards given to nine young investigators; they are recognized in this Report. We have also included several photographs to show the pleasant ambiance at this conference. We invite the readers to the next two conferences on ''Photosynthesis Research for Sustainability-2015: the first one to be held in Baku in May or June, 2015, and the second one, which will honor George C. Papageorgiou, will be held in Greece (in Colymbari, near Chania in Crete) during September 21-26, 2015. Information will be posted at: http://photosynthesis2015.cellreg.org/.

  2. Phosphorylation of AKT induced by phosphorylated Hsp27 confers the apoptosis-resistance in t-AUCB-treated glioblastoma cells in vitro.

    PubMed

    Li, Rujun; Li, Junyang; Sang, Dongping; Lan, Qing

    2015-01-01

    The aim of this study is to determine whether phosphorylation of AKT could be effected by t-AUCB-induced p-Hsp27 and whether p-AKT inhibition sensitizes glioblastoma cells to t-AUCB, and to evaluate the effects of simultaneous inhibition of p-Hsp27 and p-AKT on t-AUCB treated glioblastoma cells. Cell growth was detected using CCK-8 assay; Caspase-3 activity assay kits and flow cytometry were used in apoptosis analysis; Western blot analysis was used to detect p-Hsp27 and p-AKT levels; RNA interference using the siRNA oligos of Hsp27 was performed to knockdown gene expression of Hsp27. All data were analyzed by the Student-Newman-Keul's test. We demonstrated that t-AUCB treatment induces AKT phosphorylation by activating Hsp27 in U251 and LN443 cell lines. Inhibition of AKT phosphorylation by AKT inhibitor IV sensitizes glioblastoma cells to t-AUCB, strengthens t-AUCB suppressing cell growth and inducing cell apoptosis. We also found inhibiting both p-Hsp27 and p-AKT synergistically strengthen t-AUCB suppressing cell growth. Thus, p-AKT induced by p-Hsp27 confers the apoptosis-resistance in t-AUCB-treated glioblastoma cells. Targeting p-Hsp27 and/or p-AKT may be a potential effective strategy for the treatment of glioblastoma.

  3. Molecular recognition of avirulence protein (avrxa5) by eukaryotic transcription factor xa5 of rice (Oryza sativa L.): insights from molecular dynamics simulations.

    PubMed

    Dehury, Budheswar; Maharana, Jitendra; Sahoo, Bikash Ranjan; Sahu, Jagajjit; Sen, Priyabrata; Modi, Mahendra Kumar; Barooah, Madhumita

    2015-04-01

    The avirulence gene avrxa5 of bacterial blight pathogen Xanthomonas oryzae pv. oryzae (Xoo) recognized by the resistant rice lines having corresponding resistance (xa5) gene in a gene-for-gene manner. We used a combinatorial approach involving protein-protein docking, molecular dynamics (MD) simulations and binding free energy calculations to gain novel insights into the gene-for-gene mechanism that governs the direct interaction of R-Avr protein. From the best three binding poses predicted by molecular docking, MD simulations were performed to explore the dynamic binding mechanism of xa5 and avrxa5. Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) techniques were employed to calculate the binding free energy and to uncover the thriving force behind the molecular recognition of avrxa5 by eukaryotic transcription factor xa5. Binding free energy analysis revealed van der Waals term as the most constructive component that favors the xa5 and avrxa5 interaction. In addition, hydrogen bonds (H-bonds) and essential electrostatic interactions analysis highlighted amino acid residues Lys54/Asp870, Lys56/Ala868, Lys56/Ala866, Lys56/Glu871, Ile59/His862, Gly61/Phe858, His62/Arg841, His62/Leu856, Ser101/Ala872 and Ser105/Asp870 plays pivotal role for the energetically stability of the R-Avr complex. Insights gained from the present study are expected to unveil the molecular mechanisms that define the transcriptional activator mediated transcriptome modification in host plants. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

    PubMed

    van Montfoort, Maurits L; Meijers, Joost C M

    2013-08-01

    Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

  5. The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances apoptosis.

    PubMed

    Weber, Arnim; Heinlein, Melanie; Dengjel, Jörn; Alber, Claudia; Singh, Prafull Kumar; Häcker, Georg

    2016-05-01

    Bim is a pro-apoptotic Bcl-2 family member of the BH3-only protein subgroup. Expression levels of Bim determine apoptosis susceptibility in non-malignant and in tumour cells. Bim protein expression is downregulated by proteasomal degradation following ERK-dependent phosphorylation and ubiquitination. Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels. Overexpression of Usp27x reduces ERK-dependent Bim ubiquitination, stabilizes phosphorylated Bim, and induces apoptosis in PMA-stimulated cells, as well as in tumour cells with a constitutively active Raf/ERK pathway. Loss of endogenous Usp27x enhances the Bim-degrading activity of oncogenic Raf. Overexpression of Usp27x induces low levels of apoptosis in melanoma and non-small cell lung cancer (NSCLC) cells and substantially enhances apoptosis induced in these cells by the inhibition of ERK signalling. Finally, deletion of Usp27x reduces apoptosis in NSCLC cells treated with an EGFR inhibitor. Thus, Usp27x can trigger via its proteolytic activity the deubiquitination of Bim and enhance its levels, counteracting the anti-apoptotic effects of ERK activity, and therefore acts as a tumour suppressor. © 2016 The Authors.

  6. Rivaroxaban Levels in Patients' Plasmas are Comparable by Using Two Different Anti Xa Assay/Coagulometer Systems Calibrated with Two Different Calibrators.

    PubMed

    Martinuzzo, Marta E; Duboscq, Cristina; Lopez, Marina S; Barrera, Luis H; Vinuales, Estela S; Ceresetto, Jose; Forastiero, Ricardo R; Oyhamburu, Jose

    2018-06-01

    Rivaroxaban oral anticoagulant does not need laboratory monitoring, but in some situations plasma level measurement is useful. The objective of this paper was to verify analytical performance and compare two rivaroxaban calibrated anti Xa assays/coagulometer systems with specific or other branch calibrators. In 59 samples drawn at trough or peak from patients taking rivaroxaban, plasma levels were measured by HemosIL Liquid anti Xa in ACLTOP 300/500, and STA liquid Anti Xa in TCoag Destiny Plus. HemosIL and STA rivaroxaban calibrators and controls were used. CLSI guideline procedures EP15A3 for precision and trueness, EP6 for linearity, and EP9 for methods comparison were used. Coefficient of variation within run and total precision (CVR and CVWL respectively) of plasmatic rivaroxaban were < 4.2 and < 4.85% and BIAS < 7.4 and < 6.5%, for HemosIL-ACL TOP and STA-Destiny systems, respectively. Linearity verification 8 - 525 ng/mL a Deming regression for methods comparison presented R 0.963, 0.968 and 0.982, with a mean CV 13.3% when using different systems and calibrations. The analytical performance of plasma rivaroxaban was acceptable in both systems, and results from reagent/coagulometer systems are comparable even when calibrating with different branch material.

  7. XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

    NASA Astrophysics Data System (ADS)

    Neverov, V. S.

    XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D) diffraction patterns and pair-distribution functions (PDF) for amorphous or crystalline nanoparticles (up to ∼107 atoms) of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

  8. Daboxin P, a Major Phospholipase A2 Enzyme from the Indian Daboia russelii russelii Venom Targets Factor X and Factor Xa for Its Anticoagulant Activity

    PubMed Central

    Iyer, Janaki Krishnamurthy; Shih, Norrapat; Majumder, Munmi; Mattaparthi, Venkata Satish Kumar; Mukhopadhyay, Rupak; Doley, Robin

    2016-01-01

    In the present study a major protein has been purified from the venom of Indian Daboia russelii russelii using gel filtration, ion exchange and Rp-HPLC techniques. The purified protein, named daboxin P accounts for ~24% of the total protein of the crude venom and has a molecular mass of 13.597 kDa. It exhibits strong anticoagulant and phospholipase A2 activity but is devoid of any cytotoxic effect on the tested normal or cancerous cell lines. Its primary structure was deduced by N-terminal sequencing and chemical cleavage using Edman degradation and tandem mass spectrometry. It is composed of 121 amino acids with 14 cysteine residues and catalytically active His48 -Asp49 pair. The secondary structure of daboxin P constitutes 42.73% of α-helix and 12.36% of β-sheet. It is found to be stable at acidic (pH 3.0) and neutral pH (pH 7.0) and has a Tm value of 71.59 ± 0.46°C. Daboxin P exhibits anticoagulant effect under in-vitro and in-vivo conditions. It does not inhibit the catalytic activity of the serine proteases but inhibits the activation of factor X to factor Xa by the tenase complexes both in the presence and absence of phospholipids. It also inhibits the tenase complexes when active site residue (His48) was alkylated suggesting its non-enzymatic mode of anticoagulant activity. Moreover, it also inhibits prothrombinase complex when pre-incubated with factor Xa prior to factor Va addition. Fluorescence emission spectroscopy and affinity chromatography suggest the probable interaction of daboxin P with factor X and factor Xa. Molecular docking analysis reveals the interaction of the Ca+2 binding loop; helix C; anticoagulant region and C-terminal region of daboxin P with the heavy chain of factor Xa. This is the first report of a phospholipase A2 enzyme from Indian viper venom which targets both factor X and factor Xa for its anticoagulant activity. PMID:27089306

  9. Identification of potent orally active factor Xa inhibitors based on conjugation strategy and application of predictable fragment recommender system.

    PubMed

    Ishihara, Tsukasa; Koga, Yuji; Iwatsuki, Yoshiyuki; Hirayama, Fukushi

    2015-01-15

    Anticoagulant agents have emerged as a promising class of therapeutic drugs for the treatment and prevention of arterial and venous thrombosis. We investigated a series of novel orally active factor Xa inhibitors designed using our previously reported conjugation strategy to boost oral anticoagulant effect. Structural optimization of anthranilamide derivative 3 as a lead compound with installation of phenolic hydroxyl group and extensive exploration of the P1 binding element led to the identification of 5-chloro-N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzamide (33, AS1468240) as a potent factor Xa inhibitor with significant oral anticoagulant activity. We also reported a newly developed Free-Wilson-like fragment recommender system based on the integration of R-group decomposition with collaborative filtering for the structural optimization process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27.

    PubMed

    Gan, Nanqin; Wu, Yu-Chieh; Brunet, Mathilde; Garrido, Carmen; Chung, Fung-Lung; Dai, Chengkai; Mi, Lixin

    2010-11-12

    It is conceivable that stimulating proteasome activity for rapid removal of misfolded and oxidized proteins is a promising strategy to prevent and alleviate aging-related diseases. Sulforaphane (SFN), an effective cancer preventive agent derived from cruciferous vegetables, has been shown to enhance proteasome activities in mammalian cells and to reduce the level of oxidized proteins and amyloid β-induced cytotoxicity. Here, we report that SFN activates heat shock transcription factor 1-mediated heat shock response. Specifically, SFN-induced expression of heat shock protein 27 (Hsp27) underlies SFN-stimulated proteasome activity. SFN-induced proteasome activity was significantly enhanced in Hsp27-overexpressing cells but absent in Hsp27-silenced cells. The role of Hsp27 in regulating proteasome activity was further confirmed in isogenic REG cells, in which SFN-induced proteasome activation was only observed in cells stably overexpressing Hsp27, but not in the Hsp27-free parental cells. Finally, we demonstrated that phosphorylation of Hsp27 is irrelevant to SFN-induced proteasome activation. This study provides a novel mechanism underlying SFN-induced proteasome activity. This is the first report to show that heat shock response by SFN, in addition to the antioxidant response mediated by the Keap1-Nrf2 pathway, may contribute to cytoprotection.

  11. Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23-27 July 2007).

    PubMed

    Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

    2008-05-21

    The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged.

  12. Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors.

    PubMed

    Tao, Jing; Bukanova, Elena N; Akhtar, Shamsuddin

    2018-01-01

    Although factor Xa inhibitors have become a popular choice for chronic oral anticoagulation, effective drug reversal remains difficult due to a lack of specific antidote. Currently, 4-factor prothrombin complex concentrate (4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used for this off-label purpose remain unclear. The purpose of this retrospective study is to determine the rate of thromboembolism when 4F-PCC is used for the emergent reversal of factor Xa inhibitors. We conducted a single-center retrospective review of medical records between 2013 and 2017. Patients were included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban for emergent invasive procedures or during episodes of major bleeding defined as bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion. Thrombotic events including myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and arterial thrombosis of the limb or mesentery were recorded if they occurred within 14 days of 4F-PCC administration. Data was analyzed using point and interval estimation to approximate the rate and confidence interval of thromboembolic events. Forty-three patients were identified in our review. Doses of 4F-PCC were determined by the treating physician and mainly ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty-one patients (48.8%) were placed on SCDs only. Three patients received concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration occurred in 1 out of 43 patients (2.1%, 95% CI [0.1-12.3]). This thrombotic event was an upper extremity DVT which occurred 1 day after the patient received 1325 IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial

  13. Suppression of bacterial infection in rice by treatment with a sulfated peptide.

    PubMed

    Wei, Tong; Chern, Mawsheng; Liu, Furong; Ronald, Pamela C

    2016-12-01

    The rice XA21 receptor kinase confers robust resistance to bacterial blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo). A tyrosine-sulfated peptide from Xoo, called RaxX, triggers XA21-mediated immune responses, including the production of ethylene and reactive oxygen species and the induction of defence gene expression. It has not been tested previously whether these responses confer effective resistance to Xoo. Here, we describe a newly established post-inoculation treatment assay that facilitates investigations into the effect of the sulfated RaxX peptide in planta. In this assay, rice plants were inoculated with a virulent strain of Xoo and then treated with the RaxX peptide 2 days after inoculation. We found that post-inoculation treatment of XA21 plants with the sulfated RaxX peptide suppresses the development of Xoo infection in XA21 rice plants. The treated plants display restricted lesion development and reduced bacterial growth. Our findings demonstrate that exogenous application of sulfated RaxX activates XA21-mediated immunity in planta, and provides a potential strategy for the control of bacterial disease in the field. © 2016 BSPP and John Wiley & Sons Ltd.

  14. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    NASA Astrophysics Data System (ADS)

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-07-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency.

  15. 6 CFR 27.410 - Third party actions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 6 Domestic Security 1 2011-01-01 2011-01-01 false Third party actions. 27.410 Section 27.410 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Other § 27.410 Third party actions. (a) Nothing in this part shall confer upon any person except...

  16. 6 CFR 27.410 - Third party actions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 6 Domestic Security 1 2014-01-01 2014-01-01 false Third party actions. 27.410 Section 27.410 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Other § 27.410 Third party actions. (a) Nothing in this part shall confer upon any person except...

  17. 6 CFR 27.410 - Third party actions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 6 Domestic Security 1 2013-01-01 2013-01-01 false Third party actions. 27.410 Section 27.410 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Other § 27.410 Third party actions. (a) Nothing in this part shall confer upon any person except...

  18. 6 CFR 27.410 - Third party actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 6 Domestic Security 1 2012-01-01 2012-01-01 false Third party actions. 27.410 Section 27.410 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Other § 27.410 Third party actions. (a) Nothing in this part shall confer upon any person except...

  19. 6 CFR 27.410 - Third party actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Third party actions. 27.410 Section 27.410 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Other § 27.410 Third party actions. (a) Nothing in this Part shall confer upon any person except...

  20. Preface: Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23 27 July 2007)

    NASA Astrophysics Data System (ADS)

    Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

    2008-05-01

    The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged.

  1. Partnerships and Linkages for Success. Enhancing the Employment Potential of Persons with Disabilities. Report of the Los Angeles Regional Conference (September 25-27, 1989).

    ERIC Educational Resources Information Center

    Walker, Sylvia, Ed.; Asbury, Charles A., Ed.

    This report provides highlights from a conference that focused on strategies for assisting minority youth with disabilities to face labor market challenges. An introduction lists conference objectives. Section I contains a profile of the high school students with disabilities who participated in the workshops. The profile includes demographic…

  2. Proceedings of the International Miconia Conference

    USGS Publications Warehouse

    Loope, L.L.; Meyer, J.-Y.; Hardesty, B. D.; Smith, C.W.

    2015-01-01

    This proceedings is a compilation of 15 of the 27 papers and posters that were presented at the 2009 International Miconia Conference. The Conference was held in Keanae Hawaii May 4th to 7th 2009, hosted by the Maui Invasive Species Committee. *No official abstract was available for the proceedings...K. Keck

  3. Up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis in human papillary thyroid cancer cells.

    PubMed

    Mo, Xiao-Mei; Li, Li; Zhu, Ping; Dai, Yu-Jie; Zhao, Ting-Ting; Liao, Ling-Yao; Chen, George G; Liu, Zhi-Min

    2016-08-15

    17β-estradiol (E2) has been suggested to play a role in the development and progression of papillary thyroid cancer. Heat shock protein 27 (Hsp27) is a member of the Hsp family that is responsible for cell survival under stressful conditions. Previous studies have shown that the 5'-promoter region of Hsp27 gene contains a specificity protein-1 (Spl) and estrogen response element half-site (ERE-half), which contributes to Hsp27 induction by E2 in breast cancer cells. However, it is unclear whether Hsp27 can be up-regulated by E2 and which estrogen receptor (ER) isoform and tethered transcription factor are involved in this regulation in papillary thyroid cancer cells. In the present study, we demonstrated that Hsp27 can be effectively up-regulated by E2 at mRNA and protein levels in human K1 and BCPAP papillary thyroid cancer cells which have more than two times higher level of ERα than that of ERβ. The up-regulation of Hsp27 by E2 is mediated by ERα/Sp1 and ERβ has repressive effect on this ERα/Sp1-mediated up-regulation of Hsp27. Moreover, we showed that the up-regulation of Hsp27 by ERα/Sp1 facilitates proliferation and confers resistance to apoptosis through interaction with procaspase-3. Targeting this pathway may be a potential strategy for therapy of papillary thyroid cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Sulfated Low Molecular Weight Lignins, Allosteric Inhibitors of Coagulation Proteinases via the Heparin Binding Site, Significantly Alter the Active Site of Thrombin and Factor Xa Compared to Heparin

    PubMed Central

    Henry, Brian L.; Desai, Umesh R.

    2014-01-01

    Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. PMID:25242245

  5. Sulfated low molecular weight lignins, allosteric inhibitors of coagulation proteinases via the heparin binding site, significantly alter the active site of thrombin and factor xa compared to heparin.

    PubMed

    Henry, Brian L; Desai, Umesh R

    2014-11-01

    Sulfated low molecular weight lignins (LMWLs) have been found to bind in the heparin binding sites of coagulation proteinases. LMWLs represent a library of diverse non-carbohydrate, aromatic molecules which are structures different from heparin, but still potently inhibit thrombin and factor Xa. To better understand their mechanism of action, we studied the effects of three sulfated LMWLs (CDSO3, FDSO3, and SDSO3) on the active sites of thrombin and factor Xa. LMWLs were found to uniformly inhibit the catalytic activity of thrombin and factor Xa, regardless of the substrate used. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of each chromogenic substrate decreases significantly in the presence of sulfated LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. These studies indicate that LMWLs inhibit thrombin and factor Xa through allosteric disruption of the catalytic apparatus, specifically through the catalytic step. As opposed to heparin, LMWLs significantly alter the binding of the active site fluorescent ligand p-aminobenzamidine. LMWLs also had a greater effect on the molecular orientation of fluorescein-labeled His 57 than heparin. The molecular geometry surrounding the most important catalytic amino acid, Ser 195, was significantly altered by the binding of LMWLs while heparin had no measurable effect on Ser 195. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. 40 CFR 304.31 - Pre-hearing conference.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Pre-hearing conference. 304.31 Section 304.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY... CLAIMS Hearings Before the Arbitrator § 304.31 Pre-hearing conference. (a) The Arbitrator and the parties...

  7. A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom.

    PubMed

    Kong, Yi; Shao, Yu; Chen, Hao; Ming, Xin; Wang, Jin-Bin; Li, Zhi-Yu; Wei, Ji-Fu

    2013-01-01

    Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipes mutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC 50 value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.

  8. Expedition 27 Landing

    NASA Image and Video Library

    2011-05-23

    Expedition 27 Flight Engineer Cady Coleman answers reporters questions in traditional Kazakh dress during a press conference at the Karaganda airport shortly after she and Commander Dmitry Kondratyev and Flight Engineer Paolo Nespoli landed in their Soyuz TMA-20 southeast of the town of Zhezkazgan, Kazakhstan, on Tuesday, May 24, 2011. NASA Astronaut Coleman, Russian Cosmonaut Kondratyev and Italian Astronaut Nespoli are returning from more than five months onboard the International Space Station where they served as members of the Expedition 26 and 27 crews. Photo Credit: (NASA/Bill Ingalls)

  9. Preclinical and Clinical Data for Factor Xa and “Universal” Reversal Agents

    PubMed Central

    Milling, Truman J.; Kaatz, Scott

    2017-01-01

    Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitor–associated major hemorrhage. PMID:27575436

  10. Minitrack on data and knowledge base issues in genomics at the 27th Hawaii International Conference on system sciences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-05-01

    This report is a summary of the proceedings from the Minitrack on Data and Knowledge Base Issues in Genomics at the 27th Hawaii International Conference on System Science, January 4 - 7, 1994. The minitrack was organized by Dong-Guk Shin (University of Connecticut) and Francois Rechenmann (INRIA, France). Support was jointly provided by the NSF, NIH and DOE. The minitrack included, after rigorous review, ten full papers and four extended abstracts in the following five different research subareas of genome informatics: data modeling and management, sequence analysis, graphical user interface, interoperation in a heterogenous computing environment, and system integration inmore » a knowledge-based approach.« less

  11. Direct thrombin and factor Xa inhibition for stroke prevention in patients with atrial fibrillation.

    PubMed

    Galanis, Taki; Merli, Geno J

    2013-02-01

    Nonvalvular atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia occurring in patients in the United States. The primary clinical consequence of AF is an increase in the risk and severity of strokes. Treatment guidelines recommend anticoagulation therapy for most patients with AF. One risk-stratification scheme, the CHADS2 index, is simple and widely used to determine the management of patients with AF in regard to stroke prevention. However, new schemes, such as CHA2DS2-VASc, further refine risk stratification to identify patients who would obtain a net clinical benefit from a particular management strategy, thus improving the quality of management. For patients with AF for whom oral anticoagulation (OAC) is advisable, vitamin K antagonist (VKA) therapy is well established and effective. However, OAC with VKAs presents challenges to prescribers and patients in maintaining therapeutic efficacy. Novel OACs may offer alternatives to VKAs. Dabigatran etexilate, a direct thrombin inhibitor, was approved by the US Food and Drug Administration (FDA) in 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. The activated factor X (factor Xa) inhibitor rivaroxaban was recently approved by the FDA both for prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip arthroplasty, and for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. Apixaban, another factor Xa inhibitor, was recently shown to be effective for stroke prevention in patients with nonvalvular AF. This article reviews clinical considerations regarding new agents that may offer alternatives to VKA therapy for the prevention of stroke in patients with AF.

  12. Chemical Analysis of a Carbon-enhanced Very Metal-poor Star: CD-27 14351

    NASA Astrophysics Data System (ADS)

    Karinkuzhi, Drisya; Goswami, Aruna; Masseron, Thomas

    2017-01-01

    We present, for the first time, an abundance analysis of a very metal-poor carbon-enhanced star CD-27 14351 based on a high-resolution (R ˜ 48,000) FEROS spectrum. Our abundance analysis performed using local thermodynamic equilibrium model atmospheres shows that the object is a cool star with stellar atmospheric parameters, effective temperature Teff = 4335 K, surface gravity log g = 0.5, microturbulence ξ = 2.42 km s-1, and metallicity [Fe/H] = -2.6. The star exhibits high carbon and nitrogen abundances with [C/Fe] = 2.89 and [N/Fe] = 1.89. Overabundances of neutron-capture elements are evident in Ba, La, Ce, and Nd, with estimated [X/Fe] > 1, the largest enhancement being seen in Ce with [Ce/Fe] = 2.63. While the first peak s-process elements Sr and Y are found to be enhanced with respect to Fe, ([Sr/Fe] = 1.73 and [Y/Fe] = 1.91), the third peak s-process element Pb could not be detected in our spectrum at the given resolution. Europium, primarily an r-process element also shows an enhancement with [Eu/Fe] = 1.65. With [Ba/Eu] = 0.12, the object CD-27 14351 satisfies the classification criterion for a CEMP-r/s star. The elemental abundance distributions observed in this star are discussed in light of the chemical abundances observed in other CEMP stars in the literature.

  13. Protection by Flavanol-Rich Foods Against Vascular Dysfunction and Oxidative Damage: 27th Hohenheim Consensus Conference1

    PubMed Central

    Sies, Helmut; Hollman, Peter C.H.; Grune, Tilman; Stahl, Wilhelm; Biesalski, Hans K.; Williamson, Gary

    2012-01-01

    Criteria for assessing the purported protection by flavanol-rich foods against vascular dysfunction and oxidative damage to biomolecules was the subject of the 27th Hohenheim Consensus Conference held on July 11, 2011. State-of-the-art evidence was put into perspective, focusing on several questions that were followed by a consensus answer. Among the topics addressed were the major sources of flavanols in the human diet, the bioavailability of flavanols, biomarkers for “health benefit,” and the biological function of flavanols. Consensus was reached on these topics. No conclusion was reached on the design of randomized, controlled trials for substantiation of health claims for flavanol-rich foods as to the necessity of a study arm with an isolated pharmacologically active compound, e.g., (−)-epicatechin. PMID:22516731

  14. Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

    PubMed

    Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2017-11-01

    Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 13th International Conference on Chlamydomonas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Silflow, Carolyn D.

    2014-03-11

    The 13th International Conference on Chlamydomonas (EMBO Workshop on the Cell and Molecular Biology of Chlamydomonas) was held May 27 to June 1, 2008 in Hyeres, France. The conference was the biennial meeting for all researchers studying the green algal systems Chlamydomonas and Volvox. The conference brought together approximately 200 investigators from around the world (North America, Asia, Europe and Australia) representing different fields and disciplines (cell biology, genetics, biochemistry, biophysics, plant physiology, genomics). It provided an opportunity for investigators from different countries to share methodologies and to discuss recent results with a focus on the Chlamydomonas experimental system.

  16. Enhanced light emission near 2.7 μm from Er-Nd co-doped germanate glass

    NASA Astrophysics Data System (ADS)

    Bai, Gongxun; Tao, Lili; Li, Kefeng; Hu, Lili; Tsang, Yuen Hong

    2013-04-01

    Laser glass gain medium that can convert low cost 808 nm diode laser into 2.7 μm has attracted considerable interest due to its potential application for medical surgery fiber laser system. In this study, enhanced 2.7 μm emission has been achieved in Er3+:germanate glass by co-doping with Nd3+ ions under the excitation of an 808 nm diode laser. In the co-doped sample, the experimental results show that the harmful visible emissions via up-conversion were effectively restricted. The reduction of 1.5 μm emission was also detected in the co-doped sample, which indicates significant de-excitation of 4I13/2 Er3+ ion through energy transfer and non-radiative decay in Nd3+ ions. In conclusion, the 2.7 μm emission enhancement achieved was due to the increased optical absorption of 808 nm, efficient energy transfer (ET) with efficiency of 81.73% between Er3+ and Nd3+ ions, and shortening the lifetime of the lower lasing level 4I13/2 Er3+ in the co-doped sample. Therefore, Er3+/Nd3+ co-doped germanate glass could be used to fabricate fiber optical gain media for 2.7 μm laser generation.

  17. p27(kip1) Knockout enhances collateralization in response to hindlimb ischemia.

    PubMed

    Ankri-Eliahoo, Galit; Weitz, Kevin; Cox, Timothy C; Tang, Gale L

    2016-05-01

    ± 6%; P < .05) and caused more gel contraction (18% ± 5% of the initial area vs 43% ± 4%; P < .05) than wt cells. Migration and collagen contraction were abolished in p27(-/-) and wt cells by MMP inhibition. p27(-/-) cells expressed significantly more MMP-2 mRNA than wt cells did. Knockout of p27 enhances arterial collateralization in response to hindlimb ischemia through enlargement of a new collateral pathway. In vitro, knockout of p27 increases collagen gel contraction in addition to stimulating VSMC migration. We speculate that p27 may affect collateralization through its role in regulating MMP-2 expression. Published by Elsevier Inc.

  18. NATIONAL CONFERENCE ON URBAN STORM WATER: ENHANCING PROGRAMS AT THE LOCAL LEVEL - PROCEEDINGS CHICAGO, IL FEBRUARY 17-20, 2003

    EPA Science Inventory

    A wide array of effective storm water management and resource protection tools have been developed for urban environments, but their implementation continues to be hampered by a lack of technology transfer opportunities. At the national conference Urban Storm Water: Enhancing Pro...

  19. Expedition 27 Docking

    NASA Image and Video Library

    2011-04-06

    Top officials from the Russian Federal Space Agency and NASA hold a Soyuz post-docking press conference at the Russian Mission Control Center in Korolev, Russia on Thursday, April 7, 2011. The Soyuz TMA-21 docked to the International Space Station carrying Expedition 27 Soyuz Commander Alexander Samokutyaev, NASA Flight Engineer Ron Garan and Russian Flight Engineer Andrey Borisenko. Photo Credit: (NASA/Carla Cioffi)

  20. Between Grownups & Kids: Conference Proceedings (Austin, Texas, August 27, 1977).

    ERIC Educational Resources Information Center

    Evans, Joyce, Comp.

    Presented are proceedings of a conference designed to increase awareness, knowledge, and feelings of competency of adults who work with children, with particular emphasis on the positive aspects of child rearing and practical suggestions for daily activities and interactions. In the keynote address titled "How to Drive Your Child Sane," A. Ginott…

  1. The Science of Enhanced Student Engagement and Employability: Introducing the Psychology Stream of the Inaugural HEA STEM Conference

    ERIC Educational Resources Information Center

    Hulme, Julie; Taylor, Jacqui; Davies, Mark N. O.; Banister, Peter

    2012-01-01

    The Higher Education Academy (HEA) is committed to enhancing the quality of learning and teaching for all university students in the UK, and the inaugural conference for the Science, Technology, Engineering and Mathematics (STEM) subjects, held in April 2012 at Imperial College, London, aimed to showcase research and evidence-based educational…

  2. The Conference Facilitator Model: Improving the Value of Conference Attendance for Attendees and the Organization.

    PubMed

    Nebrig, Dawn; Munafo, Jennifer; Goddard, Julie; Tierney, Carol

    2015-09-01

    Healthcare leaders face a multitude of priorities demanding their attention and resources, from patient, employee safety and hospital-acquired conditions to predicting future revenue in the context of healthcare reform. Assessing value requires balancing outcomes and experience with cost. How does allocating funds for professional nursing conferences measure up? What is a valid return on investment when we send staff nurses to professional conferences, specifically the annual Magnet® conference? The following article describes how Cincinnati Children's Hospital Medical Center answered these questions and redefined the expectations for conference attendees while enhancing the experience and the reportable outcomes for practice and the organization.

  3. Mutations Enhancing Amino Acid Catabolism Confer a Growth Advantage in Stationary Phase

    PubMed Central

    Zinser, Erik R.; Kolter, Roberto

    1999-01-01

    Starved cultures of Escherichia coli undergo successive rounds of population takeovers by mutants of increasing fitness. These mutants express the growth advantage in stationary phase (GASP) phenotype. Previous work identified the rpoS819 allele as a GASP mutation allowing cells to take over stationary-phase cultures after growth in rich media (M. M. Zambrano, D. A. Siegele, M. A. Almirón, A. Tormo, and R. Kolter, Science 259:1757–1760, 1993). Here we have identified three new GASP loci from an aged rpoS819 strain: sgaA, sgaB, and sgaC. Each locus is capable of conferring GASP on the rpoS819 parent, and they can provide successively higher fitnesses for the bacteria in the starved cultures. All four GASP mutations isolated thus far allow for faster growth on both individual and mixtures of amino acids. Each mutation confers a growth advantage on a different subset of amino acids, and these mutations act in concert to increase the overall catabolic capacity of the cell. We present a model whereby this enhanced ability to catabolize amino acids is responsible for the fitness gain during carbon starvation, as it may allow GASP mutants to outcompete the parental cells when growing on the amino acids released by dying cells. PMID:10482523

  4. Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine--induced immunity.

    PubMed

    He, Yong; Manischewitz, Jody; Meseda, Clement A; Merchlinsky, Michael; Vassell, Russell A; Sirota, Lev; Berkower, Ira; Golding, Hana; Weiss, Carol D

    2007-10-01

    The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27.

  5. The emergence of factor Xa inhibitors for the treatment of cardiovascular diseases: a patent review.

    PubMed

    Pinto, Donald J P; Qiao, Jennifer X; Knabb, Robert M

    2012-06-01

    Factor Xa (FXa) is a critical enzyme in the coagulation cascade responsible for thrombin generation, the final enzyme that leads to fibrin clot formation. Significant success has recently been reported with compounds such as rivaroxaban, apixaban and edoxaban in the treatment and prevention of venous thromboembolism (VTE) and more recently in the prevention of stroke in atrial fibrillation (AF). The success these agents have demonstrated is now being reflected by a narrowing of new FXa patents over the past few years. The new patents appear to be structural modifications of previously published, small molecule inhibitors and bind in a similar manner to the FXa enzyme. SciFinder®, PubMed and Google websites were used as the main source of literature retrieval. Patent searches were conducted in the patent databases: HCAPlus, WPIX and the full text databases (USPAT2, USPATFULL, EPFULL, PCTFULL) using the following keywords: ((FXa) OR (F OR factor) (W) (Xa)) (S) (inhibit? or block? or modulat? or antagonist? or regulat?). The search was restricted to patent documents with the entry date on or after 1 January 2009. Literature and information related to clinical development was retrieved from Thomson Reuter's Pharma. A large body of Phase II and Phase III data is now available for FXa inhibitors such as rivaroxaban, apixaban, edoxaban and betrixaban. The clinical data demonstrate favorable benefit-risk profiles compared with the standards of care for short- and long-term anticoagulation (i.e., low molecular weight heparins (LMWHs) and wafarin). The potential exists that these agents will eventually be the agents of choice for the treatment of a host of cardiovascular disease states, offering improved efficacy, safety, and ease of use compared with existing anticoagulants.

  6. Proceedings of the Ninth Biennial Southern Silvicultural Research Conference

    Treesearch

    Thomas A. Waldrop; [Editor

    1998-01-01

    The Ninth Biennial Southern Silvicultural Research Conference was held February 25-27, 1997 on the campus of Clemson University in Clemson, SC. This conference was the latest in a series of meetings designed to provide a forum for the exchange of research information among silviculturists and researchers in related areas, research coordination, review of research in...

  7. At-line nanofractionation with parallel mass spectrometry and bioactivity assessment for the rapid screening of thrombin and factor Xa inhibitors in snake venoms.

    PubMed

    Mladic, Marija; Zietek, Barbara M; Iyer, Janaki Krishnamoorthy; Hermarij, Philip; Niessen, Wilfried M A; Somsen, Govert W; Kini, R Manjunatha; Kool, Jeroen

    2016-02-01

    Snake venoms comprise complex mixtures of peptides and proteins causing modulation of diverse physiological functions upon envenomation of the prey organism. The components of snake venoms are studied as research tools and as potential drug candidates. However, the bioactivity determination with subsequent identification and purification of the bioactive compounds is a demanding and often laborious effort involving different analytical and pharmacological techniques. This study describes the development and optimization of an integrated analytical approach for activity profiling and identification of venom constituents targeting the cardiovascular system, thrombin and factor Xa enzymes in particular. The approach developed encompasses reversed-phase liquid chromatography (RPLC) analysis of a crude snake venom with parallel mass spectrometry (MS) and bioactivity analysis. The analytical and pharmacological part in this approach are linked using at-line nanofractionation. This implies that the bioactivity is assessed after high-resolution nanofractionation (6 s/well) onto high-density 384-well microtiter plates and subsequent freeze drying of the plates. The nanofractionation and bioassay conditions were optimized for maintaining LC resolution and achieving good bioassay sensitivity. The developed integrated analytical approach was successfully applied for the fast screening of snake venoms for compounds affecting thrombin and factor Xa activity. Parallel accurate MS measurements provided correlation of observed bioactivity to peptide/protein masses. This resulted in identification of a few interesting peptides with activity towards the drug target factor Xa from a screening campaign involving venoms of 39 snake species. Besides this, many positive protease activity peaks were observed in most venoms analysed. These protease fingerprint chromatograms were found to be similar for evolutionary closely related species and as such might serve as generic snake protease

  8. Expedition 40 Press Conference

    NASA Image and Video Library

    2014-05-27

    A man taking a picture with a cell phone is seen reflected in the glass separating the quarantined crew during a press conference on Tuesday, May 27, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission to the International Space Station is set to launch May 29 from the Baikonur Cosmodrome. Photo Credit: (NASA/Joel Kowsky)

  9. Major Conference about Astronomical Technology in Munich

    NASA Astrophysics Data System (ADS)

    2000-03-01

    Press Conference on Monday, March 27, 2000 Which are the latest astronomical discoveries made with the new 8-10 metre class astronomical telescopes? Will it be possible to construct even more powerful instruments on the ground and in space to explore the near and distant Universe at all wavelengths from gamma-rays to radio waves? Which research areas in this dynamical science are likely to achieve break-throughs with emerging new technologies? These are some of the central themes that will be discussed by more than 600 specialists from all over the world at an international conference in Munich (Germany), "Astronomical Telescopes and Instruments 2000" , beginning on Monday, March 27, 2000. During five days, the modern architecture of the new International Congress Center in the Bavarian capital will be the scene of lively exchanges about recent progress at the world's top-class astronomical research facilities and the presentation of inspired new ideas about future technological opportunities. The conference will be accompanied by numerous on-site exhibition stands by the major industries and research organisations in this wide field. This meeting is the latest in a series, organised every second year, alternatively in the USA and Europe by the International Society for Optical Engineering (SPIE) , this year with the European Southern Observatory (ESO) as co-sponsor and host institution. The conference will be opened in the morning of March 27 by the Bavarian Minister of Science, Research and Arts, Hans Zehetmair . His address will be followed by keynote speeches by Massimo Tarenghi (European Southern Observatory), James B. Breckenridge (National Science Foundation, USA), Harvey Butcher (Netherlands Foundation for Research in Astronomy) and Albrecht Ruediger (Max Planck Institut für Quantenoptik, Germany). The conference is subtitled "Power Telescopes and Instrumentation into the New Millennium" and will be attended by leading scientists and engineers from all

  10. Expedition 27 Docking

    NASA Image and Video Library

    2011-04-06

    Russian Federal Space Agency Director of Human Space Flight, Alexey Krasnov, third from right, answers reporter’s questions during a Soyuz post-docking press conference at the Russian Mission Control Center in Korolev, Russia on Thursday, April 7, 2011. The Soyuz TMA-21 docked to the International Space Station carrying Expedition 27 Soyuz Commander Alexander Samokutyaev, NASA Flight Engineer Ron Garan and Russian Flight Engineer Andrey Borisenko. Photo Credit: (NASA/Carla Cioffi)

  11. Energy Technology Training Conference Proceedings (Atlanta, Georgia, October 27-29, 1976).

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Conference goals included identifying projected technical manpower needs and skill mix requirements, potential obstacles to developing an adequate technical education base, and stimulating education, industry, and labor cooperation in technical program development and federal interagency coordination and cooperation. Findings of the conference…

  12. Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants.

    PubMed

    Vigani, Gianpiero; Rolli, Eleonora; Marasco, Ramona; Dell'Orto, Marta; Michoud, Grégoire; Soussi, Asma; Raddadi, Noura; Borin, Sara; Sorlini, Claudia; Zocchi, Graziano; Daffonchio, Daniele

    2018-05-22

    It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H + -ATPase (V-ATPase) and H + -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H + -ATPase (V-ATPase) and H + -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. IL-27 regulates the adherence, proliferation, and migration of MSCs and enhances their regulatory effects on Th1 and Th2 subset generations.

    PubMed

    Xu, Fenghuang; Yi, Junzhu; Wang, Zhuoya; Hu, Yejia; Han, Chunlei; Xue, Qun; Zhang, Xueguang; Luan, Xiying

    2017-08-01

    Interleukin 27 (IL-27) regulates T cell function and is involved in inflammation. It has been reported that human placenta-derived mesenchymal stromal cells (hPMSCs) can inhibit T cell responses and attenuate inflammation reactions. However, it is unclear whether IL-27 can regulate hPMSC function. Here, we examined the effects of IL-27 upon adherence, migration, and proliferation as well as the immunomodulatory effects of hPMSCs. The results show that IL-27 receptor α chain (IL-27Rα) is expressed in hPMSCs. IL-27 at 30 ng/ml inhibited hPMSC adherence and proliferation, while the migration of hPMSCs was promoted with IL-27 at doses of 20 or 30 ng/ml, as determined with use of real-time cell analysis (RTCA). Moreover, IL-27 promoted regulatory effects of hPMSCs through enhancing Th2 and suppressing Th1 subset generation from activated T cells in human peripheral blood. IL-27 also enhanced the ability of hPMSCs to secrete IL-10 from CD4 + T cells through increased expression levels of the programmed death ligand 1 (PDL1) in hPMSCs via the Janus kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway. In conclusion, IL-27 has significant modulatory effects on adherence, proliferation, and migration of hPMSCs. IL-27 increased PDL1 expression levels in hPMSCs via the JAK/STAT1 pathway, which then enhanced the regulatory effects of hPMSCs upon Th1 and Th2 cell generations and IL-10 secretion from CD4 + T cells.

  14. Seventh Copper Mountain Conference on Multigrid Methods. Part 2

    NASA Technical Reports Server (NTRS)

    Melson, N. Duane (Editor); Manteuffel, Tom A. (Editor); McCormick, Steve F. (Editor); Douglas, Craig C. (Editor)

    1996-01-01

    The Seventh Copper Mountain Conference on Multigrid Methods was held on April 2-7, 1995 at Copper Mountain, Colorado. This book is a collection of many of the papers presented at the conference and so represents the conference proceedings. NASA Langley graciously provided printing of this document so that all of the papers could be presented in a single forum. Each paper was reviewed by a member of the conference organizing committee under the coordination of the editors. The vibrancy and diversity in this field are amply expressed in these important papers, and the collection clearly shows the continuing rapid growth of the use of multigrid acceleration techniques.

  15. Anti-Xa activity in apixaban overdose: a case report.

    PubMed

    Barton, James; Wong, Anselm; Graudins, Andis

    2016-11-01

    Apixaban is a novel oral anticoagulation agent that exerts its effect through direct factor Xa inhibition. We present a case of multi-drug overdose including apixaban with associated apixaban concentrations. A 53 year-old man presented to our metropolitan hospital following a deliberate self-poisoning with 200 mg apixaban, 35 mg ramipril, 105 mg bisoprolol, 280 mg atorvastatin, 6 mg colchicine, 37.4 mg magnesium, 4 × 500 mg paracetamol/9.5 mg codeine/5 mg phenylephrine and alcohol. He developed hypotension that was treated with noradrenaline. His initial and peak apixaban concentration was 1022.6 ng/ml and was associated with only minor bleeding from his femoral central line insertion site, which improved with local compression. Vitamin K 10 mg (at 9 h post-ingestion) and Prothrombinex-VF 2000 units (at 13 h post-ingestion) were also administered without any observed effect on coagulation studies. Apixaban elimination appeared to display first-order kinetics with an elimination half-life of 7.4 h. His plasma apixaban concentration was within the therapeutic dose range 10 h post-ingestion and he recovered uneventfully. A case of apixaban overdose with associated apixaban concentrations is presented. There was rapid resolution of anticoagulation with no demonstrable benefit of currently available clotting factor replacement.

  16. 2010 CATALYSIS GORDON RESEARCH CONFERENCE, JUNE 27 - JULY 2, 2010, NEW LONDON, NEW HAMPSHIRE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abhaya Datye

    2010-07-02

    Catalysis is a key technology for improving the quality of life while simultaneously reducing the adverse impact of human activities on the environment. The discovery of new catalytic processes and the improvement of existing ones are also critically important for securing the nation's energy supply. The GRC on Catalysis is considered one the most prestigious conference for catalysis research, bringing together leading researchers from both academia, industry and national labs to discuss the latest, most exciting research in catalysis and the future directions for the field. The 2010 GRC on Catalysis will follow time-honored traditions and feature invited talks frommore » the world's leading experts in the fundamentals and applications of catalytic science and technology. We plan to have increased participation from industry. The extended discussions in the company of outstanding thinkers will stimulate and foster new science. The conference will include talks in the following areas: Alternative feedstocks for chemicals and fuels, Imaging and spectroscopy, Design of novel catalysts, Catalyst preparation fundamentals, Molecular insights through theory, Surface Science, Catalyst stability and dynamics. In 2010, the Catalysis conference will move to a larger conference room with a new poster session area that will allow 40 posters per session. The dorm rooms provide single and double accommodations, free WiFi and the registration fee includes all meals and the famous lobster dinner on Thursday night. Afternoons are open to enjoy the New England ambiance with opportunities for hiking, sailing, golf and tennis to create an outstanding conference that will help you network with colleagues, and make long lasting connections.« less

  17. Adult Literacy & Technology National Conference (Pittsburgh, Pennsylvania, July 27-31, 1988).

    ERIC Educational Resources Information Center

    Pennsylvania State Univ., University Park. Inst. for the Study of Adult Literacy.

    This document provides advance information on the symposia, workshops, and presentations of a conference the purpose of which was to teach about new techniques and methodologies for applying technology as a solution to adult illiteracy. Brief summaries are provided of the content of the symposia, workshops, and presentations. Representative topics…

  18. Impact damage resistance of carbon/epoxy composite tubes for the DC-XA liquid hydrogen feedline

    NASA Technical Reports Server (NTRS)

    Nettles, A. T.

    1995-01-01

    Low-velocity impacts were inflicted upon two elbow sections of carbon/epoxy feedline that are to be a part of the Delta Clipper-XA flight vehicle. A soap-based liquid leak detector solution was used to inspect the impact sites for leaks of pressurized gas that was pumped into the tube. Visual surface damage was noted and recorded for each impact site. After impact testing of each of the two sections of tubes was completed, the damage zones were disected from the tube and cross sectioned through the impact site. These specimens were polished after potting them in epoxy and were examined for microcracking using a fluorescent dye penetrant technique. The results showed that nonvisible damage could cause microcracking, thereby resulting in leaks through the tube wall.

  19. Preclinical and clinical data for factor Xa and “universal” reversal agents☆,☆☆,★

    PubMed Central

    Milling, Truman J.; Kaatz, Scott

    2017-01-01

    Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoymolecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitoreassociated major hemorrhage. PMID:27697443

  20. Fifth International Conference on High Energy Density Physics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beg, Farhat

    The Fifth International Conference on High Energy Density Physics (ICHED 2015) was held in the Catamaran Hotel in San Diego from August 23-27, 2015. This meeting was the fifth in a series which began in 2008 in conjunction with the April meeting of the American Physical Society (APS). The main goal of this conference has been to bring together researchers from all fields of High Energy Density Science (HEDS) into one, unified meeting.

  1. Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

    PubMed

    Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

    2017-01-01

    The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

  2. Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

    PubMed Central

    Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

    2017-01-01

    The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension. PMID:28507519

  3. MAb 806 Enhances the Efficacy of Ionizing Radiation in Glioma Xenografts Expressing the de2-7 Epidermal Growth Factor Receptor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johns, Terrance G.; McKay, Michael J.; Cvrljevic, Anna N.

    2010-10-01

    Purpose: Mutations of the epidermal growth factor receptor (EGFR) are common in glioma. The most frequent mutation, de2-7 EGFR/EGFRvIII, occurs in approximately 40% of high-grade gliomas and confers resistance to ionizing radiation (IR). We have previously shown that mAb 806, a novel EGFR-specific antibody, is able to inhibit the growth of U87MG.{Delta}2-7 glioma xenografts expressing the de2-7 EGFR and may have potential as a therapeutic. Methods and Materials: Nude mice bearing U87MG.{Delta}2-7 xenografts were treated with mAb 806 and/or IR. Comparison of tumor volumes, the effect of treatment on angiogenesis as determined by mean vessel density, and expression changes inmore » prosurvival protein pAkt between treatment groups were undertaken. Results: Treatment of mice bearing U87MG.{Delta}2-7 xenografts with mAb 806 and IR resulted in schedule-dependent radiosensitization. Maximal benefit was obtained when antibody treatment was given before irradiation, with the greatest inhibition of both tumor angiogenesis and tumor growth. Combination treatment mediated radiosensitization by selectively blocking the phosphorylation of the prosurvival protein Akt at serine 473, a process that is independent of DNA-dependent protein kinase catalytic subunit. Conclusions: Our results provide a rationale for the use of mAb 806 in combination with IR for the treatment of glioma and potentially other solid tumors bearing the de2-7 EGFR.« less

  4. 10th international conference on high-occupancy vehicle systems : compendium of technical papers

    DOT National Transportation Integrated Search

    2001-08-01

    This report provides the technical papers submitted as part of the 10th International High-Occupancy Vehicle (HOV) Systems Conference held in Dallas, Texas on August 27-30, 2000. The Conference was sponsored by the Transportation Research Board (TRB)...

  5. Transgenic tobacco expressing Pinellia ternata agglutinin confers enhanced resistance to aphids.

    PubMed

    Yao, Jianhong; Pang, Yongzhen; Qi, Huaxiong; Wan, Bingliang; Zhao, Xiuyun; Kong, Weiwen; Sun, Xiaofen; Tang, Kexuan

    2003-12-01

    Tobacco leaf discs were transformed with a plasmid, pBIPTA, containing the selectable marker neomycin phosphotransferase gene (nptII) and Pinellia ternata agglutinin gene (pta) via Agrobacterium tumefaciens-mediated transformation. Thirty-two independent transgenic tobacco plants were regenerated. PCR and Southern blot analyses confirmed that the pta gene had integrated into the plant genome and northern blot analysis revealed transgene expression at various levels in transgenic plants. Genetic analysis confirmed Mendelian segregation of the transgene in T1 progeny. Insect bioassays showed that transgenic plants expressing PTA inhibited significantly the growth of peach potato aphid (Myzus persicae Sulzer). This is the first report that transgenic plants expressing pta confer enhanced resistance to aphids. Our study indicates that the pta gene can be used as a supplement to the snowdrop (Galanthus nivalis) lectin gene (gna) in the control of aphids, a sap-sucking insect pest causing significant yield losses of crops.

  6. Seventh Copper Mountain Conference on Multigrid Methods. Part 1

    NASA Technical Reports Server (NTRS)

    Melson, N. Duane; Manteuffel, Tom A.; McCormick, Steve F.; Douglas, Craig C.

    1996-01-01

    The Seventh Copper Mountain Conference on Multigrid Methods was held on 2-7 Apr. 1995 at Copper Mountain, Colorado. This book is a collection of many of the papers presented at the conference and so represents the conference proceedings. NASA Langley graciously provided printing of this document so that all of the papers could be presented in a single forum. Each paper was reviewed by a member of the conference organizing committee under the coordination of the editors. The multigrid discipline continues to expand and mature, as is evident from these proceedings. The vibrancy in this field is amply expressed in these important papers, and the collection shows its rapid trend to further diversity and depth.

  7. Lack of tyrosine 320 impairs spontaneous endocytosis and enhances release of HLA-B27 molecules.

    PubMed

    Santos, Susana G; Antoniou, Antony N; Sampaio, Paula; Powis, Simon J; Arosa, Fernando A

    2006-03-01

    Several lines of evidence suggest that endocytosis of MHC class I molecules requires conserved motifs within the cytoplasmic domain. In this study, we show, in the C58 rat thymoma cell line transfected with HLA-B27 molecules, that replacement of the highly conserved tyrosine (Tyr320) in the cytoplasmic domain of HLA-B27 does not hamper cell surface expression of beta2-microglobulin H chain heterodimers or formation of misfolded molecules. However, Tyr320 replacement markedly impairs spontaneous endocytosis of HLA-B27. Although wild-type molecules are mostly internalized via endosomal compartments, Tyr320-mutated molecules remain at the plasma membrane in which partial colocalization with endogenous transferrin receptors can be observed, also impairing their endocytosis. Finally, we show that Tyr320 substitution enhances release of cleaved forms of HLA-B27 from the cell surface. These studies show for the first time that Tyr320 is most likely part of a cytoplasmic sorting motif involved in spontaneous endocytosis and shedding of MHC class I molecules.

  8. Tensile properties of HK31XA-H24 magnesium-alloy sheet under rapid-heating conditions and constant elevated temperatures

    NASA Technical Reports Server (NTRS)

    Gibbs, Thomas W

    1956-01-01

    Specimens of HK31XA-H24 magnesium-alloy sheet from an experimental batch were heated to failure at nominal temperature rates from 0.2 F to 100 F per second under constant-load conditions. Rapid-heating yield and rupture stresses are presented and compared with the yield and ultimate stresses from elevated-temperature tensile stress-strain tests for 1/2-hour exposure. Linear temperature-rate parameters were used to correlate rapid-heating results by constructing master curves which can be used for predicting yield stresses and temperatures and for estimating rupture stresses and temperatures.

  9. Proceedings of the International Association for Development of the Information Society (IADIS) International Conference on Cognition and Exploratory Learning in the Digital Age (CELDA) (11th, Porto, Portugal, October 25-27, 2014)

    ERIC Educational Resources Information Center

    Sampson, Demetrios G., Ed.; Spector, J. Michael, Ed.; Ifenthaler, Dirk, Ed.; Isaias, Pedro, Ed.

    2014-01-01

    These proceedings contain the papers of the 11th International Conference on Cognition and Exploratory Learning in the Digital Age (CELDA 2014), October 25-27, 2014, which has been organized by the International Association for Development of the Information Society (IADIS) and endorsed by the Japanese Society for Information and Systems in…

  10. Report of Conference of New Manpower Researchers (September 26-27, 1968).

    ERIC Educational Resources Information Center

    National Manpower Policy Task Force, Washington, DC.

    The second annual Conference of New Manpower Researchers was held to: (1) provide an opportunity for new researchers to meet and establish contact with other professionals in the field and to exchange ideas and information, (2) aid new researchers by allowing them to present their work to their peers and senior manpower people, and (3) permit the…

  11. 2009 TOXICOLOGY AND RISK ASSESSMENT CONFERENCE

    EPA Science Inventory

    EPA has announced

    The 2009 Toxicology and Risk Assessment Conference
    Cincinnati Marriott North, West Chester (Cincinnati), OH
    April 27-30, 2009 - Click to register!

    The Annual Toxicology and Risk Ass...

  12. Teaching Games for Understanding Conference Supplement from the German Sport University

    ERIC Educational Resources Information Center

    Research Quarterly for Exercise and Sport, 2016

    2016-01-01

    By bringing together the national German sports game community and an international scientific community in a joint conference, the 6th International Teaching Games for Understanding Conference (TGfU) Meets the 10th German Sports Games Symposium of the German Association of Sport Science (DVS), held July 25-27, 2016, at the German Sport University…

  13. CHEMICAL ANALYSIS OF A CARBON-ENHANCED VERY METAL-POOR STAR: CD-27 14351

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karinkuzhi, Drisya; Goswami, Aruna; Masseron, Thomas

    2017-01-01

    We present, for the first time, an abundance analysis of a very metal-poor carbon-enhanced star CD-27 14351 based on a high-resolution ( R  ∼ 48,000) FEROS spectrum. Our abundance analysis performed using local thermodynamic equilibrium model atmospheres shows that the object is a cool star with stellar atmospheric parameters, effective temperature T {sub eff} = 4335 K, surface gravity log g  = 0.5, microturbulence ξ  = 2.42 km s{sup −1}, and metallicity [Fe/H] = −2.6. The star exhibits high carbon and nitrogen abundances with [C/Fe] = 2.89 and [N/Fe] = 1.89. Overabundances of neutron-capture elements are evident in Ba, La, Ce, and Nd, with estimated [X/Fe] > 1, the largest enhancementmore » being seen in Ce with [Ce/Fe] = 2.63. While the first peak s -process elements Sr and Y are found to be enhanced with respect to Fe, ([Sr/Fe] = 1.73 and [Y/Fe] = 1.91), the third peak s -process element Pb could not be detected in our spectrum at the given resolution. Europium, primarily an r -process element also shows an enhancement with [Eu/Fe] = 1.65. With [Ba/Eu] = 0.12, the object CD-27 14351 satisfies the classification criterion for a CEMP-r/s star. The elemental abundance distributions observed in this star are discussed in light of the chemical abundances observed in other CEMP stars in the literature.« less

  14. Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding.

    PubMed

    Pannucci, Christopher J; Fleming, Kory I; Momeni, Arash; Prazak, Ann Marie; Agarwal, Jayant; Rockwell, W Bradford

    2018-06-01

    Low anti-factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti-factor Xa level, postoperative venous thromboembolism, and bleeding. Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti-factor Xa levels, which quantify enoxaparin's antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified. The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti-factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti-factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti-factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation. When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti-factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti-factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients. Therapeutic, IV.

  15. Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses.

    PubMed

    Schwessinger, Benjamin; Bahar, Ofir; Thomas, Nicholas; Thomas, Nicolas; Holton, Nicolas; Nekrasov, Vladimir; Ruan, Deling; Canlas, Patrick E; Daudi, Arsalan; Petzold, Christopher J; Singan, Vasanth R; Kuo, Rita; Chovatia, Mansi; Daum, Christopher; Heazlewood, Joshua L; Zipfel, Cyril; Ronald, Pamela C

    2015-03-01

    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components.

  16. Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

    DOE PAGES

    Schwessinger, Benjamin; Bahar, Ofir; Thomas, Nicolas; ...

    2015-03-30

    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistancemore » to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components.« less

  17. Transgenic Expression of the Dicotyledonous Pattern Recognition Receptor EFR in Rice Leads to Ligand-Dependent Activation of Defense Responses

    PubMed Central

    Thomas, Nicolas; Holton, Nicolas; Nekrasov, Vladimir; Ruan, Deling; Canlas, Patrick E.; Daudi, Arsalan; Petzold, Christopher J.; Singan, Vasanth R.; Kuo, Rita; Chovatia, Mansi; Daum, Christopher; Heazlewood, Joshua L.; Zipfel, Cyril; Ronald, Pamela C.

    2015-01-01

    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components. PMID:25821973

  18. Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schwessinger, Benjamin; Bahar, Ofir; Thomas, Nicolas

    Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistancemore » to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components.« less

  19. 77 FR 28375 - Dixie Pipeline Company LLC; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-14

    ....1.0.\\1\\ The technical conference will address the issues raised by the protesters in the proceeding and the issues discussed by the Commission in P 19 of the April 27, 2012 order concerning the effect... conference on Wednesday, May 30, 2012, at 9:00 a.m. (EDT), in a room to be designated at the offices of the...

  20. Inactivation of p27kip1 Promoted Nonspecific Inflammation by Enhancing Macrophage Proliferation in Islet Transplantation.

    PubMed

    Li, Yang; Ding, Xiaoming; Fan, Ping; Guo, Jian; Tian, Xiaohui; Feng, Xinshun; Zheng, Jin; Tian, Puxun; Ding, Chenguang; Xue, Wujun

    2016-11-01

    Islet transplantation suffers from low efficiency caused by nonspecific inflammation-induced graft loss after transplantation. This study reports increased islet loss and enhanced inflammatory response in p27-deficient mice (p27-/-) and proposes a possible mechanism. Compared with wild type, p27-/- mice showed more severe functional injury of islet, with increased serum levels of inflammatory cytokines IL-1 and TNF-α, inducing macrophage proliferation. Furthermore, the increased number, proapoptotic proteins, and nuclear factor-kappa b (NF-κB) phosphorylation status of the infiltrating macrophages were accompanied by increased TNF-α mRNA level of islet graft site in p27-/- mice. Moreover, in vitro, we found that macrophages were still activated and cocultured with islet and promoted islet loss even blocking the direct effect of TNF-α on islets. Malondialdehyde (MDA, an end product of lipid peroxidation) in islet and media were increased after cocultured with macrophages. p27 deficiency also increased macrophage proliferation and islet injury. Therefore, p27 inactivation promotes injury islet graft loss via the elevation of proliferation and inflammatory cytokines secretion in infiltrating macrophages which induced nonspecific inflammation independent of TNF-α/nuclear factor-kappa b pathway. This potentially represents a promising therapeutic target in improving islet graft survival.

  1. 27 CFR 447.54 - Administrative procedures inapplicable.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Administrative procedures inapplicable. 447.54 Section 447.54 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO... conferred under section 38, Arms Export Control Act of 1976, as amended, are excluded from the operation of...

  2. Technology for Career Information Delivery. Conference Proceedings.

    ERIC Educational Resources Information Center

    Kimmel, Karen S., Ed.; Blank, Joan C., Ed.

    These proceedings contain 27 papers developed for a conference at which information was provided on currently available and future technological alternatives for delivery of career information. The presentations by staff of State Occupational Information Coordinating Committees, Career Information Delivery Systems, and hardware vendors are grouped…

  3. First International Conference on Laboratory Research for Planetary Atmospheres

    NASA Technical Reports Server (NTRS)

    Fox, Kenneth (Editor); Allen, John E., Jr. (Editor); Stief, Louis J. (Editor); Quillen, Diana T. (Editor)

    1990-01-01

    Proceedings of the First International Conference on Laboratory Research for Planetary Atmospheres are presented. The covered areas of research include: photon spectroscopy, chemical kinetics, thermodynamics, and charged particle interactions. This report contains the 12 invited papers, 27 contributed poster papers, and 5 plenary review papers presented at the conference. A list of attendees and a reprint of the Report of the Subgroup on Strategies for Planetary Atmospheres Exploration (SPASE) are provided in two appendices.

  4. Inhibition of coagulation proteases Xa and IIa decreases ischemia-reperfusion injuries in a preclinical renal transplantation model.

    PubMed

    Tillet, Solenne; Giraud, Sébastien; Kerforne, Thomas; Saint-Yves, Thibaut; Joffrion, Sandrine; Goujon, Jean-Michel; Cau, Jerôme; Mauco, Gérard; Petitou, Maurice; Hauet, Thierry

    2016-12-01

    Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation. Kidneys were clamped for 60 minutes (warm ischemia), then flushed and preserved for 24 hours at 4°C in University of Wisconsin (UW) solution (supplemented or not). EP217609-supplemented UW solution (UW-EP), compared with unfractionated heparin-supplemented UW solution (UW-UFH) or UW alone (UW). A mechanistic investigation was conducted in vitro: addition of EP217609 to endothelial cells during hypoxia at 4°C in the UW solution inhibited thrombin generation during reoxygenation at 37°C in human plasma and reduced tumor necrosis factor alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 messenger RNA cell expressions. In vivo, function recovery was markedly improved in the UW-EP group. Interestingly, levels of thrombin-antithrombin complexes (reflecting thrombin generation) were reduced 60 minutes after reperfusion in the UW-EP group. In addition, 3 months after transplantation, lower fibrosis, epithelial-mesenchymal transition, inflammation, and leukocyte infiltration were observed. Using this new dual anticoagulant, anti-Xa/IIa activity during kidney flush and preservation is protected by reducing thrombin generation at revascularization, improving early function recovery, and decreasing chronic lesions. Such an easy-to-deploy clinical strategy could improve marginal graft outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Determination of rivaroxaban in patient's plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS).

    PubMed

    Derogis, Priscilla Bento Matos; Sanches, Livia Rentas; de Aranda, Valdir Fernandes; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana Caschera Leme; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo Dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos

    2017-01-01

    Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p < 0.001). In addition, we validated hemolytic, icteric or lipemic plasma samples for rivaroxaban measurement by HPLC-MS/MS without interferences. The chromogenic and HPLC-MS/MS methods were highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels.

  6. Teaching of Psychology: Ideas and Innovations. Proceedings of the Conference (Farmingdale, New York, March 27, 1987).

    ERIC Educational Resources Information Center

    Levine, Judith R., Ed.

    These conference proceedings contain 17 presentations covering aspects of undergraduate instruction in psychology. Along with an introduction and conference program, the proceedings present: (1) "Paired Psychology and Reading Course at Medgar Evers," by Gloria G. Loewenthal and Thomas O. Edwards; (2) "Thinking through Psychology and Literature: An…

  7. Proceedings of the Undergraduate Mathematics Teaching Conference (Birmingham, England, September 3-6, 2001).

    ERIC Educational Resources Information Center

    Egerton, Patricia, Ed.

    The 27th Undergraduate Mathematics Teaching Conference took place in September of 2001 at the University of Birmingham. Major topics of the conference included preparing a teaching portfolio, engineering mathematics should be taught by engineers, issues in teaching discrete mathematics, action research, study skills, and issues for web-delivered…

  8. Transit security in the 90's : conference summary

    DOT National Transportation Integrated Search

    1996-10-01

    As a result of the Federal Transit Administration's concern for the potential of terrorist attacks on our Nation's : transit systems, especially in a year when we are hosting the Olympics, a conference was held in Atlanta, Georgia, on : February 27-2...

  9. Proceedings 19th Central Hardwood Forest Conference

    Treesearch

    John W. Groninger; Eric J. Holzmueller; Clayton K. Nielsen; Daniel C., eds. Dey

    2014-01-01

    Proceedings from the 2014 Central Hardwood Forest Conference in Carbondale, IL. The published proceedings include 27 papers and 47 abstracts pertaining to research conducted on biofuels and bioenergy, forest biometrics, forest ecology and physiology, forest economics, forest health including invasive species, forest soils and hydrology, geographic information systems,...

  10. Proceedings of the second conference on the human dimensions of wildland fire

    Treesearch

    Sarah M. McCaffrey; Cherie LeBlanc, eds. Fisher

    2011-01-01

    This proceedings contains articles, posters, and abstracts of presentations from the second Human Dimensions of Wildland Fire Conference held 27-29 April 2010 in San Antonio, Texas. The conference covered the social issues at the root of wildland fire management’s most serious challenges. Specific topics included: firefighter and public safety; social acceptance of...

  11. Endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 1 targets misfolded HLA-B27 dimers for endoplasmic reticulum-associated degradation.

    PubMed

    Guiliano, David B; Fussell, Helen; Lenart, Izabela; Tsao, Edward; Nesbeth, Darren; Fletcher, Adam J; Campbell, Elaine C; Yousaf, Nasim; Williams, Sarah; Santos, Susana; Cameron, Amy; Towers, Greg J; Kellam, Paul; Hebert, Daniel N; Gould, Keith G; Powis, Simon J; Antoniou, Antony N

    2014-11-01

    HLA-B27 forms misfolded heavy chain dimers, which may predispose individuals to inflammatory arthritis by inducing endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). This study was undertaken to define the role of the UPR-induced ER-associated degradation (ERAD) pathway in the disposal of HLA-B27 dimeric conformers. HeLa cell lines expressing only 2 copies of a carboxy-terminally Sv5-tagged HLA-B27 were generated. The ER stress-induced protein ER degradation-enhancing α-mannosidase-like protein 1 (EDEM1) was overexpressed by transfection, and dimer levels were monitored by immunoblotting. EDEM1, the UPR-associated transcription factor X-box binding protein 1 (XBP-1), the E3 ubiquitin ligase hydroxymethylglutaryl-coenzyme A reductase degradation 1 (HRD1), and the degradation-associated proteins derlin 1 and derlin 2 were inhibited using either short hairpin RNA or dominant-negative mutants. The UPR-associated ERAD of HLA-B27 was confirmed using ER stress-inducing pharamacologic agents in kinetic and pulse chase assays. We demonstrated that UPR-induced machinery can target HLA-B27 dimers and that dimer formation can be controlled by alterations to expression levels of components of the UPR-induced ERAD pathway. HLA-B27 dimers and misfolded major histocompatibility complex class I monomeric molecules bound to EDEM1 were detected, and overexpression of EDEM1 led to inhibition of HLA-B27 dimer formation. EDEM1 inhibition resulted in up-regulation of HLA-B27 dimers, while UPR-induced ERAD of dimers was prevented in the absence of EDEM1. HLA-B27 dimer formation was also enhanced in the absence of XBP-1, HRD1, and derlins 1 and 2. The present findings indicate that the UPR ERAD pathway can dispose of HLA-B27 dimers, thus presenting a potential novel therapeutic target for modulation of HLA-B27-associated inflammatory disease. Copyright © 2014 by the American College of Rheumatology.

  12. Ninth Annual V. M. Goldschmidt Conference

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This volume contains abstracts that have been accepted for presentation at the Ninth Annual V. M. Goldschmidt Conference, August 22-27, 1999, hosted by the Department of Earth and Planetary Sciences, Harvard University, Cambridge, Massachusetts. The meeting is a forum for presenting and discussing new chemical and isotopic measurements, experimental and theoretical results, and discoveries in geochemistry and cosmochemistry.

  13. The 3rd international conference on reproductive immunology in Shanghai: September 27-29, 2013. Shanghai, China.

    PubMed

    Du, MeiRong; Piao, HaiLan; Li, DaJin

    2014-03-01

    After the first and second international conferences on reproductive immunology held by Dr. DaJin Li in Shanghai, the related investigators all over the world hope to get together to share their latest findings with each other. Drs. DaJin Li and MeiRong Du sponsored and organized the third international conference on reproductive immunology at the Obstetrics and Gynecology Hospital affiliated with Fudan University, Shanghai, China, in the autumn of 2013. This congress brought together more than 100 International and National investigators representing a wide range of scientific disciplines. All the investigators actively work on reproductive immunology using human or large and small animal models. A range of reproductive immunological topics including the maternal-fetal immune regulation, reproductive tract mucosal immunology, immunocontraception, and pregnancy complications were highlighted and discussed in this conference. This conference supplied a good platform for the international reproductive immunologists to exchange their latest study progression and discuss the development direction of reproductive immunology in the near future. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS)

    PubMed Central

    Derogis, Priscilla Bento Matos; Sanches, Livia Rentas; de Aranda, Valdir Fernandes; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana Caschera Leme; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos

    2017-01-01

    Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p < 0.001). In addition, we validated hemolytic, icteric or lipemic plasma samples for rivaroxaban measurement by HPLC-MS/MS without interferences. The chromogenic and HPLC-MS/MS methods were highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels. PMID:28170419

  15. The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion *

    PubMed Central

    Barnea, Eilon; Melamed Kadosh, Dganit; Haimovich, Yael; Satumtira, Nimman; Dorris, Martha L.; Nguyen, Mylinh T.; Hammer, Robert E.; Tran, Tri M.; Colbert, Robert A.; Taurog, Joel D.

    2017-01-01

    HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502. PMID:28188227

  16. The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion.

    PubMed

    Barnea, Eilon; Melamed Kadosh, Dganit; Haimovich, Yael; Satumtira, Nimman; Dorris, Martha L; Nguyen, Mylinh T; Hammer, Robert E; Tran, Tri M; Colbert, Robert A; Taurog, Joel D; Admon, Arie

    2017-04-01

    HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. PREFACE: Proceedings of the 7th Liquid Matter Conference (Lund, Sweden, 27 June 1 July 2008)

    NASA Astrophysics Data System (ADS)

    Kahl, Gerhard; Sciortino, Francesco; Ullner, Magnus

    2008-12-01

    The three-yearly Liquid Matter Conference is organized by the Liquids Section of the Condensed Matter Division of the European Physical Society. This series of meetings began in Lyon in 1990. The previous meeting was held in 2005 in Utrecht. The original aim of the Liquid Matter Conference was to bring together scientists working on the liquid state of matter. A closer analysis of the program booklets over the past 18 years reveals that new and highly active research fields that are closely related to liquid matter have been successfully integrated in the scope of the conference, notably the rapidly developing fields of soft matter and biophysics. Concomitantly, a broadening of the spectrum from the classical liquid state to a wide spectrum of phases and systems could be observed. Therefore, the rapidly growing field covered by this conference series at present includes physics, chemistry, biology, and chemical engineering as well as various applied research areas. Liquid state physics is at the interface of many research fields. As a consequence, many of the attendants come from adjacent fields and encounter at the Liquid Matter Conference a community where they can meet experts from other research areas. This aspect of the Liquid Matter Conference makes it an exciting meeting as it not only offers the participants an up-to-date picture of the status of research into the liquid state of matter, but it also allows them to establish new (and often unexpected) transdisciplinary contacts for joint scientific endeavours. This applies in particular to the area of soft condensed matter such as colloidal suspensions, polymeric systems and biological materials. The Lund meeting, organized in collaboration with Lund University, had 574 registered participants from five continents. During the conference, and following the tradition established at the Utrecht meeting, the second Liquid Matter Prize of the European Physical Society was awarded to Professor Henk Lekkerkerker

  18. Student Support for EIPBN 2014 Conference - Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Farrow, Reginald C.

    The 58th International Conference on Electron, Ion and Photon Beam Technology and Nanofabrication (EIPBN), 2014, was held at the Omni Shoreham Hotel in Washington, DC, May 27 to 30, 2014. The EIPBN Conference is recognized as the foremost international meeting dedicated to lithographic science and technology and its application to micro and nanofabrication techniques. The conference brought together 386 engineers and scientists from industries and universities from all over the world to discuss recent progress and future trends. Among the emerging technologies that are within the scope of EIPBN is Nanofabrication for Energy Sources along with nanofabrication for the realizationmore » of low power integrated circuits. Every year, EIPBN provides financial support for students to attend the conference. Travel support for 43 students came from a mixture of government agencies and corporate donors. The Department of Energy Office of Basic Energy Sciences provided $5,000 to support student travel from US universities to participate at EIPBN 2014 through grant DE-SC0011789.« less

  19. Xanthomonas oryzae pv. oryzae TALE proteins recruit OsTFIIAγ1 to compensate for the absence of OsTFIIAγ5 in bacterial blight in rice.

    PubMed

    Ma, Wenxiu; Zou, Lifang; Ji, Zhiyuan; Xu, Xiameng; Xu, Zhengyin; Yang, Yangyang; Alfano, James R; Chen, Gongyou

    2018-04-28

    Xanthomonas oryzae pv. oryzae (Xoo), causal agent of bacterial blight (BB) of rice, uses transcription activator-like effectors (TALEs) to interact with the basal transcription factor gama subunit OsTFIIAγ5 (Xa5) and activates transcription of host genes. However, how OsTFIIAγ1, the other OsTFIIAγ protein, functions in the presence of TALEs remains unclear. In this study, we show that OsTFIIAγ1 plays a compensatory role in the absence of Xa5. The expression of OsTFIIAγ1, which is activated by TALE PthXo7, increased the expression of host genes targeted by avirulent and virulent TALEs. Defective OsTFIIAγ1 rice lines showed reduced expression of the TALE-targeted susceptibility (S) genes, OsSWEET11 and OsSWEET14, which resulted in increased BB resistance. Selected TALEs (PthXo1, AvrXa7, and AvrXa27) were evaluated for interactions with OsTFIIAγ1, Xa5 and xa5 (naturally-occurring mutant form of Xa5) using biomolecular fluorescence complementation (BiFC) and microscale thermophoresis (MST). BiFC and MST demonstrated that the three TALEs bind Xa5 and OsTFIIAγ1 with a stronger affinity than xa5. These results provide insight into the complex roles of OsTFIIAγ1 and OsTFIIAγ5 in TALE-mediated host gene transcription. This article is protected by copyright. All rights reserved. © 2018 BSPP and John Wiley & Sons Ltd.

  20. 6 CFR 27.100 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 6 Domestic Security 1 2012-01-01 2012-01-01 false Purpose. 27.100 Section 27.100 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS General § 27.100 Purpose. The purpose of this part is to enhance the security of our Nation by furthering the...

  1. 6 CFR 27.100 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 6 Domestic Security 1 2014-01-01 2014-01-01 false Purpose. 27.100 Section 27.100 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS General § 27.100 Purpose. The purpose of this part is to enhance the security of our Nation by furthering the...

  2. 6 CFR 27.100 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 6 Domestic Security 1 2013-01-01 2013-01-01 false Purpose. 27.100 Section 27.100 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS General § 27.100 Purpose. The purpose of this part is to enhance the security of our Nation by furthering the...

  3. 6 CFR 27.100 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 6 Domestic Security 1 2011-01-01 2011-01-01 false Purpose. 27.100 Section 27.100 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS General § 27.100 Purpose. The purpose of this part is to enhance the security of our Nation by furthering the...

  4. 6 CFR 27.100 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Purpose. 27.100 Section 27.100 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS General § 27.100 Purpose. The purpose of this Part is to enhance the security of our Nation by furthering the...

  5. Heat-shock protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibitors and confers resistance to MET-targeted therapy.

    PubMed

    Musiani, Daniele; Konda, John David; Pavan, Simona; Torchiaro, Erica; Sassi, Francesco; Noghero, Alessio; Erriquez, Jessica; Perera, Timothy; Olivero, Martina; Di Renzo, Maria Flavia

    2014-09-01

    The tyrosine kinase encoded by the MET oncogene is activated by gene mutation or amplification in tumors, which in most instances maintain addiction, i.e., dependency, to MET activation. This makes MET an attractive candidate for targeted therapies. Here we show that, in 3/3 MET-addicted human gastric cancer cell lines, MET kinase inhibition resulted in a 3- to 4-fold increased expression of the antiapoptotic small heat-shock protein of 27 kDa (HSP27, HSPB1). HSP27 increase depended on the inhibition of the MEK/ERK pathway and on heat-shock factor 1 (HSF1) and hypoxia-inducible factor-1α (HIF-1α) regulation. Importantly, HSP27-silenced MET-addicted cells underwent 2- and 3-fold more apoptosis following MET inhibition in vitro and in vivo, respectively. Likewise, in human cancer cells susceptible to epidermal growth factor receptor (EGFR) inhibition, EGFR inhibitors induced HSP27 expression and were strengthened by HSP27 suppression. In control cell lines that were not affected by drugs targeting MET or EGFR, these drugs did not induce HSP27 increase. Therefore, in cancer therapies targeting the MET pathway, the induction of HSP27 might limit the efficacy of anti-MET agents. As HSP27 increase also impairs the effectiveness of EGFR inhibitors and is known to protect cells from chemotherapeutics, the induction of HSP27 by targeted agents might strongly affect the success of combination treatments. © FASEB.

  6. An Arabidopsis Soil-Salinity–Tolerance Mutation Confers Ethylene-Mediated Enhancement of Sodium/Potassium Homeostasis[W

    PubMed Central

    Jiang, Caifu; Belfield, Eric J.; Cao, Yi; Smith, J. Andrew C.; Harberd, Nicholas P.

    2013-01-01

    High soil Na concentrations damage plants by increasing cellular Na accumulation and K loss. Excess soil Na stimulates ethylene-induced soil-salinity tolerance, the mechanism of which we here define via characterization of an Arabidopsis thaliana mutant displaying transpiration-dependent soil-salinity tolerance. This phenotype is conferred by a loss-of-function allele of ETHYLENE OVERPRODUCER1 (ETO1; mutant alleles of which cause increased production of ethylene). We show that lack of ETO1 function confers soil-salinity tolerance through improved shoot Na/K homeostasis, effected via the ETHYLENE RESISTANT1–CONSTITUTIVE TRIPLE RESPONSE1 ethylene signaling pathway. Under transpiring conditions, lack of ETO1 function reduces root Na influx and both stelar and xylem sap Na concentrations, thereby restricting root-to-shoot delivery of Na. These effects are associated with increased accumulation of RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF)–dependent reactive oxygen species in the root stele. Additionally, lack of ETO1 function leads to significant enhancement of tissue K status by an RBOHF-independent mechanism associated with elevated HIGH-AFFINITY K+ TRANSPORTER5 transcript levels. We conclude that ethylene promotes soil-salinity tolerance via improved Na/K homeostasis mediated by RBOHF-dependent regulation of Na accumulation and RBOHF-independent regulation of K accumulation. PMID:24064768

  7. Proceedings, 15th central hardwood forest conference

    Treesearch

    David S. Buckley; Wayne K. Clatterbuck; [Editors

    2007-01-01

    Proceedings of the 15th central hardwood forest conference held February 27–March 1, 2006, in Knoxville, TN. Includes 86 papers and 30 posters pertaining to forest health and protection, ecology and forest dynamics, natural and artificial regeneration, forest products, wildlife, site classification, management and forest resources, mensuration and models, soil and...

  8. Volunteer Venture '92. Proceedings of the Annual Statewide Conference on Volunteerism (Columbus, Ohio, May 27-29, 1992).

    ERIC Educational Resources Information Center

    Safrit, R. Dale, Ed.

    These conference proceedings contain abstracts of papers that were submitted for presentation and descriptions of all presentations and workshops from a conference on volunteerism. Three papers are included in full. Organized in five sections, the following are included: "Building Better Young People: Powerful and Practical Techniques to Teach…

  9. PLA 2010 Conference: Plenty for the Price

    ERIC Educational Resources Information Center

    Miller, Rebecca

    2010-01-01

    This article outlines Public Library Association (PLA) 2010 annual conference to be held in Oregon Convention Center, Portland on March 23-27. The days quickly fill up with the picks of over 100 programs as well as valuable "talk tables" and special events. The well-organized schedule, divided into eight broad tracks (e.g., technology,…

  10. Proceedings of the Sixth Conference on African Linguistics. Working Papers in Linguistics, No. 20.

    ERIC Educational Resources Information Center

    Herbert, Robert K., Ed.

    This volume contains a selection of 27 papers presented at the Sixth Conference on African Linguistics. The papers cover a very wide range of topics, and are organized into three sections: (1) Historical and Comparative Studies; (2) Phonology; and (3) Syntax. The conference program, the program of the symposium on African language, culture and…

  11. 27 CFR 555.62 - State or other law.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false State or other law. 555.62... other law. A license or permit issued under this part confers no right or privilege to conduct business or operations, including storage, contrary to State or other law. The holder of a license or permit...

  12. 27 CFR 555.62 - State or other law.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false State or other law. 555.62... other law. A license or permit issued under this part confers no right or privilege to conduct business or operations, including storage, contrary to State or other law. The holder of a license or permit...

  13. 27 CFR 555.62 - State or other law.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... other law. A license or permit issued under this part confers no right or privilege to conduct business or operations, including storage, contrary to State or other law. The holder of a license or permit... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false State or other law. 555.62...

  14. Report of Ninth Biennial Conference on Chemical Education.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1987

    1987-01-01

    Provides a summary of the events occurring at the Ninth Biennial Conference on Chemical Education, held in Bozeman, Montana, on July 27-August 2, 1986. Contains brief descriptions of sessions on the role of chemists, demonstrations of laboratory experiences, learning chemistry with computers, teacher training, and chemistry for elementary school…

  15. Laboratory measurement of apixaban using anti-factor Xa assays in acute ischemic stroke patients with non-valvular atrial fibrillation.

    PubMed

    Shin, Hyoshim; Cho, Min-Chul; Kim, Rock Bum; Kim, Chang-Hun; Choi, Nack-Cheon; Kim, Soo-Kyung; Koh, Eun-Ha

    2018-02-01

    Apixaban is effective and safe for preventing stroke, and its usage has increased exponentially in recent years. However, data concerning the therapeutic range of apixaban is limited. This study determined the trough and peak levels of apixaban-specific anti-factor Xa activity (AFXaA) in acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) in Korea. The study included 85 patients who received apixaban. Blood samples were taken to measure the trough and peak levels of AFXaA using a chromogenic anti-factor assay, as well as prothrombin time (PT) and activated partial thromboplastin time (aPTT). We also reviewed complications such as major bleeding of patients treated with apixaban. In patients given a 5.0-mg apixaban dose, the median trough and peak levels of AFXaA were 104.5 and 202.0 ng/mL. In patients given a 2.5-mg apixaban dose, the median trough and peak AFXaA levels were 76.0 and 151.0 ng/mL. The PT showed a positive correlation with increased AFXaA activity at both levels (Trough R = 0.486, Peak R = 0.592), but the aPTT had no relationship with AFXaA activity at both levels (Trough R = 0.181, Peak R = 0.129). Two cases with intracranial bleeding belonged to the highest AFXaA quartile (Trough, p = 0.176; Peak, p = 0.053). In conclusion, we determined the trough and peak levels of AFXaA in patients with NVAF while being treated with the apixaban in Korea. Our results could be used as a starting point when setting the reference ranges for laboratories using anti-Xa assay. Large-scale studies are needed to establish the reference range for AFXaA in patients with NVAF.

  16. Contemporary developments in the discovery of selective factor Xa inhibitors: A review.

    PubMed

    Patel, Nirav R; Patel, Dushyant V; Murumkar, Prashant R; Yadav, Mange Ram

    2016-10-04

    Thrombosis is a leading cause of death in cardiovascular diseases such as myocardial infarction (MI), unstable angina and acute coronary syndrome (ACS) in the industrialized world. Venous thromboembolism is observed in about 1 million people every year in United States causing significant morbidity and mortality. Conventional antithrombotic therapy has been reported to have several disadvantages and limitations like inconvenience in oral administration, bleeding risks (heparin analogs), narrow therapeutic window and undesirable interactions with food and drugs (vitamin K antagonist-warfarin). The unmet medical demand for orally active safe anticoagulants has generated widespread interest among the medicinal chemists engaged in this field. To modulate blood coagulation, various enzymes involved in the coagulation process have received great attention as potential targets by various research groups for the development of oral anticoagulants. Among these enzymes, factor Xa (FXa) has remained the centre of attention in the last decade. Intensive research efforts have been made by various research groups for the development of small, safe and orally bioavailable FXa inhibitors. This review is an attempt to compile the research work of various researchers in the direction of development of FXa inhibitors reported since 2010 onward. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Effect of SanOrg123781A, a synthetic hexadecasaccharide, on clot-bound thrombin and factor Xa in vitro and in vivo.

    PubMed

    Hérault, J-P; Cappelle, M; Bernat, A; Millet, L; Bono, F; Schaeffer, P; Herbert, J-M

    2003-09-01

    Factor (F)Xa and thrombin bound to the clot during its formation contribute to the propensity of thrombi to activate the coagulation system. The aim of this work was to study the inhibition of clot-bound FXa and clot-bound thrombin by SanOrg123781A, a synthetic hexadecasaccharide that enhances the inhibition of thrombin and FXa by antithrombin (AT). SanOrg123781A, designed to exhibit low non-specific binding to proteins other than AT, was compared with heparin. In buffer, heparin and SanOrg123781A inhibited FXa and thrombin at similar concentrations [concentration inhibiting 50% (IC50) of Xa and IIa activity were, respectively: heparin 120 +/- 7 and 3 +/- 1 ng mL-1; SanOrg123781A 77 +/- 5 and 4 +/- 1 ng mL-1]. In human plasma, the activity of both compounds was reduced, although the activity of heparin was much more affected than that of SanOrg123781A (IC50 values for inhibition of FXa and FIIa activity were, respectively: heparin 100 +/- 5 and 800 +/- 40 ng mL-1; SanOrg123781A 10 +/- 5 and 30 +/- 3 ng mL-1). We demonstrated, in agreement with our previous results, that the procoagulant activity of the clot is essentially due to clot-bound FXa and to some extent to clot-bound thrombin. We showed that heparin and SanOrg123781A were able to inhibit fragment F1+2 generation induced by clot-bound FXa with IC50 values of 2 +/- 0.5 micro g mL-1 and 0.6 +/- 0.2 micro g mL-1, respectively. Both compounds also inhibited clot-bound thrombin activity, the IC50 values of heparin and SanOrg123781A being 1 +/- 0.01 micro g mL-1 and 0.1 +/- 0.1 micro g mL-1, respectively. Moreover, both heparin and SanOrg123781A significantly inhibited fibrinopeptide A generated by the action of clot-bound thrombin on fibrinogen but also by free thrombin generated from prothrombin by clot-bound FXa with IC50 values of 4 +/- 0.6 and 1 +/- 0.1 micro g mL-1, respectively. As with clot-bound enzymatic activities, SanOrg123781A was three times more active than heparin in vivo on fibrinogen accretion

  18. Trivial topological phase of CaAgP and the topological nodal-line transition in CaAg (P1 -xA sx)

    NASA Astrophysics Data System (ADS)

    Xu, N.; Qian, Y. T.; Wu, Q. S.; Autès, G.; Matt, C. E.; Lv, B. Q.; Yao, M. Y.; Strocov, V. N.; Pomjakushina, E.; Conder, K.; Plumb, N. C.; Radovic, M.; Yazyev, O. V.; Qian, T.; Ding, H.; Mesot, J.; Shi, M.

    2018-04-01

    By performing angle-resolved photoemission spectroscopy and first-principles calculations, we address the topological phase of CaAgP and investigate the topological phase transition in CaAg (P1 -xA sx) . We reveal that in CaAgP, the bulk band gap and surface states with a large bandwidth are topologically trivial, in agreement with hybrid density functional theory calculations. The calculations also indicate that application of "negative" hydrostatic pressure can transform trivial semiconducting CaAgP into an ideal topological nodal-line semimetal phase. The topological transition can be realized by partial isovalent P/As substitution at x =0.38 .

  19. Plasma Membrane Intrinsic Proteins SlPIP2;1, SlPIP2;7 and SlPIP2;5 Conferring Enhanced Drought Stress Tolerance in Tomato.

    PubMed

    Li, Ren; Wang, Jinfang; Li, Shuangtao; Zhang, Lei; Qi, Chuandong; Weeda, Sarah; Zhao, Bing; Ren, Shuxin; Guo, Yang-Dong

    2016-08-22

    The function of aquaporin (AQP) protein in transporting water is crucial for plants to survive in drought stress. With 47 homologues in tomato (Solanum lycopersicum) were reported, but the individual and integrated functions of aquaporins involved in drought response remains unclear. Here, three plasma membrane intrinsic protein genes, SlPIP2;1, SlPIP2;7 and SlPIP2;5, were identified as candidate aquaporins genes because of highly expressed in tomato roots. Assay on expression in Xenopus oocytes demonstrated that SlPIP2s protein displayed water channel activity and facilitated water transport into the cells. With real-time PCR and in situ hybridization analysis, SlPIP2s were considered to be involved in response to drought treatment. To test its function, transgenic Arabidopsis and tomato lines overexpressing SlPIP2;1, SlPIP2;7 or SlPIP2;5 were generated. Compared with wild type, the over-expression of SlPIP2;1, SlPIP2;7 or SlPIP2;5 transgenic Arabidopsis and tomato plants all showed significantly higher hydraulic conductivity levels and survival rates under both normal and drought conditions. Taken together, this study concludes that aquaporins (SlPIP2;1, SlPIP2;7 and SlPIP2;5) contribute substantially to root water uptake in tomato plants through improving plant water content and maintaining osmotic balance.

  20. Off-Campus Library Services Conference Proceedings (8th, Providence, Rhode Island, April 22-24, 1998).

    ERIC Educational Resources Information Center

    Thomas, P. Steven, Comp.; Jones, Maryhelen, Comp.

    The 27 papers that make up this Proceedings were presented at the Eighth Off-Campus Library Services Conference. The primary objective of the conference was to provide a forum where practitioners involved in library services for off-campus constituents could gather to exchange relevant ideas, concerns and perspectives, and to share research.…

  1. National Educational Computing Conference Proceedings (11th, Nashville, Tennessee, June 25-27, 1990).

    ERIC Educational Resources Information Center

    Ellis, Edwin, Ed.

    This volume of proceedings of the 1990 National Educational Computing Conference (NECC) provides a record of the state-of-the-art in the use of computing in a variety of educational settings. Special sessions, panels, projects, 153 abstracts, and 44 papers are reported here on subjects including: elementary and secondary educational software,…

  2. Combination Treatment with Apricoxib and IL-27 Enhances Inhibition of Epithelial-Mesenchymal Transition in Human Lung Cancer Cells through a STAT1 Dominant Pathway

    PubMed Central

    Lee, Mi-Heon; Kachroo, Puja; Pagano, Paul C; Yanagawa, Jane; Wang, Gerald; Walser, Tonya C; Krysan, Kostyantyn; Sharma, Sherven; John, Maie St.; Dubinett, Steven M; Lee, Jay M

    2015-01-01

    Background The cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many malignancies, including lung cancer. Apricoxib, a selective COX-2 inhibitor, has been described to inhibit epithelial-mesenchymal transition (EMT) in human malignancies. The mechanism by which apricoxib may alter the tumor microenvironment by affecting EMT through other important signaling pathways is poorly defined. IL-27 has been shown to have anti-tumor activity and our recent study showed that IL-27 inhibited EMT through a STAT1 dominant pathway. Objective The purpose of this study is to investigate the role of apricoxib combined with IL-27 in inhibiting lung carcinogenesis by modulation of EMT through STAT signaling. Methods and Results Western blot analysis revealed that IL-27 stimulation of human non-small cell lung cancer (NSCLC) cell lines results in STAT1 and STAT3 activation, decreased Snail protein and mesenchymal markers (N-cadherin and vimentin) and a concomitant increase in expression of epithelial markers (E-cadherin, β-and γ-catenins), and inhibition of cell migration. The combination of apricoxib and IL-27 resulted in augmentation of STAT1 activation. However, IL-27 mediated STAT3 activation was decreased by the addition of apricoxib. STAT1 siRNA was used to determine the involvement of STAT1 pathway in the enhanced inhibition of EMT and cell migration by the combined IL-27 and apricoxib treatment. Pretreatment of cells with STAT1 siRNA inhibited the effect of combined IL-27 and apricoxib in the activation of STAT1 and STAT3. In addition, the augmented expression of epithelial markers, decreased expression mesenchymal markers, and inhibited cell migration by the combination treatment were also inhibited by STAT1 siRNA, suggesting that the STAT1 pathway is important in the enhanced effect from the combination treatment. Conclusion Combined apricoxib and IL-27 has an enhanced effect in inhibition of epithelial-mesenchymal transition and cell

  3. Development of breeding lines with three pyramided resistance genes that confer broad-spectrum bacterial blight resistance and their molecular analysis in rice.

    PubMed

    Suh, Jung-Pil; Jeung, Ji-Ung; Noh, Tae-Hwan; Cho, Young-Chan; Park, So-Hyun; Park, Hyun-Su; Shin, Mun-Sik; Kim, Chung-Kon; Jena, Kshirod K

    2013-02-08

    The development of resistant cultivars has been the most effective and economical strategy to control bacterial leaf blight (BB) disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Molecular markers have made it possible to identify and pyramid valuable genes of agronomic importance in resistance rice breeding. In this study, three resistance genes (Xa4 + xa5 + Xa21) were transferred from an indica donor (IRBB57), using a marker-assisted backcrossing (MAB) breeding strategy, into a BB-susceptible elite japonica rice cultivar, Mangeumbyeo, which is high yielding with good grain quality. Our analysis led to the development of three elite advanced backcross breeding lines (ABL) with three resistance genes by foreground and phenotypic selection in a japonica genetic background without linkage drag. The background genome recovery of the ABL expressed more than 92.1% using genome-wide SSR marker analysis. The pathogenicity assays of three resistance-gene-derived ABL were conducted under glasshouse conditions with the 18 isolates of Xoo prevalent in Korea. The ABL exhibited very small lesion lengths, indicating a hypersensitive reaction to all 18 isolates of Xoo, with agronomic and grain quality traits similar to those of the recurrent parent. Pyramiding the resistance genes Xa4, xa5 and Xa21 provided a higher resistance to Xoo than the introduction of the individual resistance genes. Additionally, the combination of two dominant and one recessive BB resistance gene did not express any negative effect on agronomic traits in the ABL. The strategy of simultaneous foreground and phenotypic selection to introduce multiple R genes is very useful to reduce the cost and the time required for the isolation of desirable recombinants with target resistance genes in rice. The resistance-gene-derived ABL have practical breeding value without a yield penalty by providing broad-spectrum resistance against most of the existing isolates of BB in South Korea and will

  4. Microbicides 2008 conference: From discovery to advocacy

    PubMed Central

    Ramjee, Gita; Doncel, Gustavo F; Mehendale, Sanjay; Tolley, Elizabeth E; Dickson, Kim

    2008-01-01

    Recently revised statistics show the number of individuals living with HIV at over 33 million worldwide, with 68% being in sub-Saharan Africa. Current HIV prevention methods, such as condom use, monogamy and abstinence, are not always feasible. The need for improved HIV preventative technologies remains urgent. Of these, microbicides represent a promising female-initiated preventative method. Microbicides are designed to be applied vaginally to prevent HIV and STI acquisition. Research is also being undertaken to assess the safety of the product during rectal application. The biannual Microbicides conference took place in New Delhi, India from 24–27 February 2008. The conference was open to delegates from the scientific and medical fields, as well as communities and advocates. In addition to microbicide research and development, the conference afforded the opportunity for the discussion of key issues such as ethics, acceptability, access, and community involvement. In this conference report we provide brief summaries of recent advancements made and challenges experienced in microbicide research and development, including updates on basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities pertaining to clinical trials. PMID:18702834

  5. Expedition 40 Press Conference

    NASA Image and Video Library

    2014-05-27

    A reflection of the audience can been seen in the quarantine glass as Expedition 40 Flight Engineer Alexander Gerst of the European Space Agency, ESA, left, Soyuz Commander Maxim Suraev of the Russian Federal Space Agency, Roscosmos, center, and Flight Engineer Reid Wiseman of NASA, right, pose for a group picture at the conclusion of a press conference, Tuesday, May 27, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission to the International Space Station is set to launch May 29 from the Baikonur Cosmodrome. Photo Credit: (NASA/Joel Kowsky)

  6. Expedition 40 Press Conference

    NASA Image and Video Library

    2014-05-27

    Expedition 40 Soyuz Commander Maxim Suraev of the Russian Federal Space Agency, Roscosmos, center, takes a picture with his cell phone during a press conference, Tuesday, May 27, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. Expedition 40 Soyuz Commander Maxim Suraev of the Russian Federal Space Agency, Roscosmos, Flight Engineer Alexander Gerst of the European Space Agency, ESA, and Flight Engineer Reid Wiseman of NASA will launch aboard their Soyuz TMA-13M spacecraft on their mission to the International Space Station in the early hours of May 29. Photo Credit: (NASA/Joel Kowsky)

  7. Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral ischemia in mice.

    PubMed

    Shimada, Y; Tanaka, R; Shimura, H; Yamashiro, K; Urabe, T; Hattori, N

    2014-10-10

    Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults including cerebral ischemia. We previously indicated that intravenous injection of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct volume following cerebral ischemia-reperfusion injury, while recombinant HSP27 (rHSP27) was less effective. Phosphorylation is important for HSP27 function, and hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain protection. Mice underwent transient 1-h middle cerebral artery occlusion (MCAO), and then received tail-vein injections of one of the following 1h after reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin (BSA) as control. We measured infarct volume, neurological deficits, neurological severity, physiological parameters, cell-death, oxidative stress, and inflammatory response. Compared with BSA controls (30.7±3.1mm(3), n=5), infarct volume was reduced by 67% in the hHSP27 positive-control group (10.1±4.6mm(3), P<0.001, n=5), 17% following rHSP27 (25.4±3.6mm(3), P<0.05, n=5), and 46% following prHSP27 (16.5±4.0mm(3), P<0.001, n=9). Compared to the rHSP27 and BSA-treated groups, prHSP27 also reduced functional deficits, and significantly suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we showed the superior neuroprotective effects of phosphorylated HSP27 by administering prHSP27. prHSP27 may be a useful therapeutic agent to protect against acute cerebral ischemic stroke. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Error-prone PCR mutation of Ls-EPSPS gene from Liriope spicata conferring to its enhanced glyphosate-resistance.

    PubMed

    Mao, Chanjuan; Xie, Hongjie; Chen, Shiguo; Valverde, Bernal E; Qiang, Sheng

    2017-09-01

    Liriope spicata (Thunb.) Lour has a unique LsEPSPS structure contributing to the highest-ever-recognized natural glyphosate tolerance. The transformed LsEPSPS confers increased glyphosate resistance to E. coli and A. thaliana. However, the increased glyphosate-resistance level is not high enough to be of commercial value. Therefore, LsEPSPS was subjected to error-prone PCR to screen mutant EPSPS genes capable of endowing higher resistance levels. A mutant designated as ELs-EPSPS having five mutated amino acids (37Val, 67Asn, 277Ser, 351Gly and 422Gly) was selected for its ability to confer improved resistance to glyphosate. Expression of ELs-EPSPS in recombinant E. coli BL21 (DE3) strains enhanced resistance to glyphosate in comparison to both the LsEPSPS-transformed and -untransformed controls. Furthermore, transgenic ELs-EPSPS A. thaliana was about 5.4 fold and 2-fold resistance to glyphosate compared with the wild-type and the Ls-EPSPS-transgenic plants, respectively. Therefore, the mutated ELs-EPSPS gene has potential value for has potential for the development of glyphosate-resistant crops. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 76 FR 14379 - Marine Fisheries Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-16

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XA265 Marine... Atmospheric Administration (NOAA), Commerce. ACTION: Notice of open public meeting. SUMMARY: This notice sets...: The meeting is scheduled for March 30, 2011, 2-3:30 p.m., Eastern Daylight Time. ADDRESSES: Conference...

  10. Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

    PubMed

    Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

    2013-12-01

    Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. More than One Voice: Enhancing Our AHRD Research Conference

    ERIC Educational Resources Information Center

    Storberg-Walker, Julia

    2010-01-01

    Between March 26 and April 3, 2009, 136 Academy of Human Resource Development (AHRD) members accessed an on-line survey to provide feedback about the AHRD annual research conferences. The primary purpose of the survey was to understand more about members' experiences in order to improve what is arguably one of the most important "products" of the…

  12. Academy of Human Resource Development Conference Proceedings (Honolulu, Hawaii, February 27-March 3, 2002). Volumes 1 and 2.

    ERIC Educational Resources Information Center

    Egan, T. Marshall, Ed.; Lynham, Susan A., Ed.

    This document contains 143 papers and innovative sessions, three poster sessions presented at a conference on human resource development (HRD). A program overview, author index, and a keyword index are also included. The papers are grouped by the conference's 42 symposia, which were devoted to the following topics: women's HRD-related issues;…

  13. HLA-B27 Alters the Response to TNFα and Promotes Osteoclastogenesis in Bone Marrow Monocytes from HLA-B27 Transgenic Rats

    PubMed Central

    Layh-Schmitt, Gerlinde; Yang, Eva Y.; Kwon, Grace; Colbert, Robert A.

    2013-01-01

    Objective To determine whether HLA-B27 expression alters the response of bone marrow monocytes (BMMo) from HLA-B27/human β2-microglobulin transgenic (B27-Tg) rats to tumor necrosis factor-α (TNFα), and whether this affects cells involved in bone homeostasis. Methods BMMo were treated with receptor activator of NF-κB ligand or TNFα to promote osteoclast formation. Osteoclasts were quantified by counting. Gene expression was measured using quantitative polymerase chain reaction, and protein was detected by enzyme-linked immunosorbent assay, immunoblotting, or immunofluorescence. Effects of endogenously produced cytokines on osteoclast formation were determined with neutralizing antibodies. Results TNFα enhanced osteoclast formation 2.5-fold in HLA-B27-expressing cells compared to either wild type or HLA-B7/human β2-microglobulin expressing monocytes. TNFα induced approximately 4-fold upregulation of HLA-B27, which was associated with accumulation of misfolded heavy chains, binding of the ER chaperone BiP, and activation of an ER stress response, which was not seen with HLA-B7. No differences were seen with RANKL-induced osteoclastogenesis. Enhanced interleukin-1α (IL-1α) production from ER stressed B27-Tg BMMo was found to be necessary and sufficient for enhanced osteoclast formation. However, B27-Tg BMMo also produced more interferon-β (IFNβ), which attenuated the effect of IL-1α on osteoclast formation. Conclusions HLA-B27-induced ER stress alters the response of BMMo from B27-Tg rats to TNFα, which is associated with enhanced production of IL-1α and IFNβ, cytokines that exhibit opposing effects on osteoclast formation. The altered response of cells expressing HLA-B27 to pro-inflammatory cytokines suggests that this MHC class I allele may contribute to the pathogenesis of spondyloarthritis and its unique phenotype through downstream effects involving alterations in bone homeostasis. PMID:23666508

  14. 42 CFR 51.27 - Training.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... mental health services and family members of such individuals. (b) Training to enhance sensitivity to and... 42 Public Health 1 2010-10-01 2010-10-01 false Training. 51.27 Section 51.27 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS REQUIREMENTS APPLICABLE TO THE PROTECTION...

  15. Annual Quality Assurance Conference Presentations by Johnathan Beck

    EPA Pesticide Factsheets

    25th Annual Quality Assurance Conference Presentation: Disinfectants/Disinfection Byproducts –Rules and Requirements and Presentation: Long Term 2 Enhanced Surface Water Treatment Rule (LT2) Cryptosporidium Monitoring

  16. PREFACE: The Irago Conference 2012

    NASA Astrophysics Data System (ADS)

    Sandhu, Adarsh; Okada, Hiroshi

    2013-04-01

    The Irago Conference 2012 - 360 degree outlook on critical scientific and technological challenges for a sustainable society Organized by the Electronics-Inspired Interdisciplinary Research Institute (EIIRIS) at Toyohashi University of Technology, the Irago Conference, held recently (15-16 November) in Aichi, Japan, aimed to enhance mutual understanding between scientists, engineers and policymakers. Over 180 participants tackled topics ranging from energy and natural resources to public health and disaster prevention. The 360-degree outlook of the conference impressed speakers and guests. ''This conference has been extremely informative,'' noted Robert Gellar from the University of Tokyo. ''A unique conference with experts from a range of backgrounds,'' agreed Uracha Ruktanonchai from the National Nanotechnology Center (NANOTEC) in Thailand. Similarly, G P Li, professor of electrical engineering and computer science at the University of California Irvine commented that he had been ''able to think the unthinkable'' as a range of topics came together. The conference was streamed live on Ustream to ensure that researchers from across the world could benefit from thought-provoking presentations examining global issues such as energy, disaster mitigation and nanotechnology. ''This was wonderful,'' said Oussama Khatib from Stanford University, ''A good recipe of speakers from such a range of backgrounds.'' Manuscripts submitted to the organizers were peer-reviewed, and the papers in this proceedings were accepted for Journal of Physics: Conference Series. In addition to the formal speaker programme, graduate-student sessions provided a platform for graduate students to describe their latest findings as oral presentations. A series of excursions to relevant locations, such as the Tahara megasolar region under construction and a local car-manufacturing factory, gave participants the opportunity to further consider practical applications of their research in industry

  17. Report on the National Conference for Youth on Drinking and Driving (Washington, D.C., April 27-30, 1984).

    ERIC Educational Resources Information Center

    Birch & Davis Associates, Inc., Silver Spring, MD.

    This report on the second National Conference for Youth on Drinking and Driving focuses on the potential of the workplace as a site for the prevention of teenage alcohol abuse, with a special emphasis on drinking and driving. Features of the conference are described which may be of interest to employers of youth, youth specialists, and alcohol…

  18. Identification and fine-mapping of Xa33, a novel gene for resistance to Xanthomonas oryzae pv. oryzae.

    PubMed

    Kumar, P Natraj; Sujatha, K; Laha, G S; Rao, K Srinivasa; Mishra, B; Viraktamath, B C; Hari, Y; Reddy, C S; Balachandran, S M; Ram, T; Madhav, M Sheshu; Rani, N Shobha; Neeraja, C N; Reddy, G Ashok; Shaik, H; Sundaram, R M

    2012-02-01

    Broadening of the genetic base for identification and transfer of genes for resistance to insect pests and diseases from wild relatives of rice is an important strategy in resistance breeding programs across the world. An accession of Oryza nivara, International Rice Germplasm Collection (IRGC) accession number 105710, was identified to exhibit high level and broad-spectrum resistance to Xanthomonas oryzae pv. oryzae. In order to study the genetics of resistance and to tag and map the resistance gene or genes present in IRGC 105710, it was crossed with the bacterial blight (BB)-susceptible varieties 'TN1' and 'Samba Mahsuri' (SM) and then backcrossed to generate backcross mapping populations. Analysis of these populations and their progeny testing revealed that a single dominant gene controls resistance in IRGC 105710. The BC(1)F(2) population derived from the cross IRGC 105710/TN1//TN1 was screened with a set of 72 polymorphic simple-sequence repeat (SSR) markers distributed across the rice genome and the resistance gene was coarse mapped on chromosome 7 between the SSR markers RM5711 and RM6728 at a genetic distance of 17.0 and 19.3 centimorgans (cM), respectively. After analysis involving 49 SSR markers located between the genomic interval spanned by RM5711 and RM6728, and BC(2)F(2) population consisting of 2,011 individuals derived from the cross IRGC 105710/TN1//TN1, the gene was fine mapped between two SSR markers (RMWR7.1 and RMWR7.6) located at a genetic distance of 0.9 and 1.2 cM, respectively, from the gene and flanking it. The linkage distances were validated in a BC(1)F(2) mapping population derived from the cross IRGC 105710/SM//2 × SM. The BB resistance gene present in the O. nivara accession was identified to be novel based on its unique map location on chromosome 7 and wider spectrum of BB resistance; this gene has been named Xa33. The genomic region between the two closely flanking SSR markers was in silico analyzed for putatively expressed

  19. Silencing of miR156 confers enhanced resistance to brown planthopper in rice.

    PubMed

    Ge, Yafei; Han, Junyou; Zhou, Guoxin; Xu, Yunmin; Ding, Yue; Shi, Min; Guo, Changkui; Wu, Gang

    2018-06-22

    Silencing of miR156 in rice confers enhanced resistance to brown planthopper through reducing JA and JA-Ile biosynthesis. Rice brown planthopper (BPH, Nilaparvata lugens Stål) threatens the sustainability of rice production and global food security. Due to the rapid adaptation of BPH to current germplasms in rice, development of novel types of resistant germplasms becomes increasingly important. Plant ontogenetic defense against pathogen and herbivores offers a broad spectrum and durable resistance, and has been experimentally tested in many plants; however, the underlying molecular mechanism remains unclear. miR156 is the master regulator of ontogeny in plants; modulation of miR156 is, therefore, expected to cause corresponding changes in BPH resistance. To test this hypothesis, we silenced miR156 using a target mimicry method in rice, and analyzed the resistance of miR156-silenced plants (MIM156) to BPH. MIM156 plants exhibited enhanced resistance to BPH based on analyses of honeydew excretion, nymph survival, fecundity of BPH, and the survival ratio of rice plants after BPH infestation. Molecular analysis indicated that the expression of MPK3, MPK6, and WRKY70, three genes involved in BPH resistance and jasmonic acid (JA) signaling, was altered in MIM156 plants. The JA and bioactive jasmonoyl-isoleucine levels and the expression of genes involved in JA biosynthesis were significantly reduced in MIM156 plants. Restoration of JA level by exogenous application increased the number of BPH feeding on MIM156 plants and reduced its resistance to BPH. Our findings suggest that miR156 negatively regulates BPH resistance by increasing JA level in rice; therefore, modulation of miR156-SPLs' pathway may offer a promising way to breed rice varieties with enhanced resistance against BPH and elite agronomically important traits.

  20. The Utilisation of Highly Qualified Personnel. Venice Conference, 25th-27th October 1971.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France).

    This document reports the highlights of an international conference designed to study the utilization of highly qualified personnel. Following the opening addresses by various participants, discussion documents and basic reports are presented. Four areas of concern include the state of employment and employment policy, the conditions and aims of…

  1. CALL Communities & Culture: Short Papers from EUROCALL 2016 (23rd, Limassol, Cyprus, August 24-27, 2016)

    ERIC Educational Resources Information Center

    Papadima-Sophocleous, Salomi, Ed.; Bradley, Linda, Ed.; Thouësny, Sylvie, Ed.

    2016-01-01

    The 23rd EUROCALL conference was held in Cyprus from the 24th to the 27th of August 2016. The theme of the conference this year was "CALL Communities and Culture." It offered a unique opportunity to hear from real-world CALL practitioners on how they practice CALL in their communities, and how the CALL culture has developed in local and…

  2. Expedition 43 Press Conference

    NASA Image and Video Library

    2015-03-26

    Expedition 43 NASA Astronaut Scott Kelly waves hello to family and friends as he and, Russian cosmonauts Gennady Padalka, and Mikhail Kornienko of the Russian Federal Space Agency (Roscosmos) participate in a crew press conference, Thursday, March 26, 2015, at the Cosmonaut Hotel in Baikonur, Kazakhstan. Kelly, Kornienko, and Padalka launched to the International Space Station in the Soyuz TMA-16M spacecraft from the Baikonur Cosmodrome in Kazakhstan March 28, Kazakh time (March 27 Eastern time.) As the one-year crew, Kelly and Kornienko will return to Earth on Soyuz TMA-18M in March 2016. Photo Credit (NASA/Bill Ingalls)

  3. Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced by TALEN-mediated targeted mutagenesis.

    PubMed

    Yamamoto, Daisuke S; Sumitani, Megumi; Hatakeyama, Masatsugu; Matsuoka, Hiroyuki

    2018-02-01

    Anopheline mosquitoes are major vectors of malaria parasites. When the gametocytes of the malaria parasite are transferred from a vertebrate to mosquitoes, they differentiate into gametes, and are fertilized in the midguts of mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis pathway, has been shown to induce exflagellation during microgametogenesis in vitro; however, it currently remains unclear whether endogenous XA affects the infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack of appropriate experimental systems such as a XA-deficient line. In the present study, we produced a XA-deficient line in Anopheles stephensi using transcription activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that participates in the ommochrome synthesis pathway. The knockout of kmo resulted in the absence of XA, and oocyst formation was inhibited in the midguts of these XA-deficient mosquitoes, which, in turn, reduced sporozoite numbers in their salivary glands. These results suggest that endogenous XA stimulates exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria parasites in vivo. The XA-deficient line of the anopheline mosquito provides a useful system for analyzing and understanding the associated factors of malaria gametogenesis in the mosquito midgut.

  4. Small heat shock protein 27: An effective adjuvant for enhancement of HIV-1 Nef antigen-specific immunity.

    PubMed

    Milani, Alireza; Bolhassani, Azam; Shahbazi, Sepideh; Motevalli, Fatemeh; Sadat, Seyed Mehdi; Soleymani, Sepehr

    2017-11-01

    Novel vaccine modalities have been designed to improve the efficiency of vaccines against HIV infections. In this way, the HIV-1 Nef protein has been known as an attractive antigenic candidate in therapeutic vaccine development. Moreover, the endogenous adjuvants such as heat shock proteins (HSPs) and high mobility group box 1 protein (HMGB1) have been suggested effectively to induce antigen-specific humoral and cellular immune responses. In this study, different Nef DNA and protein constructs were produced in eukaryotic and prokaryotic expression systems, and their immunostimulatory properties were evaluated using small heat shock protein 27 (Hsp27) and the HMGB1-derived peptide (Hp91) in a mouse model. Generally, our results indicated that the Hsp27-Nef fusion DNA or protein could significantly elicit higher humoral and cellular immune responses than Nef DNA or protein, respectively. Analysis of the immune responses demonstrated that the Hsp27-Nef fusion protein, and also the mixture of Nef and Hp91 significantly enhanced the Nef-specific T cell responses. Indeed, these regimens induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also Granzyme B secretion as compared to other immunization strategies. The immunostimulatory properties of Freund's adjuvant were significantly less than Hsp27 and Hp91 peptide in various immunization strategies. These findings showed that the use of Hsp27 and Hp91 in protein strategy could improve HIV-1 Nef-specific B- and T-cell immune responses, and also represent a promising HIV-1 vaccine candidate in future. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  5. SAR and X-ray Structures of Enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and Cyclohexyldiamine Derivativies as Inhibitors of Coagulation Factor Xa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qiao,J.; Chang, C.; Cheney, D.

    In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.

  6. RGS Spectroscopy of the Cygnus Loop XA Knot

    NASA Technical Reports Server (NTRS)

    Gaetz, Terrance J.; Mushotzky, Richard F. (Technical Monitor)

    2003-01-01

    The observations were performed at the end of April 2002, and the data were received in July 2002. Unfortunately, the observations were badly compromised by high levels of background radiation; one the three observations lost entirely. Two replacement observations were scheduled for November 2002, and were only made available in January of 2003. Consequently, we have had little time to grapple with the unusual data analysis challenges. The search for a postdoctoral fellow has been successfully concluded, and Manami Sasaki began working for us in January 2003. She will be supported in part by these funds, and will be working to help understand these data. Examination of the RGS 'Orders' images indicate the presence of broad emission lines (as expected for the diffuse XA knot). However, examination of the 'Spatial' dispersion/cross-dispersion images indicate that the emission is also broad in the cross-dispersion direction. (As a crosscheck, some of the 'Lockman Hole' datasets were also examined as representative 'sky background' datasets; in these, both types of images are relatively flat (outside the calibration source regions). The quicklook plots of the spectra show the expected O VII and O VIII lines, in addition to a complex around 35 Angstroms; the approx. 35 Angstrom line is likely the C V He-beta line at 34.97 Angstrom, but identifying the additional line(s) will require a more careful reduction of the data. Consequently, there is valuable information to be extracted from these data, but it is complicated by diffuse nature of the emission. Because the angular scale is large, we will have to make use of sky background datasets in order to do the background fitting. A color composite image of OM data in the three UV bands was presented at the 'How does the Galaxy Work?' meeting, and compared to optical and X-ray imaging data. Quantitative analysis will require obtaining the effective bandpasses of the UV filters so that the predominant line and continuum

  7. Are there too few women presenting at emergency medicine conferences?

    PubMed

    Carley, Simon; Carden, Richard; Riley, Rebecca; May, Natalie; Hruska, Katrin; Beardsell, Iain; Johnston, Michelle; Body, Richard

    2016-10-01

    There is a perception that women are under-represented as speakers at emergency medicine (EM) conferences. We aimed to evaluate the ratio of male to female speakers and the proportion of presenting time by gender at major international EM conferences. Conference programmes of the major English-speaking EM conferences occurring from 2014 to 2015 were obtained. The number of presentations, the gender of the speaker and the duration of each presentation were recorded. We analysed eight major EM conferences. These included 2382 presentations, of which 29.9% (range 22.5%-40.9%) were given by women. In total, 56 104 min of presentations were analysed, of which 27.6% (range 21%-36.7%) were delivered by women. On average, presentations by women were 95 s shorter than presentations by men (23 vs 21 min 25 s). Male speakers exceed female speakers at major EM conferences. The reasons for this imbalance are likely complex and multifactorial and may reflect the gender imbalance within the specialty. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. PREFACE AND CONFERENCE SUMMARY: Advanced Metrology for Ultrasound in Medicine, 27 28 April 2004

    NASA Astrophysics Data System (ADS)

    Shaw, Adam

    2004-01-01

    AMUM 2004 proved to be a great success and provided a fantastic opportunity for the world's ultrasound experts from medicine, industry and academia to explore the measurement challenges presented by new and emerging clinical ultrasound equipment. There were a total of 88 attendees. Of these 39 were from the UK, 22 from the rest of Europe, and 27 from outside Europe. 31 of the delegates were from industry, 22 were university-based, 18 from hospitals, 10 from other National Metrology Institutes and regulatory bodies, and 7 from NPL. Test your knowledge of the ultrasound community by trying to name all the faces in the group photograph! It was especially gratifying to see so many major medical equipment manufacturers represented—including Siemens, Philips, Esaote, Kontron, Pie Medical, G.E., Hitachi, Aloka and Imasonic—since it is essential that there is a good dialogue between industry and the measurement community. The presentations were split into 8 oral sessions—Hydrophones, Hydrophone measurements, Safety and thermal hazard, Measurement challenges for diagnostic ultrasound, Measurement of therapy fields, Tissue interaction, Novel measurement methods, and Measurement challenges for therapeutic ultrasound; and 3 poster sessions—Performance of diagnostic equipment, Measurement and safety, and Field modelling. It was always my hope that this conference would provide a framework for the development of measurement methods to meet the metrological challenges we face over the next decade. To this end, I have asked the Chairs of each oral and poster session to give their views of their own session and of the more general requirements in that topic area. The feedback I received both during and subsequent to the meeting was almost uniformly good; this was borne out by the returned questionnaires, with most categories being scored excellent or good. I was delighted at the high standard of the presentations and to see delegates of such reputation and experience in the

  9. The Speaker Gender Gap at Critical Care Conferences.

    PubMed

    Mehta, Sangeeta; Rose, Louise; Cook, Deborah; Herridge, Margaret; Owais, Sawayra; Metaxa, Victoria

    2018-06-01

    To review women's participation as faculty at five critical care conferences over 7 years. Retrospective analysis of five scientific programs to identify the proportion of females and each speaker's profession based on conference conveners, program documents, or internet research. Three international (European Society of Intensive Care Medicine, International Symposium on Intensive Care and Emergency Medicine, Society of Critical Care Medicine) and two national (Critical Care Canada Forum, U.K. Intensive Care Society State of the Art Meeting) annual critical care conferences held between 2010 and 2016. Female faculty speakers. None. Male speakers outnumbered female speakers at all five conferences, in all 7 years. Overall, women represented 5-31% of speakers, and female physicians represented 5-26% of speakers. Nursing and allied health professional faculty represented 0-25% of speakers; in general, more than 50% of allied health professionals were women. Over the 7 years, Society of Critical Care Medicine had the highest representation of female (27% overall) and nursing/allied health professional (16-25%) speakers; notably, male physicians substantially outnumbered female physicians in all years (62-70% vs 10-19%, respectively). Women's representation on conference program committees ranged from 0% to 40%, with Society of Critical Care Medicine having the highest representation of women (26-40%). The female proportions of speakers, physician speakers, and program committee members increased significantly over time at the Society of Critical Care Medicine and U.K. Intensive Care Society State of the Art Meeting conferences (p < 0.05), but there was no temporal change at the other three conferences. There is a speaker gender gap at critical care conferences, with male faculty outnumbering female faculty. This gap is more marked among physician speakers than those speakers representing nursing and allied health professionals. Several organizational strategies can

  10. RCDPM 1992 Conference Book of Abstracts.

    ERIC Educational Resources Information Center

    1992

    This booklet contains 51 abstracts of papers presented at the 1992 conference for the Research Council for Diagnostic and Prescriptive Mathematics (RCDPM). Topics covered include: the use of expressive writing to enhance metacognition, adult assessment, cooperative learning assessment, visualization in problem solving, deaf students' beliefs about…

  11. International Society for the Social Studies Annual Conference Proceedings (Orlando, Florida, February 26-27, 2009). Volume 2009, Issue 1

    ERIC Educational Resources Information Center

    Russell, William Benedict, III, Ed.

    2009-01-01

    The "International Society for the Social Studies Annual Conference Proceedings" is a peer-reviewed professional publication published once a year following the annual conference. It contains the following papers: (1) Teacher Perceptions of Authentic Pedagogy: A Case Study of Professional Development in an African American High School's…

  12. PnLRR-RLK27, a novel leucine-rich repeats receptor-like protein kinase from the Antarctic moss Pohlia nutans, positively regulates salinity and oxidation-stress tolerance

    PubMed Central

    Wang, Jing; Liu, Shenghao; Li, Chengcheng; Wang, Tailin; Chen, Kaoshan

    2017-01-01

    Leucine-rich repeats receptor-like kinases (LRR-RLKs) play important roles in plant growth and development as well as stress responses. Here, 56 LRR-RLK genes were identified in the Antarctic moss Pohlia nutans transcriptome, which were further classified into 11 subgroups based on their extracellular domain. Of them, PnLRR-RLK27 belongs to the LRR II subgroup and its expression was significantly induced by abiotic stresses. Subcellular localization analysis showed that PnLRR-RLK27 was a plasma membrane protein. The overexpression of PnLRR-RLK27 in Physcomitrella significantly enhanced the salinity and ABA tolerance in their gametophyte growth. Similarly, PnLRR-RLK27 heterologous expression in Arabidopsis increased the salinity and ABA tolerance in their seed germination and early root growth as well as the tolerance to oxidative stress. PnLRR-RLK27 overproduction in these transgenic plants increased the expression of salt stress/ABA-related genes. Furthermore, PnLRR-RLK27 increased the activities of reactive oxygen species (ROS) scavengers and reduced the levels of malondialdehyde (MDA) and ROS. Taken together, these results suggested that PnLRR-RLK27 as a signaling regulator confer abiotic stress response associated with the regulation of the stress- and ABA-mediated signaling network. PMID:28241081

  13. 77 FR 38306 - GFIRST Conference Stakeholder Evaluation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ...), National Cyber Security Division (NCSD), United States Computer Emergency Readiness Team (US-CERT) will...- CERT, [email protected] . SUPPLEMENTARY INFORMATION: GFIRST is DHS's premier cyber conference and continually seeks to enhance collaborative efforts among cyber constituencies, partners, and stakeholders. The...

  14. Machine Learning: Proceedings of the Fifteenth International Conference

    DTIC Science & Technology

    1998-07-01

    Machine Learning Proceedings of the Fifteenth International Conference (ICML 󈨦) Edited by Jude Shavlik MADISON , WISCONSIN JULY 24-27, 1998 fc...W. Dayton Street Madison , WI 53706 PERFORMING ORGANIZATION REPORT NUMBER 144-HD17 9. SPONSORING /MONITORING AGENCY NAMES(S) AND ADDRESS(ES...ANISE Sad 239-18 298-102 University of Wisconsin - Madison Jude W. Shavlik Department of Computer Sciences Professor 1210 West Dayton Street

  15. Enhanced 2.7- and 2.9-μm emissions in Er{sup 3+}/Ho{sup 3+} doped fluoride glasses sensitized by Pr{sup 3+} ions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tian, Ying, E-mail: tianyingcjlu@163.com; Wei, Tao; Jing, Xufeng

    2016-04-15

    Highlights: • Enhanced 2.7 and 2.9 μm emissions were observed in fluoride glass. • Energy transfer mechanism among Er{sup 3+}, Ho{sup 3+} and Pr{sup 3+} was investigated. • High emission cross sections at 2.7- and 2.9-μm were obtained. - Abstract: In this report, Er{sup 3+}/Ho{sup 3+}/Pr{sup 3+} tri-doped fluoride glass was prepared. The enhancement of 2.7 and 2.9 μm emissions from Er{sup 3+}/Ho{sup 3+}doped system were achieved successfully after the addition of Pr{sup 3+}. The combination of low OH{sup −} concentration, low maximum phonon energy and high mid-infrared transmittance is beneficial to the realization of mid-infrared emissions. The energy transfermore » mechanism among Er{sup 3+}, Ho{sup 3+} and Pr{sup 3+} was investigated. The decay profiles of several levels were measured to further examine the enhanced mid-infrared emissions. Moreover, high stimulated emission cross sections at 2.7- and 2.9 μm (1.08 × 10{sup −20} cm{sup 2} and 2.0 × 10{sup −20} cm{sup 2}, respectively) were determined. Er{sup 3+}/Ho{sup 3+}/Pr{sup 3+} tri-doped fluoride glass might provide a new choice for mid-infrared laser.« less

  16. IL-27 Found to Play Significant Role in Conferring HIV Resistance | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer The human immunodeficiency virus (HIV) targets specific immune cells in the body known as macrophages because these are the cells that eliminate foreign material such as bacteria or viruses. HIV is able to reproduce and spread throughout the body if it can avoid destruction by macrophages. A recent study by Lue Dai, Ph.D., and colleagues revealed that the human cytokine IL-27 helps promote the body’s production of macrophages that are resistant to HIV. The study further found that IL-27 suppresses a gene known as SPTBN1, which facilitates the survival of HIV cells. This breakthrough research was recently published in the Journal of Experimental Medicine.

  17. Summit Conference on Environmental Education, Report and Recommendations. Conference Developed Under the Auspices of the Environmental Education Association of Illinois. Document No. 79/25.

    ERIC Educational Resources Information Center

    Buckman, Emily

    This report documents the recommendations derived from conference attention to five areas of concern: (1) responsibility of all sectors to enhance the individual's ability to make informed decisions on environmental issues; (2) the responsibility of all sectors to share information leading to enhanced ability to function in an environmentally…

  18. KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

    PubMed

    Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

    2015-01-01

    Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS.

  19. CONFERENCE NOTE: 1986 Conference on Precision Electromagnetic Measurements

    NASA Astrophysics Data System (ADS)

    1985-01-01

    The 1986 CPEM—the next in the series of biennial international conferences on electromagnetic metrology and related fundamental physical constants— will be held on June 23 through June 27, 1986, at the National Bureau of Standards, Gaithersburg, Maryland, USA. Sponsors are: NBS, the IEEE Instrumentation and Measurement Society and the Union Radio Scientifique Internationale. Papers describing original work, not previously published or presented, covering the theory, design, performance, simulation, or application of electromagnetic standards, measurements, techniques, instruments, or systems, are sought for presentation at CPEM '86. Papers on absolute electrical measurements and the use of quantum phenomena as electrical standards are especially sought in preparation for the meeting late in 1986 of the Comité Consultatif D'Electricité of the CIPM to decide on the adoption of international values for the constants 2e/h and h/e2 for the definition of the volt and the ohm, respectively. All papers concerned with electromagnetic measurements and standards and with related fundamental physics will be considered. Papers in the following fields are considered to be especially appropriate: EM-related fundamental constants and standards Direct current, low frequency, and RF Time, time interval, and frequency Antennas and fields Microwaves and millimeter waves Infrared, visible, and ultraviolet radiation Lasers Electro- and fibre optics Cryo-electronics Automated measurements Technical calibration services. The Conference language will be English. Authors should request an author's kit for the submission of a summary (500 to 1000 words) and abstract (maximum of 50 words) to be used to facilitate paper selection by the Program Committee. The summary must describe clearly the new and significant results and their importance. Summaries must be received on or before 1 February 1986 and should be sent to: Mr Norman B Belecki, Technical Program Chairman, CPEM '86, National

  20. 9th International Conference on Multiphase Flow (ICMF 2016)

    DTIC Science & Technology

    2016-08-12

    Office of Naval Research Global (ONRG) Final CSP (Collaborative Science Program) Report Administrative Details: Event Name: 9th ...International Conference on Multiphase Flows Event Dates: May 22-27, 2016 Event City and Country: Florence, Italy Grantee (Name and Contact...2043 Date of the Final Report: August 12, 2016 Abstract: This report summarizes the main activities and outcomes of the 9th International

  1. PREFACE: International Conference on Computing in High Energy and Nuclear Physics (CHEP'07)

    NASA Astrophysics Data System (ADS)

    Sobie, Randall; Tafirout, Reda; Thomson, Jana

    2007-07-01

    The 2007 International Conference on Computing in High Energy and Nuclear Physics (CHEP) was held on 2-7 September 2007 in Victoria, British Columbia, Canada. CHEP is a major series of international conferences for physicists and computing professionals from the High Energy and Nuclear Physics community, Computer Science and Information Technology. The CHEP conference provides an international forum to exchange information on computing experience and needs for the community, and to review recent, ongoing, and future activities. The CHEP'07 conference had close to 500 attendees with a program that included plenary sessions of invited oral presentations, a number of parallel sessions comprising oral and poster presentations, and an industrial exhibition. Conference tracks covered topics in Online Computing, Event Processing, Software Components, Tools and Databases, Software Tools and Information Systems, Computing Facilities, Production Grids and Networking, Grid Middleware and Tools, Distributed Data Analysis and Information Management and Collaborative Tools. The conference included a successful whale-watching excursion involving over 200 participants and a banquet at the Royal British Columbia Museum. The next CHEP conference will be held in Prague in March 2009. We would like thank the sponsors of the conference and the staff at the TRIUMF Laboratory and the University of Victoria who made the CHEP'07 a success. Randall Sobie and Reda Tafirout CHEP'07 Conference Chairs

  2. Dynamics of H3K27me3 methylation and demethylation in plant development

    PubMed Central

    Gan, Eng-Seng; Xu, Yifeng; Ito, Toshiro

    2015-01-01

    Epigenetic regulation controls multiple aspects of the plant development. The N-terminal tail of histone can be differently modified to regulate various chromatin activities. One of them, the trimethylation of histone H3 lysine 27 (H3K27me3) confers a repressive chromatin state with gene silencing. H3K27me3 is dynamically deposited and removed throughout development. While components of the H3K27me3 writer, Polycomb repressive complex 2 (PRC2), have been reported for almost 2 decades, it is only recently that JUMONJI (JMJ) proteins are reported as H3K27me3 demethylases, affirming the dynamic nature of histone modifications. This review highlights recent progress in plant epigenetic research, focusing on the H3K27me3 demethylases. PMID:26313233

  3. Linking information and people in a social system for academic conferences

    NASA Astrophysics Data System (ADS)

    Brusilovsky, Peter; Oh, Jung Sun; López, Claudia; Parra, Denis; Jeng, Wei

    2017-04-01

    This paper investigates the feasibility of maintaining a social information system to support attendees at an academic conference. The main challenge of this work was to create an infrastructure where users' social activities, such as bookmarking, tagging, and social linking could be used to enhance user navigation and maximize the users' ability to locate two important types of information in conference settings: presentations to attend and attendees to meet. We developed Conference Navigator 3, a social conference support system that integrates a conference schedule planner with a social linking service. We examined its potential and functions in the context of a medium-scale academic conference. In this paper, we present the design of the system's socially enabled features and report the results of a conference-based study. Our study demonstrates the feasibility of social information systems for supporting academic conferences. Despite the low number of potential users and the short timeframe in which conferences took place, the usage of the system was high enough to provide sufficient data for social mechanisms. The study shows that most critical social features were highly appreciated and used, and provides direction for further research.

  4. National Conference on the Educational Applications of Geographic Information Systems (EdGIS): Conference Report (1st, Washington, D.C., January 27-29, 1994).

    ERIC Educational Resources Information Center

    Barstow, Daniel, Ed.; And Others

    The goals of the Educational Applications of Geographic Information Systems (EdGIS) Conference were to: showcase current applications of Geographic Information Systems (GIS), remote sensing, and other mapping software in pre-college education; develop a better understanding of the current state of the art in both GIS software and related…

  5. Proceeding of the 2014 sorghum improvement conference of north america (SICNA)

    USDA-ARS?s Scientific Manuscript database

    The 2014 Sorghum Improvement Conference of North America (SICNA 2014) meeting was held at the Texas A&M AgriLife Research and Extension Center , Agnes, Corpus Christi, TX on June 25-27, 2014. The meeting was attended by about 80 participants representing a diverse cross section of the sorghum indus...

  6. The Residential Conference Center as a Learning Sanctuary.

    ERIC Educational Resources Information Center

    Simpson, Edward G., Jr.

    1990-01-01

    Adult learning in residential conference centers is enhanced when a philosophical basis underlies their design. Six integrated elements for the development of learning sanctuaries are historical context, educational program, physical environment, support services, technology, and human resources. (SK)

  7. The Conference Board and Education: A Long Standing Commitment. Annual Report 1989.

    ERIC Educational Resources Information Center

    Conference Board, Inc., New York, NY.

    Since its founding in 1916, the goals of the Conference Board have been to improve the business enterprise system and to enhance the contribution of business to society. To accomplish this, the Conference Board sponsors forums and research to identify areas of concern and to stimulate the exchange of ideas among leading industry executives. The…

  8. The International Society for the Social Studies Annual Conference Proceedings (Orlando, Florida, February 27-28, 2014). Volume 2014, Issue 1

    ERIC Educational Resources Information Center

    Russell, William Benedict, III, Ed.

    2014-01-01

    The "International Society for the Social Studies (ISSS) Annual Conference Proceedings" is a peer-reviewed professional publication published once a year following the annual conference. The following papers are included in the 2014 proceedings: (1) Legal Profession in the Technological Era with Special Reference to Women Lawyers in…

  9. 2014 Global Conference on Polymer and Composite Materials (PCM 2014)

    NASA Astrophysics Data System (ADS)

    2014-08-01

    The 2014 Global Conference on Polymer and Composite Materials (PCM 2014) sponsored by Ningbo Adhesives and Products Industry Association, Shanghai Bonding Technology Association, Zhejiang Bonding Technology Association, Wuhan Bonding Technology Association, Hebei Bonding and Coatings Association and Polyurethane Industry Association was held from May 27 to May 29 2014 in Ningbo, China. The technical program consisted of 8 international keynote speakers, oral presentations, and a poster session. The conference also included an industrial exhibition where more than 50 companies displayed in their booths their most recent advanced products and services. The present issue of IOP Conference Series: Materials Science and Engineering (MSE) records the proceedings of PCM 2014 and contains 37 specially selected manuscripts submitted to PCM2014 conference. The electronic submission and handling of manuscripts via the conference website, including the selection of reviewers and evaluation of manuscripts, were identical to the procedures applied to manuscripts submitted as regular contributions for publication. The organization of this conference and the preparation of proceedings volumes would have been impossible without the tremendous efforts and dedication of many individuals, especially from Ms. Yin Pan, who oversaw the organization of the conference and the program; and a large team of reviewers with their timely submission of quality reports. We express our sincere thanks to all authors and presenters for their contributions. We also thank very much our sponsors for their generous support. The 2015 Global Conference on Polymer and Composite Materials (PCM2015) will be held in Beijing, China on May 16-18, 2015. Beijing, the capital of the People's Republic of China and one of the most populous cities in the world, will welcome to all participants for a renewed and vibrant conference. Prof. Dr. Esteban Broitman Linköping University, Sweden Editor in Chief — PCM2014

  10. Serving Deaf-Blind Children. Theme of the International Conference on Deaf-Blind Children (4th, 22-27 August 1971, Perkins School for the Blind).

    ERIC Educational Resources Information Center

    Perkins School for the Blind, Watertown, MA.

    Presented are 30 papers given at a 5-day international conference on serving deaf-blind children. Additionally provided are the conference agenda, a review of the conference, reports of the nominations and resolutions committees, and a list of conference participants. Among the papers are the following titles: "Programs for Non-Verbal Children",…

  11. The International Society for the Social Studies Annual Conference Proceedings (Orlando, Florida, February 26-27, 2015) Volume 2015, Issue 1

    ERIC Educational Resources Information Center

    Russell, William Benedict, III, Ed.

    2015-01-01

    The "International Society for the Social Studies (ISSS) Annual Conference Proceedings" is a peer-reviewed professional publication published once a year following the annual conference. The following papers are included in the 2015 proceedings: (1) Local History and Local Culture at the Core of Elementary Social Studies Curriculum (C.…

  12. Annual NASSGP/NCHELP Research Network Conference Proceedings (5th, Denver, Colorado, May 25-27, 1988).

    ERIC Educational Resources Information Center

    Webster, Jeff, Ed.

    This volume presents papers from a 1988 conference on collegiate student financial aid which focused on trends in the cost of higher education, student loan defaults, trends in borrowing, the impact of congressional legislation, and state-level financial aid research. The papers are grouped in five sections corresponding to the five topics, and…

  13. Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

    PubMed

    Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2018-01-01

    Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

  14. Financial Measures Conference: Progress in Measuring Financial Conditions of Colleges and Universities. Proceedings of the 1979 Working Conference (Annapolis, Maryland, September 27-28, 1979).

    ERIC Educational Resources Information Center

    Stich, Judith, Ed.

    Proceedings of the 1979 Financial Measures Conference which assess "Progress in Measuring Financial Conditions of Colleges and Universities" are presented. Focus is the prospective uses of financial indicators and the results of attempts to employ indicators at the institutional, state, regional, and federal levels for management, and…

  15. Charleston Conference Proceedings (21st, Charleston, South Carolina, November 1-3, 2001).

    ERIC Educational Resources Information Center

    Strauch, Katina, Ed.

    This proceedings of the 2001 Charleston Conference on library science contains the keynote address and the text of 27 presentations discussing the latest developments in the digital environment, serials, collection development, books and publishing, consortia, and personnel development as follows: "The Trends They Are A'Changing" (Tom Sanville);…

  16. PREFACE: International Conference "Trends in Spintronics and Nanomagnetism" (TSN-2010)

    NASA Astrophysics Data System (ADS)

    Maruccio, Giuseppe; Sanvito, Stefano; Hoffmann, Germar; Wiesendanger, Roland; Rowan, Alan

    2011-03-01

    Conference banner The International Conference "Trends in Spintronics and Nanomagnetism" (TSN-2010), was organized by partners of the EU-project SpiDME and held in the historical city of Lecce, Italy from 23-27 May 2010, at the Ecotekne Campus, University of Salento. The conference provided an international forum to discuss recent progress and future trends in the field. In particular, the aim was to bring together the community of more conventional spin-transport, with that of molecular and nano-magnetism. The main topics of TSN-2010 were: MATERIALSSPIN-PHYSICS AND THEORY - Molecular Magnets- Spin injection - Magnetic nanoparticles and nanowires- Domain walls, spin torque and vortex dynamics - Magnetic semiconductors- Numerical modeling of organic nanomagnetism - Multiferroics and transition metal oxides APPLICATIONSADVANCES IN CHARACTERIZATION - Magnetic Multilayers- Magneto-optical characterization and spin manipulation - Spin-photonics- Intrinsic spin transport mechanism in organics - Molecular and nano-spintronics- Organometallic molecules on surfaces - Spin-based quantum computation- Single molecular magnets on surfaces - Magnetism for sensing and nanomedicine- Nanoscale characterization and spin-sensitive SPM The scientific programme started on Monday 24 May and ended on Thursday 27 May. The Nobel Laureate A Fert attended the conference giving a plenary talk and the programme also featured invited presentations by (in alphabetical order): M Aeschlimann, M Affronte, N Atodiresei, P A Bobbert, A Dediu, N Kioussis, L W Molenkamp, J Moodera, V Prigodin, M Ruben, R Sessoli, R Tan, and H Wende. TSN2010 had 150 attendees who came from around the globe to present their latest research in 100 oral presentations. Contributed talks were selected by the program committee, composed of Giuseppe Maruccio, Ross Rinaldi, Valentina Arima, Fabio Della Sala, Maurizio Martino (Universitá del Salento, NNL Institute Nanoscience-CNR, Lecce, Italy), Stefano Sanvito (Trinity College

  17. COERC 2002: Appreciating Scholarship. Proceedings of the Annual College of Education Research Conference (1st, Miami, Florida, April 27, 2002).

    ERIC Educational Resources Information Center

    Nielsen, Sarah M., Ed.; Rocco, Tonette S., Ed.

    This conference was designed to offer a view to novice scholars of what scholarship is and provide insights on how to share knowledge with others. The keynote speech by Lisa Delpit, "The Role of Scholarship," is not included in this volume. Other conference papers, presented in alphabetical order by first author, include: (1) "Social Studies in…

  18. Fifth International Conference on Squeezed States and Uncertainty Relations

    NASA Technical Reports Server (NTRS)

    Han, D. (Editor); Janszky, J. (Editor); Kim, Y. S. (Editor); Man'ko, V. I. (Editor)

    1998-01-01

    The Fifth International Conference on Squeezed States and Uncertainty Relations was held at Balatonfured, Hungary, on 27-31 May 1997. This series was initiated in 1991 at the College Park Campus of the University of Maryland as the Workshop on Squeezed States and Uncertainty Relations. The scientific purpose of this series was to discuss squeezed states of light, but in recent years the scope is becoming broad enough to include studies of uncertainty relations and squeeze transformations in all branches of physics including quantum optics and foundations of quantum mechanics. Quantum optics will continue playing the pivotal role in the future, but the future meetings will include all branches of physics where squeeze transformations are basic. As the meeting attracted more participants and started covering more diversified subjects, the fourth meeting was called an international conference. The Fourth International Conference on Squeezed States and Uncertainty Relations was held in 1995 was hosted by Shanxi University in Taiyuan, China. The fifth meeting of this series, which was held at Balatonfured, Hungary, was also supported by the IUPAP. In 1999, the Sixth International Conference will be hosted by the University of Naples in 1999. The meeting will take place in Ravello near Naples.

  19. Thrombin and factor Xa link the coagulation system with liver fibrosis.

    PubMed

    Dhar, Ameet; Sadiq, Fouzia; Anstee, Quentin M; Levene, Adam P; Goldin, Robert D; Thursz, Mark R

    2018-05-08

    Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated. C57BL/6 J mice were administered thioacetamide (TAA) for 8 weeks with Rivaroxaban (n = 15) or Dabigatran (n = 15). Control animals received TAA alone (n = 15). Fibrosis was scored and quantified using digital image analysis and hepatic tissue hydroxyproline estimated. Stellate cells treated with FXa and thrombin demonstrated upregulation of procollagen, TGF-beta, αSMA and significant cell contraction (43.48%+/- 4.12) compared to culturing with FXa or thrombin alone (26.90%+/- 8.90, p = 0.02; 13.1%+/- 9.84, p < 0.001). Mean fibrosis score, percentage area of fibrosis and hepatic hydroxyproline content (2.46 vs 4.08, p = 0.008; 2.02% vs 3.76%, p = 0.012; 276.0 vs 651.3, p = 0.0001) were significantly reduced in mice treated with the FXa inhibitor compared to control mice. FXa inhibition was significantly more effective than thrombin inhibition in reducing percentage area of fibrosis and hepatic hydroxyproline content (2.02% vs 3.70%,p = 0.031; 276.0 vs 413.1,p = 0.001). FXa promotes stellate cell contractility and activation. Early inhibition of coagulation using a FXa inhibitor significantly reduces TAA induced murine liver fibrosis and may be a viable treatment for liver fibrosis in patients.

  20. Enhanced surveillance for the Third United Nations Conference on Small Island Developing States, Apia, Samoa, September 2014

    PubMed Central

    Saketa, Salanieta; Durand, Alexis; Vaai-Nielsen, Saine; Leong-Lui, Tile Ah; Naseri, Take; Matalima, Ailuai; Amosa, Filipina; Mercier, Alize; Lepers, Christelle; Lal, Vjesh; Wojcik, Richard; Lewis, Sheri; Roth, Adam; Souares, Yvan; Merilles, Onofre Edwin; Hoy, Damian

    2017-01-01

    The Ministry of Health in Samoa, in partnership with the Pacific Community, successfully implemented enhanced surveillance for the high-profile Third United Nations Conference on Small Island Developing States held concurrently with the popular local Teuila festival during a widespread chikungunya outbreak in September 2014. Samoa’s weekly syndromic surveillance system was expanded to 12 syndromes and 10 sentinel sites from four syndromes and seven sentinel sites; sites included the national hospital, four private health clinics and three national health service clinics. Daily situation reports were produced and were disseminated through PacNet (the e-mail alert and communication tool of the Pacific Public Health Surveillance Network) together with daily prioritized line lists of syndrome activity to facilitate rapid response and investigation by the Samoan EpiNet team. Standard operating procedures for surveillance and response were introduced, together with a sustainability plan, including a monitoring and evaluation framework, to facilitate the transition of the mass gathering surveillance improvements to routine surveillance. The enhanced surveillance performed well, providing vital disease early warning and health security assurance. A total of 2386 encounters and 708 syndrome cases were reported. Influenza-like illness was the most frequently seen syndrome (17%). No new infectious disease outbreaks were recorded. The experience emphasized: (1) the need for a long lead time to pilot the surveillance enhancements and to maximize their sustainability; (2) the importance of good communication between key stakeholders; and (3) having sufficient staff dedicated to both surveillance and response. PMID:28409055

  1. Enhanced surveillance for the Third United Nations Conference on Small Island Developing States, Apia, Samoa, September 2014.

    PubMed

    White, Paul; Saketa, Salanieta; Durand, Alexis; Vaai-Nielsen, Saine; Leong-Lui, Tile Ah; Naseri, Take; Matalima, Ailuai; Amosa, Filipina; Mercier, Alize; Lepers, Christelle; Lal, Vjesh; Wojcik, Richard; Lewis, Sheri; Roth, Adam; Souares, Yvan; Merilles, Onofre Edwin; Hoy, Damian

    2017-01-01

    The Ministry of Health in Samoa, in partnership with the Pacific Community, successfully implemented enhanced surveillance for the high-profile Third United Nations Conference on Small Island Developing States held concurrently with the popular local Teuila festival during a widespread chikungunya outbreak in September 2014. Samoa's weekly syndromic surveillance system was expanded to 12 syndromes and 10 sentinel sites from four syndromes and seven sentinel sites; sites included the national hospital, four private health clinics and three national health service clinics. Daily situation reports were produced and were disseminated through PacNet (the e-mail alert and communication tool of the Pacific Public Health Surveillance Network) together with daily prioritized line lists of syndrome activity to facilitate rapid response and investigation by the Samoan EpiNet team. Standard operating procedures for surveillance and response were introduced, together with a sustainability plan, including a monitoring and evaluation framework, to facilitate the transition of the mass gathering surveillance improvements to routine surveillance. The enhanced surveillance performed well, providing vital disease early warning and health security assurance. A total of 2386 encounters and 708 syndrome cases were reported. Influenza-like illness was the most frequently seen syndrome (17%). No new infectious disease outbreaks were recorded. The experience emphasized: (1) the need for a long lead time to pilot the surveillance enhancements and to maximize their sustainability; (2) the importance of good communication between key stakeholders; and (3) having sufficient staff dedicated to both surveillance and response.

  2. First CLIPS Conference Proceedings, volume 1

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The first Conference of C Language Production Systems (CLIPS) hosted by the NASA-Lyndon B. Johnson Space Center in August 1990 is presented. Articles included engineering applications, intelligent tutors and training, intelligent software engineering, automated knowledge acquisition, network applications, verification and validation, enhancements to CLIPS, space shuttle quality control/diagnosis applications, space shuttle and real-time applications, and medical, biological, and agricultural applications.

  3. 7th international conference on case histories in geotechnical engineering.

    DOT National Transportation Integrated Search

    2013-08-01

    Funding used to enhance objectives of conference and to present successful case histories of varied project, orally, in posters and in : proceedings. This will become a storehouse of knowledge for future reference.

  4. The Off-Campus Library Services Conference Proceedings (7th, San Diego, California, October 25-27, 1995).

    ERIC Educational Resources Information Center

    Jacob, Carol J., Comp.

    This conference proceedings of off-campus library services includes 37 papers covering the following topics: ensuring excellence in distance library services; DePaul University's research consultation service; using videos to promote library service; a virtual academic library project in England; student-centered library instruction off campus;…

  5. Annual Quality Assurance Conference Presentations by Glynda Smith and Carrie Miller

    EPA Pesticide Factsheets

    25th Annual Quality Assurance Conference Presentation: Disinfectants/Disinfection Byproducts –Rules and Requirements and Presentation: Long Term 2 Enhanced Surface Water Treatment Rule (LT2) Cryptosporidium Monitoring

  6. PREFACE: 27th Summer School and International Symposium on the Physics of Ionized Gases (SPIG 2014)

    NASA Astrophysics Data System (ADS)

    Marić, Dragana; Milosavljević, Aleksandar R.; Mijatović, Zoran

    2014-12-01

    This volume of Journal of Physics: Conference Series contains a selection of papers presented at the 27th Summer School and International Symposium on the Physics of Ionized Gases - SPIG 2014, as General Invited Lectures, Topical Invited Lectures, Progress Reports and associated Workshop Lectures. The conference was held in Belgrade, Serbia, from 26-29 August 2014 at the Serbian Academy of Sciences and Arts. It was organized by the Institute of Physics Belgrade, University of Belgrade and Serbian Academy of Sciences and Arts, under the auspices of the Ministry of Education, Science and Technological Development, Republic of Serbia. A rare virtue of a SPIG conference is that it covers a wide range of topics, bringing together leading scientists worldwide to present and discuss state-of-the art research and the most recent applications, thus stimulating a modern approach of interdisciplinary science. The Invited lectures and Contributed papers are related to the following research fields: 1. Atomic Collision Processes (Electron and Photon Interactions with Atomic Particles, Heavy Particle Collisions, Swarms and Transport Phenomena) 2. Particle and Laser Beam Interactions with Solids (Atomic Collisions in Solids, Sputtering and Deposition, Laser and Plasma Interaction with Surfaces) 3. Low Temperature Plasmas (Plasma Spectroscopy and other Diagnostic Methods, Gas Discharges, Plasma Applications and Devices) 4. General Plasmas (Fusion Plasmas, Astrophysical Plasmas and Collective Phenomena) Additionally, the 27th SPIG encompassed three workshops that are closely related to the scope of the conference: • The Workshop on Dissociative Electron Attachment (DEA) - Chaired by Prof. Nigel J Mason, OBE, The Open University, United Kingdom • The Workshop on X-ray Interaction with Biomolecules in Gas Phase (XiBiGP), Chaired by Dr. Christophe Nicolas, Synchrotron SOLEIL, France • The 3rd International Workshop on Non-Equilibrium Processes (NonEqProc) - Chaired by Prof

  7. 49 CFR 1562.27 - Costs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY OPERATIONS IN THE WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for Certain Operations § 1562.27...

  8. 49 CFR 1562.27 - Costs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY OPERATIONS IN THE WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for Certain Operations § 1562.27...

  9. 49 CFR 1562.27 - Costs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY OPERATIONS IN THE WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for Certain Operations § 1562.27...

  10. 49 CFR 1562.27 - Costs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY OPERATIONS IN THE WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for Certain Operations § 1562.27...

  11. 49 CFR 1562.27 - Costs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY OPERATIONS IN THE WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for Certain Operations § 1562.27...

  12. PREFACE: 8th International Conference on Advanced Infocomm Technology (ICAIT 2015)

    NASA Astrophysics Data System (ADS)

    Qiu, M.; Zhao, W.; Shum, P. Ping

    2016-02-01

    The 2015 IEEE 8th International Conference on Advanced Infocomm Technology (ICAIT 2015) was held in Hangzhou, China, during 25-27, October 2015, following the successes of previous events held in Shenzhan, Xi'an, Haikou, Wuhan, Paris, Hsinchu, and Fuzhou. This year the ICAIT 2015 aimed to bring together researchers, developers, and users in both industry and academia in the world for sharing state-of-art results, for exploring new areas of research and development, and to discuss emerging issues on advanced infocomm technology. The conference was hosted by Zhejiang University and China Satellite Maritime Tracking and Control Department. It was organized by the State Ley Laboratory of Modern Optical Instrumentation of Zhejiang University, in collaboration with the Joint International Research Laboratory of Photonics of Zhejiang University. More than 150 international participants from 9 foreign countries attended the conference. The ICAIT 2015 was featured with 4 plenary lectures (by Xiaoyi Bao, Benjamin J. Eggleton, Min Gu, and Chinlon Lin, respectively), and 40 invited talks, in which a wide range of topics were covered and the most recent significant results were presented. Including oral and poster presentations, 138 abstracts were presented in the conference, some of which were selected to publish in full papers in this edition of Journal of Physics: Conference Series. With the excellent quality of the presentations, the ICAIT 2015 was a success. We also wish to thank the sponsors of the conference, and particularly the technical program committee and the local organizing committee.

  13. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together,more » and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site

  14. Incorporation of Bacterial Blight Resistance Genes Into Lowland Rice Cultivar Through Marker-Assisted Backcross Breeding.

    PubMed

    Pradhan, Sharat Kumar; Nayak, Deepak Kumar; Pandit, Elssa; Behera, Lambodar; Anandan, Annamalai; Mukherjee, Arup Kumar; Lenka, Srikanta; Barik, Durga Prasad

    2016-07-01

    Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in many rice growing countries. Pyramided lines carrying two BB resistance gene combinations (Xa21+xa13 and Xa21+xa5) were developed in a lowland cultivar Jalmagna background through backcross breeding by integrating molecular markers. In each backcross generation, markers closely linked to the disease resistance genes were used to select plants possessing the target genes. Background selection was continued in those plants carrying resistant genes until BC(3) generation. Plants having the maximum contribution from the recurrent parent genome were selected in each generation and hybridized with the recipient parent. The BB-pyramided line having the maximum recipient parent genome recovery of 95% was selected among BC3F1 plants and selfed to isolate homozygous BC(3)F(2) plants with different combinations of BB resistance genes. Twenty pyramided lines with two resistance gene combinations exhibited high levels of tolerance against the BB pathogen. In order to confirm the resistance, the pyramided lines were inoculated with different X. oryzae pv. oryzae strains of Odisha for bioassay. The genotypes with combination of two BB resistance genes conferred high levels of resistance to the predominant X. oryzae pv. oryzae isolates prevalent in the region. The pyramided lines showed similarity with the recipient parent with respect to major agro-morphologic traits.

  15. Dielectric platforms for surface-enhanced spectroscopies (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Maier, Stefan A.

    2016-03-01

    Plasmonic nanostructures serve as the main backbone of surface enhanced sensing methodologies, yet the associated optical losses lead to localized heating as well as quenching of molecules, complicating their use for enhancement of fluorescent emission. Additionally, conventional plasmonic materials are limited to operation in the visible part of the spectrum. We will elucidate how nanostructures consisting of conventional and polar dielectrics can be employed as a highly promising alternative platform. Dielectric nanostructures can sustain scattering resonances due to both electric and magnetic Mie modes. We have recently predicted high enhanced local electromagnetic field hot spots in dielectric nanoantenna dimers, with the hallmark of spot sizes comparable to those achievable with plasmonic antennas, but with lower optical losses. Here, we will present first experimental evidence for both fluorescence and Raman enhancement in dielectric nanoantennas, including a direct determination of localized heating, and compare to conventional Au dimer antennas. The second part of the talk will focus on the mid-infrared regime of the electromagnetic spectrum, outlining possibilities for surface enhanced infrared absorption spectroscopy based on polar and hyperbolic dielectrics.

  16. The Challenge of Change. Annual National SOICC Conference Summary (10th, Portland, Oregon, July 27-30, 1987).

    ERIC Educational Resources Information Center

    National Occupational Information Coordinating Committee (DOL/ETA), Washington, DC.

    This document contains summaries of 43 presentations given at the state Occupational Information Coordinating Committee (SOICC) conference: "DoD Career Information Resources" (Wright, Sellman); "Public Relations in a Changing Political Environment: Strategies for SOICCs" (Walker); "Updating Career Exploration and…

  17. The Conference Proceedings of the 1997 Air Transport Research Group (ATRG) of the WCTR Society. Volume 1

    NASA Technical Reports Server (NTRS)

    Oum, Tae Hoon (Editor); Bowen, Brent D. (Editor)

    1997-01-01

    The UNO Aviation Institute has published the 1997 Proceedings of the Air Transport Research Group of the World Conference on Transportation Research (WCTR) Society. Items published in this three volume, seven monograph series were presented at the triennial ATRG Conference held at the University of British Columbia, June 25-27, 1997. A wide variety of policy issues are discussed including the following: open- skies agreements, liberalization, globalization, airline competition, airport performance, pricing, hubs, and safety, among others.

  18. Conference report: Bioanalysis highlights from the 2012 American Association of Pharmaceutical Scientists National Biotechnology Conference.

    PubMed

    Crisino, Rebecca M; Geist, Brian; Li, Jian

    2012-09-01

    The American Association of Pharmaceutical Scientists (AAPS) is an international forum for the exchange of knowledge among scientists to enhance their contributions to drug development. The annual National Biotechnology Conference, organized by the AAPS on 21-23 May 2012 in San Diego, CA, USA, brings together experts from various disciplines representing private industry, academia and governing institutions dedicated toward advancing the scientific and technological progress related to discovery, development and manufacture of medical biotechnology products. Over 300 scientific poster presentations and approximately 50 oral presentation and discussion sessions examined a breadth of topics pertaining to biotechnology drug development, such as the advancement of vaccines and biosimilars, emerging and innovative technologies, nonclinical and clinical bioanalysis, and regulatory updates. This conference report highlights the existing challenges with ligand-binding assays, emerging challenges, innovative integration of various technology platforms and applicable regulatory considerations as they relate to immunogenicity and pharmacokinetic bioanalytical assessments.

  19. Silencing of copine genes confers common wheat enhanced resistance to powdery mildew.

    PubMed

    Zou, Baohong; Ding, Yuan; Liu, He; Hua, Jian

    2018-06-01

    Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt), is a major threat to the production of wheat (Triticum aestivum). It is of great importance to identify new resistance genes for the generation of Bgt-resistant or Bgt-tolerant wheat varieties. Here, we show that the wheat copine genes TaBON1 and TaBON3 negatively regulate wheat disease resistance to Bgt. Two copies of TaBON1 and three copies of TaBON3, located on chromosomes 6AS, 6BL, 1AL, 1BL and 1DL, respectively, were identified from the current common wheat genome sequences. The expression of TaBON1 and TaBON3 is responsive to both pathogen infection and temperature changes. Knocking down of TaBON1 or TaBON3 by virus-induced gene silencing (VIGS) induces the up-regulation of defence responses in wheat. These TaBON1- or TaBON3-silenced plants exhibit enhanced wheat disease resistance to Bgt, accompanied by greater accumulation of hydrogen peroxide and heightened cell death. In addition, high temperature has little effect on the up-regulation of defence response genes conferred by the silencing of TaBON1 or TaBON3. Our study shows a conserved function of plant copine genes in plant immunity and provides new genetic resources for the improvement of resistance to powdery mildew in wheat. © 2017 BSPP AND JOHN WILEY & SONS LTD.

  20. Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus.

    PubMed

    Abou El Hassan, Mohamed; Yu, Tao; Song, Lan; Bremner, Rod

    2015-05-15

    CIITA (or MHC2TA) coordinates constitutive and IFN-γ-induced expression of MHC class II genes. IFN-γ responsiveness of CIITA requires BRG1 (SMARCA4), the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF). SWI/SNF is defective in many human cancers, providing a mechanism to explain IFN-γ resistance. BRG1 dependency is mediated through remote elements. Short CIITA reporters lacking these elements respond to IFN-γ, even in BRG1-deficient cells, suggesting that BRG1 counters a remote repressive influence. The nature of this distal repressor is unknown, but it would represent a valuable therapeutic target to reactivate IFN-γ responsiveness in cancer. In this article, we show that the polycomb repressive complex 2 (PRC2) components EZH2 and SUZ12, as well as the associated histone mark H3K27me3, are codetected at interenhancer regions across the CIITA locus. IFN-γ caused a BRG1-dependent reduction in H3K27me3, associated with nucleosome displacement. SUZ12 knockdown restored IFN-γ responsiveness in BRG1-null cells, and it mimicked the ability of BRG1 to induce active histone modifications (H3K27ac, H3K4me) at the -50-kb enhancer. Thus, PRC2 confers BRG1 dependency on the CIITA locus. Our data suggest that, in addition to its known roles in promoting stemness and proliferation, PRC2 may inhibit immune surveillance, and it could be targeted to reactivate CIITA expression in SWI/SNF deficient cancers. Copyright © 2015 by The American Association of Immunologists, Inc.

  1. 27-hydroxycholesterol induces production of tumor necrosis factor-alpha from macrophages.

    PubMed

    Kim, Sun-Mi; Jang, Hyojung; Son, Yonghae; Lee, Sae-A; Bae, Sun-Sik; Park, Young Chul; Eo, Seong-Kug; Kim, Koanhoi

    2013-01-11

    Enhanced production of TNF-α from macrophages promotes development and instability of atherosclerotic plaques, but involvement of lipid component in TNF-α production has not been clarified in atherosclerosis. We attempted to determine whether cholesterol oxidation products (oxysterols) could modify TNF-α production. Treatment of THP-1 cells with 27-hydroxycholesterol (27OHChol) or 7α-hydroxycholesterol (7αOHChol) resulted in a profound increase in TNF-α transcription, while treatment with an identical concentration of cholesterol and 7-ketochoelsterol did not lead to any change in TNF-α expression. Treatment with 27OHChol resulted in increased synthesis, as well as secretion, of TNF-α, while 7αOHChol led to increased synthesis of TNF-α without affecting secretion of the cytokine. Co-treatment with 7αOHChol or 27OHChol and LPS resulted in synergistically enhanced or augmented secretion of TNF-α. Treatment with TO-901317, pertussis toxin, PP2, and LY294002 resulted not only in attenuated transcription of TNF-α induced by 27OHChol and 7αOHChol, but also secretion of TNF-α enhanced by 27OHChol. This is the first report demonstrating enhanced production of TNF-α in macrophages by treatment with oxysterols which are detected in abundance in atheromatous lesions; in addition, results of the current study provide evidence indicating that certain types of oxysterols contribute to development of atherosclerosis by promoting production of proinflammatory cytokines. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... System. The conference will explore the progress made on the priorities for addressing risks to...

  3. NIH state-of-the-science conference statement: Enhancing use and quality of colorectal cancer screening.

    PubMed

    Steinwachs, Donald; Allen, Jennifer Dacey; Barlow, William Eric; Duncan, R Paul; Egede, Leonard E; Friedman, Lawrence S; Keating, Nancy L; Kim, Paula; Lave, Judith R; LaVeist, Thomas A; Ness, Roberta B; Optican, Robert J; Virnig, Beth A

    2010-02-04

    To provide health care providers, patients, and the general public with a responsible assessment of currently available data on enhancing use and quality of colorectal cancer screening. A non-DHHS, nonadvocate 13-member panel representing the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. The panel found that despite substantial progress toward higher colorectal cancer screening rates nationally, screening rates fall short of desirable levels. Targeted initiatives to improve screening rates and reduce disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. This could be achieved by utilizing the full range of screening options and evidence-based interventions for increasing screening rates. With additional investments in quality monitoring, Americans could be assured that all

  4. Biennial Conference on Chemical Education: Abstracts of Papers (9th, Bozeman, Montana, July 27-August 2, 1986).

    ERIC Educational Resources Information Center

    1986

    This document includes summaries of conference presentations dealing with a wide variety of topics, including chemistry units for the elementary classroom, science experimentation in the secondary school, computer simulations, computer interfaces, videodisc technology, correspondence teaching of general chemistry, interdisciplinary energy courses,…

  5. Looking to the Future: Themes from the Third National Conference for Counseling Psychology.

    ERIC Educational Resources Information Center

    Rude, Stephanie S.; And Others

    1988-01-01

    Presents summary of common themes from the Third National Conference for Counseling Psychology including strategies to enhance visibility and political strength, and ways to improve training of counseling psychologists by enhancing rigor, scientific thinking, professional identity, and ability to work in diverse and emerging settings. Discusses…

  6. Materials Presented at the MU-SPIN Ninth Annual Users' Conference

    NASA Technical Reports Server (NTRS)

    Harrington, James, Jr.; Brown, Robin L.

    2000-01-01

    MU-SPIN's Ninth Annual Users' Conference was held from September 21-25, 1999, and hosted by Florida International University, a predominantly Hispanic-serving institution located in Miami, Florida. Its theme was A New MU-SPIN for the New Millennium. The MU-SPIN conference focused on showcasing successful experiences with information technology to enhance faculty and student development in areas of scientific and technical research and education. And, it provided a forum for discussing increased participation of MU-SPIN schools in NASA Flight Missions and NASA Educational and Public Outreach activities.

  7. Ada Compiler Validation Summary Report: Certificate Number 880318W1. 09042, International Business Machines Corporation, IBM Development System for the Ada Language, Version 2.1.0, IBM 4381 under MVS/XA, Host and Target

    DTIC Science & Technology

    1988-03-28

    International Business Machines Corporation IBM Development System for the Ada Language, Version 2.1.0 IBM 4381 under MVS/XA, host and target Completion...Joint Program Office, AJPO 20. ABSTRACT (Continue on reverse side if necessary and identify by block number) International Business Machines Corporation...in the compiler listed in this declaration. I declare that International Business Machines Corporation is the owner of record of the object code of

  8. PREFACE: 7th European Conference on Applied Superconductivity (EUCAS '05)

    NASA Astrophysics Data System (ADS)

    Weber, Harald W.; Sauerzopf, Franz M.

    2006-07-01

    This issue of Journal of Physics: Conference Series contains those contributed papers that were submitted to the Conference Proceedings of the 7th European Conference on Applied Superconductivity (EUCAS '05) on 11 - 15 September 2005. The plenary and invited papers were published in the journal Superconductor Science and Technology 19 2006 (March issue). The scientific aims of EUCAS '05 followed the tradition established at the preceding conferences in Göttingen, Edinburgh, Eindhoven, Sitges (Barcelona), Lyngby (Copenhagen) and finally Sorrento (Napoli). The focus was placed on the interplay between the most recent developments in superconductor research and the positioning of applications of superconductivity in the marketplace. Although initially founded as an exchange forum mainly for European scientists, it has gradually developed into a truly international meeting with significant attendance from the Far East and the United States. The Vienna conference attracted 813 participants in the scientific programme and 90 guests: of the particpants 59% were from Europe, 31% from the Far East, 6% from the United States and Canada and 4% from other nations worldwide. There were 32 plenary and invited lectures highlighting the state-of-the-art in the areas of materials, large-scale and small-scale applications, and 625 papers were contributed (556 of these were posters) demonstrating the broad range of exciting activities in all research areas of our field. A total of 27 companies presented their most recent developments in the field. This volume contains 349 papers, among them 173 on materials (49.6%), 90 on large scale applications (25.8%) and 86 on small scale applications (24.6%). EUCAS '05 generated a feeling of optimism and enthusiasm for this fascinating field of research and for its well established technological potential, especially among the numerous young researchers attending this Conference. We are grateful to all those who participated in the meeting and

  9. The Quantitative Crunch: The Impact of Bibliometric Research Quality Assessment Exercises on Academic Development at Small Conferences

    ERIC Educational Resources Information Center

    Henderson, Michael; Shurville, Simon; Fernstrom, Ken

    2009-01-01

    Purpose: Small and specialist inter-disciplinary conferences, particularly those relating to technology enhanced learning such as International Conference on Information and Communications Technology in Education, provide valuable opportunities for academics and academic-related/professional staff to report upon their research and development…

  10. 77 FR 12320 - Information Collection Request: GFIRST Conference Stakeholder Evaluation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... Communications (CS&C), National Cyber Security Division (NCSD), United States Computer Emergency Readiness Team... personal information provided. SUPPLEMENTARY INFORMATION: The purpose of DHS's premier cyber conference is to continually seek to enhance collaborative efforts between cyber constituencies, partners and...

  11. PREFACE: 1st International Conference on Mechanical Engineering Research 2011 (ICMER2011)

    NASA Astrophysics Data System (ADS)

    Abu Bakar, Rosli

    2012-09-01

    The year 2010 represented a significant milestone in the history of the Mechanical Engineering community with the organization of the first and second national level conferences (National Conference in Mechanical Engineering for Research, 1st and 2nd NCMER) at Universiti Malaysia Pahang on 26-27 May and 3-4 December 2010. The conferences attracted a large number of delegates from different premier academic and research institutions in the country to participate and share their research experiences at the conference. The International Conference on Mechanical Engineering Research (ICMER 2011) followed on from the first and second conferences due to good support from researchers. The ICMER 2011 is a good platform for researchers and postgraduate students to present their latest finding in research. The conference covers a wide range of topics including the internal combustion engine, machining processes, heat and mass transfer, fuel, biomechanical analysis, aerodynamic analysis, thermal comfort, computational techniques, design and simulation, automotive transmission, optimization techniques, hybrid electric vehicles, engine vibration, heat exchangers, finite element analysis, computational fluid dynamics, green energy, vehicle dynamics renewable energy, combustion, design, product development, advanced experimentation techniques, to name but a few. The international conference has helped to bridge the gap between researchers working at different institutions and in different countries to share their knowledge and has helped to motivate young scientists with their research. This has also given some clear direction for further research from the deliberations of the conference. Several people have contributed in different ways to the success of the conference. We thank the keynote speakers and all authors of the contributed papers, for the cooperation rendered to us in the publication of the CD conference proceedings. In particular, we would like to place on record our

  12. Proceedings of the 26th International Cryogenic Engineering Conference - International Cryogenic Material Conference 2016

    NASA Astrophysics Data System (ADS)

    Datta, T. S.; Sharma, R. G.; Kar, S.

    2017-02-01

    International Conference ICEC 26 - ICMC 2016 was organized at New Delhi, India during March 7-11, 2016. Previous conference ICEC25-ICMC 2014 was held at the University of Twente, The Netherlands in July 2014. Next Conference ICEC 27- ICMC 2018 will be held at Oxford, UK during September 3-7, 2018 1. Introduction This is a biennial international conference on cryogenic engineering and cryogenics materials organized by the International Cryogenic Engineering Committee and the International Cryogenic Material Committee. For some years, the host country has been alternating between Europe and Asia. The present conference was held at the Manekshaw Convention Centre, New Delhi, India during March 7-11, 2016 and hosted jointly by the Indian Cryogenics Council (ICC) and the Inter-University Accelerator Centre (IUAC), New Delhi. Put all together as many as 547 persons participated in the conference. Out of these 218 were foreign delegates coming from 25 countries and the rest from India. 2. Inaugural Session & Course Lectures The pre conference short course lectures on “Cryocoolers” and “Superconducting Materials for Power Applications” were organized on 7th March. Cryocooler course was given jointly by Dr. Chao Wang from M/s. Cryomech, USA and Prof. Milind Atrey from IIT Bombay, India. The Course on Superconducting Materials was given by Prof. Venkat Selvamanickam from the University of Houston, USA. The conference was inaugurated in the morning of March 8th in a typical Indian tradition and in the presence of the Chief Guest, Dr. R Chidambaram (Principle Scientific Adviser to Govt. of India), Guest of Honour, Prof. H Devaraj (Vice Chairman University Grant Commission), Prof Marcel ter Brake ( Chair, ICEC Board), Prof. Wilfried Goldacker (Chair, ICMC board), Dr. D Kanjilal (Director IUAC), Dr R K Bhandari, (President, Indian Cryogenic Council ). Dr. T S Datta, Chair Local Organizing Committee coordinated the proceedings of the inaugural function. 3. Technical

  13. Comparative study of Factor Xa fluorogenic substrates and their influence on the quantification of LMWHs.

    PubMed

    Castro-López, Vanessa; Harris, Leanne F; O'Donnell, James S; Killard, Anthony J

    2011-01-01

    Low molecular weight heparins (LMWHs) are recognised as the preferred anticoagulants in the prevention and treatment of venous thromboembolism. Anti-Factor Xa (anti-FXa) levels are used to monitor the anticoagulant effect of LMWHs and such assays are routinely employed in hospital diagnostic laboratories. In this study, a fluorogenic anti-FXa assay was developed using a commercially available fluorogenic substrate with an attached 6-amino-1-naphthalene-sulfonamide (ANSN) fluorophore and was used for the determination of two LMWHs, enoxaparin and tinzaparin and the heparinoid, danaparoid. The assay was based on the complexation of heparinised plasma with 100 nM exogenous FXa and 25 μM of the fluorogenic substrate Mes-D-LGR-ANSN (C(2)H(5))(2) (SN-7). The assay was tested with pooled plasma samples spiked with anticoagulant concentrations in the range 0-1.6 U mL(-1). The statistically sensitive assay range was 0-0.4 U mL(-1) for enoxaparin and tinzaparin and 0-0.2 U mL(-1) for danaparoid, with assay variation typically below 10.5%. This assay was then compared with a previously published fluorogenic anti-FXa assay developed with the peptide substrate, methylsulfonyl-D: -cyclohexylalanyl-glycyl-arginine-7-amino-4-methylcoumarin acetate (Pefafluor FXa). Both assays were compared in terms of fluorescence intensity, lag times and sensitivity to anticoagulants.

  14. EACR-MRS conference on Seed and Soil: In Vivo Models of Metastasis.

    PubMed

    Teles Alves, I; Cohen, N; Ersan, P G; Eyre, R; Godet, I; Holovanchuk, D; Jackstadt, R; Kyjacova, L; Mahal, K; Noguera-Castells, A; Recalde-Percaz, L; Sleeman, J P

    2017-12-01

    New experimental tools are urgently required to better understand the metastatic process. The importance of such tools is underscored by the fact that many anti-cancer therapies are generally ineffective against established metastases. This makes a major contribution to the fact that metastatic spread is responsible for over 90% of cancer patient deaths. It was therefore timely that the recent "Seed and Soil: In Vivo Models of Metastasis" conference held in Berlin, Germany (27-29 of November 2017) aimed to give an in-depth overview of the latest research models and tools for studying metastasis, and to showcase recent findings from world-leading metastasis researchers. This Meeting Report summarises the major themes of this ground-breaking conference.

  15. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  16. PREFACE: 13th High-Tech Plasma Processes Conference (HTPP-2014)

    NASA Astrophysics Data System (ADS)

    2014-11-01

    The High-Tech Plasma Processes - 13th European Plasma Conference (HTPP-2014) was held in Toulouse (France) on 22-27 June 2014. The conference series started in 1990 as a thermal plasma conference and has gradually expanded to include other related topics. Now the High-Tech Plasma Processes - European Plasma Conference (HTPP) is an international conference organised in Europe every two years with topics encompassing the whole field of plasma processing science. The aim of the conference is to bring different scientific communities together, to facilitate contacts between science, technology and industry and to provide a platform for the exploration of both the fundamental topics and new applications of plasmas. For this edition of HTPP, as was the case for the last, we have acheived a well balanced participation from the communities of both thermal and non-thermal plasma researchers. 142 people from 17 countries attended the conference with the total number of contributions being 155, consisting of 8 plenary and 8 invited talks plus 51 oral and 88 poster contributions. We have received numerous papers corresponding to the contributions of HTPP-2014 that have been submitted for publication in this volume of Journal of Physics: Conference Series. Each submitted contribution has been peer reviewed (60 referees with at least two reviewing each paper) and the Editors are very grateful to the referees for their careful support in improving the original manuscripts. In total, 52 manuscripts have been accepted for publication covering a range of topics of plasma processing science from plasma fundamentals to process applications through to experiments, diagnostics and modelling. We have grouped the papers into the following 5 topics: - Arc-Materials Interaction and Metallurgy - Plasma Torches and Spraying - Synthesis of Powders and Nanomaterials - Deposition and Surface Treatment - Non-Equilibrium Plasmas We deeply thank the authors for their enthusiastic and high

  17. Satellite Conferences

    Science.gov Websites

    NOAA- NESDIS Banner Satellite Conferences Collage images of earth, POES and GOES satellites in space HOME Call for Poster Abstracts DOC Logo NOAA Logo Satellite Conferences Welcome to the website for National Oceanic and Atmospheric Administration (NOAA) Satellite Conferences; past, present and future

  18. PREFACE: III All-Russian Scientific and Practical Conference on Innovations in Non-Destructive Testing (SibTest 2015)

    NASA Astrophysics Data System (ADS)

    2016-01-01

    This issue of the journal is devoted to the research and studies presented at the III All-Russian Scientific and Practical Conference on Innovations in Non-Destructive Testing SibTest. The conference was held in Altai, Russia, on 27-31 July 2015. The conference brought together experts from different countries and organizations who had a great opportunity to share knowledge during oral and poster presentations and to initiate discussions on topics that are of interest to the conference attendees. The conference aimed to discuss innovative methods and the application of advanced technologies in non-destructive testing. The conference also attempted to bring together university, academic and industrial science, to expand the co-operation of scientists from different countries in research and development and the commercialization of innovative technologies in non-destructive testing. The key themes of the conference were: ultrasonic and acoustic testing; electromagnetic and thermal testing; various types of radiation non-destructive testing; passive and active testing techniques. The conference organizers are the Institute of Non-Destructive Testing, Tomsk Polytechnic University, with the assistance of the Russian Society for Non-Destructive Testing and Technical Diagnostics, Institute of Strength Physics and Materials Science, Siberian Branch of the Russian Academy of Sciences, National Research Tomsk State University, Moscow State Institute of Radio Engineering, Electronics and Automation.

  19. PREFACE: Tsukuba International Conference on Materials Science 2013

    NASA Astrophysics Data System (ADS)

    Kijima, Masashi; Ohshima, Kenichi; Kojima, Seiji; Nagasaki, Yukio; Miyazaki, Shuichi; Kim, Hee Young; Kadowaki, Kazuo; Kashiwagi, Takanari; Nakamura, Junji; Yamamoto, Yohei; Goto, Hiromasa

    2014-03-01

    Tsukuba International Conference on Materials Science (TICMS) was held from 28th August to 6th September, 2013 for the celebration of 40th year anniversary of the University of Tsukuba. The conference was organized by the Division of Materials Science, in cooperation with the Graduate School of Pure and Applied Sciences, and Tsukuba Research Center for Interdisciplinary Materials Science. The purpose of the conference was to provide a unique forum for researchers and students working in various fields of materials science, which have been progressing so rapidly that no single society could cover. The conference consists of following seven workshops to cover various fields. The organizing committee believed that the conference gave all participants new insights into the widespread development of materials science and enhanced the circulation, among them, of information released at the conference. The organizers are grateful for the financial support from University of Tsukuba. This volume contains 25 selected papers from invited and contributed papers, all of which have been screened on the basis of the standard review process of the program committee. The editors express their thanks to those authors who contributed the papers published in this proceedings, which reflects the scientific value of the conference. Nov. 20, 2013 Seiji Kojima, Prof. Dr. Chair, Division of Materials Science Chair, Doctoral Program in Materials Science TICMS 2013 (http://www.ticonfms.tsukuba.ac.jp/) Workshop list The 13th Japan-Korea Joint Workshop on Materials Science Summer School of Biomaterials Science The Japan-Korea Joint Workshop on Shape Memory and Superelastic Technologies The 2nd Workshop on THz Radiation from Intrinsic Josephson Junctions The 3rd German-Japan Nanoworkshop TICMS and IWP Joint Workshop on Conjugated Polymers International Workshop on Science and Patents (IWP) 2013

  20. Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

    PubMed

    Louis, Scott G; Van, Philbert Y; Riha, Gordon M; Barton, Jeffrey S; Kunio, Nicholas R; Underwood, Samantha J; Differding, Jerome A; Rick, Elizabeth; Ginzburg, Enrique; Schreiber, Martin A

    2014-04-01

    The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent

  1. Enhancement of the p27Kip1-mediated antiproliferative effect of trastuzumab (Herceptin) on HER2-overexpressing tumor cells.

    PubMed

    Marches, Radu; Uhr, Jonathan W

    2004-11-10

    The oncogenic activity of the overexpressed HER2 tyrosine kinase receptor requires its localization in the plasma membrane. The antitumor effect of anti-HER2 antibodies (Abs) is mainly dependent on receptor downregulation and comprises p27Kip1-mediated G1 cell cycle arrest. However, one major limitation of anti-HER2 therapy is the reversibility of tumor growth inhibition after discontinuation of treatment caused by the mitogenic signaling associated with cell surface receptor re-expression. We found that the level of p27Kip1 upregulation, inhibition of Cdk2 activity and magnitude of G1 arrest induced by the humanized Ab trastuzumab (Herceptin, HCT) on BT474 and SKBr3 HER2-overexpressing breast cancer cells correlates with the level of cell surface receptor. Thus, continuous exposure of cells to HCT for 72 hr results in downregulation of the cell surface receptor and a concurrent increase in the level of p27Kip1 protein. Discontinuation of Ab exposure after the first 8 hr results in failure to upregulate p27Kip1 and arrest of cell cycle progression. We show that the lysosomotropic amine chloroquine (CQ) augments receptor internalization in HER2-overexpressing cells either pretreated or continuously treated with HCT and leads to an increased and sustained inhibitory effect. The enhanced CQ-dependent loss of functional HER2 from the cell surface resulted in sustained inactivation of the serine/threonine kinase Akt, upregulation of p27Kip1 protein and inhibition of cyclin E/Cdk2 activity. Potentiation of the inhibitory effect of HCT by CQ was directly related to loss of HER2 from the plasma membrane since prevention of Ab-mediated receptor endocytosis by engagement of the receptor with immobilized HCT abrogated the effect of CQ.

  2. The 50th Annual Maize Genetics Conference

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cone, Karen

    The 50th Annual Maize Genetics Conference was held February 27 - March 2, 2008 at the Marriott Wardman Park Hotel in Washington, D.C. As the golden anniversary of the Conference and coinciding with the release of a draft of the maize genome sequence, this was a special meeting. To publicize this unique occasion, meeting organizers hosted a press conference, which was attended by members of the press representing science and non-science publications, and an evening reception at the Smithsonian National Museum of Natural History, where the draft sequence was announced and awards were presented to Dr. Mary Clutter and Senatormore » Kit Bond to thank them for their outstanding contributions to maize genetics and genomics research. As usual, the Conference provided an invigorating forum for exchange of recent research results in many areas of maize genetics, e.g., cytogenetics, development, molecular genetics, transposable element biology, biochemical genetics, and genomics. Results were shared via both oral and poster presentations. Invited talks were given by four distinguished geneticists: Vicki Chandler, University of Arizona; John Doebley, University of Wisconsin; Susan Wessler, University of Georgia; and Richard Wilson, Washington University. There were 46 short talks and 241 poster presentations. The Conference was attended by over 500 participants. This included a large number of first-time participants in the meeting and an increasingly visible presence by individuals from underrepresented groups. Although we do not have concrete counts, there seem to be more African American, African and Hispanic/Latino attendees coming to the meeting than in years past. In addition, this meeting attracted many participants from outside the U.S. Student participation continues to be hallmark of the spirit of free exchange and cooperation characteristic of the maize genetics community. With the generous support provided by DOE, USDA NSF, and corporate/private donors

  3. PREFACE Conference on Advanced Materials and Nanotechnology (CAMAN 2009)

    NASA Astrophysics Data System (ADS)

    Ali, Aidy

    2011-02-01

    This special issue of IOP Conference Series: Materials science and Engineering contains papers contributed to the Conference on Advanced Materials and Nanotechnology (CAMAN 2009) held on 3-5 November 2009 in Putra World Trade Centre (PWTC), Kuala Lumpur, Malaysia. The objective of the congress is to provide a platform for professionals, academicians and researchers to exchange views, findings, ideas and experiences on advanced science and technology. After careful refereeing of all manuscripts, 50 papers were selected for publications in this issue. The policy of editing was the content of the material and its rapid dissemination was more important than its form. In 2009, the conference received close to 120 papers from leading researchers and participants from countries such as Iran, India, Switzerland, Myanmar, Nigeria, Canada, Yemen and Malaysia. We strongly hope the new ideas and results presented will stimulate and enhance the progress of research on the above conference theme. We are grateful to all the authors for their papers and presentations in this conference. They are also the ones who help make this conference possible through their hard work in the preparation of the manuscripts. We would also like to offer our sincere thanks to all the invited speakers who came to share their knowledge with us. We would also like to acknowledge the untiring efforts of the reviewers, research assistants and students in meeting deadlines and for their patience and perseverance. We wish to thank all the authors who contributed papers to the conference and all reviewers for their efforts to review the papers as well as the sponsors. We would also like to thank the members of the CAMAN 2009 Organising Committee and the International Advisory Committee for their efforts in making the conference a success. Thank you very much indeed. Guest Editor Aidy Ali

  4. Transforming the Morbidity and Mortality Conference to Promote Safety and Quality in a PICU.

    PubMed

    Cifra, Christina L; Bembea, Melania M; Fackler, James C; Miller, Marlene R

    2016-01-01

    Determine the effectiveness of a structured systems-oriented morbidity and mortality conference in improving the process of reviewing and responding to adverse events in a PICU. Prospective time series analysis before and after implementation of a systems-oriented morbidity and mortality conference. Single tertiary referral PICU in Baltimore, MD. Thirty-three patients discussed before and 31 patients after implementation of a systems-oriented morbidity and mortality conference over a total of 20 morbidity and mortality conferences, from April 2013 to March 2014. Systems-oriented morbidity and mortality conference incorporating elements of medical incident analysis. There was a significant increase in meeting attendance (mean, 12 vs 31 attendees per morbidity and mortality conference; p < 0.001) after the systems-oriented morbidity and mortality conference was instituted. There was no significant difference in the mean number of cases suggested (4.2 vs 4.6) or discussed (3.3 vs 3.1) per morbidity and mortality conference. There was also no significant difference in the mean number of adverse events identified per morbidity and mortality conference (3.4 vs 4.3). However, there was an increase in the proportion of cases discussed using a standard case review tool, but this did not reach statistical significance (27% vs 45%; p = 0.231). Nevertheless, we observed a significant increase in the mean number of quality improvement interventions suggested (2.4 vs 5.6; p < 0.001) and implemented (1.7 vs 4.4; p < 0.001) per morbidity and mortality conference. All adverse event categories identified had corresponding interventions suggested after the systems-oriented morbidity and mortality conference was instituted compared with before (80% vs 100%). Intervention-to-adverse event ratios per category were also higher (mean, 0.6 vs 1.5). A structured systems-oriented PICU morbidity and mortality conference incorporating elements of medical incident analysis improves the process

  5. III International Conference on Laser and Plasma Researches and Technologies

    NASA Astrophysics Data System (ADS)

    2017-12-01

    A.P. Kuznetsov and S.V. Genisaretskaya III Conference on Plasma and Laser Research and Technologies took place on January 24th until January 27th, 2017 at the National Research Nuclear University "MEPhI" (NRNU MEPhI). The Conference was organized by the Institute for Laser and Plasma Technologies and was supported by the Competitiveness Program of NRNU MEPhI. The conference program consisted of nine sections: • Laser physics and its application • Plasma physics and its application • Laser, plasma and radiation technologies in industry • Physics of extreme light fields • Controlled thermonuclear fusion • Modern problems of theoretical physics • Challenges in physics of solid state, functional materials and nanosystems • Particle accelerators and radiation technologies • Modern trends of quantum metrology. The conference is based on scientific fields as follows: • Laser, plasma and radiation technologies in industry, energetic, medicine; • Photonics, quantum metrology, optical information processing; • New functional materials, metamaterials, “smart” alloys and quantum systems; • Ultrahigh optical fields, high-power lasers, Mega Science facilities; • High-temperature plasma physics, environmentally-friendly energetic based on controlled thermonuclear fusion; • Spectroscopic synchrotron, neutron, laser research methods, quantum mechanical calculation and computer modelling of condensed media and nanostructures. More than 250 specialists took part in the Conference. They represented leading Russian scientific research centers and universities (National Research Centre "Kurchatov Institute", A.M. Prokhorov General Physics Institute, P.N. Lebedev Physical Institute, Troitsk Institute for Innovation and Fusion Research, Joint Institute for Nuclear Research, Moscow Institute of Physics and Tecnology and others) and leading scientific centers and universities from Germany, France, USA, Canada, Japan. We would like to thank heartily all of

  6. International Conference on Applied Sciences (ICAS2013)

    NASA Astrophysics Data System (ADS)

    Lemle, Ludovic Dan; Jiang, Yiwen

    2014-03-01

    The International Conference on Applied Sciences (ICAS2013) took place in Wuhan, P R China from 26-27 October 2013 at the Military Economics Academy. The conference is regularly organized, alternately in Romania and in P R China, by ''Politehnica'' University of Timişoara, Romania, and Military Economics Academy of Wuhan, P R China, with the aim to serve as a platform for the exchange of information between various areas of applied sciences, and to promote the communication between the scientists of different nations, countries and continents. The conference has been organized for the first time in 15-16 June 2012 at the Engineering Faculty of Hunedoara, Romania. The topics of the conference covered a comprehensive spectrum of issues: Economical sciences Engineering sciences Fundamental sciences Medical sciences The conference gathered qualified researchers whose expertise can be used to develop new engineering knowledge that has applicability potential in economics, defense, medicine, etc. The number of registered participants was nearly 90 from 5 countries. During the two days of the conference 4 invited and 36 oral talks were delivered. A few of the speakers deserve a special mention: Mircea Octavian Popoviciu, Academy of Romanian Scientist — Timişoara Branch, Correlations between mechanical properties and cavitation erosion resistance for stainless steels with 12% chromium and variable contents of nickel; Carmen Eleonora Hărău, ''Politehnica'' University of Timişoara, SWOT analysis of Romania's integration in EU; Ding Hui, Military Economics Academy of Wuhan, Design and engineering analysis of material procurement mobile operation platform; Serban Rosu, University of Medicine and Pharmacy ''Victor Babeş'' Timişoara, Cervical and facial infections — a real life threat, among others. Based on the work presented at the conference, 14 selected papers are included in this volume of IOP Conference Series: Materials Science and Engineering. These papers

  7. GLOBECOM '89 - IEEE Global Telecommunications Conference and Exhibition, Dallas, TX, Nov. 27-30, 1989, Conference Record. Volumes 1, 2, & 3

    NASA Astrophysics Data System (ADS)

    The present conference discusses topics in multiwavelength network technology and its applications, advanced digital radio systems in their propagation environment, mobile radio communications, switching programmability, advancements in computer communications, integrated-network management and security, HDTV and image processing in communications, basic exchange communications radio advancements in digital switching, intelligent network evolution, speech coding for telecommunications, and multiple access communications. Also discussed are network designs for quality assurance, recent progress in coherent optical systems, digital radio applications, advanced communications technologies for mobile users, communication software for switching systems, AI and expert systems in network management, intelligent multiplexing nodes, video and image coding, network protocols and performance, system methods in quality and reliability, the design and simulation of lightwave systems, local radio networks, mobile satellite communications systems, fiber networks restoration, packet video networks, human interfaces for future networks, and lightwave networking.

  8. Materials Presented at the MU-SPIN Tenth Annual Users' Conference

    NASA Technical Reports Server (NTRS)

    Harrington, James L., Jr.; Shukla, Pooja

    2000-01-01

    The Minority University-Space Interdisciplinary Network (MU-SPIN) Program and NASA's Minority University Research and Education Division (MURED) both reached their 10th anniversaries. In honor of this occasion, the 2000 Annual Users' Conference held at Morris Brown College in Atlanta, Georgia, September 11-15, 2000, was the first to be jointly hosted by MU-SPIN and MURED. With the theme 'Celebrating Our Tenth Year With Our Eyes on the Prize,' the conference provided a national forum for showcasing successful MU-SPIN and MURED Program (MUREP) experiences to enhance faculty/student development in areas of scientific and technical research and education.

  9. The Virtual Extension Annual Conference: Addressing Contemporary Professional Development Needs

    ERIC Educational Resources Information Center

    Franz, Nancy K.; Brekke, Robin; Coates, Deb; Kress, Cathann; Hlas, Julie

    2014-01-01

    Extension systems are experimenting with new models for conducting professional development to enhance staff competence and other returns on professional development investments. The ISUEO virtual annual conference provides a successful flipped classroom model of asynchronous and synchronous learning events for conducting an Extension annual…

  10. Molecular breeding for the development of multiple disease resistance in Basmati rice.

    PubMed

    Singh, Atul; Singh, Vikas K; Singh, S P; Pandian, R T P; Ellur, Ranjith K; Singh, Devinder; Bhowmick, Prolay K; Gopala Krishnan, S; Nagarajan, M; Vinod, K K; Singh, U D; Prabhu, K V; Sharma, T R; Mohapatra, T; Singh, A K

    2012-01-01

    Basmati rice grown in the Indian subcontinent is highly valued for its unique culinary qualities. Production is, however, often constrained by diseases such as bacterial blight (BB), blast and sheath blight (ShB). The present study developed Basmati rice with inbuilt resistance to BB, blast and ShB using molecular marker-assisted selection. The rice cultivar 'Improved Pusa Basmati 1' (carrying the BB resistance genes xa13 and Xa21) was used as the recurrent parent and cultivar 'Tetep' (carrying the blast resistance gene Pi54 and ShB resistance quality trait loci (QTL), qSBR11-1) was the donor. Marker-assisted foreground selection was employed to identify plants possessing resistance alleles in the segregating generations along with stringent phenotypic selection for faster recovery of the recurrent parent genome (RPG) and phenome (RPP). Background analysis with molecular markers was used to estimate the recovery of RPG in improved lines. Foreground selection coupled with stringent phenotypic selection identified plants homozygous for xa13, Xa21 and Pi54, which were advanced to BC(2)F(5) through pedigree selection. Marker-assisted selection for qSBR11-1 in BC(2)F(5) using flanking markers identified seven homozygous families. Background analysis revealed that RPG recovery was up to 89.5%. Screening with highly virulent isolates of BB, blast and ShB showed that the improved lines were resistant to all three diseases and were on a par with 'Improved Pusa Basmati 1' for yield, duration and Basmati grain quality. This is the first report of marker-assisted transfer of genes conferring resistance to three different diseases in rice wherein genes xa13 and Xa21 for BB resistance, Pi54 for blast resistance, and a major QTL qSBR11-1 have been combined through marker-assisted backcross breeding. In addition to offering the potential for release as cultivars, the pyramided lines will serve as useful donors of gene(s) for BB, blast and ShB in future Basmati rice breeding

  11. Federal Pre-White House Conference on Library and Information Services Proceedings (Bethesda, Maryland, November 26-27, 1990).

    ERIC Educational Resources Information Center

    Federal Library and Information Center Committee, Washington, DC.

    This report presents the recommendations and proceedings of the Federal Pre-White House Conference on Library and Information Services (WHCLIS II) in two sections. Thirteen issues and recommendations of high national priority identified by the federal delegates to the WHCLIS II are provided in the first section: (1) Preservation Plan for Federal…

  12. Proceedings, I.U.F.R.O. Beech Bark Disease Working Party Conference

    Treesearch

    Forest Service. U.S.

    1983-01-01

    This conference was the first full meeting of the Working Party since its inception at the Beech Bark Disease Colloquium held in Nancy, France in 1979. The meeting from 27 September to 7 October 1982 took the form of a study tour convened at the College of Forestry, University of Maine,with field trips in the Central New England States and New York and concluding at...

  13. Innovations and Challenges in Renal Cancer: Summary Statement From the Third Cambridge Conference

    PubMed Central

    Atkins, Michael B.; Bukowski, Ronald M.; Escudier, Bernard J.; Figlin, Robert A.; Hudes, Gary H.; Kaelin, William G.; Linehan, W. Marston; McDermott, David F.; Mier, James W.; Pedrosa, Ivan; Rini, Brian I.; Signoretti, Sabina; Sosman, Jeffrey A.; Teh, Bin Tean; Wood, Christopher G.; Zurita, Amado J.; King, Laura

    2009-01-01

    The Third Cambridge Conference on Innovations and Challenges in Renal Cancer, a symposium held in Cambridge, Massachusetts, June 27–28, 2008, and chaired by Michael B. Atkins, was convened to discuss the current state of knowledge in the field, critique new data, stimulate communication among those involved in basic and clinical research, and offer recommendations for further study. Four main topics were discussed: genetics and molecular biology of renal cell cancer, staging and prognosis, systemic therapy, and correlative science and biomarkers in stage IV disease. The conference format combined brief presentations with extended periods of discussion. The conclusions and recommendations are summarized in this paper and presented in more detail in the individual papers that follow. PMID:19402064

  14. Low-temperature magnetic ordering in the perovskites Pr 1-xA xCoO 3 (A=Ca, Sr)

    NASA Astrophysics Data System (ADS)

    Deac, Iosif G.; Tetean, Romulus; Balasz, Istvan; Burzo, Emil

    2010-05-01

    The magnetic and electrical properties of polycrystalline Pr 1-xA xCoO 3 cobaltites with A=Ca, Sr and 0≤ x≤0.5 were studied in the temperature range 4 K≤ T≤1000 K and field up to 7 T. The X-ray analyses show the presence of only one phase having monoclinic or orthorhombic symmetry. The magnetic measurements indicate that the Ca-doped samples have at low temperatures, similar properties to the frustrated magnetic materials. PrCoO 3 is a paramagnetic insulator in the range from 4 to 1000 K. The Sr-doped cobaltites exhibit two phase transitions: a paramagnetic-ferromagnetic (or magnetic phase separated state) phase transition at about 240 K and a second one at about 100 K. The magnetic measurements suggest the presence of magnetic clusters and a change in the nature of magnetic coupling between Co ions at low temperatures. A semiconducting type behavior and high negative magnetoresistance was found for the Ca-doped samples, while the Sr-doped ones were metallic and with negligible magnetoresistance. The results are analyzed in the frame of a phase separation scenario in the presence of the spin-state transitions of Co ions.

  15. "Elderly Deafblindness." Proceedings of the European Conference of Deafblind International's Acquired Deafblindness Network (3rd, Marcelli di Numana, Italy, October 2-7, 1998).

    ERIC Educational Resources Information Center

    Deafblind International, London (England).

    This text includes all of the plenary presentations from the 3rd European Conference of Deafblind International's Acquired Deafblindness Network. This international conference was the first to focus specifically on older people with dual sensory impairment. Presentations addressed the awareness of the needs of older people with deafblind or dual…

  16. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

    PubMed Central

    Frost, Charles E; Byon, Wonkyung; Song, Yan; Wang, Jessie; Schuster, Alan E; Boyd, Rebecca A; Zhang, Donglu; Yu, Zhigang; Dias, Clapton; Shenker, Andrew; LaCreta, Frank

    2015-01-01

    Aim Apixaban is an orally active inhibitor of coagulation factor Xa and is eliminated by multiple pathways, including renal and non-renal elimination. Non-renal elimination pathways consist of metabolism by cytochrome P450 (CYP) enzymes, primarily CYP3A4, as well as direct intestinal excretion. Two single sequence studies evaluated the effect of ketoconazole (a strong dual inhibitor of CYP3A4 and P-glycoprotein [P-gp]) and diltiazem (a moderate CYP3A4 inhibitor and a P-gp inhibitor) on apixaban pharmacokinetics in healthy subjects. Method In the ketoconazole study, 18 subjects received apixaban 10 mg on days 1 and 7, and ketoconazole 400 mg once daily on days 4–9. In the diltiazem study, 18 subjects received apixaban 10 mg on days 1 and 11 and diltiazem 360 mg once daily on days 4–13. Results Apixaban maximum plasma concentration and area under the plasma concentration–time curve extrapolated to infinity increased by 62% (90% confidence interval [CI], 47, 78%) and 99% (90% CI, 81, 118%), respectively, with co-administration of ketoconazole, and by 31% (90% CI, 16, 49%) and 40% (90% CI, 23, 59%), respectively, with diltiazem. Conclusion A 2-fold and 1.4-fold increase in apixaban exposure was observed with co-administration of ketoconazole and diltiazem, respectively. PMID:25377242

  17. Proceedings: Conference on Institutional Planning in Community Colleges (Seattle, Washington, April 29-30, 1976). Occasional Paper Number 27.

    ERIC Educational Resources Information Center

    Morishima, James K., Ed.; And Others

    This document contains three conference papers concerning institutional research at the community college level. Ann Bromley discusses the practical implications of institutional research. The president, administrative staff, and faculty must be involved in identification of research issues, formulation of design, and application of findings.…

  18. Arabidopsis Enhanced Drought Tolerance1/HOMEODOMAIN GLABROUS11 Confers Drought Tolerance in Transgenic Rice without Yield Penalty1[W][OA

    PubMed Central

    Yu, Linhui; Chen, Xi; Wang, Zhen; Wang, Shimei; Wang, Yuping; Zhu, Qisheng; Li, Shigui; Xiang, Chengbin

    2013-01-01

    Enhancing drought tolerance without yield decrease has been a great challenge in crop improvement. Here, we report the Arabidopsis (Arabidopsis thaliana) homodomain-leucine zipper transcription factor Enhanced Drought Tolerance/HOMEODOMAIN GLABROUS11 (EDT1/HDG11) was able to confer drought tolerance and increase grain yield in transgenic rice (Oryza sativa) plants. The improved drought tolerance was associated with a more extensive root system, reduced stomatal density, and higher water use efficiency. The transgenic rice plants also had higher levels of abscisic acid, proline, soluble sugar, and reactive oxygen species-scavenging enzyme activities during stress treatments. The increased grain yield of the transgenic rice was contributed by improved seed setting, larger panicle, and more tillers as well as increased photosynthetic capacity. Digital gene expression analysis indicated that AtEDT1/HDG11 had a significant influence on gene expression profile in rice, which was consistent with the observed phenotypes of transgenic rice plants. Our study shows that AtEDT1/HDG11 can improve both stress tolerance and grain yield in rice, demonstrating the efficacy of AtEDT1/HDG11 in crop improvement. PMID:23735506

  19. Left-Skew L Distribution Function Application in Hurricane Categories Using its Center-Pressure in Context of Warming Climate

    NASA Astrophysics Data System (ADS)

    Wang, W.

    2017-12-01

    Theory resultsWang wanli left-skew L distribution density function is formula below, its interval is from -∞ to +1 , x indicates center pressure of hurricane, xA represents its long term mean, [(x-xA)/x] is standard random variable on boundary condition f(+1) =0 and f(-∞) =0 Standard variable is negative when x is less than xA ;standard variable is positive when x is more than xA : the standard variable is equal to zero when x is just xA; thus, standard variable is just -∞ if x is zero ,standard variable is also +1 if x is +∞ , finally standard random variable fall into interval of - ∞ 1 to +1 Application in table "-" signal presents individual hurricane center pressure is less than the hurricane long term averaged value; "+" signal presents individual hurricane center pressure is more than the hurricane its mean of long term, of course the mean (xA) is also substituted by other "standard" or "expected value" Tab multi-levels of hurricane strength or intense Index of Hurricane [(X-XA)/X]% XA / X Categories Descriptions X/ XA Probabilities Formula -∞ +∞ → 0 → 0 …… …… …… …… …… …… < -900 > 10.0 < -15 > extreme ( Ⅵ ) < 0.10 -800, -900 9.0, 10.0 -15 extreme ( Ⅵ ) 0.11, 0.10 -700, -800 8.0, 9.0 -14 extreme ( Ⅴ ) 0.13, 0.11 -600, -700 7.0, 8.0 -13 extreme ( Ⅳ ) 0.14, 0.13 -500, -600 6.0, 7.0 -12 extreme ( Ⅲ ) 0.17, 0.14 0.05287 % L(-5.0)- L(-6.0) -400, -500 5.0, 6.0 -11 extreme ( Ⅱ ) 0.20, 0.17 0.003 % L(-4.0)- L(-5.0) -300, -400 4.0, 5.0 -10 extreme ( Ⅰ ) 0.25, 0.20 0.132 % L(-3.0)- L(-4.0) -267, -300 3.67, 4.00 -9 strongest ( Ⅲ )-superior 0.27, 0.25 0.24 % L(-2.67)-L(-3.00) -233, -267 3.33, 3.67 -8 strongest ( Ⅱ )-medium 0.30, 0.27 0.61 % L(-2.33)-L(-2.67) -200, -233 3.00, 3.33 -7 strongest ( Ⅰ )-inferior 0.33, 0.30 1.28 % L(-2.00)- L(-2.33) -167, -200 2.67, 3.00 -6 strong ( Ⅲ )-superior 0.37, 0.33 2.47 % L(-1.67)-L(-2.00) -133, -167 2.33, 2.67 -5 strong ( Ⅱ )-medium 0.43, 0.37 4.43 % L(-1.33)- L(-1

  20. 77 FR 17460 - Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-26

    .... 120214135-2203-02] RIN 0660-XA27 Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct... request for public comments on the multistakeholder process to develop consumer data privacy codes of...-multistakeholder-process without change. All personal identifying information (for example, name, address...

  1. Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2.

    PubMed

    Yang, Zhe; Follett, Jordan; Kerr, Markus C; Clairfeuille, Thomas; Chandra, Mintu; Collins, Brett M; Teasdale, Rohan D

    2018-05-04

    Alanine-, serine-, cysteine-preferring transporter 2 (ASCT2, SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian target of rapamycin (mTOR) activation. Furthermore, ASCT2 expression has been reported in several human cancers, making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane-trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of sorting nexin 27 (SNX27). Using both membrane fractionation and subcellular localization approaches, we demonstrate that the majority of ASCT2 resides at the plasma membrane. This is significantly reduced within CrispR-mediated SNX27 knockout (KO) cell lines, as it is missorted into the lysosomal degradation pathway. The reduction of ASCT2 levels in SNX27 KO cells leads to decreased glutamine uptake, which, in turn, inhibits cellular proliferation. SNX27 KO cells also present impaired activation of the mTOR complex 1 (mTORC1) pathway and enhanced autophagy. Taken together, our data reveal a role for SNX27 in glutamine uptake and amino acid-stimulated mTORC1 activation via modulation of ASCT2 intracellular trafficking. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Design of New Antibacterial Enhancers Based on AcrB's Structure and the Evaluation of Their Antibacterial Enhancement Activity.

    PubMed

    Song, Yi; Qin, Rongxin; Pan, Xichun; Ouyang, Qin; Liu, Tianyu; Zhai, Zhaoxia; Chen, Yingchun; Li, Bin; Zhou, Hong

    2016-11-18

    Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have antibacterial enhancement activity against Escherichia coli via inhibition of the efflux pump AcrB. However, they were only effective against E. coli standard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity. It could potentiate the antibacterial effects of ampicillin against not only E. coli standard strain but also clinical strains, and of β-lactam antibiotics, not non-β-lactamantibiotics. DHA27 could increase the accumulation of daunomycin and nile red within E. coli ATCC 35218, but did not increase the bacterial membrane permeability. DHA27 reduced acrB 's mRNA expression of E. coli ATCC 35218 in a dose-dependent manner, and its antibacterial enhancement activity is related to the degree of acrB mRNA expression in E. coli clinical strains. The polypeptides from AcrB were obtained via molecular docking assay; the pre-incubated polypeptides could inhibit the activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation. In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable physical and pharmacological properties with no significant cytotoxicity at effective concentrations, and might serve as a potential efflux pump inhibitor in the future.

  3. BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein

    PubMed Central

    Mackenzie, Ryan J.; Besson, Arnaud; Jeng, Sophia; Carey, Alyssa; LaTocha, Dorian H.; Fleischman, Angela G.; Duquesnes, Nicolas; Eide, Christopher A.; Vasudevan, Kavin B.; Loriaux, Marc M.; Firpo, Eduardo; Cortes, Jorge E.; McWeeney, Shannon; O’Hare, Thomas; Roberts, James M.; Druker, Brian J.; Deininger, Michael W.

    2014-01-01

    Recent studies have revealed that p27, a nuclear cyclin-dependent kinase (Cdk) inhibitor and tumor suppressor, can acquire oncogenic activities upon mislocalization to the cytoplasm. To understand how these antagonistic activities influence oncogenesis, we dissected the nuclear and cytoplasmic functions of p27 in chronic myeloid leukemia (CML), a well-characterized malignancy caused by the BCR-ABL1 tyrosine kinase. p27 is predominantly cytoplasmic in CML and nuclear in normal cells. BCR-ABL1 regulates nuclear and cytoplasmic p27 abundance by kinase-dependent and -independent mechanisms, respectively. p27 knockdown in CML cell lines with predominantly cytoplasmic p27 induces apoptosis, consistent with a leukemogenic role of cytoplasmic p27. Accordingly, a p27 mutant (p27CK−) devoid of Cdk inhibitory nuclear functions enhances leukemogenesis in a murine CML model compared with complete absence of p27. In contrast, p27 mutations that enhance its stability (p27T187A) or nuclear retention (p27S10A) attenuate leukemogenesis over wild-type p27, validating the tumor-suppressor function of nuclear p27 in CML. We conclude that BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. These findings suggest that cytoplasmic mislocalization of p27 despite BCR-ABL1 inhibition by tyrosine kinase inhibitors may contribute to drug resistance, and effective therapeutic strategies to stabilize nuclear p27 must also prevent cytoplasmic mislocalization. PMID:25293778

  4. FIBER-TEX 1992: The Sixth Conference on Advanced Engineering Fibers and Textile Structures for Composites

    NASA Technical Reports Server (NTRS)

    Buckley, John D. (Editor)

    1993-01-01

    The FIBER-TEX 1992 proceedings contain the papers presented at the conference held on 27-29 Oct. 1992 at Drexel University. The conference was held to create a forum to encourage an interrelationship of the various disciplines involved in the fabrication of materials, the types of equipment, and the processes used in the production of advanced composite structures. Topics discussed were advanced engineering fibers, textile processes and structures, structural fabric production, mechanics and characteristics of woven composites, and the latest requirements for the use of textiles in the production of composite materials and structures as related to global activities focused on textile structural composites.

  5. Introducing a Morbidity and Mortality Conference in Rwanda.

    PubMed

    Abahuje, Egide; Nzeyimana, Innocent; Rickard, Jennifer L

    To assess the structure, format, and educational features of a morbidity and mortality (M&M) conference in Rwanda. To determine factors associated with adverse events and to define opportunities for improvement. Retrospective, descriptive study of all cases presented at a surgical M&M conference over a 1-year period. Cases were reviewed for factors associated with adverse events and opportunities for improvement. Factors were characterized as delays in presentation, delays in diagnosis, delays in the operating room, errors in judgment, technical errors, advanced disease, and missing resources or malnutrition. Opportunities for improvement were categorized at the physician or hospital level. University Teaching Hospital of Kigali, a tertiary referral hospital in Rwanda. Cases presented at the surgical M&M conference over a 1-year period. Over a 1-year period, there were a total of 2231 operations with 131 in-hospital mortalities. There were 62 patients discussed at M&M conference. Of those discussed, there were 34 (55%) in-hospital deaths and 32 (52%) unplanned reoperations. Common diagnostic categories included 30 (48%) gastrointestinal, 15 (24%) trauma, and 10 (16%) neoplasm. Delays were commonly cited factors affecting outcomes. There were 22 (35%) delays in presentation, 23 (37%) delays in diagnosis or management, and 20 (32%) delays to the operating room. Errors in judgment occurred in 15 (24%) cases and technical errors occurred in 18 (29%) cases. Twenty-three (37%) patients had a critical resource missing and 17 (27%) patients had advanced disease. Malnutrition was associated with 11 (18%) adverse events. Participants identified opportunities for improvement in 48 (77%) cases. M&M conference can be used in a low-resource setting as an educational tool to address core competencies of practice-based learning and improvement and systems-based practice. It can define factors associated with surgical adverse events and opportunities for improvement at the

  6. Organizational Enhancement. Symposium 30. [AHRD Conference, 2001].

    ERIC Educational Resources Information Center

    2001

    This document contains four papers on organizational enhancement and human resource development (HRD). "Motivation to Improve Work through Learning in Human Resource Development" (Sharon S. Naquin, Elwood F. Holton III) argues that HRD's traditional conceptualization of motivation should be expanded to incorporate motivation to use…

  7. Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference.

    PubMed

    Atkins, Michael B; Bukowski, Ronald M; Escudier, Bernard J; Figlin, Robert A; Hudes, Gary H; Kaelin, William G; Linehan, W Marston; McDermott, David F; Mier, James W; Pedrosa, Ivan; Rini, Brian I; Signoretti, Sabina; Sosman, Jeffrey A; Teh, Bin Tean; Wood, Christopher G; Zurita, Amado J; King, Laura

    2009-05-15

    The Third Cambridge Conference on Innovations and Challenges in Renal Cancer, a symposium held in Cambridge, Massachusetts, June 27-28, 2008, and chaired by Michael B. Atkins, was convened to discuss the current state of knowledge in the field, critique new data, stimulate communication among those involved in basic and clinical research, and offer recommendations for further study. Four main topics were discussed: genetics and molecular biology of renal cell cancer, staging and prognosis, systemic therapy, and correlative science and biomarkers in stage IV disease. The conference format combined brief presentations with extended periods of discussion. The conclusions and recommendations are summarized in this paper and presented in more detail in the individual papers that follow. (c) 2009 American Cancer Society.

  8. Evaluating the 2008 consensus conference on genetically modified foods in Taiwan.

    PubMed

    Fan, Mei-Fang

    2015-07-01

    Genetically modified foods have become one of the most popular topics for deliberative exercises involving ordinary citizens worldwide. This paper examines the Taiwanese consensus conference on GM foods held in June 2008, and the implications and limitations of the public deliberations. The consensus conference facilitated multiparty dialogues and enhanced citizens' knowledge, and affected their attitudes. This study demonstrates the ways contextual factors have influenced the outcome of the citizens' deliberative practices, including the government's conventional technocratic decision-making style, the strong influence of the U.S. government, the political and technological culture, the government's framing of economic development concerns, and a lack of pressure from civil society to compel the government to formally respond to their concerns. The consensus conference had a limited effect on policy decision-making, and seemed to serve as a socio-political experiment. © The Author(s) 2013.

  9. A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens.

    PubMed

    Providência, Rui; Grove, Erik Lerkevang; Husted, Steen; Barra, Sérgio; Boveda, Serge; Morais, João

    2014-12-01

    Previous studies evaluating the ability of novel oral anticoagulants (NOAC) to prevent thromboembolism in patients with non-valvular atrial fibrillation (AF) have identified differences between the efficacy and safety of the drugs tested. Whether these differences reflect differences in direct thrombin or Xa inhibition, different dosing regimens or specific aspects of each agent or trial has not yet been explored. A search was performed on MEDLINE, EMBASE and COCHRANE, and ongoing studies were tracked on clinicaltrials.gov. Phase III randomized controlled trials of direct thrombin inhibitors (DTI) and factor Xa inhibitors (FXaI) vs. warfarin in patients with AF were eligible. Data were pooled using random-effects, according to the Mantel-Haenszel model. Sensitivity analyses were performed on DTI, FXaI, once-daily and twice-daily regimens. Seven studies were pooled, including a total of 80,290 patients. Both DTI and FXaI outperformed warfarin regarding stroke or systemic embolism, intracranial bleeding, total and cardiovascular mortality. No significant differences were found between DTI and FXaI or between once-daily and twice-daily regimens. Some drugs performed worse than warfarin regarding some secondary endpoints, including: edoxaban 30 mg bid on ischaemic stroke, dabigatran on acute myocardial infarction, dabigatran 150 mg bid and rivaroxaban 20mgod on gastrointestinal bleeding. Our pooled data do not support the hypothesis of a significant class-effect of DTI or FXaI, nor the benefit of once-daily vs. twice-daily dosing in the setting of AF, reinforcing that the choice of NOAC should be adapted to the specific patient and focused on the agent itself, rather than the pharmacological class or dosing regimen.

  10. Conference Model: Guidelines...for Science Supervisors on How to Conduct a Successful Leadership Conference.

    ERIC Educational Resources Information Center

    DeBlasi, Robert V.

    Guidelines of a four-phase model for conducting leadership conferences are outlined. Phase I focuses on initial conference planning, including (1) identifying need and purpose for the conference; (2) selecting a conference chairperson; (3) forming the conference planning committee, listing suggested committees and their responsibilities (program,…

  11. Conference Support, 23rd Western Photosynthesis Conference 2014, Final Technical Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wachter, Rebekka

    The Western Photosynthesis Conference is a regional conference that is held on an annual basis to bring together researchers primarily from the Western United States to share their newest research advances on photosynthetic processes. The 23rd conference was focused on both fundamental and more applied research on the biological conversion of solar energy to various energy storage forms. Several particular areas of solar energy conversion were emphasized in this conference (see below). Some of these topics, such as carbon limitations on photosynthesis, biomimicry and phenotyping, have traditionally not been incorporated extensively in the Western Photosynthesis Conference. We found that thesemore » topics have substantially broadened of the scope of this meeting.« less

  12. Paired and interacting galaxies: Conference summary

    NASA Technical Reports Server (NTRS)

    Norman, Colin A.

    1990-01-01

    The author gives a summary of the conference proceedings. The conference began with the presentation of the basic data sets on pairs, groups, and interacting galaxies with the latter being further discussed with respect to both global properties and properties of the galactic nuclei. Then followed the theory, modelling and interpretation using analytic techniques, simulations and general modelling for spirals and ellipticals, starbursts and active galactic nuclei. Before the conference the author wrote down the three questions concerning pairs, groups and interacting galaxies that he hoped would be answered at the meeting: (1) How do they form, including the role of initial conditions, the importance of subclustering, the evolution of groups to compact groups, and the fate of compact groups; (2) How do they evolve, including issues such as relevant timescales, the role of halos and the problem of overmerging, the triggering and enhancement of star formation and activity in the galactic nuclei, and the relative importance of dwarf versus giant encounters; and (3) Are they important, including the frequency of pairs and interactions, whether merging and interactions are very important aspects of the life of a normal galaxy at formation, during its evolution, in forming bars, shells, rings, bulges, etc., and in the formation and evolution of active galaxies? Where possible he focuses on these three central issues in the summary.

  13. The transcription factor Lc-Maf participates in Col27a1 regulation during chondrocyte maturation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mayo, Jaime L.; Holden, Devin N.; Barrow, Jeffery R.

    2009-08-01

    The transcription factor Lc-Maf, which is a splice variant of c-Maf, is expressed in cartilage undergoing endochondral ossification and participates in the regulation of type II collagen through a cartilage-specific Col2a1 enhancer element. Type XXVII and type XI collagens are also expressed in cartilage during endochondral ossification, and so enhancer/reporter assays were used to determine whether Lc-Maf could regulate cartilage-specific enhancers from the Col27a1 and Col11a2 genes. The Col27a1 enhancer was upregulated over 4-fold by Lc-Maf, while the Col11a2 enhancer was downregulated slightly. To confirm the results of these reporter assays, rat chondrosarcoma (RCS) cells were transiently transfected with anmore » Lc-Maf expression plasmid, and quantitative RT-PCR was performed to measure the expression of endogenous Col27a1 and Col11a2 genes. Endogenous Col27a1 was upregulated 6-fold by Lc-Maf overexpression, while endogenous Col11a2 was unchanged. Finally, in situ hybridization and immunohistochemistry were performed in the radius and ulna of embryonic day 17 mouse forelimbs undergoing endochondral ossification. Results demonstrated that Lc-Maf and Col27a1 mRNAs are coexpressed in proliferating and prehypertrophic regions, as would be predicted if Lc-Maf regulates Col27a1 expression. Type XXVII collagen protein was also most abundant in prehypertrophic and proliferating chondrocytes. Others have shown that mice that are null for Lc-Maf and c-Maf have expanded hypertrophic regions with reduced ossification and delayed vascularization. Separate studies have indicated that Col27a1 may serve as a scaffold for ossification and vascularization. The work presented here suggests that Lc-Maf may affect the process of endochondral ossification by participating in the regulation of Col27a1 expression.« less

  14. Building dialogue on complex conservation issues in a conference setting.

    PubMed

    Rock, Jenny; Sparrow, Andrew; Wass, Rob; Moller, Henrik

    2014-10-01

    Dialogue about complex science and society issues is important for contemporary conservation agendas. Conferences provide an appropriate space for such dialogue, but despite its recognized worth, best practices for facilitating active dialogue are still being explored. Face-to-face (FTF) and computer-mediated communication (CMC) are two approaches to facilitating dialogue that have different strengths. We assessed the use of these approaches to create dialogue on cultural perspectives of conservation and biodiversity at a national ecology conference. In particular, we aimed to evaluate their potential to enhance dialogue through their integrated application. We used an interactive blog to generate CMC on participant-sourced issues and to prime subsequent discussion in an FTF conference workshop. The quantity and quality of both CMC and FTF discussion indicated that both approaches were effective in building dialogue. Prior to the conference the blog averaged 126 views per day, and 44 different authors contributed a total of 127 comments. Twenty-five participants subsequently participated in active FTF discussion during a 3-h workshop. Postconference surveys confirmed that CMC had developed participants' thinking and deepened FTF dialogue; 88% indicated specifically that CMC helped facilitate the FTF discussion. A further 83% of respondents concluded that preliminary blog discussion would be useful for facilitating dialogue at future conferences. © 2014 Society for Conservation Biology.

  15. Proceedings of the 1978 National Conference on Technology for Energy Conservation (Albuquerque, New Mexico, January 24-27, 1978).

    ERIC Educational Resources Information Center

    Information Transfer, Inc., Rockville, MD.

    This publication contains the proceedings of the National Conference on Technology for Energy Conservation held in January 1978, in Albuquerque, New Mexico. The 112 papers included are organized under the following topics: (1) Legal Considerations; (2) Energy from Biomass; (3) Energy Conservation in Agriculture; (4) Status of Energy Conservation;…

  16. Piloting Vertical Flight Aircraft: A Conference on Flying Qualities and Human Factors

    NASA Technical Reports Server (NTRS)

    Blanken, Christopher L. (Editor); Whalley, Matthew S. (Editor)

    1993-01-01

    This document contains papers from a specialists' meeting entitled 'Piloting Vertical Flight Aircraft: A Conference on Flying Qualities and Human Factors.' Vertical flight aircraft, including helicopters and a variety of Vertical Takeoff and Landing (VTOL) concepts, place unique requirements on human perception, control, and performance for the conduct of their design missions. The intent of this conference was to examine, for these vehicles, advances in: (1) design of flight control systems for ADS-33C standards; (2) assessment of human factors influences of cockpit displays and operational procedures; (3) development of VTOL design and operational criteria; and (4) development of theoretical methods or models for predicting pilot/vehicle performance and mission suitability. A secondary goal of the conference was to provide an initial venue for enhanced interaction between human factors and handling qualities specialists.

  17. 27 CFR 27.42 - Wines.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Wines. 27.42 Section 27.42... TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER Tax On Imported Distilled Spirits, Wines, and Beer Wines § 27.42 Wines. All wines (including imitation, substandard, or artificial wine, and...

  18. Rural Education: A Hope for the Future. Proceedings of the Annual Rural and Small Schools Conference (9th, Manhattan, Kansas, October 26-27, 1987).

    ERIC Educational Resources Information Center

    Parmley, Fran, Ed.

    This collection of conference papers covers various aspects of rural education in changing times. The conference focused on changes and innovations in rural education and on reasons why rural educators can be optimistic. The proceedings report includes brief papers and workshop summaries on topics ranging from rural public relations to…

  19. Federal Information Resources: Identification, Availability and Use; Proceedings of a Conference, Washington, D.C., March 26-27, 1970.

    ERIC Educational Resources Information Center

    1970

    The Conference was held because of a recognition by the Committee on Scientific and Technical Information (COSATI) Task Group on Library Programs and the Federal Library Committee of a fundamental responsibility to interact in a meaningful way with the non-Federal sector--the state, local and private users of Federal information resources. This…

  20. 27 CFR 27.59 - Wines.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Wines. 27.59 Section 27.59... TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.59 Wines. All imported wines containing not less than 7 percent and not...

  1. 27 CFR 27.60 - Beer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Beer. 27.60 Section 27.60... TREASURY ALCOHOL IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.60 Beer. All imported beer is required to be released from customs custody...

  2. 27 CFR 27.60 - Beer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Beer. 27.60 Section 27.60... TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.60 Beer. All imported beer is required to be released from customs custody...

  3. 27 CFR 27.60 - Beer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Beer. 27.60 Section 27.60... TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.60 Beer. All imported beer is required to be released from customs custody...

  4. 27 CFR 27.60 - Beer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Beer. 27.60 Section 27.60... TREASURY ALCOHOL IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.60 Beer. All imported beer is required to be released from customs custody...

  5. 27 CFR 27.60 - Beer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Beer. 27.60 Section 27.60... TREASURY LIQUORS IMPORTATION OF DISTILLED SPIRITS, WINES, AND BEER General Requirements Marking and Labeling of Wines and Beer § 27.60 Beer. All imported beer is required to be released from customs custody...

  6. MEETING EDUCATIONAL NEEDS FOR POST-HIGH SCHOOL AGE YOUTH AND ADULTS IN ALABAMA, A REPORT OF CONFERENCES HELD ON VOCATIONAL, TECHNICAL, AND JUNIOR COLLEGE EDUCATION (AUBURN UNIVERSITY, 1964).

    ERIC Educational Resources Information Center

    Auburn Univ., AL. School of Education.

    SPEECHES GIVEN AT THREE MEETINGS ARE INCLUDED--(1) A FACULTY MEETING OF THE SCHOOL OF EDUCATION, AUBURN UNIVERSITY (JANUARY 31, 1964), (2) THE ANNUAL SPRING CONFERENCE OF THE ALABAMA ASSOCIATION OF SCHOOL ADMINISTRATORS (APRIL 26-27, 1964), AND (3) A CONFERENCE SPONSORED BY THE SCHOOL OF EDUCATION AUBURN UNIVERSITY (JUNE 22-23, 1964). THE SPEECHES…

  7. Quantum enhanced superresolution microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Oron, Dan; Tenne, Ron; Israel, Yonatan; Silberberg, Yaron

    2017-02-01

    Far-field optical microscopy beyond the Abbe diffraction limit, making use of nonlinear excitation (e.g. STED), or temporal fluctuations in fluorescence (PALM, STORM, SOFI) is already a reality. In contrast, overcoming the diffraction limit using non-classical properties of light is very difficult to achieve due to the fragility of quantum states of light. Here, we experimentally demonstrate superresolution microscopy based on quantum properties of light naturally emitted by fluorophores used as markers in fluorescence microscopy. Our approach is based on photon antibunching, the tendency of fluorophores to emit photons one by one rather than in bursts. Although a distinctively quantum phenomenon, antibunching is readily observed in most common fluorophores even at room temperature. This nonclassical resource can be utilized directly to enhance the imaging resolution, since the non-classical far-field intensity correlations induced by antibunching carry high spatial frequency information on the spatial distribution of emitters. Detecting photon statistics simultaneously in the entire field of view, we were able to detect non-classical correlations of the second and third order, and reconstructed images with resolution significantly beyond the diffraction limit. Alternatively, we demonstrate the utilization of antibunching for augmenting the capabilities of localization-based superresolution imaging in the presence of multiple emitters, using a novel detector comprised of an array of single photon detectors connected to a densely packed fiber bundle. These features allow us to enhance the spatial and temporal resolution with which multiple emitters can be imaged compared with other techniques that rely on CCD cameras.

  8. National Conference[s] on Career Education: Final Report.

    ERIC Educational Resources Information Center

    Clark, Joseph F.; And Others

    The report describes a series of conferences whose objective was to orient selected educational leaders to the implications of preparing educational personnel with a career education perspective. The first 32 pages of the report discuss project objectives and procedures, and detail participant profiles, pre- and post-conference career education…

  9. The Role of the Church in Rural Development. Report on the Proceedings and Recommendations of the Working Conference (Salisbury, Rhodesia, August 27-30, 1972).

    ERIC Educational Resources Information Center

    Smith, G. A., Ed.; Jolson, A., Ed.

    The proceedings of a national conference to examine the present situation and needs in rural areas of Rhodesia and to formulate a strategy of joint Christian participation in development are provided. The conference program centered around three main themes: Training Schemes, Extension and Development in Rural Areas, and Ecumenical Action in Rural…

  10. The Seattle Conference: The Role of the State Department of Education in Teacher Education (April 27-29, 1966).

    ERIC Educational Resources Information Center

    Edelfelt, Roy A.; Allen, Wendell C.

    This book includes the papers and speeches which were part of the Seattle Conference in which representatives of 49 states met to reevaluate beliefs and procedures regarding the future role of state departments of education particularly with reference to the identification and setting of goals. There are seven speeches and papers: "The Dynamic Duo…

  11. 27 CFR 27.133 - General requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false General requirements. 27.133 Section 27.133 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Reports Record and Report of Imported Liquors § 27.133 General requirements. Except as provided in § 27...

  12. Innovative Language Teaching and Learning at University: Enhancing Participation and Collaboration

    ERIC Educational Resources Information Center

    Goria, Cecilia, Ed.; Speicher, Oranna, Ed.; Stollhans, Sascha, Ed.

    2016-01-01

    The School of Cultures, Languages and Area Studies at the University of Nottingham hosted the fifth annual conference in the "Innovative Language Teaching at University" series. Under the heading "Enhancing participation and collaboration" the conference, organised by Cecilia Goria, Oranna Speicher and Sascha Stollhans, took…

  13. CONFERENCE NOTE: Conference on Precision Electromagnetic Measurements

    NASA Astrophysics Data System (ADS)

    1991-01-01

    The next Conference on Precision Electromagnetic Measurements (CPEM), will be held from 9 to 12 June 1992 at the Centre des Nouvelles Industries et Technologies (CNIT), La Défense, Paris, France. This conference, which is held every two years and whose importance and high level, confirmed by thirty years' experience, are recognized throughout the world, can be considered as a forum in which scientists, metrologists and professionals will have the opportunity to present and compare their research results on fundamental constants, standards and new techniques of precision measurement in the electromagnetic domain. Topics The following topics are regarded as the most appropriate for this conference: realization of units and fundamental constants d.c. a.c. and high voltage time and frequency radio-frequency and microwaves dielectrics, antennas, fields lasers, fibre optics advanced instrumentation, cryoelectronics. There will also be a session on international cooperation. Conference Language The conference language will be English. No translation will be provided. Organizers Société des Electriciens et des Electroniciens (SEE). Bureau National de Métrologie (BNM) Sponsors Institute of Electrical and Electronics Engineers (IEEE) Instrumentation & Measurement Society Union Radio Scientifique Internationale United States National Institute of Standards and Technology Centre National d'Etudes des Télécommunications Mouvement Français pour la Qualité, Section Métrologie Comité National Français de Radioélectricité Scientifique Contact Jean Zara, CPEM 92 publicity, Bureau National de Métrologie, 22, rue Monge, 75005 Paris Tel.: (33) 1 46 34 48 16, Fax: (33) 1 46 34 48 63

  14. Impact of Gender and Conference Size on Conference Preferences--Employing Natural Language Processing

    ERIC Educational Resources Information Center

    Eckhaus, Eyal; Davidovitch, Nitza

    2018-01-01

    This pilot study focuses on the impact of academic conferences from a gender-based perspective. What motivates faculty members to attend conferences? Which conferences do they choose? Can differences be found between men and women in their attitude to the effect of the conference and its contribution to their academic work, in light of many…

  15. Assessment of Mycobacterium bovis deleted in p27-p55 virulence operon as candidate vaccine against tuberculosis in animal models.

    PubMed

    Bianco, María V; Clark, Simon; Blanco, Federico C; Garbaccio, Sergio; García, Elizabeth; Cataldi, Angel A; Williams, Ann; Bigi, Fabiana

    2014-01-01

    A Mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental vaccine in animal models. The mutant MbΔp27-p55 was significantly more attenuated in nude mice than its parental strain but more virulent than BCG Pasteur. Challenge experiments in mice and guinea pigs using M. bovis or M. tuberculosis strains showed similar protection conferred by MbΔp27-p55 mutant than BCG in terms of pathology and bacterial loads in spleen but lower protection than BCG in lungs. When tested in cattle, MbΔp27-p55 did not induce IL-2 expression and induced a very low production of IFNγ, suggesting that the lack of P27/P55 reduces the capacity of M. bovis of triggering an adequate Th1 response.

  16. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis

    PubMed Central

    Zhou, Ying; Wang, Jian; Tseng, I-Chu; Huang, Timothy; Zhao, Yingjun; Zheng, Qiuyang; Gao, Yue; Luo, Hong; Zhang, Xian; Bu, Guojun; Hong, Wanjin

    2016-01-01

    Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis. SIGNIFICANCE STATEMENT Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch

  17. Crisis or Conference! Master List for Conference Planners.

    ERIC Educational Resources Information Center

    Carey, Tony

    This conference organizer's guide contains 42 lists of ideas, reminders, things to check, and questions to ask when a person is planning an event such as a conference, workshop, or training session. Written from a British point of view, the guide is organized into four parts in chronological order: preplanning, planning, onsite, and…

  18. 47 CFR 27.61-27.62 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false [Reserved] 27.61-27.62 Section 27.61-27.62 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Technical Standards §§ 27.61-27.62 [Reserved] ...

  19. 47 CFR 27.61-27.62 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false [Reserved] 27.61-27.62 Section 27.61-27.62 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Technical Standards §§ 27.61-27.62 [Reserved] ...

  20. Statins induce apoptosis through inhibition of Ras signaling pathways and enhancement of Bim and p27 expression in human hematopoietic tumor cells.

    PubMed

    Fujiwara, Daichiro; Tsubaki, Masanobu; Takeda, Tomoya; Tomonari, Yoshika; Koumoto, Yu-Ichi; Sakaguchi, Katsuhiko; Nishida, Shozo

    2017-10-01

    Recently, statins have been demonstrated to improve cancer-related mortality or prognosis in patients of various cancers. However, the details of the apoptosis-inducing mechanisms remain unknown. This study showed that the induction of apoptosis by statins in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of mevalonate or geranylgeranyl pyrophosphate biosynthesis. In addition, statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin through suppressing Ras prenylation. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin by statins induced Bim expression via inhibition of Bim phosphorylation and ubiquitination and cell-cycle arrest at G1 phase via enhancement of p27 expression. Moreover, combined treatment of U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, and rapamycin, a mammalian target of rapamycin inhibitor, induced Bim and p27 expressions. The present results suggested that statins induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, enhancing Bim expression, and inducing cell-cycle arrest at G1 phase through inhibition of Ras/extracellular signal-regulated kinase and Ras/mammalian target of rapamycin pathways. Therefore, our findings support the use of statins as potential anticancer agents or concomitant drugs of adjuvant therapy.

  1. Ada Compiler Validation Summary Report: Certificate Number: 880318W1. 09043 International Business Machines Corporation IBM Development System for the Ada Language, Version 2.1.0 IBM 4381 under VM/HPO, Host IBM 4381 under MVS/XA, Target

    DTIC Science & Technology

    1988-03-28

    International Business Machines Corporation IBM Development System for the Ada Language, Version 2.1.0 IBM 4381 under VM/HPO, host IBM 4381 under MVS/XA, target...Program Office, AJPO 20. ABSTRACT (Continue on reverse side if necessary and identify by block number) International Business Machines Corporation, IBM...Standard ANSI/MIL-STD-1815A in the compiler listed in this declaration. I declare that International Business Machines Corporation is the owner of record

  2. Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor.

    PubMed

    Fujimoto, Takuya; Imaeda, Yasuhiro; Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki; Textor, Garret P; Aertgeerts, Kathleen; Kubo, Keiji

    2010-05-13

    Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.

  3. Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a review of design, development and potential place in therapy.

    PubMed

    Sartori, Michelangelo; Cosmi, Benilde

    2018-04-01

    Direct oral anticoagulants are associated with rates of major bleeding which are not negligible, albeit lower than those associated with vitamin K antagonists. No specific reversal agent for factor Xa (FXa) direct inhibitors is currently available for clinical use. A modified activated human FXa decoy protein, andexanet alfa, is being developed that binds FXa direct inhibitors in their active site, thus reversing their anticoagulant effect. The purpose of this article is to review the design, development and clinical trials of andexanet alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding. Andexanet alfa has been studied in double-blind, placebo-controlled phase II and III studies. A preliminary report of the phase III study showed that an effective hemostasis was obtained after andexanet alfa infusion in the majority of the patients with acute major bleeding associated with FXa inhibitors. Additional studies are ongoing and andexanet alfa is expected to be launched in the market in the near future.

  4. 78 FR 62360 - PJM Interconnection, L.L.C.; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER13-2108-000] PJM Interconnection, L.L.C.; Notice of Technical Conference Federal Energy Regulatory Commission (Commission) staff... consider issues related to PJM Interconnection, L.L.C.'s (PJM) proposed demand response plan enhancements...

  5. 47 CFR 27.322-27.325 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false [Reserved] 27.322-27.325 Section 27.322-27.325 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.322-27.325 [Reserved] ...

  6. 47 CFR 27.304-27.307 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false [Reserved] 27.304-27.307 Section 27.304-27.307 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.304-27.307 [Reserved] ...

  7. 47 CFR 27.310-27.320 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false [Reserved] 27.310-27.320 Section 27.310-27.320 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.310-27.320 [Reserved] ...

  8. 47 CFR 27.322-27.325 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false [Reserved] 27.322-27.325 Section 27.322-27.325 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.322-27.325 [Reserved] ...

  9. 47 CFR 27.310-27.320 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false [Reserved] 27.310-27.320 Section 27.310-27.320 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.310-27.320 [Reserved] ...

  10. 47 CFR 27.304-27.307 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false [Reserved] 27.304-27.307 Section 27.304-27.307 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Application, Licensing, and Processing Rules for WCS §§ 27.304-27.307 [Reserved] ...

  11. ICCK Conference Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Green, William H.

    2013-05-28

    The 7th International Conference on Chemical Kinetics (ICCK) was held July 10-14, 2011, at Massachusetts Institute of Technology (MIT), in Cambridge, MA, hosted by Prof. William H. Green of MIT's Chemical Engineering department. This cross-disciplinary meeting highlighted the importance of fundamental understanding of elementary reactions to the full range of chemical investigations. The specific conference focus was on elementary-step kinetics in both the gas phase and in condensed phase. The meeting provided a unique opportunity to discuss how the same reactive species and reaction motifs manifest under very different reaction conditions (e.g. atmospheric, aqueous, combustion, plasma, in nonaqueous solvents, onmore » surfaces.). The conference featured special sessions on new/improved experimental techniques, improved models and data analysis for interpreting complicated kinetics, computational kinetics (especially rate estimates for large kinetic models), and a panel discussion on how the community should document/archive kinetic data. In the past, this conference had been limited to homogeneous gas-phase and liquid-phase systems. This conference included studies of heterogeneous kinetics which provide rate constants for, or insight into, elementary reaction steps. This Grant from DOE BES covered about half of the subsidies we provided to students and postdocs who attended the conference, by charging them reduced-rate registration fees. The complete list of subsidies provided are listed in Table 1 below. This DOE funding was essential to making the conference affordable to graduate students, and indeed the attendance at this conference was higher than at previous conferences in this series. Donations made by companies provided additional subsidies, leveraging the DOE funding. The conference was very effective in educating graduate students and important in fostering scientific interactions, particularly between scientists studying gas phase and liquid phase

  12. Building on the Future. NECC 2001: National Educational Computing Conference Proceedings (22nd, Chicago, Illinois, June 25-27, 2001).

    ERIC Educational Resources Information Center

    National Educational Computing Association, Eugene, OR.

    This document contains the proceedings of the National Educational Computing Conference (NECC) 2001. The following research papers are included: "UCI Computer Arts: Building Gender Equity While Meeting ISTE NETS" (Kimberly Bisbee Burge); "From Mythology to Technology: Sisyphus Makes the Leap to Learn" (Patricia J. Donohue, Mary…

  13. Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

    PubMed Central

    Upreti, Vijay V; Song, Yan; Wang, Jessie; Byon, Wonkyung; Boyd, Rebecca A; Pursley, Janice M; LaCreta, Frank; Frost, Charles E

    2013-01-01

    Background Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist), on the pharmacokinetics of apixaban in healthy subjects. Methods This two-period, two-treatment crossover study randomized 18 healthy subjects to receive a single oral dose of apixaban 10 mg with and without a single oral dose of famotidine 40 mg administered 3 hours before dosing with apixaban. Plasma apixaban concentrations were measured up to 60 hours post-dose and pharmacokinetic parameters were calculated. Results Famotidine did not affect maximum apixaban plasma concentration (Cmax) or area under the plasma concentration-time curve from zero to infinite time (AUC∞). Point estimates for ratios of geometric means with and without famotidine were close to unity for Cmax (0.978) and AUC∞ (1.007), and 90% confidence intervals were entirely contained within the 80%–125% no-effect interval. Administration of apixaban alone and with famotidine was well tolerated. Conclusion Famotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility). Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to underlying conditions (eg, achlorhydria), or by gastrointestinal pH-mediated effects of other histamine H2-receptor antagonists, antacids, or proton pump inhibitors. Given that famotidine is also an inhibitor of the human organic cation transporter (hOCT), these results indicate that apixaban pharmacokinetics are not influenced by hOCT uptake transporter inhibitors. Overall, these results support that apixaban can be administered without regard to coadministration

  14. HSP27 knockdown produces synergistic induction of apoptosis by HSP90 and kinase inhibitors in glioblastoma multiforme.

    PubMed

    Belkacemi, Louiza; Hebb, Matthew O

    2014-09-01

    The heat-shock proteins HSP27 and HSP90 perpetuate the malignant nature of glioblastoma multiforme (GBM) and offer promise as targets for novel cancer therapeutics. The present study sought to define synergistic antitumor benefits of concurrent HSP27-knockdown and the HSP90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) or, comparatively, the non-selective kinase inhibitor, staurosporine, in GBM cells. Dose-response relations were determined for 17-AAG and staurosporine in three GBM cell lines. HSP27-targeted siRNA was administered alone or in combination with subtherapeutic concentrations of each drug and cells were evaluated for viability, proliferation and apoptosis. Adjuvant HSP27 knockdown with 17-AAG or staurosporine produced marked and synergistic decrease in GBM cell viability and proliferation, with robust elevation of apoptotic fractions and caspase-3 activation. HSP27 knockdown confers potent chemosensitization of GBM cells. These novel data support the development of HSP-targeting strategies and, specifically, anti-HSP27 agents for the treatment of GBM. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Overexpression of human Hsp27 inhibits serum-induced proliferation in airway smooth muscle myocytes and confers resistance to hydrogen peroxide cytotoxicity.

    PubMed

    Salinthone, Sonemany; Ba, Mariam; Hanson, Lisa; Martin, Jody L; Halayko, Andrew J; Gerthoffer, William T

    2007-11-01

    Airway smooth muscle (ASM) hypertrophy and hyperplasia are characteristics of asthma that lead to thickening of the airway wall and obstruction of airflow. Very little is known about mechanisms underlying ASM remodeling, but in vascular smooth muscle, it is known that progression of atherosclerosis depends on the balance of myocyte proliferation and cell death. Small heat shock protein 27 (Hsp27) is antiapoptotic in nonmuscle cells, but its role in ASM cell survival is unknown. Our hypothesis was that phosphorylation of Hsp27 may regulate airway remodeling by modifying proliferation, cell survival, or both. To test this hypothesis, adenoviral vectors were used to overexpress human Hsp27 in ASM cells. Cells were infected with empty vector (Ad5) or wild-type Hsp27 (AdHsp27 WT), and proliferation and death were assessed. Overexpressing Hsp27 WT caused a 50% reduction in serum-induced proliferation and increased cell survival after exposure to 100 microM hydrogen peroxide (H(2)O(2)) compared with mock-infected controls. Overexpression studies utilizing an S15A, S78A, and S82A non-phosphorylation mutant (AdHsp27 3A) and an S15D, S78D, and S82D pseudo-phosphorylation mutant (AdHsp27 3D) showed phosphorylation of Hsp27 was necessary for regulation of ASM proliferation, but not survival. Hsp27 provided protection against H(2)O(2)-induced cytotoxicity by upregulating cellular glutathione levels and preventing necrotic cell death, but not apoptotic cell death. The results support the notion that ASM cells can be stimulated to undergo proliferation and death and that Hsp27 may regulate these processes, thereby contributing to airway remodeling in asthmatics.

  16. CONFERENCE LEADERSHIP.

    ERIC Educational Resources Information Center

    Louisiana State Vocational Curriculum Development and Research Center, Natchitoches.

    THIS INSTRUCTIONAL MATERIAL IS FOR USE BY PERSONS WHO CONDUCT CONFERENCE LEADER TRAINING PROGRAMS. SPECIFICALLY, ITS PURPOSE IS TO TRAIN VOCATIONAL TRADE AND INDUSTRIAL EDUCATION PEOPLE TO CONDUCT TRAINING CONFERENCES FOR INDUSTRY. IT IS INTENDED FOR USE IN AREA VOCATIONAL SCHOOLS IN THE PROMOTION AND DEVELOPMENT OF SUPERVISORY PERSONNEL…

  17. 76 FR 78641 - Southwestern Gas Storage Technical Conference; Notice of Public Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... Storage Technical Conference; Notice of Public Conference Take notice that on February 16, 2012 at 9 a.m... technical conference with interested parties to discuss issues related to natural gas storage development in... Cold Weather Event of February 1-5, 2011: Causes and Recommendations, ``[a]dditional gas storage...

  18. Young Women's Conference in STEM: Our starting point for getting women into STEM fields

    NASA Astrophysics Data System (ADS)

    Ortiz, Deedee; Zwicker, Andrew; Greco, Shannon; Dominguez, Arturo

    2015-11-01

    The number of women in STEM careers is staggeringly low; just one in seven engineers are female and only 27% of all computer science jobs are held by women. A recent US Dept. of Commerce report found that between 2000-2011 women experienced no employment growth in STEM jobs. According to the AIP, the percentage of women in physics overall is 26% and women make up less than 7% of the fusion energy workforce. To address this problem we have, since 2001, run a conference to introduce young women to the wide range of careers in STEM fields in a way that is not part of their typical education. By introducing students in a meaningful way to successful women in STEM, from graduate students to senior researchers, the intent of the conference is to foster interest, develop mentoring relationships, and to provide role models that will have a positive influence on future educational and career choices. Data from surveys indicate that this is indeed the impact. For example, 86% of 2015 attendees indicated they are more likely to major in a scientific field after attending the conference then they were before. We are now in the process of expanding and improving the conference in order to reach more students and increase the overall impact.

  19. Addressing a silent killer - The International Conference on Betel Quid and Areca Nut

    Cancer.gov

    The Center for Global Health, National Cancer Institute, in coordination with the National Institute of Dental and Craniofacial Research , The University of Texas at MD Anderson Cancer Center, Oral Cancer Research Coordinating Center, University of Malaya, Taiwan Health Promotion Administration, Ministry of Health and Welfare, and with the generous support of the Malaysia Ministry of Health, hosted the International Conference on Betel Quid and Areca Nut in Kuala Lumpur Malaysia on April 27-28, 2016.

  20. Architecture of conference control functions

    NASA Astrophysics Data System (ADS)

    Kausar, Nadia; Crowcroft, Jon

    1999-11-01

    Conference control is an integral part in many-to-many communications that is used to manage and co-ordinate multiple users in conferences. There are different types of conferences which require different types of control. Some of the features of conference control may be user invoked while others are for internal management of a conference. In recent years, ITU (International Telecommunication Union) and IETF (Internet Engineering Task Force) have standardized two main models of conferencing, each system providing a set of conference control functionalities that are not easily provided in the other one. This paper analyzes the main activities appropriate for different types of conferences and presents an architecture for conference control called GCCP (Generic Conference Control Protocol). GCCP interworks different types of conferencing and provides a set of conference control functions that can be invoked by users directly. As an example of interworking, interoperation of IETF's SIP and ITU's H.323 call control functions have been examined here. This paper shows that a careful analysis of a conferencing architecture can provide a set of control functions essential for any group communication model that can be extensible if needed.

  1. Modulation of CD4+ and CD8+ T Cell Function and Cytokine Responses in Strongyloides stercoralis Infection by Interleukin-27 (IL-27) and IL-37.

    PubMed

    Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

    2017-11-01

    Strongyloides stercoralis infection is associated with diminished antigen-specific Th1- and Th17-associated responses and enhanced Th2-associated responses. Interleukin-27 (IL-27) and IL-37 are two known anti-inflammatory cytokines that are highly expressed in S. stercoralis infection. We therefore wanted to examine the role of IL-27 and IL-37 in regulating CD4 + and CD8 + T cell responses in S. stercoralis infection. To this end, we examined the frequency of Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 cells in 15 S. stercoralis -infected individuals and 10 uninfected individuals stimulated with parasite antigen following IL-27 or IL-37 neutralization. We also examined the production of prototypical type 1, type 2, type 9, type 17, and type 22 cytokines in the whole-blood supernatants. Our data reveal that IL-27 or IL-37 neutralization resulted in significantly enhanced frequencies of Th1/Tc1, Th2/Tc2, Th17/Tc17, Th9, and Th22 cells with parasite antigen stimulation. There was no induction of any T cell response in uninfected individuals following parasite antigen stimulation and IL-27 or IL-37 neutralization. Moreover, we also observed increased production of gamma interferon (IFN-γ), IL-5, IL-9, IL-17, and IL-22 and decreased production of IL-10 following IL-27 and IL-37 neutralization and parasite antigen stimulation in whole-blood cultures. Thus, we demonstrate that IL-27 and IL-37 limit the induction of particular T cell subsets along with cytokine responses in S. stercoralis infections, which suggest the importance of IL-27 and IL-37 in immune modulation in a chronic helminth infection. Copyright © 2017 American Society for Microbiology.

  2. The linker connecting the two kringles plays a key role in prothrombin activation

    PubMed Central

    Pozzi, Nicola; Chen, Zhiwei; Pelc, Leslie A.; Shropshire, Daniel B.; Di Cera, Enrico

    2014-01-01

    The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that is accelerated >3,000-fold by cofactor Va. This physiologically important effect is paradigmatic of analogous cofactor-dependent reactions in the coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3). Recent developments indicate that the linkers, and particularly Lnk2, confer on the zymogen significant flexibility in solution and enable prothrombin to sample alternative conformations. The role of this flexibility in the context of prothrombin activation was tested with several deletions. Removal of Lnk2 in almost its entirety (ProTΔ146–167) drastically reduces the enhancement of thrombin generation by cofactor Va from >3,000-fold to 60-fold because of a significant increase in the rate of activation in the absence of cofactor. Deletion of Lnk2 mimics the action of cofactor Va and offers insights into how prothrombin is activated at the molecular level. The crystal structure of ProTΔ146–167 reveals a contorted architecture where the domains are not vertically stacked, kringle-1 comes within 9 Å of the protease domain, and the Gla-domain primed for membrane binding comes in contact with kringle-2. These findings broaden our molecular understanding of a key reaction of the blood coagulation cascade where cofactor Va enhances activation of prothrombin by factor Xa by compressing Lnk2 and morphing prothrombin into a conformation similar to the structure of ProTΔ146–167. PMID:24821807

  3. Increasing uptake of comparative effectiveness and patient-centered outcomes research among stakeholders: insights from conference discussion.

    PubMed

    Law, Ernest; Harrington, Rachel; Alexander, G Caleb; Saha, Soumi; Oehrlein, Elisabeth; Perfetto, Eleanor M

    2018-02-01

    The goal of comparative effectiveness research (CER) and patient-centered outcomes research (PCOR) is to improve health outcomes by providing stakeholders with evidence directly relevant to decision making. In January 2017, the Pharmaceutical Research and Manufacturers Association Foundation, alongside the Academy for Managed Care Pharmacy, organized a conference aimed at engaging experts and opinion leaders representing clinicians, patients and payers to identify and discuss barriers and strategies to enhancing uptake and use of CER/PCOR. This report summarizes the conference discussion in the following sections: preconference survey; summary of barriers and strategies to the uptake of CER/PCOR identified by conference attendees; and future perspectives on the field.

  4. Educational Assessment. Proceedings: Conference of the University/Urban Schools National Task Force (13th, Atlanta, Georgia, November 8-9, 1991).

    ERIC Educational Resources Information Center

    Bossone, Richard M., Ed.; Polishook, Irwin H., Ed.

    At this conference on educational assessment, there was consensus among participants on the importance of the use of assessment to improve instruction, enhance the curriculum, and allow policy makers to measure achievement. There was less consensus about the best forms of assessment to use. The following conference papers are provided in this…

  5. Pathotype profile of Xanthomonas oryzae pv. oryzae isolates from North Sumatera

    NASA Astrophysics Data System (ADS)

    Noer, Z.; Hasanuddin; Lisnawita; Suryanto, D.

    2018-02-01

    The Bacterial blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most important diseases and has caused crop failure in rice crops. This pathogen infects the leaves in all plant growth phases. The purpose of this study is to investigation 10 Xoo isolates pathotype obtained from North Sumatra based on their interactions with 10 near-isogenic rice lines (NIL) of IRRI. The results showed that there are 6 pathotypes of virulence in North Sumatra, they are; pathotype I with incompatible interaction to all Xa genes, pathotype II with compatible interaction to Xa1 and Xa3 genes, while it has incompatible interaction to other genes, pathotype III with compatible interaction to Xa1, Xa5, Xa7, Xa8, Xa10 and Xa11 genes, but it has incompatible interaction to other genes, pathotype IV with compatible interaction to all Xa genes, pathotype V with compatible interaction to Xa1 gene and incompatible interaction to other genes, and pathotype VI with compatible interaction to Xa3 gene and incompatible interaction to other genes. Based on the resistant genes in each individual Xa2, Xa4, and Xa21 genes are the combination of Xa genes which are most suitable for use in the development of rice cultivars in North Sumatra.

  6. PREFACE: 3rd International Conference of Mechanical Engineering Research (ICMER 2015)

    NASA Astrophysics Data System (ADS)

    Mamat, Riazalman; Rahman, Mustafizur; Mohd. Zuki Nik Mohamed, Nik; Che Ghani, Saiful Anwar; Harun, Wan Sharuzi Wan

    2015-12-01

    The 3rd ICMER2015 is the continuity of the NCMER2010. The year 2010 represents a significant milestone in the history for Faculty of Mechanical Engineering, Universiti Malaysia Pahang (UMP) Malaysia with the organization of the first and second national level conferences (1st and 2nd NCMER) at UMP on May 26-27 and Dec 3-4 2010. The Faculty then changed the name from National Conference on Mechanical Engineering Research (NCMER) to International Conference on Mechanical Engineering Research (ICMER) in 2011 and this year, 2015 is our 3rd ICMER. These proceedings contain the selected scientific manuscripts submitted to the conference. It is with great pleasure to welcome you to the "International Conference on Mechanical Engineering Research (ICMER2015)" that is held at Zenith Hotel, Kuantan, Malaysia. The call for papers attracted submissions of over two hundred abstracts from twelve different countries including Japan, Iran, China, Kuwait, Indonesia, Norway, Philippines, Morocco, Germany, UAE and more. The scientific papers published in these proceedings have been revised and approved by the technical committee of the 3rd ICMER2015. All of the papers exhibit clear, concise, and precise expositions that appeal to a broad international readership interested in mechanical engineering, combustion, metallurgy, materials science as well as in manufacturing and biomechanics. The reports present original ideas or results of general significance supported by clear reasoning and compelling evidence, and employ methods, theories and practices relevant to the research. The authors clearly state the questions and the significance of their research to theory and practice, describe how the research contributes to new knowledge, and provide tables and figures that meaningfully add to the narrative. In this edition of ICMER representatives attending are from academia, industry, governmental and private sectors. The plenary and invited speakers will present, discuss, promote and

  7. Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa.

    PubMed

    Jiang, Lilong; Wang, Qiong; Shen, Shu; Xiao, Tongshu; Li, Youbin

    2014-03-01

    Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 4th integrated transportation management systems (ITMS) conference : conference proceedings

    DOT National Transportation Integrated Search

    2001-08-01

    This report documents the proceedings from the 4th Integrated Transportation Management Systems (ITMS) Conference, ITMS: A Key Strategy to Optimize Surface Transportation System Performance, held in Newark, New Jersey on July 15-18, 2001. The Confere...

  9. EZH2 and histone deacetylase inhibitors induce apoptosis in triple negative breast cancer cells by differentially increasing H3 Lys27 acetylation in the BIM gene promoter and enhancers.

    PubMed

    Huang, Julia P; Ling, Kun

    2017-11-01

    Enhancer of zeste homolog 2 (EZH2), a subunit of polycomb repressive complex 2, is a histone methyl-transferase and is considered to work cooperatively with histone deacetylases (HDACs) in the same protein complex to mediate gene transcription repression by increasing histone H3 Lys 27 trimethylation (H3K27me3), in particular in the nucleosome (s). EZH2 is overexpressed in numerous types of cancer, including triple negative breast cancer (TNBC), a subtype of breast cancer, which there are no effective treatment options for. Thus, inhibition of EZH2 may be harnessed for targeted therapy of this disease. The present study demonstrated that co-treatment with an EZH2 inhibitor and a HDAC inhibitor additively induced apoptosis in two TNBC cell lines, namely MDA-MB-231 and MDA-MB-436. The increased rate of cell death was associated with an elevation of B cell lymphoma-2 like 11 (BIM) expression level, a pro-apoptotic protein at the protein and mRNA expression levels in these two cell lines. The expression of forkhead box O1 (FOXO1), a known upstream transcriptional activator of BIM , was upregulated in both cell lines by the HDAC inhibitor, and the effect was more pronounced in MDA-MB-436 cells with higher phosphorylation levels of protein kinase B, a negative regulator of FOXO1, compared with MDA-MB-231 cells. Conversely, FOXO1 expression was inhibited following treatment with the EZH2 inhibitor, suggesting that EZH2 and HDAC inhibitors induced BIM expression via a FOXO1-independent mechanism. The present study further revealed that the EZH2 inhibitor, but not the HDAC inhibitor, induced high levels of H3K27 acetylation (H3K27ac) in the BIM promoter. By contrast, compared with the effect of the EZH2 inhibitor, HDAC inhibitor treatment resulted in an increase in H3K27ac at two BIM enhancers. Collectively, the results of the present study indicated that EZH2 and HDACs act differentially on H3K27ac levels in the nucleosome at the promoter and enhancer regions of the BIM

  10. 27 CFR 6.27 - Proprietary interest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Proprietary interest. 6.27 Section 6.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership....

  11. 27 CFR 6.27 - Proprietary interest.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Proprietary interest. 6.27 Section 6.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership....

  12. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents shall...

  13. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents shall...

  14. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents shall...

  15. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents shall...

  16. 27 CFR 7.27 - Net contents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Net contents. 7.27 Section 7.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES Labeling Requirements for Malt Beverages § 7.27 Net contents. (a) Net contents shall...

  17. Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

    PubMed

    Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

    2016-01-01

    To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

  18. The 2009 National Environmental Public Health Conference: one model for planning green and healthy conferences.

    PubMed

    Ruckart, Perri Zeitz; Moore, Cory; Burgin, Deborah; Byrne, Maggie Kelly

    2011-01-01

    The Centers for Disease Control and Prevention's National Center for Environmental Health and the Agency for Toxic Substances and Disease Registry committed to making their 2009 National Environmental Public Health Conference a model for green and healthy conferences. The conference included increased opportunities for physical activity, both as part of conference events and for transportation to the conference. In addition, conference meals were healthy and sustainably sourced. The conference also implemented intuitive, accessible recycling; online scheduling and evaluation to minimize hard-copy materials; and the purchase of carbon offsets to reduce the unwanted environmental impact of the conference. Public health professionals have an opportunity and obligation to support healthy behaviors at their events and to serve as leaders in this area. Facilitating healthy and sustainable choices is in alignment with goals for both public health and broader social issues-such as environmental quality-that have a direct bearing on public health.

  19. Conference Resolution

    NASA Astrophysics Data System (ADS)

    2009-04-01

    Since the first IUPAP International Conference on Women in Physics (Paris, March 2002) and the Second Conference (Rio de Janeiro, May 2005), progress has continued in most countries and world regions to attract girls to physics and advance women into leadership roles, and many working groups have formed. The Third Conference (Seoul, October 2008), with 283 attendees from 57 countries, was dedicated to celebrating the physics achievements of women throughout the world, networking toward new international collaborations, building each participant's capacity for career success, and aiding the formation of active regional working groups to advance women in physics. Despite the progress, women remain a small minority of the physics community in most countries.

  20. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice.

    PubMed

    Fero, M L; Rivkin, M; Tasch, M; Porter, P; Carow, C E; Firpo, E; Polyak, K; Tsai, L H; Broudy, V; Perlmutter, R M; Kaushansky, K; Roberts, J M

    1996-05-31

    Targeted disruption of the murine p27(Kip1) gene caused a gene dose-dependent increase in animal size without other gross morphologic abnormalities. All tissues were enlarged and contained more cells, although endocrine abnormalities were not evident. Thymic hyperplasia was associated with increased T lymphocyte proliferation, and T cells showed enhanced IL-2 responsiveness in vitro. Thus, p27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens. In the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells. p27 deletion, like deletion of the Rb gene, uniquely caused neoplastic growth of the pituitary pars intermedia, suggesting that p27 and Rb function in the same regulatory pathway. The absence of p27 also caused an ovulatory defect and female sterility. Maturation of secondary ovarian follicles into corpora lutea, which express high levels of p27, was markedly impaired.

  1. The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I Secretion System, in Activation of the Rice XA21-Mediated Immune Response

    PubMed Central

    Ronald, Pamela C.

    2014-01-01

    Tyrosine sulfation is an important posttranslational modification that determines the outcome of serious diseases in plants and animals. We have recently demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo) carries a functional sulfotransferase (RaxST). raxST is required for activation of rice Xa21-mediated immunity indicating the critical, but unknown, function of raxST in mediating the Xoo/rice interaction. The raxST gene resides in the same operon (raxSTAB) as components of a predicted type I secretion and processing system (RaxA and RaxB). These observations suggest a model where RaxST sulfates a molecule that contains a leader peptide, which is cleaved by the peptidase domain of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS. PMID:25386383

  2. The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I Secretion System, in Activation of the Rice XA21-Mediated Immune Response.

    PubMed

    Ronald, Pamela C

    2014-01-01

    Tyrosine sulfation is an important posttranslational modification that determines the outcome of serious diseases in plants and animals. We have recently demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo) carries a functional sulfotransferase (RaxST). raxST is required for activation of rice Xa21-mediated immunity indicating the critical, but unknown, function of raxST in mediating the Xoo/rice interaction. The raxST gene resides in the same operon (raxSTAB) as components of a predicted type I secretion and processing system (RaxA and RaxB). These observations suggest a model where RaxST sulfates a molecule that contains a leader peptide, which is cleaved by the peptidase domain of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS.

  3. Eighteen Years of the Great Lakes Regional Counseling Psychology Conference: Revisiting the Need for Regional Conferences

    ERIC Educational Resources Information Center

    Delgado-Romero, Edward A.; Bowman, Sharon L.; Gerstein, Lawrence H.

    2006-01-01

    The Great Lakes Regional Conference on Counseling Psychology is the only conference to continuously fulfill the 1987 mandate issued by Division 17 for regional counseling conferences. The rationale for regional conferences is reviewed, and the 18-year history of the Great Lakes Regional Conference is examined. The authors conclude by noting the…

  4. 27 CFR 27.121 - Containers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Containers. 27.121 Section... Spirits In Bulk § 27.121 Containers. Imported distilled spirits may be bottled in either domestic or imported containers conforming to the provisions of subpart N of this part. (72 Stat. 1374; 26 U.S.C. 5301...

  5. Parent Conferences. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Duffy, Roslyn; And Others

    1997-01-01

    Presents six workshop sessions on parent conferences: (1) "Parents' Perspectives on Conferencing" (R. Duffy); (2) "Three Way Conferences" (G. Zeller); (3) "Conferencing with Parents of Infants" (K. Albrecht); (4) "Conferencing with Parents of School-Agers" (L. G. Miller); (5) "Cross Cultural Conferences" (J. Gonzalez-Mena); and (6) "Working with…

  6. Threats, protests greet conference.

    PubMed

    Struck, D

    1994-09-04

    In preparation for the 1994 International Conference on Population and Development, Egypt has deployed 14,000 police to protect participants from threatened violence. The Vatican has joined forces with Muslim fundamentalists to condemn the conference as a vehicle for imposing Western ideals, particularly abortion, on Third world countries. In addition, the opposition is raising the specter of a descent of homosexuals onto Cairo and Muslim fundamentalists have threatened to murder Western representatives. A suit filed by Islamic lawyers, aimed at stopping the conference, failed. Sudan and Saudi Arabia plan to boycott the conference, and it remains uncertain whether Libya will be represented. Conference organizers have not been deterred by the threats and note that the controversy has drawn public attention to the central issues under debate.

  7. A Case-Conference Exercise to Facilitate Understanding of Paradigms in Abnormal Psychology

    ERIC Educational Resources Information Center

    Lafosse, Jose M.; Zinser, Michael C.

    2002-01-01

    In this article we describe an in-class case-conference exercise designed to enhance the teaching of paradigms in abnormal psychology courses. The primary pedagogical goals are to increase awareness of how paradigms are applied in real-life settings; better distinguish between paradigms; and recognize how paradigms influence understanding of…

  8. The General Conference Mennonites.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    General Conference Mennonites and Old Order Amish are compared and contrasted in the areas of physical appearance, religious beliefs, formal education, methods of farming, and home settings. General Conference Mennonites and Amish differ in physical appearance and especially in dress. The General Conference Mennonite men and women dress the same…

  9. Waterside Security 2010 (WSS 2010) Conference: Post Conference Report

    DTIC Science & Technology

    2011-02-01

    Memorandum Report NURC-MR-2011-002 Waterside Security 2010 (WSS2010) Conference: post conference report Ronald Kessel and...in NATO, NURC conducts maritime research in support of NATO’s operational and transformation requirements. Reporting to the Supreme Allied Commander...independent business process certification. Copyright © NURC 2011. NATO member nations have unlimited rights to use, modify, reproduce, release

  10. Parent Satisfaction With Communication Is Associated With Physician's Patient-Centered Communication Patterns During Family Conferences.

    PubMed

    October, Tessie W; Hinds, Pamela S; Wang, Jichuan; Dizon, Zoelle B; Cheng, Yao I; Roter, Debra L

    2016-06-01

    To evaluate the association between physician's patient-centered communication patterns and parental satisfaction during decision-making family conferences in the PICU. Single-site, cross-sectional study. Forty-four-bed PICUs in a free-standing children's hospital. Sixty-seven English-speaking parents of 39 children who participated in an audiorecorded family conference with 11 critical care attending physicians. Thirty-nine family conferences were audiorecorded. Sixty-seven of 77 (92%) eligible parents were enrolled. The conference recordings were coded using the Roter Interaction Analysis System and a Roter Interaction Analysis System-based patient-centeredness score, which quantitatively evaluates the conversations for physician verbal dominance and discussion of psychosocial elements, such as a family's goals and preferences. Higher patient-centeredness scores reflect higher proportionate dialogue focused on psychosocial, lifestyle, and socioemotional topics relative to medically focused talk. Parents completed satisfaction surveys within 24 hours of the conference. Conferences averaged 45 minutes in length (SD, 19 min), during which the medical team contributed 73% of the dialogue compared with parental contribution of 27%. Physicians dominated the medical team, contributing 89% of the team contribution to the dialogue. The majority of physician speech was medically focused (79%). A patient-centeredness score more than 0.75 predicted parental satisfaction (β = 12.05; p < 0.0001), controlling for the length of conference, child severity of illness, parent race, and socioeconomic status. Parent satisfaction was negatively influenced by severity of illness of the patient (β = -4.34; p = 0.0003), controlling for previously mentioned factors in the model. Parent-physician interactions with more patient-centered elements, such as increased proportions of empathetic statements, question asking, and emotional talk, positively influence parent satisfaction despite

  11. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients.

    PubMed

    Tang, Jieting; Chen, Huarong; Wong, Chi-Chun; Liu, Dabin; Li, Tong; Wang, Xiaohong; Ji, Jiafu; Sung, Joseph Jy; Fang, Jing-Yuan; Yu, Jun

    2018-03-14

    Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Conversely, silencing of DDX27 exerted opposite effects in vitro and significantly inhibited murine xenograft tumor growth and lung metastasis in vivo. Up-regulation of DDX27 enhanced and prolonged TNF-α-mediated NF-κB signaling. Nucleophosmin (NPM1) was identified as a binding partner of DDX27. DDX27 increased nuclear NPM1 and NF-κB-p65 interaction to enhance DNA binding activity of NF-κB. Silencing NPM1 abrogated DDX27-activating NF-κB signaling and its tumor-promoting function. Together, DDX27 is overexpressed and plays a pivotal oncogenic role in CRC.

  12. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis.

    PubMed

    Wang, Xin; Zhou, Ying; Wang, Jian; Tseng, I-Chu; Huang, Timothy; Zhao, Yingjun; Zheng, Qiuyang; Gao, Yue; Luo, Hong; Zhang, Xian; Bu, Guojun; Hong, Wanjin; Xu, Huaxi

    2016-12-14

    Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis. Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch/γ-secretase pathway can also be of

  13. CERN automatic audio-conference service

    NASA Astrophysics Data System (ADS)

    Sierra Moral, Rodrigo

    2010-04-01

    Scientists from all over the world need to collaborate with CERN on a daily basis. They must be able to communicate effectively on their joint projects at any time; as a result telephone conferences have become indispensable and widely used. Managed by 6 operators, CERN already has more than 20000 hours and 5700 audio-conferences per year. However, the traditional telephone based audio-conference system needed to be modernized in three ways. Firstly, to provide the participants with more autonomy in the organization of their conferences; secondly, to eliminate the constraints of manual intervention by operators; and thirdly, to integrate the audio-conferences into a collaborative working framework. The large number, and hence cost, of the conferences prohibited externalization and so the CERN telecommunications team drew up a specification to implement a new system. It was decided to use a new commercial collaborative audio-conference solution based on the SIP protocol. The system was tested as the first European pilot and several improvements (such as billing, security, redundancy...) were implemented based on CERN's recommendations. The new automatic conference system has been operational since the second half of 2006. It is very popular for the users and has doubled the number of conferences in the past two years.

  14. Additional sex combs interacts with enhancer of zeste and trithorax and modulates levels of trimethylation on histone H3K4 and H3K27 during transcription of hsp70.

    PubMed

    Li, Taosui; Hodgson, Jacob W; Petruk, Svetlana; Mazo, Alexander; Brock, Hugh W

    2017-09-19

    Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues. In Drosophila S2 cell nuclei, Asx interacts with E(z) and Trx in vivo. Drosophila Asx is required for repression of heat-shock gene hsp70 and is recruited downstream of the hsp70 promoter. Changes in the levels of H3K4me3 and H3K27me3 downstream of the hsp70 promoter in Asx mutants relative to wild type show that Asx regulates H3K4 and H3K27 trimethylation. We propose that during transcription Asx modulates the ratio of H3K4me3 to H3K27me3 by selectively recruiting the antagonistic HMTs, E(z) and Trx or other nucleosome-modifying enzymes to hsp70.

  15. 76 FR 67725 - Technical Conference on Penalty Guidelines; Second Notice of Technical Conference on Penalty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-02

    ... Conference on Penalty Guidelines; Second Notice of Technical Conference on Penalty Guidelines On September 21... Conference on Penalty Guidelines to be held on November 17, 2011. The conference will be held from 1 p.m. to... impact of the Penalty Guidelines, which the Commission issued on September 17, 2010,\\1\\ on compliance and...

  16. Leveraging a Redesigned Morbidity and Mortality Conference That Incorporates the Clinical and Educational Missions of Improving Quality and Patient Safety.

    PubMed

    Tad-Y, Darlene B; Pierce, Read G; Pell, Jonathan M; Stephan, Lindsie; Kneeland, Patrick P; Wald, Heidi L

    2016-09-01

    The morbidity and mortality (M&M) conference is a vital event that can affect medical education, quality improvement, and peer review in academic departments. Historically, M&M conferences have emphasized cases that highlight diagnostic uncertainty or complex management conundrums. In this report, the authors describe the development, pilot, and refinement of a systems-based M&M conference model that combines the educational and clinical missions of improving quality and patient safety in the University of Colorado Department of Medicine. In 2011, a focused taskforce completed a literature review that informed the development of a framework for the redesigned systems-based M&M conference. The new model included a restructured monthly conference, longitudinal curriculum for residents, and formal channels for interaction with clinical effectiveness departments. Each conference features an in-depth discussion of an adverse event using specific quality improvement tools. Areas for improvement and suggested action items are identified during the conference and delegated to the relevant clinical departments. The new process has enabled the review of 27 adverse events over two years. Sixty-three action items were identified, and 33 were pursued. An average of 50 to 60 individuals participate in each conference, including interprofessional and interdisciplinary colleagues. Resident and faculty feedback regarding the new format has been positive, and other departments are starting to adopt this model. A more robust process for identifying and selecting cases to discuss is needed, as is a stable, sufficient mechanism to manage the improvement initiatives that come out of each conference.

  17. 78 FR 27963 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD13-6-000] Reliability Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory... related to the reliability of the Bulk-Power System. A more formal agenda will be issued at a later date...

  18. Bioanalysis-related highlights from the 2011 AAPS National Biotechnology Conference.

    PubMed

    Crisino, Rebecca M; Dulanto, Beatriz

    2011-08-01

    The American Association of Pharmaceutical Scientists is a dynamic international forum for the exchange of knowledge among scientists to enhance their contributions to drug development. The annual National Biotechnology Conference, conducted and organized by the American Association of Pharmaceutical Scientists, is a forum dedicated to advancements in science and technology related to discovery, development and manufacture of medical biotechnology products. The 2011 National Biotechnology Conference meeting convened in San Francisco, CA, USA on 16-18 May. Over 300 abstracts were submitted and approximately 50 sessions examined topics pertaining to advances in drug development, emerging analytical technologies, bioanalysis-related issues, biosimilar therapies, updates on global regulatory documents and expectations, and other topics. The focus of this article is to highlight key developments relevant to immunogenicity and pharmacokinetic drug concentration bioanalysis.

  19. PREFACE: IX International Conference on Modern Techniques of Plasma Diagnostics and their Application

    NASA Astrophysics Data System (ADS)

    Savjolov, A. S.; Dodulad, E. I.

    2016-01-01

    Ministry of Education and Science contract 02.•03.21.0005 of August 27th 2013). Papers selected by the Program Committee for publishing were reviewed under control of invited editors Prof. Andrey Kukushkin, Dr. Sci. Alexander Kukushkin, Dr. Sci. Elena Baronova, Dr. Emil Dodulad. We would like to thank heartily all of the speakers, participants and organizing committee members for their contribution to the conference

  20. Report from the Second International Conference of Traditional and Complementary Medicine on Health 2015

    PubMed Central

    Isidoro, Ciro; Huang, Chia-Chi; Sheen, Lee-Yan

    2016-01-01

    The Second International Conference of Traditional and Complementary Medicine on Health was held from October 24th through 27th at the GIS National Taiwan University Convention Center in Taipei. Twenty-seven invited speakers, representative of fourteen Countries, delivered their lecture in front of an audience of more than two hundreds of attendees. In addition, a poster exhibition with seventy-two presenters completed the scientific sessions. The leitmotif of the Conference was to promote a common platform in which all medical knowledge is integrated to improve the health care system. Traditional medicine and complementary medicine are characterized by a holistic approach to prevent and cure diseases, making use of natural products and/or physical manipulations. In this context, the Conference emphasized the importance of the Quality Control and of standardized methods for the authentication, preparation and characterization of the herbal products and nutrient supplements, as well as the need for controlled clinical trials and for experimental studies to demonstrate the efficacy and to understand the underlying mechanisms of the preventive and curative treatments. In this report, we highlight the novel findings and the perspectives in Traditional and Complementary Medicine (TCM; 傳統暨互補醫學 chuán tǒng jì hù bǔ yī xué) that emerged during the conference. PMID:26870692

  1. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

    PubMed Central

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

  2. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

    PubMed

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

    2014-01-01

    The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  3. Molecular Mapping and Validation of a Major QTL Conferring Resistance to a Defoliating Isolate of Verticillium Wilt in Cotton (Gossypium hirsutum L.)

    PubMed Central

    Wei, Ze; Guo, Xian; Guo, Yuping; Zhang, Suqing; Zhao, Junsheng; Zhang, Guihua; Song, Xianliang; Sun, Xuezhen

    2014-01-01

    Verticillium wilt (VW) caused by Verticillium dahliae Kleb is one of the most destructive diseases of cotton. Development and use of a VW resistant variety is the most practical and effective way to manage this disease. Identification of highly resistant genes/QTL and the underlining genetic architecture is a prerequisite for developing a VW resistant variety. A major QTL qVW-c6-1 conferring resistance to the defoliating isolate V991 was identified on chromosome 6 in LHB22×JM11 F2∶3 population inoculated and grown in a greenhouse. This QTL was further validated in the LHB22×NNG F2∶3 population that was evaluated in an artificial disease nursery of V991 for two years and in its subsequent F4 population grown in a field severely infested by V991. The allele conferring resistance within the QTL qVW-c6-1 region originated from parent LHB22 and could explain 23.1–27.1% of phenotypic variation. Another resistance QTL qVW-c21-1 originated from the susceptible parent JM11 was mapped on chromosome 21, explaining 14.44% of phenotypic variation. The resistance QTL reported herein provides a useful tool for breeding a cotton variety with enhanced resistance to VW. PMID:24781706

  4. FLT3-ITD induces expression of Pim kinases through STAT5 to confer resistance to the PI3K/Akt pathway inhibitors on leukemic cells by enhancing the mTORC1/Mcl-1 pathway.

    PubMed

    Okada, Keigo; Nogami, Ayako; Ishida, Shinya; Akiyama, Hiroki; Chen, Cheng; Umezawa, Yoshihiro; Miura, Osamu

    2018-02-06

    FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells. These cooperative effects were enhanced or inhibited by knock down of mTOR or expression of its activated mutant, respectively. Overexpression of Mcl-1 conferred the resistance on 32D/ITD cells to combined inhibition of the PI3K/Akt pathway and Pim kinases, while the Mcl-1-specific BH3 mimetic A-1210477 conquered the resistance of MV4-11 cells to GDC-0941. Furthermore, overexpression of Pim-1 in 32D/TKD enhanced the mTORC1/Mcl-1 pathway and partially protected it from the PI3K/Akt inhibitors or the FLT3 inhibitor gilteritinib to confer the resistance to PI3K/Akt inhibitors. Finally, AZD1208 and GDC-0941 cooperatively inhibited the mTORC1/Mcl-1 pathway and reduced viable cell numbers of primary AML cells from some FLT3-ITD positive cases. Thus, Pim kinases may protect the mTORC1/4EBP1/Mcl-1 pathway to confer the resistance to the PI3K/Akt inhibitors on FLT3-ITD cells and represent promising therapeutic targets.

  5. Phosphorylation of HSP27 by Protein Kinase D is Essential for Mediating Neuroprotection Against Ischemic Neuronal Injury

    PubMed Central

    Stetler, R. Anne; Gao, Yanqin; Zhang, Lili; Weng, Zhongfang; Zhang, Feng; Hu, Xiaoming; Wang, Suping; Vosler, Peter; Cao, Guodong; Sun, Dandan; Graham, Steven H.; Chen, Jun

    2012-01-01

    Heat shock protein 27 (HSP27, or HSPB1) exerts cytoprotection against many cellular insults, including cerebral ischemia. We previously identified apoptosis signal-regulating kinase 1 (ASK1) as a critical downstream target of HSP27 conferring the neuroprotective effects of HSP27 against neuronal ischemia. However, the function of HSP27 is highly influenced by post-translational modification, with differential cellular effects based on phosphorylation at specific serine residues. The role of phosphorylation in neuronal ischemic neuroprotection is currently unknown. We have created transgenic mice and viral vectors containing HSP27 mutated at three critical serine residues (Ser15, Ser78 and Ser82) to either alanine (HSP27-A, non-phosphorylatable) or aspartate (HSP27-D, phospho-mimetic) residues. Under both in vitro and in vivo neuronal ischemic settings, overexpression of wild-type HSP27 (HSP27) and HSP27-D, but not HSP27-A, was neuroprotective and inhibited downstream ASK1 signaling pathways. Consistently, overexpressed HSP27 was phosphorylated by endogenous mechanisms when neurons were under ischemic stress, and single point mutations identified Ser15 and Ser82 as critical for neuroprotection. Using a panel of inhibitors and gene knockdown approaches, we identified the upstream kinase protein kinase D (PKD) as the primary kinase targeting HSP27 directly for phosphorylation. PKD and HSP27 co-immunoprecipitated, and inhibition or knockdown of PKD abrogated the neuroprotective effects of HSP27 as well as the interaction with and inhibition of ASK1 signaling. Taken together, these data demonstrate that HSP27 requires PKD-mediated phosphorylation for its suppression of ASK1 cell death signaling and neuroprotection against ischemic injury. PMID:22357851

  6. Enhancement of Cd phytoextraction by two Amaranthus species with endophytic Rahnella sp. JN27.

    PubMed

    Yuan, Ming; He, Huaidong; Xiao, Li; Zhong, Ting; Liu, Hui; Li, Shubin; Deng, Peiyan; Ye, Zhihong; Jing, Yuanxiao

    2014-05-01

    Microbe-assisted phytoextraction shows a potential for the remediation of metal-contaminated soils. The aim of this study was to isolate, characterize, and evaluate the potential of endophytic bacteria in improving plant growth and metal uptake by Cd-hyperaccumulators-Amaranthus hypochondriacus and Amaranthus mangostanus. An endophytic bacterial strain JN27 isolated from roots of Zea mays displayed high tolerance and mobilization to Cd, and was identified as Rahnella sp. based on 16S rDNA sequencing. The strain also exhibited multiple plant growth beneficial features including the production of indole-3-acetic acid, siderophore, 1-aminocyclopropane-1-carboxylic acid deaminase and solubilization of insoluble phosphate. Subsequently, a pot trial was performed to elucidate the effects of inoculation with JN27 on plant growth and Cd uptake by A. hypochondriacus, A. mangostanus, Solanum nigrum and Z. mays grown in soils with different levels of Cd (25, 50, 100 mg Cd kg(-1)). The results revealed that inoculation with JN27 significantly increased the biomasses of all the tested plants and the Cd concentrations of all the tested plants except Z. mays in both above-ground and root tissues. Moreover, strain JN27 could successfully re-colonized in rhizosphere soils of all the tested plants and root interior of A. hypochondriacus and Z. mays. The present results indicated that the symbiont of A. hypochondriacus (or A. mangostanus) and strain JN27 can effectively improve the Cd uptake by plants and would be a new strategy in microbe-assisted phytoextraction for metal-contaminated soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Insertion of transposon in the vicinity of SSK2 confers enhanced tolerance to furfural in Saccharomyces cerevisiae.

    PubMed

    Kim, Hyun-Soo; Kim, Na-Rae; Kim, Wankee; Choi, Wonja

    2012-07-01

    Furfural is one of the major inhibitors generated during sugar production from cellulosic materials and, as an aldehyde, inhibits various cellular activities of microorganisms used, leading to prolonged lag time during ethanologenic fermentation. Since Saccharomyces cerevisiae strains tolerant to furfural are of great economic benefit in producing bioethanol, much effort to obtain more efficient strains continues to be made. In this study, we examined the furfural tolerance of transposon mutant strains (Tn 1-5) with enhanced ethanol tolerance and found that one of them (Tn 2), in which SSK2 is downregulated at the transcriptional level, displayed improved furfural tolerance. Such phenotype was abolished by complementation of the entire open reading frame of SSK2, which encodes a mitogen-activated protein (MAP) kinase kinase kinase of the high osmolarity glycerol (HOG) signaling pathway, suggesting an inhibitory effect of SSK2 in coping with furfural stress. Tn 2 showed a significant decrease in the intracellular level of reactive oxygen species (ROS) and early and high activation of Hog1p, a MAP kinase integral to the HOG pathway in response to furfural. The transcriptional levels of CTT1 and GLR1, two of known Hog1p downstream target genes whose protein products are involved in reducing ROS, were increased by 43 % and 56 % respectively compared with a control strain, probably resulting in the ROS decrease. Tn 2 also showed a shortened lag time during fermentation in the presence of furfural, resulting from efficient conversion of furfural to non-toxic (or less toxic) furfuryl alcohol. Taken together, the enhanced furfural tolerance of Tn 2 is suggested to be conferred by the combined effect of an early event of less ROS accumulation and a late event of efficient detoxification of furfural.

  8. International Conference on Organometallic Chemistry (13th) Held in Torino, Europe on 4-9 September 1988. Abstracts

    DTIC Science & Technology

    1988-09-09

    On Synthesis Of Dialkyl d-Trimethylsilyloxyalkylphosphonates Zhao Yong-Zhen and Li Zhong- Rua Dpartment o chemistry, Hua Zhong Normal University, Wuhan...Jose Vicente. Jose-AntelC hAd. Na-Yeij~xa Qhicote. Ju~an-Francisco Gutliez-Jugo. Carmen Ramirez do Arel lano. Departamento do Oulmica InordanIca...Peruzzini, Jos& Antonio Ramirez , Alberto Vacca, Francesco Vizza and Fabrizio Zanobini, Istituto per lo Studio della Stereochimica ed Energetica dei

  9. Implementing and evaluating an interprofessional minority health conference for social work and healthcare professionals.

    PubMed

    Washington, Tiffany R; Ward, Trina Salm; Young, Henry N; Orpinas, Pamela; Cornelius, Llewellyn J

    2017-11-01

    Interprofessional education (IPE) is one strategy for addressing health inequities; however, little attention has been paid to continuing IPE for practicing social work and healthcare professionals. This article offers guidance to faculty in social work and health-related academic units on offering continuing IPE on the topic of minority health. An interprofessional group of faculty offered a day-long conference on minority health, ethics, and social justice. The conference goal was to promote interprofessional communication in a co-learning environment and promote dialogue on social determinants of health and health equity in the state. Data were obtained from surveys and analysis of work plans developed during the conference. Workshop participants were majority White (62%), social workers (79%), and practiced for 14 years on average. The most useful topics were dementia and polypharmacy. Takeaway strategies included interprofessional work, being mindful of access to resources, and engagement in continuing education. Lessons learned include plan in advance for all professions; recruit faculty and students from multiple departments to increase interprofessional diversity; offer strategies and incentives to increase student participation; be strategic about conference location and format; and identify a strategic format and theme. IPE is a means of preparing learners for working together in their future careers to provide high-quality patient-centred care and reduce health disparities. Professional development can provide an opportunity to enhance skills to address health disparities, and learning can be significantly enhanced when participants connect with colleagues from different professions, discuss diverse opinions, and share successful practices.

  10. Conference of University Administrators Conference Proceedings (12th, Surrey, England, March 21-23, 1985).

    ERIC Educational Resources Information Center

    Conference of Univ. Administrators.

    Conference proceedings for the Conference of University Administrators include summaries of conference sessions, along with Austin Pearce's paper, "The Needs of Industry: What Are They?" Sessions focused on: forming a university company, financial diversification, financial modeling, stock exchange investment and universities, funding of…

  11. Consumer Interests Annual. Annual Conference of the American Council on Consumer Interests (42nd, Nashville, Tennessee, March 27-30, 1996).

    ERIC Educational Resources Information Center

    Folk, Karen Fox, Ed.

    Among the 99 conference papers presented are the following: "Whither the Consumer Interest: The Role of Consumer Education and Research in an Era of Public Reinvention" (Colien Hefferan); "The Scientific Foundations of Consumer Advice: Some Comments" (E. Scott Maynes); "Self-Employment: A Viable Economic Alternative for the California Hispanic…

  12. Making Connections, Building Communities. Proceedings of the Annual Rural & Small Schools Conference (19th, Manhattan, Kansas, October 26-27, 1997).

    ERIC Educational Resources Information Center

    Kansas State Univ., Manhattan. Center for Rural Education and Small Schools.

    This proceedings contains 26 summaries of conference presentations and discussions. Titles and authors are: "Is a Sexual Harassment Policy Enough To Protect Against Liability?" (Camille Barnett); "Recreating the Communities of Our Youth" (Marlyn Benson); "Creating a Language of Ethics in Rural Schooling" (Terry R. Berkeley, Linda P. Thurston);…

  13. Twitter use in physics conferences.

    PubMed

    Webb, Stephen

    An analysis of Twitter use in 116 conferences suggests that the service is used more extensively at PACS10 conferences (those devoted to the physics of elementary particles and fields) and PACS90 conferences (those devoted to geophysics, astronomy, and astrophysics) than at conferences in other fields of physics. Furthermore, Twitter is used in a qualitatively different manner. A possible reason for these differences is discussed.

  14. Harbor in the Storm: Institutional Research in the Age of Accountability. NEAIR 36th Annual Conference Proceedings (Baltimore, Maryland, November 7-10, 2009)

    ERIC Educational Resources Information Center

    D'Alessandro, Michael, Ed.

    2009-01-01

    The NEAIR 2009 Conference Proceedings is a compilation of papers presented at the Baltimore, Maryland conference. Papers in this document include: (1) A Principle Components Analysis of The Determinants of Student Satisfaction at a Historically Black Institution (Tao Gong and Jacqueline V. Parham); (2) Assessing and Enhancing Graduates'…

  15. PREFACE: 31st UIT (Italian Union of Thermo-fluid-dynamics) Heat Transfer Conference 2013

    NASA Astrophysics Data System (ADS)

    Vitali, Luigi; Niro, Alfonso; Colombo, Luigi; Sotgia, Giorgio

    2014-04-01

    The annual Conference of the ''Unione Italiana di Termofluidodinamica'' (UIT) aims at promoting cooperation in the field of heat transfer and thermal sciences, by bringing together scientists and engineers working in related areas. The 31st UIT Conference was held in Moltrasio (Como), Italy, 25-27 June, 2013 at the Grand Hotel Imperiale. The response has been enthusiastic, with more than 70 quality contributions from 224 authors on heat transfer related topics: natural, forced and mixed convection, conduction, radiation, multi-phase fluid dynamics and interface phenomena, computational fluid dynamics, micro- and nano-scales, efficiency in energy systems, environmental technologies and buildings. To encourage the debate, the Conference Program has scheduled ample poster sessions and invited lectures from the best experts in the field along with a few of the most talented researchers. Keynote Lectures were given by Professor Roberto Mauri (University of Pisa), Professor Lounés Tadrist (Polytech Marseille) and Professor Maurizio Quadrio (Politecnico di Milano). This special volume collects a selection of the scientific contributions discussed during this conference; these works give a good overview of the state-of-the art Italian research in the field of Heat Transfer related topics. I would like to thank sincerely the authors for presenting their works at the conference and in this special issue. I would also like to extend my thanks to the Scientific Committee and the authors for their accurate review process of each paper for this special issue. Special thanks go to the organizing committee and to our sponsors. As a professor of Politecnico di Milano, let me say I am very proud to have been the chair of this conference in the 150th anniversary of my university. Professor Alfonso Niro Details of organizers, sponsors and committees, as well as further information, are available in the PDF

  16. 27 CFR 18.27 - Additional requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Additional requirements. 18.27 Section 18.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Qualification Application...

  17. 27 CFR 18.27 - Additional requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Additional requirements. 18.27 Section 18.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Qualification Application...

  18. 27 CFR 18.27 - Additional requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Additional requirements. 18.27 Section 18.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Qualification Application...

  19. 27 CFR 18.27 - Additional requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Additional requirements. 18.27 Section 18.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Qualification Application...

  20. 27 CFR 18.27 - Additional requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Additional requirements. 18.27 Section 18.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Qualification Application...

  1. Stroke care conference.

    PubMed

    Watkins, Caroline

    2016-10-28

    The 11th UK Stroke Forum Conference, hosted by the Stroke Association, is the largest stroke conference in the UK. It aims to provide nurses and other healthcare professionals with opportunities to share learning and best practice in stroke care and rehabilitation.

  2. Resistance to maribavir is associated with the exclusion of pUL27 from nucleoli during human cytomegalovirus infection

    PubMed Central

    Hakki, Morgan; Drummond, Coyne; Houser, Benjamin; Marousek, Gail; Chou, Sunwen

    2011-01-01

    Select mutations in the human cytomegalovirus (HCMV) gene UL27 confer low-grade resistance to the HCMV UL97 kinase inhibitor maribavir (MBV). It has been reported that the 608-amino acid UL27 gene product (pUL27) normally localizes to cell nuclei and nucleoli, whereas its truncation at codon 415, as found in a MBV-resistant mutant, results in cytoplasmic localization. We now show that in the context of full-length pUL27, diverse single amino acid substitutions associated with MBV resistance result in loss of its nucleolar localization when visualized after transient transfection, whereas substitutions representing normal interstrain polymorphism had no such effect. The same differences in localization were observed during a complete infection cycle with recombinant HCMV strains over-expressing full-length fluorescent pUL27 variants. Nested UL27 C-terminal truncation expression plasmids showed that amino acids 596–599 were required for the nucleolar localization of pUL27. These results indicate that the loss of a nucleolar function of pUL27 may contribute to MBV resistance, and that the nucleolar localization of pUL27 during HCMV infection depends not only on a carboxy-terminal domain but also on a property of pUL27 that is affected by MBV-resistant mutations, such as an interaction with component(s) of the nucleolus. PMID:21906628

  3. 38 CFR 59.123 - Conference.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TO STATES FOR CONSTRUCTION OR ACQUISITION OF STATE HOMES § 59.123 Conference. At any time, VA may recommend that a conference (such as a design development conference) be held in VA Central Office in...

  4. Conference call.

    PubMed

    2002-03-01

    The RCN A&E Nursing Association, Black Country A&E professional development group and University of Wolverhampton school of health are holding the Emergency Nursing Research 2002 conference on March 6 in Wolverhampton. For more information, contact Alastair Gray by phone on 01902 307999 ext 2055 or by email at a.d.gray@wlv.ac.uk. Details available at www.man.ac.uk/rcn/conference/enrc2002.doc.

  5. International Conference of the Australasian Association of Institutional Research (3rd, Auckland, New Zealand, November 25-27, 1992). Selected Papers.

    ERIC Educational Resources Information Center

    Ng, Gan Che, Ed.; And Others

    1993-01-01

    Eight papers presented at the Third International Conference of the Australasian Association of Institutional Research (AAIR) are published in this journal issue. They represent the diversity and richness of the field of Planning in the Public Sector" (Jack Smith); (2) "Futures Planning for Tertiary Education: Curricula for the 21st…

  6. History of NAMES Conferences

    NASA Astrophysics Data System (ADS)

    Filippov, Lev

    2013-03-01

    Franco-Russian NAMES Seminars are held for the purpose of reviewing and discussing actual developments in the field of materials science by researchers from Russia and from the Lorraine Region of France. In more precise terms, as set down by the organizers of the seminar (the Moscow Institute of Steel and Alloys and the Institut National Polytechnique de Lorraine), the mission of the seminars is as follows: the development of scientific and academic contacts, giving a new impulse to joint fundamental research and technology transfer the development and consolidation of scientific, technical and business collaboration between the regions of Russia and Lorraine through direct contact between the universities, institutes and companies involved The first Seminar took place on 27-29 October 2004, at the Institut National Polytechnique de Lorraine (on the premises of the Ecole Européenne d'Ingénieurs en Génie des Matériaux, Nancy, France). The number, variety and quality of the oral presentations given and posters exhibited at the first Seminar were of high international standard. 30 oral presentations were given and 72 posters were presented by 19 participants from five universities and three institutes of the Russian Academy of Sciences participants from 11 laboratories of three universities from the Lorraine region three industrial companies, including the European Aeronautic Defence and Space Company—EADS, and ANVAR (Agence Nationale de Valorisation de la Recherche) From 2005 onwards, it was decided to organize the Seminar every other year. The second Seminar convened on the occasion of the 75th Anniversary of the Moscow Institute of Steel and Alloys on 10-12 November 2005 in Moscow, Russia. The seminar demonstrated the efficiency of the scientific partnership founded between the research groups of Russia and France during the first Seminar. High productivity of the Franco-Russian scientific cooperation on the basis of the Research-Educational Franco

  7. 27 CFR 6.27 - Proprietary interest.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Proprietary interest. 6.27... OF THE TREASURY ALCOHOL âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership. Outright ownership of a retail business by an industry member is...

  8. 27 CFR 6.27 - Proprietary interest.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Proprietary interest. 6.27... OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership. Outright ownership of a retail business by an industry member is...

  9. Conference scene: DGVS spring conference 2009.

    PubMed

    Kolligs, Frank Thomas

    2009-10-01

    The 3rd annual DGVS Spring Conference of the German Society for Gastroenterology (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) was held at the Seminaris Campus Hotel in Berlin, Germany, on 8-9 May, 2009. The conference was organized by Roland Schmid and Matthias Ebert from the Technical University of Munich, Germany. The central theme of the meeting was 'translational gastrointestinal oncology: towards personalized medicine and individualized therapy'. The conference covered talks on markers for diagnosis, screening and surveillance of colorectal cancer, targets for molecular therapy, response prediction in clinical oncology, development and integration of molecular imaging in gastrointestinal oncology and translational research in clinical trial design. Owing to the broad array of topics and limitations of space, this article will focus on biomarkers, response prediction and the integration of biomarkers into clinical trials. Presentations mentioned in this summary were given by Matthias Ebert (Technical University of Munich, Germany), Esmeralda Heiden (Epigenomics, Berlin, Germany), Frank Kolligs (University of Munich, Germany), Florian Lordick (University of Heidelberg, Germany), Hans Jorgen Nielsen (University of Copenhagen, Denmark), Anke Reinacher-Schick (University of Bochum, Germany), Christoph Röcken (University of Berlin, Germany), Wolff Schmiegel (University of Bochum, Germany) and Thomas Seufferlein (University of Halle, Germany).

  10. 14 CFR 27.27 - Center of gravity limits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Center of gravity limits. 27.27 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight General § 27.27 Center of gravity limits. The extreme forward and aft centers of gravity and, where critical, the extreme lateral centers of gravity must be...

  11. 14 CFR 27.27 - Center of gravity limits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Center of gravity limits. 27.27 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight General § 27.27 Center of gravity limits. The extreme forward and aft centers of gravity and, where critical, the extreme lateral centers of gravity must be...

  12. 14 CFR 27.27 - Center of gravity limits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Center of gravity limits. 27.27 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight General § 27.27 Center of gravity limits. The extreme forward and aft centers of gravity and, where critical, the extreme lateral centers of gravity must be...

  13. 14 CFR 27.27 - Center of gravity limits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Center of gravity limits. 27.27 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight General § 27.27 Center of gravity limits. The extreme forward and aft centers of gravity and, where critical, the extreme lateral centers of gravity must be...

  14. 14 CFR 27.27 - Center of gravity limits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Center of gravity limits. 27.27 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Flight General § 27.27 Center of gravity limits. The extreme forward and aft centers of gravity and, where critical, the extreme lateral centers of gravity must be...

  15. Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells.

    PubMed

    Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R

    2012-03-27

    Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37, and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150, and Arg-154), and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

  16. Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol.

    PubMed

    Kim, Bo-Young; Son, Yonghae; Lee, Jeonga; Choi, Jeongyoon; Kim, Chi Dae; Bae, Sun Sik; Eo, Seong-Kug; Kim, Koanhoi

    2017-01-01

    Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol.

  17. Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol

    PubMed Central

    Kim, Bo-Young; Son, Yonghae; Lee, Jeonga; Choi, Jeongyoon; Kim, Chi Dae; Bae, Sun Sik; Eo, Seong-Kug

    2017-01-01

    Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol. PMID:29236764

  18. First Virtual Live Conference in Healthcare.

    PubMed

    Parthasarathi, Ramakrishnan; Gomes, Rachel M; Palanivelu, Praveen Raj; Senthilnathan, Palanisamy; Rajapandian, Subbiah; Venkatachalam, Ramasamy; Palanivelu, Chinnusamy

    2017-07-01

    Conferences and meetings bring together thousands of doctors from diverse locations. However, the traveling, accommodation, and arrangement of venues for conferences and meetings are expensive and a lot of time needs to be devoted to these logistics. The purpose of this article was to present our own virtual live conference experience using web conferencing and to briefly outline the basics and advantages of this technology in organization of healthcare conferences. Web conferencing technology was used to organize an international bariatric surgery conference, allowing a large number of attendees to participate and interact from wherever they were, using merely an Internet connection with a video player on their personal computers, laptops, or smartphones. A virtual live conference saves a lot of time and cost and simplifies the logistics needed to organize a learning conference with worldwide participation. As far as we know, this is the first report of a virtual live conference in healthcare. We see it as the future of organizing experts as well as medical teaching conferences.

  19. 7 CFR 1.167 - Conference.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... that conducting the conference by audio-visual telecommunication: (i) Is necessary to prevent prejudice.... If the Judge determines that a conference conducted by audio-visual telecommunication would... correspondence, the conference shall be conducted by audio-visual telecommunication unless the Judge determines...

  20. 7 CFR 1.167 - Conference.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... that conducting the conference by audio-visual telecommunication: (i) Is necessary to prevent prejudice.... If the Judge determines that a conference conducted by audio-visual telecommunication would... correspondence, the conference shall be conducted by audio-visual telecommunication unless the Judge determines...

  1. 7 CFR 1.167 - Conference.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... that conducting the conference by audio-visual telecommunication: (i) Is necessary to prevent prejudice.... If the Judge determines that a conference conducted by audio-visual telecommunication would... correspondence, the conference shall be conducted by audio-visual telecommunication unless the Judge determines...

  2. 7 CFR 1.167 - Conference.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... that conducting the conference by audio-visual telecommunication: (i) Is necessary to prevent prejudice.... If the Judge determines that a conference conducted by audio-visual telecommunication would... correspondence, the conference shall be conducted by audio-visual telecommunication unless the Judge determines...

  3. 7 CFR 1.167 - Conference.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... that conducting the conference by audio-visual telecommunication: (i) Is necessary to prevent prejudice.... If the Judge determines that a conference conducted by audio-visual telecommunication would... correspondence, the conference shall be conducted by audio-visual telecommunication unless the Judge determines...

  4. Declining Enrollment. An NSBA Conference (Colorado Springs, Colorado, August 4-6, 1976). Conference Report.

    ERIC Educational Resources Information Center

    Florio, David H.

    This report results from a National School Boards Association (NSBA) conference on declining enrollment and from a survey of state school boards associations conducted in advance of the conference. The conference drew school board leaders and school administrators together with population experts to achieve several purposes that are reflected in…

  5. 10th Conference on Bayesian Nonparametrics

    DTIC Science & Technology

    2016-05-08

    RETURN YOUR FORM TO THE ABOVE ADDRESS. North Carolina State University 2701 Sullivan Drive Admin Srvcs III, Box 7514 Raleigh, NC 27695 -7514 ABSTRACT...the conference. The findings from the conference is widely disseminated. The conference web site displays slides of the talks presented in the...being published by the Electronic Journal of Statistics consisting of about 20 papers read at the conference. The conference web site displays

  6. 27 CFR 4.27 - Vintage wine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Vintage wine. 4.27 Section... THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Standards of Identity for Wine § 4.27 Vintage wine. (a) General. Vintage wine is wine labeled with the year of harvest of the grapes and made in...

  7. Advances in Knowledge Discovery and Data Mining 21st Pacific Asia Conference, PAKDD 2017 Held in Jeju, South Korea, May 23 26, 2017. Proceedings Part I, Part II.

    DTIC Science & Technology

    2017-06-27

    From - To) 05-27-2017 Final 17-03-2017 - 15-03-2018 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER FA2386-17-1-0102 Advances in Knowledge Discovery and...Springer; Switzerland. 14. ABSTRACT The Pacific-Asia Conference on Knowledge Discovery and Data Mining (PAKDD) is a leading international conference...in the areas of knowledge discovery and data mining (KDD). We had three keynote speeches, delivered by Sang Cha from Seoul National University

  8. Wisdom of the Crowds: Crowd-Based Development of a Logo for a Conference Using a Crowdsourcing Contest.

    PubMed

    Ong, Jason J; Bilardi, Jade E; Tucker, Joseph D

    2017-10-01

    Crowdsourcing methods have been widely used in business, but rarely in sexual health research. We evaluated a crowdsourced logo contest as part of an international human immunodeficiency virus conference. A logo crowdsourcing contest was conducted for the 20th International Acquired Immunodeficiency Syndrome Conference. Crowdsourcing has a group of individuals solve a task, often as part of an open contest. Semistructured interviews were conducted with key informants including contest organizers, contest contributors, and conference attendees. Interviews were transcribed verbatim and analysed using a content analysis approach. In total, 22 interviews were conducted with 3 contest organizers, 7 contest contributors, and 12 conference attendees. All individuals reported that the crowdsourced logo provided benefits beyond branding the conference, including creating a shared sense of purpose among diverse conference participants and explicitly demonstrating the strong community orientation of the conference. Conference organizers and attendees all reported deeper engagement because of the story of the Tanzanian artist who won the contest. Most conference attendees (11/12) preferred the crowdsourced logo compared with the previous company-organized logo, and all (22/22) supported the logo contest continuing. Implementing a logo contest was simple and relatively inexpensive. Stakeholders identified several ways to enhance crowdsourcing logo contest methods including wider promotion of the contest to encourage broader participation, greater transparency in the selection process, and a different prize structure which acknowledges the contribution of more contestants. We found that a crowdsourcing contest helped engage local and global communities in the lead-up before and during an international conference. Similar participatory events may be useful for sexual health conferences and research projects.

  9. Eighth Goddard Conference on Mass Storage Systems and Technologies in Cooperation with the Seventeenth IEEE Symposium on Mass Storage Systems

    NASA Technical Reports Server (NTRS)

    Kobler, Benjamin (Editor); Hariharan, P. C. (Editor)

    2000-01-01

    This document contains copies of those technical papers received in time for publication prior to the Eighth Goddard Conference on Mass Storage Systems and Technologies which is being held in cooperation with the Seventeenth IEEE Symposium on Mass Storage Systems at the University of Maryland University College Inn and Conference Center March 27-30, 2000. As one of an ongoing series, this Conference continues to provide a forum for discussion of issues relevant to the management of large volumes of data. The Conference encourages all interested organizations to discuss long term mass storage requirements and experiences in fielding solutions. Emphasis is on current and future practical solutions addressing issues in data management, storage systems and media, data acquisition, long term retention of data, and data distribution. This year's discussion topics include architecture, future of current technology, new technology with a special emphasis on holographic storage, performance, standards, site reports, vendor solutions. Tutorials will be available on stability of optical media, disk subsystem performance evaluation, I/O and storage tuning, functionality and performance evaluation of file systems for storage area networks.

  10. 2010 Defense Industrial Base Critical Infrastructure Protection Conference (DIBCIP) Risk Reduction and Mitigation in the Defense Industrial Base

    DTIC Science & Technology

    2010-04-28

    Base Critical Infrastructure Protection Conference (DIBCIP) “Risk Reduction & Mitigation in the Defense Industrial Base ” April 26-28, 2010...Philadelphia, PA Agenda Tuesday, April 27, 2010 Keynote Address: The Economic Crisis and Its Impact on the DIB: Defense Industrial Base Forecasts 2010...Ms. Nancy Pomerleau, Exercise Director, Partnership Outreach Division, DHS-IP DIB 2010 DIB CIP DEFENSE INDUSTRIAL BASE CRITICAL

  11. Innovation in Continuing Education Provision, Teaching and Learning: Research Perspectives. Papers from a Conference (Lancaster, England, United Kingdom, April 27, 1995).

    ERIC Educational Resources Information Center

    Hamilton, Mary, Ed.; Withnall, Alexandra, Ed.

    The following conference papers cover a wide spectrum of issues in continuing education: "Introduction" (Katherine Leni Oglesby); "Footprints in the Sand?--The Legacy of the University Funding Council's Support for Research in Continuing Education" (Chris Duke); "Thinking Fragments: Learning, Life Histories and the…

  12. The Learning Conference

    ERIC Educational Resources Information Center

    Ravn, Ib

    2007-01-01

    Purpose: The purpose of this paper is to call attention to the fact that conferences for professionals rely on massive one-way communication and hence produce little learning for delegates--and to introduce an alternative, the "learning conference", that involves delegates in fun and productive learning processes.…

  13. Enhancing Scientific Collaboration, Transparency, and Public Access: Utilizing the Second Life Platform to Convene a Scientific Conference in 3-D Virtual Space

    NASA Astrophysics Data System (ADS)

    McGee, B. W.

    2006-12-01

    Recent studies reveal a general mistrust of science as well as a distorted perception of the scientific method by the public at-large. Concurrently, the number of science undergraduate and graduate students is in decline. By taking advantage of emergent technologies not only for direct public outreach but also to enhance public accessibility to the science process, it may be possible to both begin a reversal of popular scientific misconceptions and to engage a new generation of scientists. The Second Life platform is a 3-D virtual world produced and operated by Linden Research, Inc., a privately owned company instituted to develop new forms of immersive entertainment. Free and downloadable to the public, Second Life offers an imbedded physics engine, streaming audio and video capability, and unlike other "multiplayer" software, the objects and inhabitants of Second Life are entirely designed and created by its users, providing an open-ended experience without the structure of a traditional video game. Already, educational institutions, virtual museums, and real-world businesses are utilizing Second Life for teleconferencing, pre-visualization, and distance education, as well as to conduct traditional business. However, the untapped potential of Second Life lies in its versatility, where the limitations of traditional scientific meeting venues do not exist, and attendees need not be restricted by prohibitive travel costs. It will be shown that the Second Life system enables scientific authors and presenters at a "virtual conference" to display figures and images at full resolution, employ audio-visual content typically not available to conference organizers, and to perform demonstrations or premier three-dimensional renderings of objects, processes, or information. An enhanced presentation like those possible with Second Life would be more engaging to non- scientists, and such an event would be accessible to the general users of Second Life, who could have an

  14. Deficiencies in the publication and reporting of the results of systematic reviews presented at scientific medical conferences.

    PubMed

    Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Ravaud, Philippe

    2015-12-01

    To evaluate the publication and quality of reporting of abstracts of systematic reviews presented at scientific medical conferences. We included all abstracts of systematic reviews published in the proceedings of nine leading international conferences in 2010. For each conference abstract, we searched PubMed (January 1, 2010, to June 2013) to identify their corresponding full publication. We assessed the extent to which conference abstracts and their corresponding journal abstract reported items included in the Preferred Reporting Items for Systematic reviews and Meta-Analysis for Abstracts checklist and recorded any important discrepancies between sources. We identified 197 abstracts of systematic reviews, representing <1% of the total number of conference abstracts presented. Of these 53% were published in full, the median time to publication was 14 months (interquartile range, 6.6-20.1 months). Although most conference and journal abstracts reported details of included studies (conference n = 83 of 103; 81% vs. journal n = 81 of 103; 79%), size and direction of effect (76% vs. 75%), and conclusions (79% vs. 81%), many failed to report the date of search (27% vs. 25%), assessment of risk of bias (18% vs. 12%), and the result for the main efficacy outcome(s) including the number of studies (37% vs. 31%) and participants (30% vs. 20%), harms(s) (17% vs. 17%), strengths (17% vs. 13%) and limitations (36% vs. 30%) of the evidence, or funding source (1% vs. 0%). There were discrepancies between journal and corresponding conference abstracts including deletion of studies (13%), changes in reported efficacy (11%), and harm (10%) outcome(s) and changes in the nature or direction of conclusions (24%). Despite the importance of systematic reviews in the delivery of evidence-based health care, very few are presented at scientific conferences and only half of those presented are published in full. Serious deficiencies in the reporting of abstracts of systematic reviews make

  15. PREFACE: 7th International Conference on Applied Electrostatics (ICAES-2012)

    NASA Astrophysics Data System (ADS)

    Li, Jie

    2013-03-01

    Faculty of Engineering, McMaster University, Canada), Haitian Scholar of Dalian University of Technology (China), who passed away on 27 February 2011. Professor Chang was active in research fields including the applications of electrostatics, electromagnetic hydrodynamics, plasma environmental pollution control technologies, etc and he contributed much to the development of these fields. Professor Chang was the visiting professor at some Key Universities in China and was the friend of Chinese scholars engaged in electrostatics. Professor Chang was also active in joining and supporting the previous ICAES. We will cherish the memory of Professor Jen-Shih Chang forever. Professor Jie Li Proceedings Editor Dalian, September 2012 Conference photograph

  16. Major Biomass Conference

    Science.gov Websites

    Top Scientists, Industry and Government Leaders to Gather for Major Biomass Conference America, South America and Europe will focus on building a sustainable, profitable biomass business at the Third Biomass Conference of the Americas in Montreal. Scheduled presentations will cover all biomass

  17. Joint conference.

    PubMed

    1999-10-01

    The Irish Emergency Nurses Association and RCN A&E Nursing Association are holding a conference in Newry, Co Down on November 25. Topics include an update on the Faculty of Emergency Nursing, the management of chest trauma, obstetric emergencies, management of pre-tibial lacerations, and what's hip on the drug scene. Cost: £50 RCN members; £70 for nonmembers (includes dinner and disco). Conference only £35. Contact, Claire Morrissy, RCN, 17 Windsor Avenue, Belfast. Tel 01232-668236.

  18. Nanotechnology Enabled Enhancement of Enzyme Activity and Thermostability: Study on Impaired Pectate Lyase from Attenuated Macrophomina phaseolina in Presence of Hydroxyapatite Nanoparticle

    PubMed Central

    Dutta, Nalok; Mukhopadhyay, Arka; Dasgupta, Anjan Kr.; Chakrabarti, Krishanu

    2013-01-01

    In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy–enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time. PMID:23691068

  19. Effectiveness and Student Success: Transforming Community Colleges for the 1990's. Proceedings from the Conference (Chicago, Illinois, June 25-27, 1989).

    ERIC Educational Resources Information Center

    Walleri, Dan, Ed.; And Others

    The eight general session, exemplary practice, and roundtable papers contained in this conference proceedings report focus on various aspects of institutional effectiveness and student outcomes. The volume includes: (1) "Effectiveness and Student Success in Community Colleges: Practices, Realities, and Imperatives," by Peter Ewell; (2) "Rhetoric…

  20. Energizing Potential: SAGE (Society for the Advancement of Gifted Education) Conference Proceedings (1st, Calgary, Alberta, Canada, September 27-29, 1990).

    ERIC Educational Resources Information Center

    Calgary Univ. (Alberta). Centre for Gifted Education.

    This conference proceedings document on gifted education presents texts of the following papers, among others: "Developing Visual Literacy--Start It Young" (Kay Anderson); "Building Provincial Exams To Challenge the Gifted" (Dennis Belyk); "Advocacy and Lobbying: An Exercise in Persuasion" (Patricia Boyle); "Program Continuity and Curriculum…