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Sample records for behandling af type

  1. Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

    PubMed Central

    Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

    2016-01-01

    We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

  2. First Report of an Infant Botulism Case Due to Clostridium botulinum Type Af

    PubMed Central

    de Jong, Laura I. T.; Fernández, Rafael A.; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R.; Dykes, Janet K.

    2014-01-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide. PMID:25502535

  3. First report of an infant botulism case due to Clostridium botulinum type Af.

    PubMed

    de Jong, Laura I T; Fernández, Rafael A; Pareja, Virtudes; Giaroli, Gabriel; Guidarelli, Sergio R; Dykes, Janet K; Lúquez, Carolina

    2015-02-01

    Most infant botulism cases worldwide are due to botulinum toxin types A and B. Rarely, Clostridium botulinum strains that produce two serotypes (Ab, Ba, and Bf) have also been isolated from infant botulism cases. This is the first reported case of infant botulism due to C. botulinum type Af worldwide.

  4. TYPE AF CERTIFICATE FOR TRANSPORTATION OF LOW ENRICHED URANIUM OXIDE (LEUO) FOR DISPOSAL

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

    Washington Savannah River Company (WSRC) operates the Savannah River Site (SRS) in Aiken, SC under contract with the U.S. Department of Energy (DOE). SRS had the need to ship 227 drums of low enriched uranium oxide (LEUO) to a disposal site. The LEUO had been packaged nearly 25 years ago in U.S. Department of Transportation (DOT) 17C 55-gallon drums and stored in a warehouse. Since the 235U enrichment was just above 1 percent by weight (wt%) the material did not qualify for the fissile material exceptions in 49 CFR 173.453, and therefore was categorized as 'fissile material' for shipping purposes. WSRC evaluated all existing Type AF packages and did not identify any feasible packaging. Applying for a new Type AF certificate of compliance was considered too costly for a one-time/one-way shipment for disposal. Down-blending the material with depleted uranium (to reduce enrichment below 1 wt% and enable shipment as low specific activity (LSA) radioactive material) was considered, but appropriate blending facilities do not exist at SRS. After reviewing all options, WSRC concluded that seeking a DOT Special Permit was the best option to enable shipment of the material for permanent disposal. WSRC submitted the Special Permit application to the DOT, and after one request-for-additional-information (RAI) the permit was considered acceptable. However, in an interesting development that resulted from the DOT Special Permit application process, it was determined that it was more appropriate for the DOE to issue a Type AF certificate [Ref. 1] for this shipping campaign. This paper will outline the DOT Special Permit application and Type AF considerations, and will discuss the issuance of the new DOE Type AF certificate of compliance.

  5. Search for A-F Spectral type pulsating components in Algol-type eclipsing binary systems

    NASA Astrophysics Data System (ADS)

    Kim, S.-L.; Lee, J. W.; Kwon, S.-G.; Youn, J.-H.; Mkrtichian, D. E.; Kim, C.

    2003-07-01

    We present the results of a systematic search for pulsating components in Algol-type eclipsing binary systems. A total number of 14 eclipsing binaries with A-F spectral type primary components were observed for 22 nights. We confirmed small-amplitude oscillating features of a recently detected pulsator TW Dra, which has a pulsating period of 0.053 day and a semi-amplitude of about 5 mmag in B-passband. We discovered new pulsating components in two eclipsing binaries of RX Hya and AB Per. The primary component of RX Hya is pulsating with a dominant period of 0.052 day and a semi-amplitude of about 7 mmag. AB Per has also a pulsating component with a period of 0.196 day and a semi-amplitude of about 10 mmag in B-passband. We suggest that these two new pulsators are members of the newly introduced group of mass-accreting pulsating stars in semi-detached Algol-type eclipsing binary systems. Table 4 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/405/231

  6. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  7. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Extrasolar planets and brown dwarfs around AF-type stars. IX. The HARPS southern sample

    NASA Astrophysics Data System (ADS)

    Borgniet, S.; Lagrange, A.-M.; Meunier, N.; Galland, F.

    2017-03-01

    Context. Massive, main-sequence (MS) AF-type stars have so far remained unexplored in past radial velocities (RV) surveys due to their small number of spectral lines and high rotational velocities that prevent the classic RV computation method. Aims: Our aim is to search for giant planets (GPs) around AF MS stars, to get primary statistical information on their occurrence rate and to compare the results with evolved stars and lower-mass MS stars. Methods: We used the HARPS spectrograph located on the 3.6 m telescope at ESO La Silla Observatory to observe 108 AF MS stars with B-V in the range -0.04 to 0.58 and masses in the range 1.1 to 3.6 M⊙. We used our SAFIR software developed to compute the RV and other spectroscopic observables of these early-type stars. We characterized the detected companions as well as the intrinsic stellar variability. We computed the detection limits and used them as well as the detected companions to derive the first estimates of the close-in brown dwarf (BD) and GP frequencies around AF stars. Results: We report the detection of a mpsini = 4.51MJup planetary companion with an 826-day period to the F6V dwarf HD 111998. We also present new data on the two-planet system around the F6IV-V dwarf HD 60532. We also report the detections of 14 binaries with long-term RV trends and/or high-amplitude RV variations combined to a flat RV-bisector span diagram. We constrain the minimal masses and semi-major axes of these companions and check that these constraints are compatible with the stellar companions previously detected by direct imaging or astrometry for six of these targets. We get detection limits deep into the planetary domain with 70% of our targets showing detection limits between 0.1 and 10 MJup at all orbital periods in the 1- to 103-day range. We derive BD (13 ≤mpsini ≤ 80 MJup) occurrence rates in the 1- to 103-day period range of 2-2+5% and 2.6-2.6+6.7% for stars with M⋆ in the ranges 1.1 to 1.5 and 1.5 to 3 M

  9. Differential modulation of plant immune responses by diverse members of the Pseudomonas savastanoi pv. savastanoi HopAF type III effector family.

    PubMed

    Castañeda-Ojeda, M Pilar; López-Solanilla, Emilia; Ramos, Cayo

    2017-06-01

    The Pseudomonas savastanoi pv. savastanoi NCPPB 3335 type III secretion system (T3SS) effector repertoire includes 33 candidates, seven of which translocate into host cells and interfere with plant defences. The present study was performed to investigate the co-existence of both plasmid- and chromosomal-encoded members of the HopAF effector family, HopAF1-1 and HopAF1-2, respectively, in the genome of NCPPB 3335. Here, we show that the HopAF1 paralogues are widely distributed in the Pseudomonas syringae complex, where HopAF1-1 is most similar to the homologues encoded by other P. syringae pathovars infecting woody hosts that belong to phylogroups 1 and 3. We show that the expression of both HopAF1-1 and HopAF-2 is transcriptionally dependent on HrpL and demonstrate their delivery into Nicotiana tabacum leaves. Although the heterologous delivery of either HopAF1-1 or HopAF1-2 significantly suppressed the production of defence-associated reactive oxygen species levels, only HopAF1-2 reduced the levels of callose deposition. Moreover, the expression of HopAF1-2 by functionally effectorless P. syringae pv. tomato DC3000D28E completely inhibited the hypersensitive response in tobacco and significantly increased the competitiveness of the strain in Nicotiana benthamiana. Despite their functional differences, subcellular localization studies reveal that green fluorescent protein (GFP) fusions to either HopAF1-1 or HopAF1-2 are targeted to the plasma membrane when they are expressed in plant cells, a process that is completely dependent on the integrity of their N-myristoylation motif. Our results further support the notion that highly similar T3SS effectors might differentially interact with diverse plant targets, even when they co-localize in the same cell compartment. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  10. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  11. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    SciTech Connect

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying E-mail: yangyg@chnu.edu.cn

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  12. Type I IFN signaling constrains IL-17A/F secretion by gammadelta T cells during bacterial infections.

    PubMed

    Henry, Thomas; Kirimanjeswara, Girish S; Ruby, Thomas; Jones, Jonathan W; Peng, Kaitian; Perret, Magali; Ho, Lena; Sauer, John-Demian; Iwakura, Yoichiro; Metzger, Dennis W; Monack, Denise M

    2010-04-01

    Recognition of intracellular bacteria by macrophages leads to secretion of type I IFNs. However, the role of type I IFN during bacterial infection is still poorly understood. Francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type I IFN. In this study, we investigated the role of type I IFNs in a mouse model of tularemia. Mice deficient for type I IFN receptor (IFNAR1(-/-)) are more resistant to intradermal infection with F. tularensis subspecies novicida (F. novicida). Increased resistance to infection was associated with a specific increase in IL-17A/F and a corresponding expansion of an IL-17A(+) gammadelta T cell population, indicating that type I IFNs negatively regulate the number of IL-17A(+) gammadelta T cells during infection. Furthermore, IL-17A-deficient mice contained fewer neutrophils compared with wild-type mice during infection, indicating that IL-17A contributes to neutrophil expansion during F. novicida infection. Accordingly, an increase in IL-17A in IFNAR1(-/-) mice correlated with an increase in splenic neutrophil numbers. Similar results were obtained in a mouse model of pneumonic tularemia using the highly virulent F. tularensis subspecies tularensis SchuS4 strain and in a mouse model of systemic Listeria monocytogenes infection. Our results indicate that the type I IFN-mediated negative regulation of IL-17A(+) gammadelta T cell expansion is conserved during bacterial infections. We propose that this newly described activity of type I IFN signaling might participate in the resistance of the IFNAR1(-/-) mice to infection with F. novicida and other intracellular bacteria.

  13. Type I Interferon signaling constrains IL-17A/F secretion by γδ T cells during bacterial infections

    PubMed Central

    Henry, Thomas; Kirimanjeswara, Girish S.; Ruby, Thomas; Jones, Jonathan W.; Peng, Kaitian; Perret, Magali; Ho, Lena; Sauer, John-Demian; Iwakura, Yoichiro; Metzger, Dennis W.; Monack, Denise M.

    2010-01-01

    Recognition of intracellular bacteria by macrophages leads to secretion of type I Interferons. However, the role of type I IFN during bacterial infection is still poorly understood. Francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type I IFN. Here, we investigated the role of type I IFN in a mouse model of tularemia. Mice deficient for type I IFN receptor (IFNAR1−/−) are more resistant to intradermal infection with F. tularensis subspecies novicida (F. novicida). Increased resistance to infection was associated with a specific increase in IL-17A/F and a corresponding expansion of an IL-17A+ γδ T cell population, indicating that type I IFN negatively regulate the number of IL-17A+ γδ T cells during infection. Furthermore, IL-17A-deficient mice contained fewer neutrophils compared to WT mice upon infection, indicating that IL-17A contributes to neutrophil expansion during F. novicida infection. Accordingly, an increase in IL-17A in IFNAR1−/− mice correlated with an increase in splenic neutrophil numbers. Similar results were obtained in a mouse model of pneumonic tularemia using the highly virulent Francisella tularensis subspecies tularensis SchuS4 strain and in a mouse model of systemic Listeria monocytogenes infection. Our results indicate that the type I IFN-mediated negative regulation of IL-17A+ γδ T cell expansion is conserved during bacterial infections. We propose that this newly described activity of type I IFN signaling might participate in the resistance of the IFNAR1−/− mice to infection with F. novicida and other intracellular bacteria. PMID:20176744

  14. FABRICATION AND DEPLOYMENT OF THE 9979 TYPE AF RADIOACTIVE WASTE PACKAGING FOR THE DEPARTMENT OF ENERGY

    SciTech Connect

    Blanton, P.; Eberl, K.

    2013-10-10

    This paper summarizes the development, testing, and certification of the 9979 Type A Fissile Packaging that replaces the UN1A2 Specification Shipping Package eliminated from Department of Transportation (DOT) 49 CFR 173. The DOT Specification Package was used for many decades by the U.S. nuclear industry as a fissile waste container until its removal as an authorized container by DOT. This paper will discuss stream lining procurement of high volume radioactive material packaging manufacturing, such as the 9979, to minimize packaging production costs without sacrificing Quality Assurance. The authorized content envelope (combustible and non-combustible) as well as planned content envelope expansion will be discussed.

  15. VizieR Online Data Catalog: Algol-type binaries. VIII. DI Peg & AF Gem (Yang+, 2014)

    NASA Astrophysics Data System (ADS)

    Yang, Y.-G.; Yang, Y.; Li, S.-Z.

    2014-10-01

    In the 2012-2013 observing season, DI Peg and AF Gem were observed using the 60cm telescope and the 85cm telescope at Xinglong station (XLs) of National Astronomical Observatories of Chinese (NAOC). The standard Johnson-Cousins UBVRcIc photometric systems were mounted upon two small telescopes. On five consecutive nights from 2012 October 9 to 13, the multi-color photometry of DI Peg was made with the 60cm telescope. The other variable star, AF Gem, was observed using the 85cm telescope on 7 nights from 2013 January 1 to 7. (5 data files).

  16. Kadcoccinones A-F, New Biogenetically Related Lanostane-Type Triterpenoids with Diverse Skeletons from Kadsura coccinea.

    PubMed

    Hu, Zheng-Xi; Shi, Yi-Ming; Wang, Wei-Guang; Li, Xiao-Nian; Du, Xue; Liu, Miao; Li, Yan; Xue, Yong-Bo; Zhang, Yong-Hui; Pu, Jian-Xin; Sun, Han-Dong

    2015-09-18

    Six new lanostane-related triterpenoids, kadcoccinones A-F (1-6), were isolated from Kadsura coccinea. Compound 3 possesses a novel 6/6/9-fused carbocyclic core containing a rare oxabicyclo[4.3.1]decane system. Compounds 4 and 5 are isomers representing the first example of the 18(13 → 12)-abeo-26-norlanostane triterpenoid. The absolute configurations of 1 and 4-6 were defined by X-ray diffraction and experimental ECD spectra, and that of 3 was elucidated by quantum chemical calculations. The plausible biogenetic pathway of 1-6 is postulated.

  17. The U2AF35-related protein Urp contacts the 3' splice site to promote U12-type intron splicing and the second step of U2-type intron splicing.

    PubMed

    Shen, Haihong; Zheng, Xuexiu; Luecke, Stephan; Green, Michael R

    2010-11-01

    The U2AF35-related protein Urp has been implicated previously in splicing of the major class of U2-type introns. Here we show that Urp is also required for splicing of the minor class of U12-type introns. Urp is recruited in an ATP-dependent fashion to the U12-type intron 3' splice site, where it promotes formation of spliceosomal complexes. Remarkably, Urp also contacts the 3' splice site of a U2-type intron, but in this case is specifically required for the second step of splicing. Thus, through recognition of a common splicing element, Urp facilitates distinct steps of U2- and U12-type intron splicing.

  18. The U2AF35-related protein Urp contacts the 3′ splice site to promote U12-type intron splicing and the second step of U2-type intron splicing

    PubMed Central

    Shen, Haihong; Zheng, Xuexiu; Luecke, Stephan; Green, Michael R.

    2010-01-01

    The U2AF35-related protein Urp has been implicated previously in splicing of the major class of U2-type introns. Here we show that Urp is also required for splicing of the minor class of U12-type introns. Urp is recruited in an ATP-dependent fashion to the U12-type intron 3′ splice site, where it promotes formation of spliceosomal complexes. Remarkably, Urp also contacts the 3′ splice site of a U2-type intron, but in this case is specifically required for the second step of splicing. Thus, through recognition of a common splicing element, Urp facilitates distinct steps of U2- and U12-type intron splicing. PMID:21041408

  19. Prevalence of cry2-type genes in Bacillus thuringiensis isolates recovered from diverse habitats in India and isolation of a novel cry2Af2 gene toxic to Helicoverpa armigera (cotton boll worm).

    PubMed

    Katara, Jawahar Lal; Kaur, Sarvjeet; Kumari, Gouthami Krishna; Singh, Nagendra Kumar

    2016-12-01

    Insecticidal cry and vip genes from Bacillus thuringiensis (Bt) have been used for control of lepidopteran insects in transgenic crops. However, novel genes are required for gene pyramiding to delay evolution of resistance to the currently deployed genes. Two PCR-based techniques were employed for screening of cry2-type genes in 129 Bt isolates from diverse habitats in India and 27 known Bt strains. cry2Ab-type genes were more prevalent than cry2Aa- and cry2Ac-type genes. Correlation between source of isolates and abundance of cry2-type genes was not observed. Full-length cry2A-type genes were amplified by PCR from 9 Bt isolates and 4 Bt strains. The genes from Bt isolates SK-758 from Sorghum grain dust and SK-793 from Chilli seeds warehouse, Andhra Pradesh, were cloned and sequenced. The gene from SK-758 (NCBI GenBank accession No. GQ866915) was novel, while that from SK-793 (NCBI GenBank accession No. GQ866914) was identical to the cry2Ab1 gene. The Bacillus thuringiensis Nomenclature Committee ( http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/toxins2.html ) named these genes cry2Af2 and cry2Ab16, respectively. The cry2Af2 gene was expressed in Escherichia coli and found to be toxic towards Helicoverpa armigera. The cry2Af2 gene will be useful for pyramiding in transgenic crops.

  20. Coaxially electrospun PVDF-Teflon AF and Teflon AF-PVDF core-sheath nanofiber mats with superhydrophobic properties.

    PubMed

    Muthiah, Palanikkumaran; Hsu, Shu-Hau; Sigmund, Wolfgang

    2010-08-03

    This work reports the coaxial electrospinning of poly(vinylidene fluoride) (PVDF)-Teflon amorphous fluoropolymer (AF) and Teflon AF-PVDF core-sheath nanofiber mats yielding superhydrophobic properties. The coaxial electrospinning configuration allows for the electrospinning of Teflon AF, a nonelectrospinnable polymer, with the help of an electrospinnable PVDF polymer. PVDF-Teflon AF and Teflon AF-PVDF core-sheath fibers have been found to a have mean fiber diameter ranging from 400 nm to less than 100 nm. TEM micrographs exhibit a typical core-sheath fiber structure for these fibers, where the sheath fiber coats the core fiber almost thoroughly. Water contact angle measurements by sessile drop method on these core-sheath nanofiber mats exhibited superhydrophobic characteristics with contact angles close to or higher than 150 degrees. Surprisingly, PVDF-Teflon AF and Teflon AF-PVDF nanofiber mat surface properties were dominated by the fiber dimensions and less influenced by the type of sheath polymer. This suggests that highly fluorinated polymer Teflon AF does not advance the hydrophobicity beyond what surface physics and slightly fluorinated polymer PVDF can achieve. It is concluded that PVDF-Teflon AF and Teflon AF-PVDF core-sheath electrospun nanofiber mats may be used in lithium (Li)-air batteries.

  1. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex

    PubMed Central

    Mück, Fabian; Bracharz, Silvia; Marschalek, Rolf

    2016-01-01

    AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of “super elongation complexes” (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P-TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs. PMID:27679741

  2. Health Information in Somali (Af-Soomaali )

    MedlinePlus

    ... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Lumbar Puncture - Af-Soomaali (Somali) Bilingual PDF Health Information Translations Neuromuscular Disorders EMG and Nerve Conduction Tests - Af-Soomaali (Somali) Bilingual PDF Health ...

  3. AF Ari - Ein heller Bedeckungsveraenderlicher mit einem G-Riesen

    NASA Astrophysics Data System (ADS)

    Hauck, Norbert

    2011-03-01

    By combining existing and including new photometric data a first solution can now be presented: AF Ari is a well detached binary having an eccentric orbit and a period of 153 days. The secondary component is identified as an A-type dwarf. The mass of the G-type giant is estimated at 2.65 solar masses. Apparently, AF Ari is a new z (zeta) Aurigae type system and suited for double-lined spectroscopy. The english version of the article will be found behind the german version.

  4. A new AF gravitational instanton

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Teo, Edward

    2011-09-01

    It has long been conjectured that the Euclidean Schwarzschild and Euclidean Kerr instantons are the only non-trivial asymptotically flat (AF) gravitational instantons. In this Letter, we show that this conjecture is false by explicitly constructing a new two-parameter AF gravitational instanton with a U (1) × U (1) isometry group, using the inverse-scattering method. It has Euler number χ = 3 and Hirzebruch signature τ = 1, and its global topology is CP2 with a circle S1 removed appropriately. Various other properties of this gravitational instanton are also discussed.

  5. The AFS Impact Study: Final Report. AFS Research Report 33.

    ERIC Educational Resources Information Center

    Hansel, Bettina

    The AFS Impact Study, initiated in 1977, is an attempt to document changes in learning and personal development associated with an intercultural "homestay" program. Completed in 1985, the study identifies several areas in which students show greater learning and educational growth than that shown by a group of students who had expressed interest…

  6. Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

    DTIC Science & Technology

    1985-09-01

    1976. Murphy Dome AFS Industrial wastes from Murphy Dome shops are similar to other LRR istallations including primarily lubricating oils and some...mn ...am........................ .. . .. FIGURE 6.6 02 mu .. . (DoI0 * 4. .J~ . .... 00- oCL c0Z 6 o2 z xo% . COW 2 N w Z -wo O<W0 V AO~L Ul w L L

  7. Tin City AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    GL&bAL CLIMATOLOGY 9 RA14CH T AC NG VERSUS Vi’SIBILITY A .FAT"E S[ PfIC /mAC I .17 TI CITY AFS AK 73-74,77-81 T 1b. 3 19.5 17.S 19.5 19.5...2. GOVT ACCESSION NO. 3 RECIPIENT’S CATALOG NUMBER USAFETAC/DS 83017 4. TITLE (d SubtII-)Reised Uniform Summary of Surface 5 TYPE OF REPORT & PERIOD...WINDS PART 0 CEILING VERSUS VISIBILITY PART F STATION PRESSURE SKYCOVER SEA LEVEL PRESSURE STANDARD 3 -HOUR GROUPS All su-nseri- requiring diurnal

  8. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

    If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

  9. Durable Superhydrophobic Surfaces via Spontaneous Wrinkling of Teflon AF.

    PubMed

    Scarratt, Liam R J; Hoatson, Ben S; Wood, Elliot S; Hawkett, Brian S; Neto, Chiara

    2016-03-01

    We report the fabrication of both single-scale and hierarchical superhydrophobic surfaces, created by exploiting the spontaneous wrinkling of a rigid Teflon AF film on two types of shrinkable plastic substrates. Sub-100 nm to micrometric wrinkles were reproducibly generated by this simple process, with remarkable control over the size and hierarchy. Hierarchical Teflon AF wrinkled surfaces showed extremely high water repellence (contact angle 172°) and very low contact angle hysteresis (2°), resulting in droplets rolling off the surface at tilt angles lower than 5°. The wrinkling process intimately binds the Teflon AF layer with its substrate, making these surfaces mechanically robust, as revealed by macroscale and nanoscale wear tests: hardness values were close to that of commercial optical lenses and aluminum films, resistance to scratch was comparable to commercial hydrophobic coatings, and damage by extensive sonication did not significantly affect water repellence. By this fabrication method the size of the wrinkles can be reproducibly tuned from the nanoscale to the microscale, across the whole surface in one step; the fabrication procedure is extremely rapid, requiring only 2 min of thermal annealing to produce the desired topography, and uses inexpensive materials. The very low roll-off angles achieved in the hierarchical surfaces offer a potentially up-scalable alternative as self-cleaning and drag-reducing coatings.

  10. Mechanisms Underlying AF: Triggers, Rotors, Other?

    PubMed

    Krummen, David E; Hebsur, Shrinivas; Salcedo, Jon; Narayan, Sanjiv M; Lalani, Gautam G; Schricker, Amir A

    2015-04-01

    There is ongoing debate regarding the precise mechanisms underlying atrial fibrillation (AF). An improved understanding of these mechanisms is urgently needed to improve interventional strategies to suppress and eliminate AF, since the success of current strategies is suboptimal. At present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for the prevention of arrhythmia. Additional targets are presently unclear, and include additional linear ablation and electrogram-guided substrate modification, without clear mechanistic relevance. PV and non-PV triggers are likely central in the first few seconds of AF initiation. Rapid activation from such triggers interacts with transitional mechanisms including conduction velocity slowing, action potential duration (APD) alternans, and steep APD restitution to cause conduction block and initiate functional reentry. However, complete suppression of potential triggers has proven elusive, and the intra-procedural mapping and targeting of transitional mechanisms has not been reported. A growing body of research implicates electrical rotors and focal sources as central mechanisms for the maintenance of AF. In several recent series, they were observed in nearly all patients with sustained arrhythmia. Ablation of rotor and focal source sites, prior to pulmonary vein isolation, substantially modulated atrial fibrillation in a high proportion of patients, and improved ablation outcomes versus pulmonary vein isolation alone. These results have subsequently been confirmed in multicenter series, and the improved outcomes have been found to persist to a mean follow-up of 3 years. Recently, rotors have been observed by multiple groups using diverse technologies. These findings represent a paradigm shift in AF, focusing on sustaining mechanisms, as is currently done with other arrhythmias such as atrioventricular node reentrant tachycardia. Studies are currently underway to assess the optimal strategy for the application

  11. Management of atrial fibrillation in Greece: the MANAGE-AF study.

    PubMed

    Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

    2014-01-01

    Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

  12. Influence of the facial pattern on ANB, AF-BF, and Wits appraisal.

    PubMed

    Tanaka, Jefferson Luis Oshiro; Ono, Evelise; Filho Medici, Edmundo; Cesar de Moraes, Luiz; Cezar de Melo Castilho, Julio; Leonelli de Moraes, Mari Eli

    2006-01-01

    To assess the correlation between Wits and AF-BF appraisals with the ANB angle, and verify the influence of the facial type on these appraisals. Lateral cephalometric radiographs from 118 untreated individuals were separated into 3 groups according to the facial pattern (brachyfacial, mesofacial, and dolichofacial). The radiographs were digitized and submitted to ANB angle and Wits and AF-BF appraisals on computer software. All radiographs were retraced for intraobserver and interobserver error tests. The Student's t test demonstrated no statistically significant differences on the intraobserver's test (P > .05). There were statistically significant differences in the readings of Wits values of the 3 groups and for AF-BF values in the brachyfacial and mesofacial groups (P <.05). The multiple linear regression tests demonstrated high correlation between ANB and AF-BF for the 3 groups (r2, 0.768). The same result was found for ANB and Wits (r2, 0.624). Facial pattern does not have an influence on the correlation between ANB and AF-BF nor between ANB and Wits, but it does influence the measurements of ANB, AF-BF, and Wits.

  13. RX-26-AY/AF rifle bullet tests

    SciTech Connect

    Sharp, D.D.

    1980-11-01

    A series of rifle bullet tests was performed on two explosives, RX-26-AY and RX-26-AF, using the Pantex version of the Picatinny Arsenal Test (PA-2). With the exception of one test, both explosives displayed a relatively low sensitivity to bullet impact. However, a marked difference was noted in the average burn time duration between the two types of explosives being tested. A minor modification was made on the rifle barrel used at the test site in order to improve the sighting procedure.

  14. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  15. Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

    PubMed

    Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

    2014-08-21

    Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

  16. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  17. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  18. Low incidence of left atrial delayed enhancement with MRI in patients with AF: a single-centre experience

    PubMed Central

    Bois, John P; Glockner, James; Young, Phillip M; Foley, Thomas A; Sheldon, Seth; Newman, Darrell B; Lin, Grace; Packer, Douglas L; Brady, Peter A

    2017-01-01

    Background Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. One potential target for ablation is left atrial (LA) scar (LAS) regions that may be the substrate for re-entry within the atria, thereby sustaining AF. Identification of LAS through LA delayed gadolinium enhancement (LADE) with MRI has been proposed. Objectives We sought to evaluate LADE in patients referred for catheter ablation of AF. Methods Prospective analysis was conducted of consecutive patients who underwent pulmonary vein antrum isolation (PVAI) ablation for AF at a single institution. Patients underwent LADE with MRI to determine LAS regions before ablation. MRI data were analysed independently in accordance with prespecified institutional protocol by two staff cardiac radiologists to whom patient outcomes were masked, and reports of LADE were documented. Where no initial consensus occurred regarding delayed enhancement (DE), a third staff cardiac radiologist independently reviewed the case and had the deciding vote. Results Of the 149 consecutive patients (mean (SD) age, 59 (9) years), AF was persistent in 64 (43%) and paroxysmal in 85 (57%); 45 (30%) had prior ablation. Only five patients (3%) had identifiable DE in LA walls (persistent AF, n=1; paroxysmal AF, n=4). LADE was present in two (4%) of the 45 patients with previous left PVAI. The presence of LADE was not associated with a higher recurrence rate of AF. Conclusions In contrast to previous studies, the finding of DE within LA walls was uncommon and, when present, did not correlate with AF type or risk of AF recurrence. It therefore is of unclear clinical significance. PMID:28123766

  19. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2015-01-01

    Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

  20. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.

    PubMed

    Steinberg, Benjamin A; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Hankey, Graeme J; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hacke, Werner; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Piccini, Jonathan P

    2015-02-01

    Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  1. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    PubMed

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-05

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  2. AF fixer: new incremental OPC method for optimizing assist feature

    NASA Astrophysics Data System (ADS)

    Jung, Sung-Gon; Kim, Sang-Wook; Suh, Sung-Soo; Kim, Young-Chang; Lee, Suk-Joo; Choi, Sung-Woon; Han, Woo-Sung; Moon, Joo-Tae; Barnes, Levi D.; Li, Xiaohai; Lugg, Robert M.; Lee, Sooryong; Koo, Kyoil; Do, Munhoe; Amoroso, Frank P.; Painter, Benjamin

    2008-05-01

    Due to shrinking design nodes and to some limitations of scanners, extreme off-axis illumination (OAI) required and its use and implementation of assist features (AF) to solve depth of focus (DOF) problems for isolated features and specific pitch regions is essential. But unfortunately, the strong periodic character of OAI illumination makes AF's print more easily. Present OPC flows generate AFs before OPC, which is also causes some AF printing problems. At present, mask manufacturers must downsize AF's below 30nm to solve this problem. This is challenging and increases mask cost. We report on an AF-fixer tool which is able to check AF printability and correct weak points with minimal cost in terms of DOF after OPC. We have devised an effective algorithm that removes printing AF's. It can not only search for the best non-printing AF condition to meet the DOF spec, but also reports uncorrectable spots, which could be marked as design errors. To limit correction times and to maximize DOF in full-chip correction, a process window (PW) model and incremental OPC method are applied. This AF fixer, which suggests optimum AF in only weak point region, solves AF printing problems economically and accurately.

  3. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1

    PubMed Central

    Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-01-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-10) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-10 males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-10 mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis. PMID:28057769

  4. Extra-nuclear effects of estrogen on cortical bone in males require ERαAF-1.

    PubMed

    Farman, H H; Wu, J; Gustafsson, K L; Windahl, S H; Kim, S H; Katzenellenbogen, J A; Ohlsson, C; Lagerquist, M K

    2017-02-01

    Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-1(0)) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-1(0) males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-1(0) mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis.

  5. First CCD Photometry of the Interacting Binary AF Geminorum: Evidence for a Gravitationally Bound Third Object?

    NASA Astrophysics Data System (ADS)

    Yuhas, Bernard J.; Reed, Phillip A.; Chambliss, Carlson R.

    2013-07-01

    AF Geminorum (AF Gem) is an unusual Algol-type eclipsing binary star system in that the primary eclipse is a transit of the cooler, more evolved secondary star in front of the main sequence primary star. Our observations of AF Gem were made using the 0.61-meter Ritchey-Chrétien telescope at the Kutztown University Observatory (Kutztown, Pennsylvania) over 9 nights from 28 Nov 2012 to 6 Feb 2013. A total of 5350 data images were obtained of AF Gem during this time, and the results of our photometry suggest evidence for a third light source which may be gravitationally bound to the system. We present the first CCD photometric study in BVRI for this system, resolve the third light source from our photometry, provide a consistent orbital solution using the Wilson-Devinney code, and present a detailed ephemeris analysis. With an orbital period of 1.24 days, an overall decreasing ephemeris, and a possible third body in the system, AF Gem certainly warrants future photometric and spectroscopic observations.

  6. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    NASA Technical Reports Server (NTRS)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  7. AF-GEOSPACE Version 2.1

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Tautz, M.; Roth, C.

    2004-05-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed and distributed by the Space Weather Center of Excellence at AFRL. A review of current (Version 2.0) and planned (Version 2.1) AF-GEOSpace capabilities will be given. A wide range of physical domains is represented enabling the software to address such things as solar disturbance propagation, radiation belt configuration, and ionospheric auroral particle precipitation and scintillation. The software is currently being used to aid with the design, operation, and simulation of a wide variety of communications, navigation, and surveillance systems. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; scientific model validation and comparison, physics research, and education. Version 2.0 provided a simplified graphical user interface, improved science and application modules, and significantly enhanced graphical performance. Common input data archive sets, application modules, and 1-D, 2-D, and 3-D visualization tools are provided to all models. Dynamic capabilities permit multiple environments to be generated at user-specified time intervals while animation tools enable displays such as satellite orbits and environment data together as a function of time. Building on the existing Version 2.0 software architecture, AF-GEOSpace Version 2.1 is currently under development and will include a host of new modules to provide, for example, geosynchronous charged particle fluxes, neutral atmosphere densities

  8. Impact of atrial fibrillation type during acute coronary syndromes: Clinical features and prognosis.

    PubMed

    Braga, Carlos Galvão; Ramos, Vítor; Martins, Juliana; Arantes, Carina; Abreu, Glória; Vieira, Catarina; Salgado, Alberto; Gaspar, António; Azevedo, Pedro; Álvares Pereira, Miguel; Magalhães, Sónia; Marques, Jorge

    2015-06-01

    Atrial fibrillation (AF) is widely recognized as an adverse prognostic factor during acute myocardial infarction, although the impact of AF type - new-onset (nAF) or pre-existing (pAF) - is still controversial. To identify the clinical differences and prognosis of nAF and pAF during acute coronary syndromes (ACS). We performed a retrospective observational cohort study including 1373 consecutive patients (mean age 64 years, 77.3% male) admitted to a single center over a three-year period, with a six-month follow-up. AF rhythm was identified in 14.5% patients, of whom 71.4% presented nAF and 28.6% pAF. When AF types were compared, patients with nAF more frequently presented with ST-elevation ACS (p=0.003). Patients with pAF, in turn, were older (p=0.032), had greater left atrial diameter (p=0.001) and were less likely to have significant coronary lesions (p=0.034). Regarding therapeutic strategy, nAF patients were more often treated by rhythm control during hospital stay (p<0.001) and were less often anticoagulated at discharge (p=0.001). Compared with the population without AF, nAF was a predictor of death during hospital stay in univariate (p<0.001) and multivariate analysis (OR 2.67, p=0.047), but pAF was not. During follow-up, pAF was associated with higher mortality (p=0.014), while nAF patients presented only a trend towards worse prognosis. AF during the acute phase of ACS appears to have a negative prognostic impact only in patients with nAF and not in those with pAF. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  9. Ligand-independent FLT3 activation does not cooperate with MLL-AF4 to immortalize/transform cord blood CD34+ cells.

    PubMed

    Montes, R; Ayllón, V; Prieto, C; Bursen, A; Prelle, C; Romero-Moya, D; Real, P J; Navarro-Montero, O; Chillón, C; Marschalek, R; Bueno, C; Menendez, P

    2014-03-01

    MLL-AF4 fusion is hallmark in high-risk infant pro-B-acute lymphoblastic leukemia (pro-B-ALL). Our limited understanding of MLL-AF4-mediated transformation reflects the absence of human models reproducing this leukemia. Hematopoietic stem/progenitor cells (HSPCs) constitute likely targets for transformation. We previously reported that MLL-AF4 enhanced hematopoietic engraftment and clonogenic potential in cord blood (CB)-derived CD34+ HSPCs but was not sufficient for leukemogenesis, suggesting that additional oncogenic lesions are required for MLL-AF4-mediated transformation. MLL-AF4+ pro-B-ALL display enormous levels of FLT3, and occasionally FLT3-activating mutations, thus representing a candidate cooperating event in MLL-AF4+ pro-B-ALL. We have explored whether FLT3.TKD (tyrosine kinase domain) mutation or increased expression of FLT3.WT (wild type) cooperates with MLL-AF4 to immortalize/transform CB-CD34+ HSPCs. In vivo, FLT3.TKD/FLT3.WT alone, or in combination with MLL-AF4, enhances hematopoietic repopulating function of CB-CD34+ HSPCs without impairing migration or hematopoietic differentiation. None of the animals transplanted with MLL-AF4+FLT3.TKD/WT-CD34+ HSPCs showed any sign of disease after 16 weeks. In vitro, enforced expression of FLT3.TKD/FLT3.WT conveys a transient overexpansion of MLL-AF4-expressing CD34+ HSPCs associated to higher proportion of cycling cells coupled to lower apoptotic levels, but does not augment clonogenic potential nor confer stable replating. Together, FLT3 activation does not suffice to immortalize/transform MLL-AF4-expressing CB-CD34+ HSPCs, suggesting the need of alternative (epi)-genetic cooperating oncogenic lesions.

  10. Activation of Wnt signaling pathway by AF1q enriches stem-like population and enhance mammosphere formation of breast cells.

    PubMed

    Tse, Charlotte Olivia; Kim, Soojin; Park, Jino

    2017-03-18

    Wnt signaling pathway is believed to be responsible for control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state. Moreover, dysregulated Wnt signaling pathway is strongly associated with several diseases including cancer. Previously, we have shown that AF1q associates with a poor prognosis in leukemia, myelodysplastic syndromes, multiple myeloid, ovarian cancer, and breast cancer. Also, AF1q plays a pivotal role as an oncogene and metastasis enhancer in breast cancer via activation of Wnt signaling pathway. AF1q is highly expressed in stem cells, and this expression is diminished by differentiation. To understand the role of AF1q in stem-like population, we examined stem-like cells derived from breast cells which dysregulated Wnt signaling pathway by alteration of AF1q expression. The effect of Wnt signaling pathway by AF1q on EMT marker expression, stem cell marker expression, and sphere formation was determined. Activated Wnt signaling pathway by AF1q enriched stem-like population showed enhanced sphere formation ability. Interestingly, Wnt signaling pathway inhibitor, Quercetin, decreased the sphere formation in these cells. These results suggest that AF1q would have a role as an enhancer in generation of stem-like population through activation of Wnt signaling pathway.

  11. Part III: AFS - A Secure Distributed File System

    SciTech Connect

    Wachsmann, A.; /SLAC

    2005-06-29

    AFS is a secure distributed global file system providing location independence, scalability and transparent migration capabilities for data. AFS works across a multitude of Unix and non-Unix operating systems and is used at many large sites in production for many years. AFS still provides unique features that are not available with other distributed file systems even though AFS is almost 20 years old. This age might make it less appealing to some but with IBM making AFS available as open-source in 2000, new interest in use and development was sparked. When talking about AFS, people often mention other file systems as potential alternatives. Coda (http://www.coda.cs.cmu.edu/) with its disconnected mode will always be a research project and never have production quality. Intermezzo (http://www.inter-mezzo.org/) is now in the Linux kernel but not available for any other operating systems. NFSv4 (http://www.nfsv4.org/) which picked up many ideas from AFS and Coda is not mature enough yet to be used in serious production mode. This article presents the rich features of AFS and invites readers to play with it.

  12. AF-Shell 1.0 User Guide

    NASA Technical Reports Server (NTRS)

    McElroy, Mark W.

    2017-01-01

    This document serves as a user guide for the AF-Shell 1.0 software, an efficient tool for progressive damage simulation in composite laminates. This guide contains minimal technical material and is meant solely as a guide for a new user to apply AF-Shell 1.0 to laminate damage simulation problems.

  13. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true [Reserved] A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... Acquisition of Real and Chattel Property Exhibits A-F to Subpart A of Part 1955 [Reserved] ...

  14. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  15. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  16. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  17. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  18. Toward a petabyte-scale AFS service at CERN

    NASA Astrophysics Data System (ADS)

    van der Ster, Daniel; Moscicki, Jakub T.; Wiebalck, Arne

    2014-06-01

    AFS is a mature and reliable storage service at CERN, having worked for more than 20 years as the provider of Unix home directories and project areas. Recently, the AFS service has grown at unprecedented rates (200% in the past year); this growth was unlocked thanks to innovations in both the hardware and software components of our file servers. This work presents how AFS is used at CERN and how the service offering is evolving with the increasing storage needs of its local and remote user communities. In particular, we demonstrate the usage patterns for home directories, workspaces and project spaces, as well as show the daily work which is required to rebalance data and maintaining stability and performance. Finally, we highlight some recent changes and optimisations made to the AFS Service, thereby revealing how AFS can possibly operate at all while being subjected to frequent-almost DDOS-like-attacks from its users.

  19. Cape Newenham AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-04-01

    TEMPERATURE DEPRESION F, ’O.AL 3 - 4 5- 6 8 9- 1 11 12 13 14 𔃿 t 11 1 9 :," 2. 4 :.! 2 2 5 . . I TAL .4’ 373 - .. .. 776 7 7 8 * ... .. H- j4 93 4 5 7...H ;AVETA: PSYCHROMETRIC SUMMARY; A:Z, %EAT ER SER VCLPI ’ 7 CARUP li i.L -AF -- AM---.- 7-. - _ PAGE 1 2 WET BLLB TEmPEPATURE DEPRESION F, " AL .’ 3

  20. Mylar and Teflon-AF as cell culture substrates for studying endothelial cell adhesion.

    PubMed

    Anamelechi, Charles C; Truskey, George A; Reichert, W Monty

    2005-12-01

    The textured and opaque nature of Dacron and ePTFE has prevented the use of these fabrics in conventional cell culture techniques normally employed to optimize cell attachment and retention. This lack of optimization has led, in part, to the poor performance of endothelialization strategies for improving vascular graft patency. Here we show that thin, transparent films of Mylar and Teflon-AF are viable in vitro cell culture mimics of Dacron and ePTFE vascular graft materials, particularly for the study of protein mediated endothelial cell (EC) attachment, spreading and adhesion. Glass substrates were used as controls. X-ray photoelectron spectroscopy (XPS) and contact angle analysis showed that Mylar and Teflon-AF have surface chemistries that closely match Dacron and ePTFE. (125)I radiolabeling was used to quantify fibronectin (FN) adsorption, and FN and biotinylated-BSA "dual ligand" co-adsorption onto glass, Mylar and Teflon-AF substrates. Native human umbilical vein endothelial cells (HUVEC) and streptavidin-incubated biotinylated-HUVEC (SA-b-HUVEC) spreading was measured using phase contrast microscopy. Cell retention and adhesion was determined using phase contrast microscopy under laminar flow. All surfaces lacking protein pre-treatment, regardless of surface type, showed the lowest degree of cell spreading and retention. Dual ligand treated Mylar films showed significantly greater SA-b-HUVEC spreading up to 2 h, but were similar to HUVEC on FN treated Mylar at longer times; whereas SA-b-HUVEC spreading on dual ligand treated Teflon-AF was never significantly different from HUVEC on FN treated Teflon-AF at any time point. SA-b-HUVEC retention was significantly greater on dual ligand treated Mylar compared to HUVEC on FN treated Mylar over the entire range of shear stresses tested (3.54-28.3 dynes/cm(2)); whereas SA-b-HUVEC retention to dual ligand and HUVEC retention to FN treated Teflon-AF gave similar results at each shear stress, with only the mid

  1. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs

    PubMed Central

    Jenkins, Jermaine L.; Agrawal, Anant A.; Gupta, Ankit; Green, Michael R.; Kielkopf, Clara L.

    2013-01-01

    Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF65 is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3′ splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF65 recognizes degenerate Py tracts, we determined six crystal structures of human U2AF65 bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF65 bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF65 for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF65 conformations. Our results highlight both local and global conformational selection as a means for universal 3′ splice site recognition by U2AF65. PMID:23376934

  2. An Implicit LU/AF FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.; Briley, W. Roger

    2001-01-01

    There has been some recent work to develop two and three-dimensional alternating direction implicit (ADI) FDTD schemes. These ADI schemes are based upon the original ADI concept developed by Peaceman and Rachford and Douglas and Gunn, which is a popular solution method in Computational Fluid Dynamics (CFD). These ADI schemes work well and they require solution of a tridiagonal system of equations. A new approach proposed in this paper applies a LU/AF approximate factorization technique from CFD to Maxwell s equations in flux conservative form for one space dimension. The result is a scheme that will retain its unconditional stability in three space dimensions, but does not require the solution of tridiagonal systems. The theory for this new algorithm is outlined in a one-dimensional context for clarity. An extension to two and threedimensional cases is discussed. Results of Fourier analysis are discussed for both stability and dispersion/damping properties of the algorithm. Results are presented for a one-dimensional model problem, and the explicit FDTD algorithm is chosen as a convenient reference for comparison.

  3. The vegetative compatibility group to which the US biocontrol agent Aspergillus flavus AF36 belongs is also endemic to Mexico.

    PubMed

    Ortega-Beltran, A; Grubisha, L C; Callicott, K A; Cotty, P J

    2016-04-01

    To assess frequencies of the Aspergillus flavus atoxigenic vegetative compatibility group (VCG) YV36, to which the biocontrol agent AF36 belongs, in maize-growing regions of Mexico. Over 3500 A. flavus isolates recovered from maize agroecosystems in four states of Mexico during 2005 through 2008 were subjected to vegetative compatibility analyses based on nitrate nonutilizing mutants. Results revealed that 59 (1·6%) isolates belong to VCG YV36. All 59 isolates had the MAT1-2 idiomorph at the mating-type locus and the single nucleotide polymorphism in the polyketide synthase gene that confers atoxigenicity. Additional degradation of the aflatoxin gene cluster was detected in three isolates. Microsatellite loci analyses revealed low levels of genetic diversity and no linkage disequilibrium within VCG YV36. The VCG to which the biocontrol agent AF36 belongs, YV36, is also native to Mexico. The North American Free Trade Agreement should facilitate adoption of AF36 for use by Mexico in aflatoxin prevention programs. An USEPA registered biocontrol agent effective at preventing aflatoxin contamination of crops in the US, is also native to Mexico. This should facilitate the path to registration of AF36 as the first biopesticide for aflatoxin mitigation of maize in Mexico. Economic and health benefits to the population of Mexico should result once aflatoxin mitigation programs based on AF36 applications are implemented. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  4. Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells

    PubMed Central

    Liu, Y; Cheng, H; Gao, S; Lu, X; He, F; Hu, L; Hou, D; Zou, Z; Li, Y; Zhang, H; Xu, J; Kang, L; Wang, Q; Yuan, W; Gao, S; Cheng, T

    2014-01-01

    The ‘Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc) are able to generate induced pluripotent stem (iPS) cells from different cell types. However, to what degree primary malignant cells can be reprogrammed into a pluripotent state has not been vigorously assessed. We established an acute myeloid leukemia (AML) model by overexpressing the human mixed-lineage leukemia-AF9 (MLL-AF9) fusion gene in mouse hematopoietic cells that carry Yamanaka factors under the control of doxycycline (Dox). On addition of Dox to the culture, the transplantable leukemia cells were efficiently converted into iPS cells that could form teratomas and produce chimeras. Interestingly, most chimeric mice spontaneously developed the same type of AML. Moreover, both iPS reprogramming and leukemia reinitiation paths could descend from the same leukemia-initiating cell. RNA-seq analysis showed reversible global gene expression patterns between these interchangeable leukemia and iPS cells on activation or reactivation of MLL-AF9, suggesting a sufficient epigenetic force in driving the leukemogenic process. This study represents an important step for further defining the potential interplay between oncogenic molecules and reprogramming factors during MLL leukemogenesis. More importantly, our reprogramming approach may be expanded to characterize a range of hematopoietic malignancies in order to develop new strategies for clinical diagnosis and treatment. PMID:24150221

  5. Indian Mountain AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-06-01

    31 8... . 1B b w., B. 0- r] N I o N.. Ob.. M.., N.. .1 N.-. it% To’p.Wo.- R. .1.__-___ 0 F 322 F *67 F *73 F 60S F *93 F To. 4 .. P , PSYCHROMETRIC...Psychrometrl- summary Surfoc, Worlds Extreme temperature Ceiling versus vis:boloi-; Helative Humidity -Climatological data (over) 20 ABSTRACT ’C- P ,, -1...uSAFETAC A2 4EATR SERVICE/MAC WEATHER CONDITIONS 70173C INDIAN MOUNTAIN AFS AK 73-8? P PEOCENTAGE FREQUENCY OF OCCURRENCE OF WEATHER CONDITIONS FROP HOURLY

  6. A novel poly(3-hydroxybutyrate)-degrading Streptoverticillium kashmirense AF1 isolated from soil and purification of PHB-depolymerase.

    PubMed

    Shah, A A; Hasan, Fariha; Hameed, A; Ahmed, Safia

    2008-12-01

    A new bacterial strain, capable of degrading poly(3-hydroxybutyrate) (PHB) was isolated from soil. This organism, identified as Streptoverticillium kashmirense AF1, secreted PHB depolymerases both on solid as well as in liquid mineral salt medium containing poly(3-hydroxybutyrate) as sole carbon source. The optimum production of PHB depolymerase was observed at pH 8 and 7, at 45 degrees C, 1% substrate concentration and in the presence of lactose as an additional carbon source. The extracellular PHB depolymerase was purified by gel permeation chromatography using Sephadex G-75. The Streptoverticillium kashmirense AF1 produced two types of PHB depolymerases having molecular weights of about 37 and 45 kDa as determined by SDS-PAGE. The difference in dry cell mass and amount of CO2 evolved in the test and control calculated gravimetrically through Sturm test indicated the degradative capabilities of Streptoverticillium kashmirense AF1.

  7. 'Real-world' management and outcomes of patients with paroxysmal vs. non-paroxysmal atrial fibrillation in Europe: the EURObservational Research Programme-Atrial Fibrillation (EORP-AF) General Pilot Registry.

    PubMed

    Boriani, Giuseppe; Laroche, Cecile; Diemberger, Igor; Fantecchi, Elisa; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Dan, Gheorghe-Andrei; Kalarus, Zbigniew; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

    2016-05-01

    Atrial fibrillation (AF) has different presentations (first detected, paroxysmal, persistent, permanent), with uncertain impact on outcome. The aim of this study was to investigate clinical presentation, management, and outcome of paroxysmal and non-paroxysmal AFs within the EURObservational Research Programme-Atrial Fibrillation General Pilot Registry. Overall 2589 patients with available 1-year follow-up data were evaluated according to AF type. Patients with paroxysmal AF (26.8%) were younger, had lower prevalence of heart disease (particularly valvular), and major co-morbidities, as well as lower CHADS2, CHA2DS2-VASc, and HAS-BLED scores. Patients with first-detected AF (29.9%) had characteristics similar to persistent AF patients (25.9%), but lower use of oral anticoagulants. Patients with permanent AF represented 17.4% of the cohort. At 1 year, the rate of stroke/transient ischaemic attack and thromboembolism was low (0.6-1.0%) and did not differ between paroxysmal and non-paroxysmal AFs. All-cause mortality was higher in non-paroxysmal vs. paroxysmal AF (log rank test, P = 0.0018). Using a multivariable Cox model, non-paroxysmal AF was not an independent predictor of death during follow-up. Independent predictors of death were age, chronic heart failure, chronic kidney disease, diabetes, restrictive cardiomyopathy, and physical activity. In this 'real-world' contemporary observational registry, patients with non-paroxysmal AF had a worse outcome, in terms of all-cause mortality, which was related to a more severe clinical profile. The risk of stroke at 1 year was relatively low, perhaps reflecting the high rates of anticoagulation use in this cohort. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  8. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR).

    PubMed

    Weber, Axel; Taube, Sylvia; Zur Stadt, Udo; Horstmann, Martin; Krohn, Knut; Bradtke, Jutta; Teigler-Schlegel, Andrea; Leiblein, Sabine; Christiansen, Holger

    2012-11-09

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available.

  9. Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

    PubMed

    Ma, Xiaorong; Zhang, Shengli; Zhou, Junmei; Chen, Baisong; Shang, Yafeng; Gao, Tongbing; Wang, Xue; Xie, Hua; Chen, Fang

    2012-08-01

    Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases. Copyright © 2012 John Wiley & Sons, Ltd.

  10. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice

    PubMed Central

    Börjesson, Anna E.; Farman, Helen H.; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K.; Windahl, Sara H.

    2016-01-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-10) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-10 mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  11. Tutorials in space physics using visualization with AF GEOSpace

    NASA Astrophysics Data System (ADS)

    Habash Krause, L.; Knipp, D.

    A set of tutorials has been developed to assist students of space physics with the visualization of three dimensional, time varying systems. AF GEOSpace is a suite of space environment specification models with a window driven interface that allows users to visualize data from well-established semi-empirical models in one, two, or three dimensions. An Open-GL windows environment provides for real-time navigation in a virtual environment representing near-Earth space, facilitating understanding of complex spatial structures of individual features and spatial relationships between constrained features. Modeled GEOSpace phenomena include realistic external magnetic fields (e.g., Hilmer-Voigt `95,) conductivity patterns in the auroral oval, VHF signal fading given a fixed ground station and a satellite altitude, and relativistic charged particle measurements made by a satellite given its orbital elements. The models included in GEOSpace are sensitive to solar and geomagnetic activity, so impacts unique to each of these types of activity are readily apparent to students using the tutorials. Thus, the students may actively discover, for example, that intensification of the pre-reversal enhancement in the equatorial post- sunset ionospheric vertical velocity is controlled primarily by solar and not geomagnetic activity, or that the compression of the magnetosphere may be so extreme during geomagnetic activity that satellites in geosynchronous orbit may experience direct exposure to the solar wind. Adding an element of student proactivity results in the students' accepting more responsibility for the learning process. This set of tutorials capitalizes on the students' positive response to learning through the discovery method, resulting in greater overall motivation to explore the near-Earth space environment.

  12. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Hall, T.; Roth, C.; Ling, A.; Ginet, G. P.; Madden, D.

    2010-12-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed by the Space Weather Center of Excellence at AFRL. The software addresses a wide range of physical domains, e.g., solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. AF-GEOSpace has become a platform for developing and prototyping space weather visualization products. The new AF-GEOSpace Version 2.5 (release scheduled for 2010) expands on the content of Version 2.1 by including modules addressing the following new topics: (1) energetic proton maps for the South Atlantic Anomaly (from Ginet et al. [2007]), (2) GPS scintillation outage simulation tools, (3) magnetopause location determination (Shue et al. [1998]), (4) a plasmasphere model (Global Core Plasma Model, 2009 version based on Gallagher et al. [2000]), (5) a standard ionospheric model (International Reference Ionosphere 2007), (6) the CAMMICE/MICS model of inner magnetosphere plasma population (based on Roeder et al. [2005]), (7) magnetic field models (e.g., Tsyganenko and Sitnov [2005]), and (8) loading and displaying externally-produced 3D gridded data sets within AF-GEOSpace. Improvements to existing Version 2.1 capabilities include: (1) a 2005 update to the geomagnetic cutoff rigidity model of Smart and Shea [2003], (2) a 2005 update to the ionospheric scintillation Wide-Band Model (WBMOD) of Secan and Bussey [1994], and (3) improved magnetic field flux mapping options for the existing set of AF-GEOSpace radiation belt models. A basic review of these new AF-GEOSpace capabilities will be provided. To obtain a copy of the software, please contact the first author.

  13. AF-GEOSpace Version 2.1 Release

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Perry, K. L.; Tautz, M.; Roth, C.

    2006-05-01

    AF-GEOSpace Version 2.1 is a graphics-intensive software program with space environment models and applications developed recently by the Space Weather Center of Excellence at AFRL. A review of new and planned AF-GEOSpace capabilities will be given. The software addresses a wide range of physical domains and addresses such topics as solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; determination of link outage regions for active ionospheric conditions; satellite magnetic conjugate studies, scientific model validation and comparison, physics research, and education. Previously, Version 2.0 provided a simplified graphical user interface, improved science and application modules, significantly enhanced graphical performance, common input data archive sets, and 1-D, 2-D, and 3- D visualization tools for all models. Dynamic capabilities permit multiple environments to be generated at user- specified time intervals while animation tools enable the display of satellite orbits and environment data together as a function of time. Building on the Version 2.0 software architecture, AF-GEOSpace Version 2.1 includes a host of new modules providing, for example, plasma sheet charged particle fluxes, neutral atmosphere densities, 3-D cosmic ray cutoff maps, low-altitude trapped proton belt flux specification, DMSP particle data displays, satellite magnetic field footprint mapping determination, and meteor sky maps and shower/storm fluxes with spacecraft impact probabilities. AF-GEOSpace Version 2.1 was

  14. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

    Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

    2014-01-01

    The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

  15. Radialgeschwindigkeiten und eine verbesserte Loesung für Doppelsternsystem AF Ari

    NASA Astrophysics Data System (ADS)

    Hauck, Norbert

    2013-03-01

    An improved solution for eclipsing binary AF Ari has been found by simultaneous fitting new radial-velocity data of the primary giant component and old photometry data to computed curves. The orbital period of 153 days and eccentricity of 0.36 has been confirmed. The new calibration has resulted in somewhat increased radii and masses of the components: 11.7 Rsun and 2.9 Msun for the G-type giant as well as 2.3 Rsun and 2.0 Msun for the A star. The english version of the paper will be found after the german article. Norbert Hauck is member of the BAV.

  16. The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

    NASA Technical Reports Server (NTRS)

    Halford, G. R.; Nachtigall, A. J.

    1979-01-01

    The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

  17. An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias.

    PubMed

    Barretto, Nisha N; Karahalios, Dean S; You, Dewen; Hemenway, Charles S

    2014-01-01

    Misregulation of transcription elongation is proposed to underlie the pathobiology of MLL leukemia. AF4, AF9, and ENL, common MLL fusion partners, are found in complex with positive transcription elongation factor b (P-TEFb). AF9 and its homolog ENL directly interact with AF4 within these complexes. Previously, we designed a peptide that mimics the AF9 binding domain of AF4 and reported that MLL leukemia cell lines are inhibited by it. Extending these studies, we have modified the peptide design in order to avoid recognition by proteases. The peptide is as effective as its predecessor in vitro and enhances survival in mice bearing MLL leukemia cell lines.

  18. Giant planets around AF and M stars

    NASA Astrophysics Data System (ADS)

    Rameau, Julien; Chauvin, Gaël; Lagrange, Anne-Marie; Delorme, Philippe; Lannier, Justine

    2014-01-01

    We present the results of two three-year surveys of young and nearby stars to search for wide orbit giant planets. On the one hand, we focus on early-type and massive, namely β Pictoris analogs. On the other hand, we observe late type and very low mass stars, i.e., M dwarfs. We report individual detections of new planetary mass objects. According to our deep detection performances, we derive the observed frequency of giant planets between these two classes of parent stars. We find frequency between 6 to 12% but we are not able to assess a/no correlation with the host-mass.

  19. Neuropharmacology and Therapeutics of AF Chemicals

    DTIC Science & Technology

    1980-08-01

    seizure types, those classified as complex- partial or psychomotor (Gastaut, 1970; Brazier, 1973). Additionally, this fact could relate the underlying...electrical afterdis- charge which gradually spreads to adjacent and contralateral tissues and then to cortex, leading eventually to generalized seizures...interpretations. It suggests that the propagation of ictal activity from limbic structures to sensorimotor cortex is at least partially mediated by

  20. An Empirical Test of Oklahoma's A-F School Grades

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.; Ware, Jordan; Mwavita, Mwarumba; Barnes, Laura L.; Khojasteb, Jam

    2016-01-01

    Oklahoma is one of 16 states electing to use an A-F letter grade as an indicator of school quality. On the surface, letter grades are an attractive policy instrument for school improvement; they are seemingly clear, simple, and easy to interpret. Evidence, however, on the use of letter grades as an instrument to rank and improve schools is scant…

  1. Action of AF64A on rat brain muscarinic receptors

    SciTech Connect

    Eva, C.; Costa, E.

    1986-03-01

    ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.

  2. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels

    PubMed Central

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2010-01-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5–15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation. PMID:20729984

  3. Optofluidic Waveguides in Teflon AF-Coated PDMS Microfluidic Channels.

    PubMed

    Cho, Sung Hwan; Godin, Jessica; Lo, Yu-Hwa

    2009-08-01

    We report a new method for fabricating an optofluidic waveguide that is compatible with polydimethylsiloxane (PDMS). The light path follows the microfluidic channels, an architecture that can maximize detection efficiency and make the most economic use of chip area in many lab-on-chip applications. The PDMS-based microfluidic channels are coated with Teflon amorphous fluoropolymers (Teflon AF) which has a lower refractive index (n = 1.31) than water (n = 1.33) to form a water/Teflon AF optical waveguide. Driven by a vacuum pump, the Teflon AF solution was flowed through the channels, leaving a thin (5-15 µm) layer of coating on the channel wall as the cladding layer of optical waveguides. This coating process resolves the limitations of spin-coating processes by reducing the elasticity mismatch between the Teflon AF cladding layer and the PDMS device body. We demonstrate that the resulting optofluidic waveguide confines and guides the laser light through the liquid core channel. Furthermore, the light in such a waveguide can be split when the fluid flow is split. This new method enables highly integrated biosensors such as lab-on-chip flow cytometers and micro-fabricated fluorescence-activated cell sorter with on-chip excitation.

  4. Sabiperones A-F, new diterpenoids from Juniperus sabina.

    PubMed

    Janar, Jenis; Nugroho, Alfarius Eko; Wong, Chin Piow; Hirasawa, Yusuke; Kaneda, Toshio; Shirota, Osamu; Morita, Hiroshi

    2012-01-01

    Six new diterpenoids, sabiperones A-F (1-6) have been isolated from the aerial part of Juniperus sabina. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. Sabiperone F showed moderate cell growth inhibitory activities against five human cancer cell lines.

  5. Abstracts of AF Materials Laboratory Reports

    DTIC Science & Technology

    1975-09-01

    composites employing compressed natural rubber foam as the sealant were fabricated which successfully sealed wounds inflicted by .30 and .50 caliber...investigated, and mirrors with three types of reflector surfaces were fabricated . Environ- mental testing including thermal cycling, thermal stability...was fabricated from AS/X-50𔃽 and cut into three sections. The sections were then cured by conventional autoclave, heated platen press and vacuum bag

  6. Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)

    PubMed Central

    Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

    2015-01-01

    Background Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. PMID:26370445

  7. Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF).

    PubMed

    Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

    2015-09-14

    Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Extracting uranium from seawater: Promising AF series adsorbents

    SciTech Connect

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.

  9. Extracting Uranium from Seawater: Promising AF Series Adsorbents

    SciTech Connect

    Das, S.; Oyola, Y.; Mayes, Richard T.; Janke, Chris J.; Kuo, L. -J.; Gill, G.; Wood, J. R.; Dai, S.

    2016-04-20

    A new family of high-surface-area polyethylene fiber adsorbents named the AF series was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series adsorbents were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/comonomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154-354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44 M KOH at 80 °C followed by screening at ORNL with sodium-based synthetic aqueous solution, spiked with 8 ppm uranium. The uranium adsorption capacity in simulated seawater screening ranged from 170 to 200 g-U/kg-ads irrespective of %DOG. A monomer/comonomer molar ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through column experiments to determine uranium loading capacity with varying KOH conditioning times at 80 °C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1 and 3 h of KOH conditioning at 80 °C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 1 to 3 h at 80 °C resulted in a 22-27% decrease in uranium adsorption capacity in seawater.

  10. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGES

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; ...

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

  11. Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

    PubMed

    Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2011-01-01

    From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

  12. Apnea-hypopnea index as a predictor of atrial fibrillation recurrence following initial pulmonary vein isolation: usefulness of type-3 portable monitor for sleep-disordered breathing.

    PubMed

    Kawakami, Hiroshi; Nagai, Takayuki; Fujii, Akira; Uetani, Teruyoshi; Nishimura, Kazuhisa; Inoue, Katsuji; Suzuki, Jun; Oka, Yasunori; Okura, Takafumi; Higaki, Jitsuo; Ogimoto, Akiyoshi; Ikeda, Shuntaro

    2016-11-01

    The relationship between atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) and sleep-disordered breathing (SDB) evaluated using type-3 portable monitoring (PM) is still unknown. We investigated high-risk patients with AF recurrence after initial PVI using the apnea-hypopnea index (AHI) measured by type-3 PM. One hundred twenty-four (85 males; age 62 ± 10 years) AF patients undergoing initial PVI were enrolled: 83, paroxysmal AF; 41, persistent AF. At baseline, all patients were subjected to in-hospital unattended overnight polygraphy using type-3 PM for SDB. During 13 ± 7 months following initial PVI, 47 patients (38 %) experienced AF recurrence. AHI and left atrial volume index (LAVI) were significantly greater in patients with than in those without AF recurrence (AHI P = 0.011; LAVI P < 0.001). LAVI was an independent predictor of AF recurrence following initial PVI in patients with both paroxysmal AF and persistent AF (paroxysmal AF P = 0.008; persistent AF P = 0.002). However, AHI was an independent predictor of AF recurrence following initial PVI in patients with paroxysmal AF (P = 0.034) but not in those with persistent AF. The optimal cutoff value was defined as AHI = 14.1. AF recurrence following PVI is three times higher in patients with AHI ≥14.1 than in patients with AHI < 14.1. AHI measured using type-3 PM is a useful predictor of outcome following initial PVI in patients with paroxysmal AF.

  13. The Joint Staff/J-5 and A-AF CLIC (Center for Low Intensity Conflict) Planning and Policy in Low Intensity Conflict Conference held in Hampton, Virginia on 13-15 December 1988

    DTIC Science & Technology

    1988-12-15

    THE JOINT STAFF/J-5 AND A-AF CLIC PLANNING AND POLICY IN LOW INTENSITY CONFLICT CLIC CONFERENCE REPORT Army -Air Force Center for Low Intensity...A-AF CLIC Planning and Policy in Low Intensity Conflict Conference Report (Unclassified) 12. PERSONAL AUTHOR(S) NA 13a. TYPE OF REPORT 13b. TIME... Planning and Policy for Low Intensity Conflict sponsored by the Joint Staff/J-5 and the A-AF CLIC drew nearly 300 participant from government and

  14. Palhicerines A-F, Lycopodium alkaloids from the club moss Palhinhaea cernua.

    PubMed

    Tang, Yu; Xiong, Juan; Zou, Yike; Zhang, Hai-Yan; Hu, Jin-Feng

    2016-11-01

    Four fawcettimine-type (palhicerines A-D, resp.) and two lycopodine-type (palhicerines E and F) Lycopodium alkaloids together with twenty known ones were isolated from the whole plant of Palhinhaea cernua. The structures and absolute configurations of the palhicerines A-F were determined by extensive spectroscopic methods, single-crystal X-ray diffraction analyses, chemical transformation, and electronic circular dichroism (ECD) calculations or induced electronic circular dichroism (IECD) spectra. Among the isolates, the new C/D-ring of the palhicerines A-C (trans-fused fawcettimine-type alkaloids) are rare, and each possesses a β-oriented C-16 methyl group and a distinctive tertiary methoxy group at C-13. Chemotaxonomy for differentiating species in the genus Palhinhaea is briefly discussed.

  15. Comparison of anti-M2-muscarinic effect of AF-DX 116 on atrioventricular nodal conduction with those of pirenzepine and atropine as antibradyarrhythmic drugs.

    PubMed

    Sasaki, S; Motomura, S

    1999-06-01

    Selectivity of antimuscarinic actions of AF-DX 116 (AF-DX) on the atrioventricular (AV) nodal conduction was compared with those of pirenzepine and atropine by using the canine isolated, blood-perfused AV node preparation and the open-chest in situ dog heart. In the isolated AV node preparation, dose-response curves for negative dromotropic effects (prolongation of Atrio-His interval) of carbachol (CCh) injected into the posterior septal artery were shifted to the right in parallel by AF-DX, pirenzepine, and atropine with apparent pA2-values of 13, 27.5, and 0.45 microg, respectively, and slopes of the modified Schild plot of nearly unity. Meanwhile, dose-response curves for coronary vasodilator effects of CCh were shifted to the right by AF-DX, pirenzepine, and atropine with the apparent pA2 values of 68, 12.5, and 0.55 microg, respectively, but the slopes were far from unity. In the in situ open-chest heart, dose-response curves for negative dromotropic effects (prolongation of AV conduction time) of CCh given intravenously were shifted to the right in parallel by AF-DX, pirenzepine, and atropine with apparent pA2 values of 36, 32, and 1.25 microg/kg, respectively, and the slope of nearly unity, whereas dose-response curves for hypotensive effects of CCh were shifted to the right by AF-DX, pirenzepine, and atropine with apparent pA2 values of 105, 15, and 0.65 microg/kg, respectively, but the slopes of AF-DX and pirenzepine were far from unity. In addition, prolongations of AV conduction time by electrical stimulation of the left vagus nerve in the in situ heart were suppressed by AF-DX, pirenzepine, and atropine with the ID50, dose for 50% suppression, of 40, 35, and 1.9 microg/kg, respectively. These results suggest that (a) the potency of antimuscarinic actions of AF-DX on the CCh-induced negative dromotropic effects was almost equal to that of pirenzepine, and approximately 30 times less potent than atropine; (b) the M2-subtype selectivity of AF-DX was

  16. Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis

    PubMed Central

    Bagislar, Sevgi; Sabò, Arianna; Kress, Theresia R.; Doni, Mirko; Nicoli, Paola; Campaner, Stefano; Amati, Bruno

    2016-01-01

    The Smyd2 protein (Set- and Mynd domain containing protein 2) is a methyl-transferase that can modify both histones and cytoplasmic proteins. Smyd2 is over-expressed in several cancer types and was shown to be limiting for tumor development in the pancreas. However, genetic evidence for a role of Smyd2 in other cancers or in mouse development was missing to date. Using germ line-deleted mouse strains, we now show that Smyd2 and the related protein Smyd3 are dispensable for normal development. Ablation of Smyd2 did not affect hematopoiesis, but retarded the development of leukemia promoted by MLL-AF9, a fusion oncogene associated with acute myeloid leukemia (AML) in humans. Smyd2-deleted leukemic cells showed a competitive disadvantage relative to wild-type cells, either in vitro or in vivo. The Smyd2 gene was directly activated by the oncogenic transcription factor Myc in either MLL9-AF9-induced leukemias, Myc-induced lymphomas, or fibroblasts. However, unlike leukemias, the development of lymphomas was not dependent upon Smyd2. Our data indicate that Smyd2 has a critical role downstream of Myc in AML. PMID:27655694

  17. Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study

    PubMed Central

    Johansson, Cecilia; Dahlqvist, Erik; Andersson, Jonas; Jansson, Jan-Håkan; Johansson, Lars

    2017-01-01

    Purpose The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA2DS2-VASc score were obtained from medical records. Results The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged ≥80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA2DS2-VASc score of 2 or more. PMID:28182159

  18. Biodegradation of BOD and ammonia-free using bacterial consortium in aerated fixed film bioreactor (AF2B)

    NASA Astrophysics Data System (ADS)

    Prayitno, Rulianah, Sri; Saroso, Hadi; Meilany, Diah

    2017-06-01

    BOD and Ammonia-free (NH3-N) are pollutants of hospital wastewater which often exceed the quality standards. It is because biological processes in wastewater treatment plant (WWTP) have not been effective in degrading BOD and NH3-N. Therefore, a study on factors that influence the biodegradation of BOD and NH3-N by choosing the type of bacteria to improve the mechanisms of biodegradation processes is required. Bacterial consortium is a collection of several types of bacteria obtained from isolation process, which is known to be more effective than a single bacterial in degrading pollutants. On the other hand, AF2B is a type of reactor in wastewater treatment system. The AF2B contains a filter media that has a large surface area so that the biodegradation process of pollutants by microorganism can be improved. The objective of this research is to determine the effect of volume of starter and air supplies on decreasing BOD and NH3-N in hospital wastewater using bacterial consortium in the AF2B on batch process. The research was conducted in three stages: the making of the growth curve of the bacterial consortium, bacterial consortium acclimatization, and hospital wastewater treatment in the AF2B with batch process. The variables used are the volume of starter (65%, 75%, and 85% in volume) and air supplies (2.5, 5, and 7.5 L/min). Meanwhile, the materials used are hospital wastewater, bacterial consortium (Pseudomonas diminuta, Pseudomonas capica, Bacillius sp, and Nitrobacter sp), blower, and AF2B. AF2B is a plastic basin containing a filter media with a wasp-nest shape used as a medium for growing the bacterial consortium. In the process of making the growth curve, a solid form of bacterial consortium was dissolved in sterilized water, then grown in a nutrient broth (NB). Then, shaking and sampling were done at any time to determine the path growth of bacterial consortium. In the acclimatization process, bacterial isolates were grown using hospital wastewater as a

  19. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  20. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  1. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  2. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form 813, Request for Environmental Impact Analysis. The Air Force uses AF Form 813 to document the need...

  3. Termination of persistent atrial fibrillation during pulmonary vein isolation: insight from the MAGIC-AF trial.

    PubMed

    Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

    2016-10-04

    Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group. The 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported for the 35 patients in the MAGIC-AF study with persistent AF termination during or upon completion of PVI.Freedom from recurrent atrial arrhythmia was achieved in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter was common when AF terminated to a macro re-entrant flutter during PVI, and responsible for 92% of all flutter circuits with AF termination. Persistent AF termination during PVI may identify a subgroup of patients who experience a similar long-term clinical outcome with PVI ablation alone when compared with other more extensive persistent AF ablation strategies. Pulmonary vein isolation alone may be an appropriate tactic in this subgroup of persistent AF patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  4. Use of statins and adverse outcomes in patients with atrial fibrillation: An analysis from the EURObservational Research Programme Atrial Fibrillation (EORP-AF) general registry pilot phase.

    PubMed

    Proietti, Marco; Laroche, Cécile; Nyvad, Ole; Haberka, Maciej; Vassilikos, Vassilios P; Maggioni, Aldo P; Boriani, Giuseppe; Lip, Gregory Y H

    2017-12-01

    Despite oral anticoagulation being highly effective in reducing stroke and thromboembolism, patients with atrial fibrillation (AF) still have a significant residual excess in mortality risk. Additional management strategies are needed to reduce the mortality risk seen in AF patients. Ancillary analysis from the EURObservational Research Programme Atrial Fibrillation (EORP-AF) General Pilot Registry, to evaluate 1-year outcomes in AF patients according to statin use at baseline. Of 2636 patients, 1286 (48.8%) patients used statins at baseline. Patients prescribed statins had more comorbidities. At 1-year follow-up, logistic regression analysis adjusted for AF type, symptomatic status and CHA2DS2-VASc score demonstrated that statin use was inversely associated with CV death (odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.30-0.82, p<0.0001), all-cause death (OR: 0.52, 95% CI: 0.37-0.73, p<0.0001) and the composite outcome of CV death/any thromboembolic event/bleeding (OR: 0.71, 95% CI: 0.52-0.98, p<0.0001). Similar findings were observed for 'high risk' subgroups including the elderly, primary prevention and high thromboembolic risk AF patients. Survival analysis showed that statins prescribed patients had a lower risk of all-cause death at follow-up (p=0.0433). Multivariate Cox regression analysis found that statin use remained independently associated with a lower risk for all-cause death (hazard ratio [HR]: 0.61, 95% CI: 0.42-0.88, p=0.0077). Statin use in AF patients was associated with improved outcomes, with an independent association with a lower risk of all-cause death at 1-year follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

    NASA Technical Reports Server (NTRS)

    Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

    2008-01-01

    A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

  6. Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

    PubMed Central

    Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

    2009-01-01

    MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

  7. Interaction between Subunits of Heterodimeric Splicing Factor U2AF Is Essential In Vivo

    PubMed Central

    Rudner, David Z.; Kanaar, Roland; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The heterodimeric pre-mRNA splicing factor, U2AF (U2 snRNP auxiliary factor), plays a critical role in 3′ splice site selection. Although the U2AF subunits associate in a tight complex, biochemical experiments designed to address the requirement for both subunits in splicing have yielded conflicting results. We have taken a genetic approach to assess the requirement for the Drosophila U2AF heterodimer in vivo. We developed a novel Escherichia coli copurification assay to map the domain on the Drosophila U2AF large subunit (dU2AF50) that interacts with the Drosophila small subunit (dU2AF38). A 28-amino-acid fragment on dU2AF50 that is both necessary and sufficient for interaction with dU2AF38 was identified. Using the copurification assay, we scanned this 28-amino-acid interaction domain for mutations that abrogate heterodimer formation. A collection of these dU2AF50 point mutants was then tested in vivo for genetic complementation of a recessive lethal dU2AF50 allele. A mutation that completely abolished interaction with dU2AF38 was incapable of complementation, whereas dU2AF50 mutations that did not effect heterodimer formation rescued the recessive lethal dU2AF50 allele. Analysis of heterodimer formation in embryo extracts derived from these interaction mutant lines revealed a perfect correlation between the efficiency of subunit association and the ability to complement the dU2AF50 recessive lethal allele. These data indicate that Drosophila U2AF heterodimer formation is essential for viability in vivo, consistent with a requirement for both subunits in splicing in vitro. PMID:9528748

  8. Variation of B1 gene and AF146527 repeat element copy numbers according to Toxoplasma gondii strains assessed using real-time quantitative PCR.

    PubMed

    Costa, Jean-Marc; Bretagne, Stéphane

    2012-04-01

    Using the multicopy B1 gene and AF146527 element for the amplification of Toxoplasma gondii DNA raises the issue of reliable quantification for clinical diagnosis. We applied relative quantification to reference strains using the single-copy P30 gene as a reference. According to the parasite type, the copy numbers for the B1 gene and AF146527 element were found to be 5 to 12 and 4 to 8 times lower than the previous estimations of 35 and 230 copies, respectively.

  9. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

    Chow, R.; Spragge, M.K.; Loomis, G.E.; Rainer, F.; Ward, R.; Thomas, I.M.; Kozlowski, M.R.

    1993-11-01

    Anti-reflective coatings made with Teflon AF2400 had the highest damage thresholds recorded for physical vapor deposited coatings at the Lawrence Livermore National Laboratory damage facility. Physical vapor deposited layers of Teflon AF2400, a perfluorinated amorphous polymer, maintained the bulk optical properties of a high transmittance from 200 nm to 1600 nm, and a low refractive index. In addition, the refractive index can be intentionally reduced by control of two common deposition parameters, deposition rate and substrate temperature. Scanning electron microscopy and nuclear magnetic resonance observations indicated that morphological changes caused the variations in the refractive index rather than compositional changes. The coatings adhered to fused silica and silicon wafers under normal laboratory handling conditions.

  10. Gymnasterkoreaynes A-F, cytotoxic polyacetylenes from Gymnaster koraiensis.

    PubMed

    Jung, Hyun-Ju; Min, Byung-Sun; Park, Jin-Young; Kim, Young-Ho; Lee, Hyeong-Kyu; Bae, Ki-Hwan

    2002-06-01

    Six new polyacetylenes, gymnasterkoreaynes A-F (1-6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using the L1210 tumor cell line as a model for cytotoxicity. The structures of compounds 1-6 were established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes A-F (1-6) are linear diacetylenes and are structurally related to falcarinol, panaxynol, panaxydiol, and panaxytriol. Of the compounds isolated, gymnasterkoreaynes B (2), C (3), F (6), and 1,9,16-heptadecatrien-4,6-diyn-3,8-diol (8) exhibited significant cytotoxicity against L1210 tumor cells with ED(50) values of 0.12-3.3 microg/mL.

  11. Adiabatic Compression Sensitivity of AF-M315E

    DTIC Science & Technology

    2015-07-01

    products of HAN (hydroxylammonium nitrate) based propellants such as AF-M315E are nitric acid and NOx gases. The presence of excess acids causes... Propellant Infusion Mission (GPIM) program. As the propulsion system developed by Aerojet- Rocketdyne for this propellant advances in maturity, studies...have been undertaken to address the knowledge gaps in the adiabatic compression sensitivity of the propellant as it relates to the system parameters for

  12. A Companion to the Eclipsing Variable AF Arietis

    NASA Astrophysics Data System (ADS)

    Ahad, Abdul

    2015-01-01

    In this paper the eclipsing variable star AF Arietis is shown to have a wide 12th magnitude companion, currently not included in the WDS catalog. The identified component appears to be following the same space motion as the 6th magnitude AB eclipsing pair and is situated at a broadly similar spectral distance from Earth, which suggest it might be a physical member of the system.

  13. Improved AF Squadron Command Structure for Leadership, Accountability, and Efficiency

    DTIC Science & Technology

    2011-04-20

    of Defense respectively focus on span of control. The concept of span of control was developed in 1922 by Sir Ian Hamilton based on the assumption...For the AF, this means squadrons must be organized across a wing to minimize inconsistency within units as well as across them. A study by Dewar ... Dewar , Robert D., and Simet, Donald P. “A Level Specific Prediction of Spans of Control Examining the Effects of Size, Technology, and

  14. Installation Restoration Program. Records Search, Newark AFS, Ohio

    DTIC Science & Technology

    1985-04-01

    plants. In this assignment and all that follow, a part of each was spent in conducting health and environment compliance inspections and audits at mili...OH 434&33 EiLO)( 2 bJATEP SYSTE-M, KTTC𔃻EN TAP, ’DATE: 76-P6-16*’.TI- E: 1304.1, APPEA0AfJCE OF SbmPLE CLEAR, TEA;:, 72 I PFE -ULTS OF ANALYS15 C T

  15. The M4.5V flare star AF Psc as seen in K2 engineering data

    NASA Astrophysics Data System (ADS)

    Ramsay, Gavin; Doyle, J. Gerry

    2014-08-01

    We present the light curve of the little studied flare star AF Psc (M4.5V) obtained using engineering data from the K2 mission. Data were obtained in long-cadence mode giving an effective exposure of 29 min and nearly 9 d of coverage. A clear modulation on a period of 1.08 d was seen which is the signature of the stellar rotation period. We identify 14 flares in the light curve, with the most luminous flares apparently coming from the same active region. We compare the flare characteristics of AF Psc to two M4V flare stars studied using Kepler data. The K2 mission will present a unique opportunity to study the rotation and flare properties of late-type dwarf stars with different ages and mass.

  16. Genomic functions of U2AF in constitutive and regulated splicing.

    PubMed

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

    The U2AF heterodimer is generally accepted to play a vital role in defining functional 3' splice sites in pre-mRNA splicing. Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors to further understand their regulatory functions in RNA metabolism in both physiological and disease settings. We recently reported that U2AF has a maximal capacity to directly bind ˜88% of functional 3' splice sites in the human genome and that numerous U2AF binding events also occur in various exonic and intronic locations, thus providing additional mechanisms for the regulation of alternative splicing besides their traditional role in titrating weak splice sites in the cell. These findings, coupled with the existence of multiple related proteins to both U2AF65 and U2AF35, beg a series of questions on the universal role of U2AF in functional 3' splice site definition, their binding specificities in vivo, potential mechanisms to bypass their requirement for certain intron removal events, contribution of splicing-independent functions of U2AF to important cellular functions, and the mechanism for U2AF mutations to invoke specific diseases in humans.

  17. Alternative splicing of U2AF1 reveals a shared repression mechanism for duplicated exons

    PubMed Central

    Kralovicova, Jana; Vorechovsky, Igor

    2017-01-01

    The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab. Each BP lacked canonical uridines at position -2 relative to the BP adenines, with efficient U2 base-pairing interactions predicted only for shifted registers reminiscent of programmed ribosomal frameshifting. The BP cluster was compensated by interactions involving unpaired cytosines in an upstream, EvoFold-predicted stem loop (termed ESL) that binds FUBP1/2. Exon Ab inclusion correlated with predicted free energies of mutant ESLs, suggesting that the ESL operates as a conserved rheostat between long inverted repeats upstream of each exon. The isoform-specific U2AF35 expression was U2AF65-dependent, required interactions between the U2AF-homology motif (UHM) and the α6 helix of U2AF35, and was fine-tuned by exon Ab/3 variants. Finally, we identify tandem homologous exons regulated by U2AF and show that their preferential responses to U2AF65-related proteins and SRSF3 are associated with unpaired pre-mRNA segments upstream of U2AF-repressed 3′ss. These results provide new insights into tissue-specific subfunctionalization of duplicated exons in vertebrate evolution and expand the repertoire of exon repression mechanisms that control alternative splicing. PMID:27566151

  18. Chinae, ROK AFS K-10, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1968-04-10

    34 . T2 A . : . . . . T .I’-.E (S ! . I . . A ._-" ., " ," . . . " ("L .- 2 i* * - * . ,. - . . S IF ......... MEA ..2 .’ TP ] ?RC C *C 2• . .. .:.. . , C...FVILLE. N. C. 2e,01 43?-78 Ch[NNhAE KCREA/ PCV AFS K-1 51-54956-61,64-C7 _ ’___ PERCENTAGE FREQUENCY OF OCCURRENCE L-- 7. (FROM HOURLY OBSERVATIONS

  19. Relation of atrial fibrillation (AF) and change of lipoproteins: male patients with AF exhibited severe pro-inflammatory and pro-atherogenic properties in lipoproteins.

    PubMed

    Kim, Seong-Min; Kim, Jong-Min; Shin, Dong-Gu; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2014-07-01

    This study was designed to search putative biomarkers for detection of relatively young-onset atrial fibrillation (AF). We analyzed serum lipoproteins from male patients with paroxysmal AF (48±9years old, n=29) and controls with similar age (50±10years old, n=27), who visited our hospital for radiofrequency catheter ablation due to paroxysmal supraventricular tachycardia. Although the AF group showed normal serum cholesterol level, they exhibited 16% lower HDL-cholesterol and 13% higher serum cholesteryl ester transfer protein activity than those of the control group. The AF group showed elevated levels of serum triglyceride (TG) and C-reactive protein with hyperuricemia. However, there was no difference between serum levels of creatinine, troponin I, and serum amyloid A. All lipoproteins from the AF group contained higher level of TG, oxidized species, and advanced glycated end products. LDL from the AF group (AF-LDL) showed 2.7-fold more content of malondialdehyde than the control group (p<0.04) and exhibited higher sensitivity of oxidation. HDL-associated paraoxonase from the AF group showed impaired antioxidant ability and lowered expressional level of apoA-I (p<0.01) and paraoxonase (p<0.005) in HDL3. Lipoprotein properties were severely impaired in the AF group with increased extent of oxidation and inflammation. The modified lipoprotein properties with impaired antioxidant functions can be used as a putative biomarker for prognostic detection for the relatively young onset AF. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Cloning and Characterization of Rainbow Trout Interleukin-17A/F2 (IL-17A/F2) and IL-17 Receptor A: Expression during Infection and Bioactivity of Recombinant IL-17A/F2

    PubMed Central

    Wang, Tiehui; Holland, Jason W.; Zou, Jun; Secombes, Christopher J.

    2013-01-01

    Lower vertebrates have been found to possess genes that have similar homology to both interleukin (IL)-17A and IL-17F, which have been termed IL-17A/F. In fish species, several of these genes can be present, but, to date, very little is known about their functional activity. This article describes the discovery and sequence analysis of a rainbow trout (Oncorhynchus mykiss) IL-17A/F2 molecule and an IL-17RA receptor. In addition, the bioactivity of the trout IL-17A/F2 is investigated for the first time in any species. The predicted IL-17A/F2 and IL-17RA proteins consist of 146 and 966 amino acids (aa), respectively, with both molecules containing conserved family motifs. Expression analysis revealed high constitutive expression of trout IL-17A/F2 in mucosal tissues from healthy fish, suggesting a potential role in mucosal immunity. When the modulation of IL-17A/F2 and IL-17RA in vitro was analyzed, it was observed that the two molecules were similarly affected. The expression of IL-17A/F2 was also induced in head kidney during bacterial, parasitic, and viral infections, revealing a possible function in defense against such pathogens. However, downregulation of IL-17RA was seen in some tissues and infections. The recombinant IL-17A/F2 protein was produced in Escherichia coli and was found to affect the expression of an antimicrobial peptide and the proinflammatory cytokines IL-6 and IL-8 in splenocytes. Consistent with mammalian IL-17 homologues, our expression and bioactivity results imply that trout IL-17A/F2 plays an important role in promoting inflammatory and host innate immune responses directed against different pathogen groups. PMID:23147036

  1. Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

    PubMed

    Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

    2016-09-28

    Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

  2. Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in Vitro

    PubMed Central

    Li, Yin; Burns, Katherine A.; Arao, Yukitomo; Luh, Colin J.

    2012-01-01

    Background: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. Objectives: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) α and ERβ. Methods: We used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERα and ERβ. Ishikawa/ERα stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. Results: The three EDCs showed strong estrogenic activity as agonists for ERα in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERα in Ishikawa cells and BPAF acted as an antagonist for ERβ in HeLa cells, whereas Zea was only a partial antagonist for ERα. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERα, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERα target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. Conclusion: BPA and BPAF can function as EDCs by acting as cell type–specific agonists (≥ 10 nM) or antagonists (≤ 10 nM) for ERα and ERβ. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ERα. In addition, all three compounds induced the rapid action-mediated response for ERα. PMID:22494775

  3. AFS dynamics in a short-lived active region

    NASA Astrophysics Data System (ADS)

    Zuccarello, F.; Battiato, V.; Contarino, L.; Romano, P.; Spadaro, D.; Vlahos, L.

    2005-11-01

    In the framework of the study on active region emergence, we report the results obtained from the analysis of the short-lived (7 days) active region NOAA 10407. The data used were acquired during an observational campaign carried out with the THEMIS telescope in IPM mode in July 2003, coordinated with other ground- and space-based instruments (INAF-OACT, DOT, BBSO, MDI/SOHO, EIT/SOHO, TRACE). We determined the morphological and magnetic evolution of NOAA 10407, as well as the velocity fields associated with its magnetic structures. Within the limits imposed by the spatial and temporal resolution of the images analyzed, the first evidence of the active region formation is initially observed in the transition region and lower corona, and later on (i.e. after about 7 h) in the inner layers, as found in a previous analysis concerning a long-lived, recurrent active region. The results also indicate that the AFS formed in the active region shows typical upward motion at the AFS's tops and downward motion at the footpoints. The velocity values relevant to the upward motions decrease over the evolution of the region, similarly to the case of the recurrent active region, while we notice an increasing trend in the downflow velocity during the early phases of the time interval analyzed by THEMIS. On the other hand, the AFS preceding legs show a higher downflow than the following ones, a result in contrast with that found in the long-lived active region. The chromospheric area overhanging the sunspot umbra shows an upward motion of ˜ 2 km s-1, while that above the pores shows a downward motion of ~4 km s-1.

  4. The Advancing State of AF-M315E Technology

    NASA Technical Reports Server (NTRS)

    Masse, Robert; Spores, Ronald A.; McLean, Chris

    2014-01-01

    The culmination of twenty years of applied research in hydroxyl ammonium nitrate (HAN)-based monopropellants, the NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) will achieve the first on-orbit demonstration of an operational AF-M315E green propellant propulsion system by the end of 2015. Following an contextual overview of the completed flight design of the GPIM propellant storage and feed system, results of first operation of a flight-representative heavyweight 20-N engineering model thruster (to be conducted in mid-2014) are presented with performance comparisons to prior lab model (heavyweight) test articles.

  5. Vulnus Cordis. Heart Suture. (Vulnus Cordis. Sutur af Hjertet),

    DTIC Science & Technology

    1977-10-12

    AD—A0’s6 830 ARMY MEDICAL INTELLIGENCE AND INFORMATION AGENCY WAS— ETC F/S 6/5 VULNUS CORalS. HEART SUTURE. (VULNUS CORDIS. SUTUR AF HJERTET),(U) OCT...Translated . ~~~~~~~ 285-288 ? ~ X J t~TU1~ Publisher: Date/Place Publication: 1896 Distribution Statement: S . 2~~1I9~ — I Vulnus cordis. Heart suture...Article by A. Cappelen, resident physician Norsk Meg, f. Laegevidensk. 11: 285—288, 1896. That ‘wounds of the heart should become th. object of surgical

  6. NMR study of the AF-SC-SC-AF phased transition in a pnictide superconductor LaFeAsO1-xHx

    NASA Astrophysics Data System (ADS)

    Fujiwara, Naoki; Sakurai, Ryosuke; Iimura, Soushi; Matsuishi, Satoru; Hosono, Hideo; Yamakawa, Youichi; Kontani, Hiroshi

    2014-03-01

    We have performed 75As and 1H NMR measurements in LaFeAsO1xHx, an isomorphic compound of LaFeAsO1xFx. LaFeAsO1xHx is an electron doped system, and O2- can be replaced with H- up to x = 0.5. LaFeAsO1xHx is known for having double superconducting (SC) domes on H doping. Recently, we discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric AF-SC-SC-AF phase alignment in the electronic phase diagram Unlike the AF ordering in the lightly H-doped regime, the AF ordering in the highly H-doped regime is attributed to the nesting between electron pockets. In the conference, we will show the data of both NMR spectra and the relaxation rate 1/T1 in the whole doping region. We will discuss the difference of electronic states between the lightly H-doped AF-SC phases and highly H-doped SC-AF phases. This work is supported by a Grant-in-Aid (Grant No. KAKENHI 23340101) from the Ministry of Education, Science, and Culture, Japan.

  7. Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

    PubMed

    Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

    2000-11-01

    A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

  8. AFS men and women differ most in their lifestyle choices

    USGS Publications Warehouse

    Connelly, N.A.; Brown, T.L.; Hardiman, J.M.

    2006-01-01

    The American Fisheries Society sponsored a survey to examine the career development choices of men and women and how they might differ by gender. A random sample of 700 men and 700 women was selected from the AFS membership database. The survey was mailed out in October 2004 and 991 questionnaires were returned for an adjusted response rate of 71%. Some differences exist between men and women in the areas of interest development, education, and employment, but the substantive differences occur in lifestyle choices. Women with a fisheries career are less likely to be married than men, even when age is controlled for, and women who are married are more likely to have dual-career considerations than their male counterparts. Among respondents without dependents in their home during their professional career, twice as many women as men think having children will adversely affect their career. For those with dependents, more than twice as many women as men said they had to put their career "on hold" because of their dependents. While AFS members do not represent all members of the fisheries profession, their experiences shed substantial light on the lifestyle choices likely faced by most members of the profession.

  9. Automation under suspicion--case flight AF-447 Air France.

    PubMed

    Martins, Edgard; Soares, Marcelo

    2012-01-01

    The probes allow the pilot to control the aircraft speed was essential to the balance of the flight. Opinions of experts who claim that "the design of the plane would have exercised a not inconsiderable role in the occurrence of a disaster." These messages revealed a series of important operating errors in a zone of turbulence, "making the plane uncontrollable, leading to a rapid depressurization device, according to these reports. A lawsuit in Toulouse and in Brazil aims to recognition of the liability of Air France and Airbus not insignificant role in the design and operation of the aircraft in the event of catastrophe. Opinions are taken from senior pilots that no commercial aviation training for certain situations abnormal flight that, if realized, could have influenced the pilots of the AF-447 to remove the plane's fatal dive show what experiments performed in simulators for military pilots, who are permanently subject to critical flight situations.

  10. Seladoeflavones A-F, six novel flavonoids from Selaginella doederleinii.

    PubMed

    Zou, ZhenXing; Xu, KangPing; Xu, PingSheng; Li, XiaoMin; Cheng, Fei; Li, Jing; Yu, Xia; Cao, DongSheng; Li, Dan; Zeng, Wei; Zhang, GuoGang; Tan, GuiShan

    2017-01-01

    Six new flavonoids, seladoeflavones A-F (1-6), were isolated from the whole herbs of Selaginella doederleinii, together with one known flavonoid (7). Their structures including absolute configuration were characterized on the basis of extensive spectroscopic methods including NMR, HRMS, and electronic circular dichroism (ECD). All compounds consist of an aryl substituent at the C-3' position of naringenin or apigenin skeletons, and compounds 1 and 6 were identified as R configurations, which are uncommonly encountered in nature. A possible biosynthetic pathway was postulated. In addition, bioassay of the isolates revealed that 5-7 exhibited moderate cytotoxicity against three human cancer cell lines NCI-H460, A549, and K562 in vitro with IC50 values ranging from 8.17 to 18.66μM.

  11. Optimised secure transmission through untrusted AF relays using link adaptation

    NASA Astrophysics Data System (ADS)

    Taki, Mehrdad; Sadeghi, Mohammad

    2016-05-01

    A new transmission scheme is presented for a two-hop relay network including two AF relays, considering physical layer security where relays are not able to detect signal with an acceptable bit error rate (BER) but the combined received signal is detected with an acceptable BER at the final receiver. It is assumed that there is no direct path between the transmitter and the receiver (relay network without diversity). Adaptive modulation and coding is utilised at the transmitter and transmission powers of the transmitter and of the relays are continuously adapted provisioning individual average power constraint for each node. Numerical evaluations show that an acceptable performance degradation is seen by the proposed secure relaying scheme compared to the optimum relay selection scheme without security constraint.

  12. Installation-restoration program. Records search, Newark AFS, Ohio

    SciTech Connect

    Not Available

    1985-04-01

    Since 1962, many hazardous and potentially hazardous wastes have been generated by industrial operations in Building 4 at Newark AFS. Dirty freon is recycled through a recovery still inside the building and reused. A beryllium dust collection system is located on the east side of Building 4. The collected dust is encapsulated in cement and sent off-station for disposal. Twelve hazardous materials storage or staging areas were identified. During interviews, it was determined that large quantities of dirty freon had been dumped along the entire perimeter fence line and in particular two specific locations. An additional spill site was located in the area at the north-east corner of Building 4 near the location of the virgin freon tanks. An unknown amount of spent battery acid and spent solvents were spilled in this area between 1962 and 1964.

  13. Rationale for and design of the CREATIVE-AF trial: randomized, double-blind, placebo-controlled, crossover study of the effect of irbesartan on oxidative stress and adhesion molecules in patients with persistent atrial fibrillation.

    PubMed

    Goette, Andreas; D'Alessandro, Alessandra; Bukowska, Alicja; Kropf, Siegfried; Mewis, Christian; Stellbrink, Christoph; Tebbenjohanns, Jürgen; Weiss, Christian; Lendeckel, Uwe

    2008-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. Recent studies suggest there is an angiotensin II-dependent increase in adhesion molecules and oxidative stress parameters during AF. These alterations appear to contribute to inflammatory and prothrombotic changes in the atrial endocardium ('endocardial remodelling'), suggesting that patients with increased levels of these factors might be at risk of thromboembolic events. The purpose of the CREATIVE-AF (Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients with Persistent Atrial Fibrillation) trial is to prove the principle concept that blockade of angiotensin II type 1 receptors by irbesartan reduces levels of circulating adhesion molecules and oxidative stress parameters in patients with persistent AF by 25% compared with placebo. This is a prospective, randomized, double-blind, placebo-controlled, crossover study in patients with persistent/permanent AF. A total of 60 patients are planned to be included in the study. Patients will receive placebo and irbesartan therapy for 9 weeks each. Levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1), inflammatory markers (high sensitivity C-reactive protein, monocyte chemoattractant protein-1, von Willebrand factor, tumour growth factor-beta1, tumour necrosis factor-alpha, interleukin-6) and oxidative stress parameters (8-iso-prostaglandin F2alpha) will be determined after each treatment phase and compared with baseline levels. Angiotensin II type 1 receptor antagonists may help reduce levels of circulating adhesion molecules and oxidative stress parameters in patients with persistent AF. This article summarizes the rationale and design of the CREATIVE-AF trial, which has been designed to test this hypothesis.

  14. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    DTIC Science & Technology

    2015-10-01

    compared to U2AF1(WT) mice. U2AF1(S34F) stem cells are at a competitive disadvantage compared to control cells, suggesting that the increase in HSC cell...cell proliferation) in KLS cells compared to controls (pɘ.05, n=8-13). Competitive repopulation studies show a disadvantage for bone marrow cells

  15. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., refined oil; cotton, undelinted seed. (b) Aspergillus flavus AF36 is temporarily exempt from the... flavis AF 36 is temporarily exempt from the requirement of a tolerance on corn, field, forage; corn, field, grain; corn, field, stover; corn, pop, grain; corn, pop, stover; corn, sweet, forage; corn, sweet...

  16. Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

    USDA-ARS?s Scientific Manuscript database

    The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

  17. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the issues to potential environmental impacts. AF Form 813 must be retained with the EA or EIS to record the focusing of environmental issues. ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact...

  18. A Conditional Role of U2AF in Splicing of Introns with Unconventional Polypyrimidine Tracts▿ †

    PubMed Central

    Sridharan, Vinod; Singh, Ravinder

    2007-01-01

    Recognition of polypyrimidine (Py) tracts typically present between the branch point and the 3′ splice site by the large subunit of the essential splicing factor U2AF is a key early step in pre-mRNA splicing. Diverse intronic sequence arrangements exist, however, including 3′ splice sites lacking recognizable Py tracts, which raises the question of how general the requirement for U2AF is for various intron architectures. Our analysis of fission yeast introns in vivo has unexpectedly revealed that whereas introns lacking Py tracts altogether remain dependent on both subunits of U2AF, introns with long Py tracts, unconventionally positioned upstream of branch points, are unaffected by U2AF inactivation. Nevertheless, mutation of these Py tracts causes strong dependence on the large subunit U2AF59. We also find that Py tract diversity influences the requirement for the conserved C-terminal domain of U2AF59 (RNA recognition motif 3), which has been implicated in protein-protein interactions with other splicing factors. Together, these results suggest that in addition to Py tract binding by U2AF, supplementary mechanisms of U2AF recruitment and 3′ splice site identification exist to accommodate diverse intron architectures, which have gone unappreciated in biochemical studies of model pre-mRNAs. PMID:17709389

  19. The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

    SciTech Connect

    Chornock, R.; Berger, E.; Zauderer, B. A.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Lunnan, R.; Marion, G. H.; Narayan, G.; Gezari, S.; Rest, A.; Riess, A. G.; Chomiuk, L.; Huber, M. E.; Lawrence, A.; and others

    2014-01-01

    We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

  20. The leukemogenic CALM/AF10 fusion protein alters the subcellular localization of the lymphoid regulator Ikaros.

    PubMed

    Greif, P A; Tizazu, B; Krause, A; Kremmer, E; Bohlander, S K

    2008-05-01

    The t(10;11)(p13;q14) translocation leads to the fusion of the CALM and AF10 genes. This translocation can be found as the sole cytogenetic abnormality in acute lymphoblastic leukemia, acute myeloid leukemia and in malignant lymphomas. The expression of CALM/AF10 in primary murine bone marrow cells results in the development of an aggressive leukemia in a murine bone marrow transplantation model. Using a yeast two-hybrid screen, we identified the lymphoid regulator Ikaros as an AF10 interacting protein. Interestingly, Ikaros is required for normal development of lymphocytes, and aberrant expression of Ikaros has been found in leukemia. In a murine model, the expression of a dominant negative isoform of Ikaros causes leukemias and lymphomas. The Ikaros interaction domain of AF10 was mapped to the leucine zipper domain of AF10, which is required for malignant transformation both by the CALM/AF10 and the MLL/AF10 fusion proteins. The interaction between AF10 and Ikaros was confirmed by GST pull down and co-immunoprecipitation. Coexpression of CALM/AF10 but not of AF10 alters the subcellular localization of Ikaros in murine fibroblasts. The transcriptional repressor activity of Ikaros is reduced by AF10. These results suggest that CALM/AF10 might interfere with normal Ikaros function, and thereby block lymphoid differentiation in CALM/AF10 positive leukemias.

  1. Type 2 diabetes mellitus and atrial fibrillation: From mechanisms to clinical practice.

    PubMed

    Tadic, Marijana; Cuspidi, Cesare

    2015-04-01

    Type 2 diabetes mellitus is one of the most common chronic conditions and its prevalence has increased continuously over the past decades, primarily due to the obesity epidemic. Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia in clinical practice and is associated with increased cardiovascular and cerebrovascular morbidity and mortality. Recent studies have shown that patients with diabetes have an increased risk of AF. However, the results about the relationship between diabetes and AF are still conflicting. Mechanisms that are responsible for an association between diabetes and AF, as well as the adequate treatment of AF in patients with diabetes, are still insufficiently studied. The aim of this review is to summarize the current knowledge of mechanisms that connect AF and diabetes, the clinical studies that include patients with both conditions, and the treatment options in modern pharmacology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial.

    PubMed

    Verma, Atul; Mantovan, Roberto; Macle, Laurent; De Martino, Guiseppe; Chen, Jian; Morillo, Carlos A; Novak, Paul; Calzolari, Vittorio; Guerra, Peter G; Nair, Girish; Torrecilla, Esteban G; Khaykin, Yaariv

    2010-06-01

    This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software. Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 +/- 10 years, LA size 42 +/- 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no mortality. In high

  3. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial†

    PubMed Central

    Verma, Atul; Mantovan, Roberto; Macle, Laurent; De Martino, Guiseppe; Chen, Jian; Morillo, Carlos A.; Novak, Paul; Calzolari, Vittorio; Guerra, Peter G.; Nair, Girish; Torrecilla, Esteban G.; Khaykin, Yaariv

    2010-01-01

    Aims This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software. Methods and results Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 ± 10 years, LA size 42 ± 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no

  4. Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair.

    PubMed

    Castaño, Julio; Herrero, Ana B; Bursen, Aldeheid; González, Federico; Marschalek, Rolf; Gutiérrez, Norma C; Menendez, Pablo

    2016-05-24

    The most frequent rearrangement of the human MLL gene fuses MLL to AF4 resulting in high-risk infant B-cell acute lymphoblastic leukemia (B-ALL). MLL fusions are also hallmark oncogenic events in secondary acute myeloid leukemia. They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. Conversely, the genome-wide mutational landscape in MLL-rearranged infant B-ALL has been reported silent. Thus, whether MLL fusions compromise the recognition and/or repair of DNA damage remains unanswered. Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. Accordingly, no differences were observed between WT, MA4- and A4M-expressing cells in the presence of master proteins involved in non-homologous end-joining (NHEJ; i.e.KU86, KU70), alternative-NHEJ (Alt-NHEJ; i.e.LigIIIa, WRN and PARP1), and homologous recombination (HR, i.e.RAD51). Moreover, functional assays revealed identical NHEJ and HR efficiency irrespective of the genotype. Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. Collectively, expression of MA4 or A4M does neither influence DNA signaling nor DNA-DSB repair.

  5. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  6. Argyrophilic nucleolar organizer regions (AgNORs) in odontogenic myxoma (OM) and ameloblastic fibroma (AF).

    PubMed

    Martins, C; Carvalho, Y R; do Carmo, M A

    2001-09-01

    Ten cases of odontogenic myxoma (OM) and six cases of ameloblastic fibroma (AF) were subjected to comparative analysis by the AgNOR technique, in order to determine a possible difference in cell proliferation index between these lesions. The mean AgNOR number of the mesenchymal component of AF was compared with its epithelial component and the difference was not found to be statistically significant. The mean AgNOR index of the AF group was significantly higher than that of the OM group. Moreover, the mesenchymal component of AF demonstrated increased AgNOR numbers compared with that of OM (P<0.05). These results suggest that the epithelial and mesenchymal components of AF may have similar cell proliferative activity. However, the cell proliferative index of this lesion seems to be higher than that of OM.

  7. Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

    PubMed Central

    Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

    2016-01-01

    Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

  8. [Design of an atrial fibrillation and embolic risk registry in Mexico: CARMEN-AF].

    PubMed

    González-Hermosillo, Jesús A; Márquez, Manlio F; Ocampo-Peña, Salvador

    Atrial fibrillation (AF) is one of the most common arrhythmias, and its prevalence increase with age. It is associated with high risk of stroke. The prevention of such thromboembolism is done with oral anticoagulants, which in our country seem to be underused. CARMEN-AF registry aims primarily to determine the current status of thromboprophylaxis of non-valvular AF in Mexico. A secondary objective is to know the morbidity and mortality associated with non-valvular AF in at least one year of follow-up. CARMEN-AF registry is an observational, longitudinal, multicenter, and national survey about the use of oral anticoagulants in patients with non-valvular AF. Patients 18years old or older, diagnosed with AF during the last 6months, and with at least one risk factor of thromboembolism based in the CHA2DS2-Vasc score are being selected. Demographic and clinical data will be collected during the visits to their usual clinic with a follow-up of 2years. The recruitment began on September 19, 2014, and the inclusion of the last patient is expected on September 18, 2016. According to the reported incidence of AF globally and taking into account the total Mexican population, the inclusion of 1,200 patients is estimated. The Atrial Fibrillation and Embolic Risk Registry (CARMEN-AF) will reveal the current status of thromboprophylaxis in patients with non-valvular AF, and will allow to get an overview of the national and international clinical practice guidelines accomplishment in this area. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  9. The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function.

    PubMed

    Jensen, Thomas; Elster, Lisbeth; Nielsen, Søren Møller; Poda, Suresh Babu; Loechel, Frosty; Volbracht, Christiane; Klewe, Ib Vestergaard; David, Laurent; Watson, Stephen P

    2014-11-15

    The identification of the novel and selective GPR3 inverse agonist AF64394, the first small molecule inhibitor of GPR3 receptor function, is described. Structure activity relationships and syntheses based around AF64394 are reported.

  10. Atrial Fibrillation, Type 2 Diabetes, and Non-Vitamin K Antagonist Oral Anticoagulants: A Review.

    PubMed

    Plitt, Anna; McGuire, Darren K; Giugliano, Robert P

    2017-04-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a 5-fold increase in the risk for stroke. Type 2 diabetes is an independent risk factor for both stroke and atrial fibrillation, and in the setting of AF, type 2 diabetes is independently associated with a 2% to 3.5% increase in absolute stroke rate per year. The overlap in the pathophysiologies of AF and type 2 diabetes are not well understood, and current practice guidelines provide few recommendations regarding patients with both conditions. In this article, we review the epidemiology and pathophysiology of the nexus of AF and type 2 diabetes. Furthermore, we analyze the subgroup of patients with type 2 diabetes enrolled in phase 3 clinical trials of non-vitamin K antagonist oral anticoagulants in prevention of arterial thromboembolism in AF, highlighting the greater absolute benefit of non-vitamin K oral anticoagulants in patients with type 2 diabetes. Finally, we offer recommendations on risk stratification and therapy for patients with concomitant AF and type 2 diabetes. We highlight the increased thromboembolic risk with coexisting AF and type 2 diabetes. We recommend that further studies be done to evaluate the potential benefits of anticoagulation for all patients who have both and the potential for non-vitamin K oral anticoagulants to have greater benefits than risks over vitamin K antagonists.

  11. The relationship between circulating irisin levels and tissues AGE accumulation in type 2 diabetes patients.

    PubMed

    Li, Zhu; Wang, Gang; Zhu, Yan-Juan; Li, Chen-Guang; Tang, Yun-Zhao; Jiang, Zhen-Huan; Yang, Min; Ni, Chang-Lin; Chen, Li-Ming; Niu, Wen-Yan

    2017-06-30

    Advanced glycation end-products (AGEs), measured by skin autofluorescence (AF), are a factor in the development or worsening of many degenerative diseases, such as diabetes and atherosclerosis. Irisin levels have been associated with diabetes, endothelial dysfunction and atherosclerosis. The objective of the present study was to investigate whether circulating irisin levels are correlated with skin AF values in type 2 diabetes patients. A total of 362 Chinese type 2 diabetic patients and 100 age- and sex-matched healthy controls were recruited in the present study. Clinical characteristics, blood biochemistry and circulating irisin levels were measured. Skin AF was measured using an AGE reader. Circulating irisin levels were significantly lower, while skin AF values were increased in type 2 diabetes compared with controls (P<0.05 respectively). By dividing the distribution of skin AF values into tertiles, serum irisin levels gradually lowered with increasing skin AF values (P<0.05). After adjusting for covariates, multivariate stepwise regression analysis demonstrated that serum lower irisin levels were independently associated with skin AF (P=0.009). Circulating irisin levels were lower in type 2 diabetes patients compared with healthy controls. Lower levels of irisin are independently associated with elevated skin AF values, indicating that circulating irisin levels could be associated with AGEs accumulation, which is one of the reasons causing vascular complications in diabetic patients. © 2017 The Author(s).

  12. Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.

    PubMed

    Glasser, Eliezra; Agrawal, Anant A; Jenkins, Jermaine L; Kielkopf, Clara L

    2017-09-12

    Acquired point mutations of pre-mRNA splicing factors recur among cancers, leukemias, and related neoplasms. Several studies have established that somatic mutations of a U2AF1 subunit, which normally recognizes 3' splice site junctions, recur among myelodysplastic syndromes. The U2AF2 splicing factor recognizes polypyrimidine signals that precede most 3' splice sites as a heterodimer with U2AF1. In contrast with those of the well-studied U2AF1 subunit, descriptions of cancer-relevant U2AF2 mutations and their structural relationships are lacking. Here, we survey databases of cancer-associated mutations and identify recurring missense mutations in the U2AF2 gene. We determine ultra-high-resolution structures of the U2AF2 RNA recognition motifs (RRM1 and RRM2) at 1.1 Å resolution and map the structural locations of the mutated U2AF2 residues. Comparison with prior, lower-resolution structures of the tandem U2AF2 RRMs in the RNA-bound and apo states reveals clusters of cancer-associated mutations at the U2AF2 RRM-RNA or apo-RRM1-RRM2 interfaces. Although the role of U2AF2 mutations in malignant transformation remains uncertain, our results show that cancer-associated mutations correlate with functionally important surfaces of the U2AF2 splicing factor.

  13. RNA Induces Conformational Changes in the SF1/U2AF65 Splicing Factor Complex

    PubMed Central

    Gupta, Ankit; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2010-01-01

    Spliceosomes assemble on pre-mRNA splice sites through a series of dynamic ribonucleoprotein complexes, yet the nature of the conformational changes remains unclear. Splicing Factor 1 (SF1) and U2 Auxiliary Factor (U2AF65) cooperatively recognize the 3’ splice site during the initial stages of pre-mRNA splicing. Here, we used small-angle X-ray scattering to compare the molecular dimensions and ab initio shape restorations of SF1 and U2AF65 splicing factors, as well as the SF1/U2AF65 complex in the absence and presence of AdML splice site RNAs. The molecular dimensions of the SF1/U2AF65/RNA complex substantially contracted by 15 Å in the maximum dimension, relative to the SF1/U2AF65 complex in the absence of RNA ligand. In contrast, no detectable changes were observed for the isolated SF1 and U2AF65 splicing factors or their individual complexes with RNA, although slight differences in the shapes of their molecular envelopes were apparent. We propose that the conformational changes that are induced by assembly of the SF1/U2AF65/RNA complex serve to position the pre-mRNA splice site optimally for subsequent stages of splicing. PMID:21146534

  14. RNA induces conformational changes in the SF1/U2AF65 splicing factor complex.

    PubMed

    Gupta, Ankit; Jenkins, Jermaine L; Kielkopf, Clara L

    2011-02-04

    Spliceosomes assemble on pre-mRNA splice sites through a series of dynamic ribonucleoprotein complexes, yet the nature of the conformational changes remains unclear. Splicing factor 1 (SF1) and U2 auxiliary factor (U2AF(65)) cooperatively recognize the 3' splice site during the initial stages of pre-mRNA splicing. Here, we used small-angle X-ray scattering to compare the molecular dimensions and ab initio shape restorations of SF1 and U2AF(65) splicing factors, as well as the SF1/U2AF(65) complex in the absence and presence of AdML (adenovirus major late) splice site RNAs. The molecular dimensions of the SF1/U2AF(65)/RNA complex substantially contracted by 15 Å in the maximum dimension, relative to the SF1/U2AF(65) complex in the absence of RNA ligand. In contrast, no detectable changes were observed for the isolated SF1 and U2AF(65) splicing factors or their individual complexes with RNA, although slight differences in the shapes of their molecular envelopes were apparent. We propose that the conformational changes that are induced by assembly of the SF1/U2AF(65)/RNA complex serve to position the pre-mRNA splice site optimally for subsequent stages of splicing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Does Type D Personality Impact on the Prognosis of Patients Who Underwent Catheter Ablation for Atrial Fibrillation? A 1-Year Follow-Up Study

    PubMed Central

    Jeon, Sang Won; Lim, Hong Euy; Yoon, Seoyoung; Na, Kyoung Se; Joe, Sook-Haeng; Kim, Young-Hoon

    2017-01-01

    Objective Although Type D personality has been associated with the prognosis of various cardiac diseases, few studies have investigated the influence of Type D personality on the cardiac and psychiatric prognoses of patients with atrial fibrillation (AF). Methods Depression, anxiety, and quality of life were measured at baseline and 6 months. The recurrence of AF was measured during 1-year following radiofrequency catheter ablation (RFCA) for AF. The Kaplan-Meier method with log-rank tests were used to compare the cumulative recurrence of AF. ACox proportional hazard model was conducted to identify factors that contribute to the recurrence of AF. Results A total of 236 patients admitted for RFCA were recruited. Patients with a Type D personality had higher levels of depression and anxiety and a poorer quality of life compared to controls. Although depression, anxiety, and quality of life had improved 6 months after RFCA, significant differences in psychiatric symptoms remained between patients with and without Type D personality. In the Cox models, the type of AF was the only factor that influenced the recurrence of AF. Conclusion Our results suggest that Type D personality predominately influences psychological distress in patients with AF, but not the recurrence of AF. PMID:28539946

  16. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF

    PubMed Central

    DeVore, Adam D.; Hellkamp, Anne S.; Becker, Richard C.; Berkowitz, Scott D.; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Nessel, Christopher C.; Singer, Daniel E.; Fox, Keith A. A.; Patel, Manesh R.; Piccini, Jonathan P.

    2016-01-01

    Aims The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. Methods and results The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Conclusion Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. PMID:27174904

  17. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF.

    PubMed

    DeVore, Adam D; Hellkamp, Anne S; Becker, Richard C; Berkowitz, Scott D; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R; Piccini, Jonathan P

    2016-08-01

    The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29-1.66], diabetes [1.22, (1.11-1.34)], prior MI [1.27, (1.13-1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04-1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  18. Doppler images and the underlying dynamo. The case of AF Leporis

    NASA Astrophysics Data System (ADS)

    Järvinen, S. P.; Arlt, R.; Hackman, T.; Marsden, S. C.; Küker, M.; Ilyin, I. V.; Berdyugina, S. V.; Strassmeier, K. G.; Waite, I. A.

    2015-02-01

    Context. The (Zeeman-)Doppler imaging studies of solar-type stars very often reveal large high-latitude spots. This also includes F stars that possess relatively shallow convection zones, indicating that the dynamo operating in these stars differs from the solar dynamo. Aims: We aim to determine whether mean-field dynamo models of late-F type dwarf stars can reproduce the surface features recovered in Doppler maps. In particular, we wish to test whether the models can reproduce the high-latitude spots observed on some F dwarfs. Methods: The photometric inversions and the surface temperature maps of AF Lep were obtained using the Occamian-approach inversion technique. Low signal-to-noise spectroscopic data were improved by applying the least-squares deconvolution method. The locations of strong magnetic flux in the stellar tachocline as well as the surface fields obtained from mean-field dynamo solutions were compared with the observed surface temperature maps. Results: The photometric record of AF Lep reveals both long- and short-term variability. However, the current data set is too short for cycle-length estimates. From the photometry, we have determined the rotation period of the star to be 0.9660 ± 0.0023 days. The surface temperature maps show a dominant, but evolving, high-latitude (around +65°) spot. Detailed study of the photometry reveals that sometimes the spot coverage varies only marginally over a long time, and at other times it varies rapidly. Of a suite of dynamo models, the model with a radiative interior rotating as fast as the convection zone at the equator delivered the highest compatibility with the obtained Doppler images. Partially based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofísica de Canarias.Based partly on STELLA SES data.Tables 1-3 and Figs. 7-14 are available in

  19. Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

    PubMed

    Kim, M H; Lin, J; Hussein, M; Battleman, D

    2009-12-01

    Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on

  20. Mutations in the small subunit of the Drosophila U2AF splicing factor cause lethality and developmental defects.

    PubMed

    Rudner, D Z; Kanaar, R; Breger, K S; Rio, D C

    1996-09-17

    The essential eukaryotic pre-mRNA splicing factor U2AF (U2 small nuclear ribonucleoprotein auxiliary factor) is required to specify the 3' splice at an early step in spliceosome assembly. U2AF binds site-specifically to the intron polypyrimidine tract and recruits U2 small nuclear ribonucleoprotein to the branch site. Human U2AF (hU2AF) is a heterodimer composed of a large (hU2AF65) and small (hU2AF35) subunit. Although these proteins associate in a tight complex, the biochemical requirement for U2AF activity can be satisfied solely by the large subunit. The requirement for the small subunit in splicing has remained enigmatic. No biochemical activity has been found for hU2AF35 and it has been implicated in splicing only indirectly by its interaction with known splicing factors. In the absence of a biochemical assay, we have taken a genetic approach to investigate the function of the small subunit in the fruit fly Drosophila melanogaster. A cDNA clone encoding the small subunit of Drosophila U2AF (dU2AF38) has been isolated and sequenced. The dU2AF38 protein is highly homologous to hU2AF35 containing a conserved central arginine- and serine-rich (RS) domain. A recessive P-element insertion mutation affecting dU2AF38 causes a reduction in viability and fertility and morphological bristle defects. Consistent with a general role in splicing, a null allele of dU2AF38 is fully penetrant recessive lethal, like null alleles of the Drosophila U2AF large subunit.

  1. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2.

    PubMed

    Huisman, Menno V; Rothman, Kenneth J; Paquette, Miney; Teutsch, Christine; Diener, Hans-Christoph; Dubner, Sergio J; Halperin, Jonathan L; Ma, Chang Sheng; Zint, Kristina; Elsaesser, Amelie; Bartels, Dorothee B; Lip, Gregory Y H

    2017-02-21

    GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and

  2. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM).

  3. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF)

    PubMed Central

    Hori, Juliana I.; Zamboni, Dario S.; Carrão, Daniel B.; Goldman, Gustavo Henrique; Berretta, Andresa A.

    2013-01-01

    Propolis extracts have gained the attention of consumers and researchers due to their unique chemical compositions and functional properties such as its anti-inflammatory activity. Recently, it was described a complex that is also important in inflammatory processes, named inflammasome. The inflammasomes are a large molecular platform formed in the cell cytosol in response to stress signals, toxins, and microbial infections. Once activated, the inflammasome induces caspase-1, which in turn induces the processing of inflammatory cytokines such as IL-1β and IL-18. So, to understand inflammasomes regulation becomes crucial to treat several disorders including autoinflammatory diseases. Since green propolis extracts are able to regulate inflammatory pathways, this work purpose was to investigate if this extract could also act on inflammasomes regulation. First, the extract was characterized and it demonstrated the presence of important compounds, especially Artepillin C. This extract was effective in reducing the IL-1β secretion in mouse macrophages and this reduction was correlated with a decrease in activation of the protease caspase-1. Furthermore, we found that the extract at a concentration of 30 μg/mL was not toxic to the cells even after a 18-hour treatment. Altogether, these data indicate that Brazilian green propolis (EPP-AF) extract has a role in regulating the inflammasomes. PMID:23690844

  4. Comparative Effects of R- and S-equol and Implication of Transactivation Functions (AF-1 and AF-2) in Estrogen Receptor-Induced Transcriptional Activity

    PubMed Central

    Shinkaruk, Svitlana; Carreau, Charlotte; Flouriot, Gilles; Bennetau-Pelissero, Catherine; Potier, Mylène

    2010-01-01

    Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1–10 µM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERα and ERβ in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERα in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERα transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERα transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo. PMID:22254026

  5. Inhibitory and Apoptosis-Inducing Effects of Newcastle Disease Virus Strain AF2240 on Mammary Carcinoma Cell Line

    PubMed Central

    Keong, Yong Yoke; Othman, Fauziah

    2015-01-01

    Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner. PMID:25821783

  6. The Armed Forces Casualty Assistance Readiness Enhancement System (AF-CARES), Version 1.0

    DTIC Science & Technology

    2007-06-08

    15 Next of Kin ( NOK ) ................................................................................................... 15 Casualty...22 Recommendations for Future Work...1.0 Casualty Tab ........................................................................... 19 Figure 10: AF-CARES 1.0 NOK Data Tab

  7. Adiabatic Compression Sensitivity of AF-M315E (Briefing Charts)

    DTIC Science & Technology

    2015-07-27

    dynamic response • Waterhammer effect Distribution A: Approved for public release; distribution unlimited Hydroxyethylhydrazinium Nitrate ...Hydroxylammonium Nitrate (HEHN) (HAN) [ ]-NO3 + [ ]HOCH2CH2N2H4 [ ]-+[ ]NH3OH NO3 AF-M315E

  8. Aerial view of Hanger AF at Cape Canaveral Air Force Station

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aerial view of Hanger AF at Cape Canaveral Air Force Station showing the solid rocket booster (SRB) disassembly facility, SRB casings from the Columbia's first launch and the retrieval vessels, UTC Freedom and Liberty.

  9. High-resolution micropatterned Teflon AF substrates for biocompatible nanofluidic devices.

    PubMed

    Czolkos, Ilja; Hakonen, Bodil; Orwar, Owe; Jesorka, Aldo

    2012-02-14

    We describe a general photolithography-based process for the microfabrication of surface-supported Teflon AF structures. Teflon AF patterns primarily benefit from superior optical properties such as very low autofluorescence and a low refractive index. The process ensures that the Teflon AF patterns remain strongly hydrophobic in order to allow rapid lipid monolayer spreading and generates a characteristic edge morphology which assists directed cell growth along the structured surfaces. We provide application examples, demonstrating the well-controlled mixing of lipid films on Teflon AF structures and showing how the patterned surfaces can be used as biocompatible growth-directing substrates for cell culture. Chinese hamster ovary (CHO) cells develop in a guided fashion along the sides of the microstructures, selectively avoiding to grow over the patterned areas.

  10. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    DTIC Science & Technology

    2016-12-01

    Model , Hematopoiesis, RNA-seq, U2AF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...Spliceosome Mouse model Hematopoiesis RNA-seq U2AF1 3. ACCOMPLISHMENTS: Task 1. Seek IACUC and DoD ACURO approval for the use of animals. Objectives...pre-clinical models using flow cytometry, progenitor assays, and bone marrow transplantation. In addition, trainees created plots, performed

  11. Services Officer Utilization Field (AFS 62XX and Equivalent-Grade Civilians).

    DTIC Science & Technology

    1986-06-01

    CHART le~ -- Sq ,.. O. pt’*. q UNITED STATES AIR FORCE cv, Lfl o D SERVICES OFFICER UTILIZATION FIELD (AFS 62XX AND EQUIVALENT-GRADE CIVILLANS) AFPT 90...Administration From January through Ma’ch 1985, job inventories were administered to all elicible AFSC 62XX nfficer: in the continental United States ... PUBLIC RELEASE: DISTRIBUTION UNLIMITED t, , . . . .. .. . . . . , . . . . . . , . _". ... , I! . . $ IJSTRIBIJTION FOR AFS( u-)XX OSR AND SUPPORTING

  12. Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT).

    PubMed

    Guhl, Emily N; Schlusser, Courtney L; Henault, Lori E; Bickmore, Timothy W; Kimani, Everlyne; Paasche-Orlow, Michael K; Magnani, Jared W

    2017-09-18

    Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the Embodied Conversational Agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. Copyright © 2017. Published by Elsevier Inc.

  13. Detection of a Light Echo from the Otherwise Normal SN 2007af

    NASA Astrophysics Data System (ADS)

    Drozdov, D.; Leising, M. D.; Milne, P. A.; Pearcy, J.; Riess, A. G.; Macri, L. M.; Bryngelson, G. L.; Garnavich, P. M.

    2015-05-01

    We present the discovery of a light echo from SN 2007af, a normal Type Ia supernova (SN Ia) in NGC 5584. Hubble Space Telescope images taken three years post explosion reveal two separate echoes: an outer echo and an extended central region, which we propose to be an inner echo for which details are unresolved. Multiple images were obtained in the F160W, F350LP, F555W, and F814W using the Wide Field Camera 3. If the outer echo is produced by an interstellar dust sheet perpendicular to the line of sight, it is located ∼800 pc in front of the SN. The dust for the inner echo is 0.45 pc \\lt d\\lt 90 pc away from the SN. The inner echo color is consistent with typical interstellar dust wavelength-dependent scattering cross-sections, while the outer echo is redder than predicted. Both dust sheets, if in the foreground, are optically thin for scattering, and the outer echo sheet thickness is consistent with the inferred extinction from peak brightness. Whether the inner echo is from interstellar or circumstellar dust is ambiguous. Overall, the echo characteristics are quite similar to previously observed SN Ia echoes.

  14. AF-M315E Propulsion System Advances and Improvements

    NASA Technical Reports Server (NTRS)

    Masse, Robert K.; Allen, May; Driscoll, Elizabeth; Spores, Ronald A.; Arrington, Lynn A.; Schneider, Steven J.; Vasek, Thomas E.

    2016-01-01

    Even as for the GR-1 awaits its first on-orbit demonstration on the planned 2017 launch of NASA's Green Propulsion Infusion Mission (GPIM) program, ongoing efforts continue to advance the technical state-of-the-art through improvements in the performance, life capability, and affordability of both Aerojet Rocketdyne's 1-N-class GR-1 and 20-N-class GR-22 green monopropellant thrusters. Hot-fire testing of a design upgrade of the GR-22 thruster successfully demonstrated resolution of a life-limiting thermo-structural issue encountered during prototype testing on the GPIM program, yielding both an approximately 2x increase in demonstrating life capability, as well as fundamental insights relating to how ionic liquid thrusters operate, thruster scaling, and operational factors affecting catalyst bed life. Further, a number of producibility improvements, related to both materials and processes and promising up to 50% unit cost reduction, have been identified through a comprehensive Design for Manufacturing and Assembly (DFMA) assessment activity recently completed at Aerojet Rocketdyne. Focused specifically on the GR-1 but applicable to the common-core architecture of both thrusters, ongoing laboratory (heavyweight) thruster testing being conducted under a Space Act Agreement at NASA Glenn Research Center has already validated a number of these proposed manufacturability upgrades, additionally achieving a greater than 40% increase in thruster life. In parallel with technical advancements relevant to conventional large spacecraft, a joint effort between NASA and Aerojet Rocketdyne is underway to prepare 1-U CubeSat AF-M315E propulsion module for first flight demonstration in 2018.

  15. Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system.

    PubMed

    Meng, Yao; Jost, Carsten; Mumme, Jan; Wang, Kaijun; Linke, Bernd

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity. Copyright © 2016. Published by Elsevier B.V.

  16. Rivaroxaban in patients with atrial fibrillation: from ROCKET AF to everyday practice.

    PubMed

    Barón-Esquivias, Gonzalo; Marín, Francisco; Sanmartín Fernandez, Marcelo

    2017-05-01

    Registries and non-interventional studies offer relevant and complementary information to clinical trials, since they have a high external validity. Areas covered: The information regarding the efficacy and safety of rivaroxaban compared with warfarin, or rivaroxaban alone in clinical practice was reviewed in this manuscript. For this purpose, a search on MEDLINE and EMBASE databases was performed. The MEDLINE and EMBASE search included both medical subject headings (MeSH) and keywords including: atrial fibrillation (AF) OR warfarin OR clinical practice OR ROCKET AF AND rivaroxaban. Case reports were not considered. Expert commentary: In ROCKET AF, rivaroxaban was at least as effective as warfarin for the prevention of stroke in patients with nonvalvular AF at high risk of stroke, but, importantly, with a lesser risk of intracranial, critical and fatal bleedings. A number of observational comparative and non-comparative studies, with more than 60,000 patients included treated with rivaroxaban, have analyzed the efficacy and safety of rivaroxaban in real-life patients with AF in different clinical settings. These studies have shown that in clinical practice, rates of stroke and major bleeding were consistently lower than those reported in ROCKET AF, likely due to the lower thromboembolic and bleeding risk observed in these patients.

  17. Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia.

    PubMed

    Okuda, Hiroshi; Stanojevic, Boban; Kanai, Akinori; Kawamura, Takeshi; Takahashi, Satoshi; Matsui, Hirotaka; Takaori-Kondo, Akifumi; Yokoyama, Akihiko

    2017-05-01

    The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4-ENL-P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia.

  18. Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia

    PubMed Central

    Okuda, Hiroshi; Kanai, Akinori; Kawamura, Takeshi; Takahashi, Satoshi; Matsui, Hirotaka

    2017-01-01

    The eleven-nineteen leukemia (ENL) protein family, composed of ENL and AF9, is a common component of 3 transcriptional modulators: AF4–ENL–P-TEFb complex (AEP), DOT1L-AF10-ENL complex (referred to as the DOT1L complex) and polycomb-repressive complex 1 (PRC1). Each complex associates with chromatin via distinct mechanisms, conferring different transcriptional properties including activation, maintenance, and repression. The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in leukemia. However, the functional interrelationship among those 3 complexes in leukemic transformation remains largely elusive. Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberrantly inducing both AEP-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1, to fully transform hematopoietic progenitors. These results reveal a cooperative transcriptional activation mechanism of AEP and DOT1L and suggest a molecular rationale for the simultaneous inhibition of the MLL fusion–AF4 complex and DOT1L for more effective treatment of MLL-rearranged leukemia. PMID:28394257

  19. Nicotine improves AF64A-induced spatial memory deficits in Morris water maze in rats.

    PubMed

    Yamada, Kazuo; Furukawa, Satoshi; Iwasaki, Tsuneo; Ichitani, Yukio

    2010-01-18

    Ethylcholine mustard aziridinium ion (AF64A) is a neurotoxic derivative of choline that produces not only long-term presynaptic cholinergic deficits, but also various memory deficits in rats similar to some characteristics observed in Alzheimer's disease patients. This study investigated whether nicotine (NCT) administration attenuated spatial learning deficits induced by intracerebroventricular AF64A treatment. AF64A (6 nmol/6 microl)-or saline (SAL)-treated rats were trained in Morris water maze task. NCT (0.025-0.25mg/kg) was subcutaneously injected 5 min before the training every day. The results showed that moderate dose (0.10mg/kg) of NCT attenuated AF64A-induced prolongation of escape latency. Furthermore, NCT dose-dependently recovered the AF64A-induced decrease of time spent in the target quadrant in the probe test. These results suggest that NCT improves AF64A-induced spatial memory deficits, and thus it is a potential therapeutic agent for the treatment of memory deficits in dementia.

  20. Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome

    PubMed Central

    Shirai, Cara Lunn; White, Brian S.; Tripathi, Manorama; Tapia, Roberto; Ley, James N.; Ndonwi, Matthew; Kim, Sanghyun; Shao, Jin; Carver, Alexa; Saez, Borja; Fulton, Robert S.; Fronick, Catrina; O'Laughlin, Michelle; Lagisetti, Chandraiah; Webb, Thomas R.; Graubert, Timothy A.; Walter, Matthew J.

    2017-01-01

    Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity to in vitro sudemycin treatment relative to controls. In vivo sudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouring U2AF1 mutations with pre-mRNA splicing modulators like sudemycins. PMID:28067246

  1. Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot).

    PubMed

    Lenarczyk, Radosław; Mitręga, Katarzyna; Mazurek, Michał; Janion, Marianna; Opolski, Grzegorz; Drożdż, Jarosław; Streb, Witold; Fuglewicz, Artur; Sokal, Adam; Laroche, Cécile; Lip, Gregory Y H; Kalarus, Zbigniew

    2016-01-01

    Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In-hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results.

  2. Civilian Manning of AE, AFS, and AD Type Support Ships. Volume II. Appendices.

    DTIC Science & Technology

    1983-04-05

    Conversion - M. Rosenblatt & Son, Inc. ........ E-i APPENDIX F - UNREP Ships - Notional Operation Schedules ......... F-i APPENDIX G - Navy Military...Manpower FYDP Cost Calculations ...... G-1 APPENDIX H - Navy Military Manpower Economic CostLA Calculations ....................................... H...1 APPENDIX I - Navy Civil Service Manpower Cost Calculations ...... I-1 APPENDIX J - Navy Civil Service Operating and Support Cost Estimates Prepared

  3. Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways

    PubMed Central

    Chen, Li; Weinmeister, Robert; Kralovicova, Jana; Eperon, Lucy P.; Vorechovsky, Igor; Hudson, Andrew J.

    2017-01-01

    Abstract The selection of 3΄ splice sites (3΄ss) is an essential early step in mammalian RNA splicing reactions, but the processes involved are unknown. We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-specified site. In the presence of adenosine triphosphate (ATP), all three components bind in a 1:1 stoichiometry with a 3΄ss. Pre-mRNA molecules with two alternative 3΄ss can be bound concurrently by two molecules of U2AF or two U2 snRNPs, so none of the components are restricted. However, concurrent occupancy inhibits splicing. Stoichiometric binding requires conditions consistent with coalescence of the 5΄ and 3΄ sites in a complex (I, initial), but if this cannot form the components show unrestricted and stochastic association. In the absence of ATP, when complex E forms, U2 snRNP association is unrestricted. However, if protein dephosphorylation is prevented, an I-like complex forms with stoichiometric association of U2 snRNPs and the U2 snRNA is base-paired to the pre-mRNA. Complex I differs from complex A in that the formation of complex A is associated with the loss of U2AF65 and 35. PMID:27683217

  4. Recognition of the 3' splice site RNA by the U2AF heterodimer involves a dynamic population shift.

    PubMed

    Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R; Sattler, Michael; Lamb, Don C

    2016-11-15

    An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3' splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein-RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3' splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants.

  5. Recognition of the 3′ splice site RNA by the U2AF heterodimer involves a dynamic population shift

    PubMed Central

    Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R.; Sattler, Michael; Lamb, Don C.

    2016-01-01

    An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3′ splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein–RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3′ splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants. PMID:27799531

  6. Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study

    PubMed Central

    Cacciani, Francesca; Zaniboni, Massimiliano

    2015-01-01

    Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation GKr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in ICaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies. PMID:26229960

  7. Muscleblind-like 1 activates insulin receptor exon 11 inclusion by enhancing U2AF65 binding and splicing of the upstream intron.

    PubMed

    Echeverria, Gloria V; Cooper, Thomas A

    2014-02-01

    Alternative splicing regulates developmentally and tissue-specific gene expression programs, disruption of which have been implicated in numerous diseases. Muscleblind-like 1 (MBNL1) regulates splicing transitions, which are disrupted on loss of MBNL1 function in myotonic dystrophy type 1 (DM1). One such event is MBNL1-mediated activation of insulin receptor exon 11 inclusion, which requires an intronic enhancer element downstream of exon 11. The mechanism of MBNL1-mediated activation of exon inclusion is unknown. We developed an in vitro splicing assay, which robustly recapitulates MBNL1-mediated splicing activation of insulin receptor exon 11 and found that MBNL1 activates removal of the intron upstream of exon 11 upon binding its functional response element in the downstream intron. MBNL1 enhances early spliceosome assembly as evidenced by enhanced complex A formation and binding of U2 small nuclear ribonucleoprotein auxiliary factor 65 kDa subunit (U2AF65) on the upstream intron. We demonstrated that neither the 5' splice site nor exon 11 sequences are required for MBNL1-activated U2AF65 binding. Interestingly, the 5' splice site is required for MBNL1-mediated activation of upstream intron removal, although MBNL1 has no effect on U1 snRNA recruitment. These results suggest that MBNL1 directly activates binding of U2AF65 to enhance upstream intron removal to ultimately activate alternative exon inclusion.

  8. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  9. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  10. Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

    PubMed

    Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

    2017-07-03

    Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( Aspergillus fumigatusMac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae, and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC, and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  11. Pre-clinical laboratory evaluation of the new 'AF' arterial line filter range.

    PubMed

    Yarham, Gemma; Mulholland, John

    2010-07-01

    The presence of emboli was recognised relatively early in the history of open heart surgery. The emboli produced during cardiopulmonary bypass have the predisposition to distribute into, and ultimately obstruct, microvessels of all tissues. The Sorin Group has recently developed a new range of arterial line filters. Before the Sorin AF range of filters was released for pre-launch clinical trials, our group performed in vitro laboratory testing of the AF range against a selection of commercially available filters on the global market. The Sorin AF620 and AF640 demonstrate both the smallest prime volume and smallest surface contact area (92ml and 290 cm(2), respectively).The results of the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In terms of an air bolus handling, the results of the Limit Bolus experiment ranged by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters was measured under steady state experimental conditions. All of the above investigations were considered against surface area and prime volume. It is clear from the results that some commercially available arterial line filters perform better than others, not only in overall performance, but also with regard to individual characteristics. Evaluating arterial line filters for hospital-specific use has to balance pressure drop, surface area, micro air handling, prime volume and gross air handling; all points need to be considered. In the AF620 and AF640, Sorin boast that they are the two smallest prime and smallest surface area filters commercially available on the global market. The Sorin AF filter range performs well in all of the areas we investigated and will be a competitive option for centres, irrespective of which characteristics they use to evaluate and select their arterial line filter.

  12. Self-detection of atrial fibrillation in an aged population: the LietoAF Study.

    PubMed

    Virtanen, Raine; Kryssi, Verneri; Vasankari, Tuija; Salminen, Marika; Kivelä, Sirkka-Liisa; Airaksinen, K E Juhani

    2014-11-01

    Early detection of atrial fibrillation (AF) in older people is important because AF is often asymptomatic and its first manifestation may be a disabling stroke. The objective of the LietoAF Study is to assess the motivation and capability of older people to learn pulse palpation and continue regular pulse measurements, and whether this self-assessment is helpful in the detection of new AF. The LietoAF Study is an intervention study. A total of 205 people aged ≥75 years were randomly selected to participate in the programme where a trained nurse gave individual education on pulse palpation. At 1 month, the eligible participants came to the first follow-up visit to assess the success of pulse self-monitoring. A total of 139 participants (68%) learned pulse palpation and performed regular measurements during the early follow-up period. The significant independent predictors for learning and motivation were high Mini-Mental State Examination score (>24) (OR 7.5, 95% CI 1.5-37.3, p = 0.014), computer use at home (OR 4.7, 95% CI 1.9-11.5, p = 0.001), independence at daily activities (OR 4.2, 95% CI 1.4-13.6, p = 0.013) and low heart rate (OR 1.04, 95% CI 1.0-1.08, p = 0.037). Education did not cause extra visits to local healthcare centres and did not affect quality of life. Four participants observed a new asymptomatic AF during the 1-month follow-up. Active older people are motivated and seem to learn pulse palpation. Our early experience suggests that simple nurse-based education is effective and useful in the early detection of asymptomatic AF. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    NASA Astrophysics Data System (ADS)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  14. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

    PubMed

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-04

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  15. Two Different Types of Antiferromagnetic Couplings and Magnetoresistances in Fe/Si Multilayers

    NASA Astrophysics Data System (ADS)

    Inomata, Koichiro; Yusu, Keiichiro; Saito, Yoshiaki

    1994-12-01

    Two different types of antiferromagnetic (AF) interlayer couplings as a function of Si layer thickness, t Si, have been observed in a series of (2.6 nm Fe/ tSi nm Si)22 multilayers. One of the AF-couplings was observed at around t Si=1.2 nm at room temperature (RT) and changed to ferromagnetic (F) coupling at a low temperature. The other AF coupling was observed for t Si thicker than 1.5 nm with a minimum around t Si=2.5 nm, and was almost temperature independent. Negative magnetoresistance has been observed in the multilayers with the AF coupling, and has similar temperature dependence as that of the AF coupling.

  16. MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.

    PubMed

    Prange, K H M; Mandoli, A; Kuznetsova, T; Wang, S-Y; Sotoca, A M; Marneth, A E; van der Reijden, B A; Stunnenberg, H G; Martens, J H A

    2017-06-08

    In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11. We uncovered both common as well as specific MLL-AF9 and MLL-AF4 target genes, which were all marked by H3K79me2, H3K27ac and H3K4me3. Apart from promoter binding, we also identified MLL-AF9 and MLL-AF4 binding at specific subsets of non-overlapping active distal regulatory elements. Despite this differential enhancer binding, MLL-AF9 and MLL-AF4 still direct a common gene program, which represents part of the RUNX1 gene program and constitutes of CD34(+) and monocyte-specific genes. Comparing these data sets identified several zinc finger transcription factors (TFs) as potential MLL-AF9 co-regulators. Together, these results suggest that MLL fusions collaborate with specific subsets of TFs to deregulate the RUNX1 gene program in 11q23 AMLs.

  17. Non-invasive Measurement of Skin Autofluorescence as a Beneficial Surrogate Marker for Atherosclerosis in Patients with Type 2 Diabetes.

    PubMed

    Temma, Jin; Matsuhisa, Munehide; Horie, Toru; Kuroda, Akio; Mori, Hiroyasu; Tamaki, Motoyuki; Endo, Itsuro; Aihara, Ken-ichi; Abe, Masahiro; Matsumoto, Toshio

    2015-01-01

    Advanced glycation end-products (AGEs) are thought to play a major role in the pathogenesis of diabetic vascular complications. Skin autofluorescence (AF) was recently reported to represent tissue AGEs accumulation with a non-invasive method. The aim of the present study was to evaluate association between AF value and diabetic vascular complications, such as retinopathy, nephropathy and cervical atherosclerosis using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease in patients with type 2 diabetes. A total of 68 patients with type 2 diabetes were enrolled in a cross-sectional manner. AGEs accumulation was measured with AF reader. Clinical parameters were collected at the time of AF and IMT measurement. Max-IMT was correlated with age and AF (r=0.407, p=0.001), but not with HbA1c, GA, and pentosidine. Also, AF was not correlated with HbA1c, GA and pentosidine, but was correlated with age (r=0.560, p<0.001), duration of diabetes (r=0.256, p<0.05). Multivariate regression analysis revealed that AF, but not age, was an independent determinant of max-IMT. In conclusion, AF might be a beneficial surrogate marker for evaluating carotid atherosclerosis in patients with type 2 diabetes non-invasively. J. Med. Invest. 62: 126-129, August, 2015.

  18. Overtreatment and undertreatment with anticoagulation in relation to cardioversion of atrial fibrillation (the RHYTHM-AF study).

    PubMed

    Lip, Gregory Y H; Gitt, Anselm K; Le Heuzey, Jean-Yves; Bash, Lori D; Morabito, Christopher J; Bernhardt, Alexandra A; Sisk, Christine McCrary; Chazelle, François; Crijns, Harry J

    2014-02-01

    Antithrombotic therapy is central to the management of atrial fibrillation. This analysis from the RHYTHM-atrial fibrillation (RHYTHM-AF) registry explored the appropriateness of antithrombotic therapy in relation to stroke risk and atrial fibrillation duration in patients with atrial fibrillation. RHYTHM-AF, a prospective multinational registry, enrolled consecutive adult patients with atrial fibrillation considered for cardioversion. We compared the type of antithrombotic therapy administered at the time of cardioversion and at discharge with stroke risk ("high stroke risk" defined by CHA2DS2-VASc >1) and duration of atrial fibrillation (≤48 vs >48 hours or unknown duration). Of 2,972 patients who were cardioverted (34.5% through pharmacologic cardioversion [PCV] and 65.5% through electrical cardioversion [ECV]), 65% were at high risk of stroke and 30% presented with atrial fibrillation of >48-hour or unknown duration. At the time of PCV and ECV, 36% (n = 242) and 84% (n = 1,075) of high-risk patients, respectively, were taking vitamin K antagonists or heparin. At discharge, these rates increased to 62% (n = 414) and 93% (n = 1,191), respectively. Of all low-stroke risk patients with short-duration atrial fibrillation undergoing PCV (n = 260) and ECV (n = 111), 7% (n = 17) and 30% (n = 33), respectively, were taking vitamin K antagonists or heparin at the time of cardioversion. At discharge, these rates increased to 19% (n = 50) and 40% (n = 44), respectively. In conclusion, ECV was frequently performed under appropriate antithrombotic therapy for most high-risk patients with atrial fibrillation, whereas PCV was frequently performed without appropriate antithrombotic therapy. To enhance pericardioversion stroke prevention, cardioversion algorithms should focus less on the type of conversion and more on stroke risk factors and atrial fibrillation duration.

  19. Acceleration of Regeneration of Large Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2016-09-01

    plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...Gap Peripheral Nerve Injuries Using 5a. CONTRACT NUMBER Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). 5b. GRANT...include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up to 72 hours after seeding. The

  20. AF Ablation Guided by Spatiotemporal Electrogram Dispersion Without Pulmonary Vein Isolation: A Wholly Patient-Tailored Approach.

    PubMed

    Seitz, Julien; Bars, Clément; Théodore, Guillaume; Beurtheret, Sylvain; Lellouche, Nicolas; Bremondy, Michel; Ferracci, Ange; Faure, Jacques; Penaranda, Guillaume; Yamazaki, Masatoshi; Avula, Uma Mahesh R; Curel, Laurence; Siame, Sabrina; Berenfeld, Omer; Pisapia, André; Kalifa, Jérôme

    2017-01-24

    The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p < 0.001). Compared with the validation set, radiofrequency times (49 ± 21 min vs. 85 ± 34.5 min; p = 0.001) and procedure times (168 ± 42 min vs. 230 ± 67 min; p < 0.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949). Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

  1. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  2. Downregulated protein expression of transcriptional activator ELK-1 in atrial myocardium of chronic AF patients.

    PubMed

    Zeng, Xiangjun; Xiao, Xuejun; Wu, Yueheng; Huang, Huanlei

    2015-01-01

    The structural alterations in atrial myocytes appear to be an adaptive response of dedifferentiation during chronic atrial fibrillation (AF). Transcriptional activator ELK-1, one of the members of ETS family, has been shown to play an important role in regulating cell differentiation, It is reasonable to presume that ELK-1 participate in the molecular and structural remodeling by which AF is sustained. To prove this hypothesis, the expression of ELK-1 protein in chronically fibrillating atria compared to that in normal rhythmic atria was detected. Right atrial myocardium were obtained from twenty-four patients undergoing valve replacement surgery, twelve patients were in chronic AF (>6 months), whereas the others were in sinus rhythm (SR). The protein expression level of ELK-1 was quantified by Western blot analysis, and the cellular localization and expression pattern of ELK-1 was examined by immunohistochemical staining and indirect immunofluorescence. Western blot analysis showed that the protein expression of ELK-1 was significantly reduced in the atrial tissue of chronic AF patients compared to that in the controls. Immunohistochemistry showed that ELK-1 immunostaining occurred in both cytosolic and nuclear compartments of atrial myocardium. Indirect immunofluorescence showed that the nuclei of normal rhythmic atrial cells were densely labeled, whereas the nuclei in chronically fibrillating atrial cells were very faintly labeled. Our results suggest that the downregulated expression of transcriptional activator ELK-1 may play an important role in the pathogenesis of AF.

  3. A simple web-based tool to compare freshwater fish data collected using AFS standard methods

    USGS Publications Warehouse

    Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill

    2016-01-01

    The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

  4. The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors

    SciTech Connect

    Entzeroth, M.; Mayer, N. )

    1991-01-01

    The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(2-(-(8-dipropylamino)methyl)-1-piperidinyl-ethyl-amino-carbonyl)-6H-pyrido (2,3-b) (1,4)benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of (3H)AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that (3H)AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.

  5. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

  6. [AF + BAF for treating effluent in the sewage plant of the resin and chemical industry park].

    PubMed

    Tu, Yong; Liu, Wei-Jing; Zhang, Yao-Hui; Xu, Jun; Tang, Min; Chen, Yong; Bai, Yong-Gang

    2014-06-01

    The anaerobic filter (AF) and biological aerated filter (BAF) were employed to treat the effluent in a sewage plant of the resin and chemical industry park. The ceramsite was used in BAF. In this study, the influent COD was 200-300 mg x L(-1) and the pilot model scale was 2-4 L x d(-1). According to the results, the AF-BAF treatment had a good effect on organic wastewater. When the AF HRT was 24 h and BAF was 12 h, the removal of COD reached 73.4%, and that of NH4(+)-N reached 93.8%. From gas chromatography-mass spectrometry (GC-MS) and three-dimensional fluorescence analysis, it was found that small organic molecules and microbial metabolites could be removed effectively. However, there was no obviously effect on the removal of saturated alkane and nitrogenous heterocyclic compounds. From the denature gradient gel electrophoresis (DGGE) spectra analysis, it was shown that there were more kinds of microorganism in the sludge of the AF than in the up-flow anaerobic sludge bed (UASB), which indicates that the AF-BAF system is more effective on treating effluent in a sewage plant of the resin and chemical industry park.

  7. Prenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity

    PubMed Central

    Cestac, Philippe; Sarrabayrouse, Guillaume; Médale-Giamarchi, Claire; Rochaix, Philippe; Balaguer, Patrick; Favre, Gilles; Faye, Jean-Charles; Doisneau-Sixou, Sophie

    2005-01-01

    Introduction We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. Methods The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. Results FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI

  8. Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

    PubMed

    Shaikh, Amir Y; Esa, Nada; Martin-Doyle, William; Kinno, Menhel; Nieto, Iryna; Floyd, Kevin C; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; McManus, David D

    2015-12-01

    Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI (>3 months post-PVI) over the 6-month follow-up period. A BNP greater than or equal to 100 pg/dL (P=0.01) and AF recurrence within 3 months after PVI (P<0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P=0.001) and a net reclassification improvement of 60% (P=0.001) for all risk scores. Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.

  9. Risk of atrial fibrillation after atrial flutter ablation: impact of AF history, gender, and antiarrhythmic drug medication.

    PubMed

    Brembilla-Perrot, Béatrice; Girerd, Nicolas; Sellal, Jean Marc; Olivier, Arnaud; Manenti, Vladimir; Villemin, Thibaut; Beurrier, Daniel; de Chillou, Christian; Louis, Pierre; Selton, Olivier; de la Chaise, Arnaud Terrier

    2014-08-01

    Atrial fibrillation (AF) and flutter (AFL) are frequently associated. We assessed the frequency and identified the predictors of AF occurrence after AFL ablation. A total of 1,121 patients referred for AFL ablation were followed for a mean duration of 2.1 ± 2.7 years. Antiarrhythmic drugs were stopped after ablation in patients with no AF prior to ablation, or continued otherwise. A total of 356 patients (31.7%) had a history of AF prior to AFL ablation. Patients with AF prior to ablation were more likely to be females (OR = 1.35, CI = 1.00-1.83, P = 0.05). After ablation, 260 (23.2%) patients experienced AF. In the multivariable model, AF prior to ablation (OR = 1.90, CI = 1.42-2.54, P < 0.001) and female gender (OR = 1.77, CI = 1.29-2.42, P < 0.001) were associated with a higher risk of AF after ablation. In patients without prior AF, class I antiarrhythmics and amiodarone prior to AFL ablation were independently associated with higher risk of AF after ablation (OR = 2.11, CI = 1.15-3.88, P = 0.02 and OR = 1.60, CI = 1.08-2.36, P = 0.02, respectively). In patients who experienced AF after ablation, 201/260 (77.3%) had a CHA2DS2-VASc ≥1. Two patients with AF prior to ablation had a stroke during the follow-up whereas none of the patients without AF prior to ablation had a stroke. AF occurrence after AFL ablation is frequent (>20%), especially in patients with a history of AF, in female patients, and in patients treated with class I antiarrythmics/amiodarone prior to AFL. Since most patients who experience AF after AFL ablation have a CHA2DS2-VASc ≥1, the decision to stop anticoagulants after ablation should be considered on an individual basis. © 2014 Wiley Periodicals, Inc.

  10. An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

    NASA Technical Reports Server (NTRS)

    Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

    2015-01-01

    The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

  11. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II (STAR AF II): design and rationale.

    PubMed

    Verma, Atul; Sanders, Prashanthan; Macle, Laurent; Deisenhofer, Isabel; Morillo, Carlos A; Chen, Jian; Jiang, Chen-yang; Ernst, Sabine; Mantovan, Roberto

    2012-07-01

    The optimal ablation approach for patients with persistent atrial fibrillation (AF) remains unknown. In particular, it is unclear if pulmonary vein (PV) antral isolation (PVI) is sufficient as a lone strategy for persistent AF. Furthermore, if additional substrate ablation is to be added, the ideal approach to substrate ablation is yet to be determined. The aim of this study is to determine the optimal strategy of catheter ablation of persistent AF by comparing the efficacy of 3 strategies: PVI vs PVI plus complex fractionated electrogram (CFE) ablation (PVI + CFE) vs PVI plus linear ablation (PVI + Lines). The STAR AF II study (ClinicalTrials.gov NCT01203748) is a prospective, multicenter, randomized trial with a blinded assessment of outcomes. A total of 549 patients will be randomized in a 1:4:4 fashion to one of the investigation arms: PVI, PVI + CFE, and PVI + Lines, respectively. Patients undergoing a first-time ablation procedure for symptomatic, persistent AF that is refractory to at least 1 antiarrhythmic medication will be included. Persistent AF will be defined as a sustained episode lasting >7 days and <3 years. Patients with a left atrial parasternal size ≥60 mm will be excluded. The primary end point is freedom from documented AF >30 seconds at 18 months after 1 or 2 ablation procedures with or without antiarrhythmic medications. The STAR AF II study is a randomized trial designed to evaluate the optimal approach for catheter ablation of persistent AF. Copyright © 2012 Mosby, Inc. All rights reserved.

  12. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

  13. Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA

    PubMed Central

    Agrawal, Anant A.; McLaughlin, Krystle J.; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2014-01-01

    Purine interruptions of polypyrimidine (Py) tract splice site signals contribute to human genetic diseases. The essential splicing factor U2AF65 normally recognizes a Py tract consensus sequence preceding the major class of 3′ splice sites. We found that neurofibromatosis- or retinitis pigmentosa-causing mutations in the 5′ regions of Py tracts severely reduce U2AF65 affinity. Conversely, we identified a preferred binding site of U2AF65 for purine substitutions in the 3′ regions of Py tracts. Based on a comparison of new U2AF65 structures bound to either A- or G-containing Py tracts with previously identified pyrimidine-containing structures, we expected to find that a D231V amino acid change in U2AF65 would specify U over other nucleotides. We found that the crystal structure of the U2AF65-D231V variant confirms favorable packing between the engineered valine and a target uracil base. The D231V amino acid change restores U2AF65 affinity for two mutated splice sites that cause human genetic diseases and successfully promotes splicing of a defective retinitis pigmentosa-causing transcript. We conclude that reduced U2AF65 binding is a molecular consequence of disease-relevant mutations, and that a structure-guided U2AF65 variant is capable of manipulating gene expression in eukaryotic cells. PMID:25422459

  14. Small-molecule inhibitors of AF6 PDZ-mediated protein-protein interactions.

    PubMed

    Vargas, Carolyn; Radziwill, Gerald; Krause, Gerd; Diehl, Anne; Keller, Sandro; Kamdem, Nestor; Czekelius, Constantin; Kreuchwig, Annika; Schmieder, Peter; Doyle, Declan; Moelling, Karin; Hagen, Volker; Schade, Markus; Oschkinat, Hartmut

    2014-07-01

    PDZ (PSD-95, Dlg, ZO-1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ-mediated protein-protein interactions has important implications in disease-related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1-fused gene from chromosome 6), which is an essential component of cell-cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile-Gln-Ser-Val-Glu-Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6-Bcr interaction and interfere with epidermal growth factor (EGF)-dependent signaling. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. [Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

    PubMed

    Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

    2013-10-01

    This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

  16. Midterm observations and recommendations from the evaluation of the AF4Q initiative.

    PubMed

    Alexander, Jeffrey A; Scanlon, Dennis P; McHugh, Megan C; Christianson, Jon B; Mittler, Jessica N; Hasnain-Wynia, Romana; Beich, Jeff

    2012-09-01

    To offer midterm observations and recommendations based on how Aligning Forces for Quality (AF4Q) alliances are faring in their journey toward improving healthcare quality at the community level. This study used a mixed method design. Longitudinal evaluation data to date were analyzed, including results from multiple surveys, qualitative analysis of key informant interviews, review of secondary documents and analysis of secondary data, and ongoing tracking of the activities of the 16 participating alliances. The observations and recommendations are based on consensus achieved by the AF4Q evaluation team investigators after in-depth iterative discussions. Six formative observations are identified and discussed: (1) stakeholder support and participation has been maintained despite changes in economic and political environments; (2) progress on program goals has been slow; (3) the "alignment" in the AF4Q initiative has been slow to materialize; (4) the AF4Q initiative has established a productive network of peer communities; (5) the impact of the AF4Q initiative, and the time to observe impact, vary by community, based on history and context; and (6) sustainability is the major future challenge for the AF4Q initiative. Multi-stakeholder alliances' efforts to improve quality should be viewed as "pieces of the health reform puzzle" rather than stand-alone solutions. As healthcare reform is challenged politically, alliances can practice the bipartisanship that focuses conversation on what is good for the community and how best to achieve community goals amid a potential sea of change in both federal and state policy and funding.

  17. Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways.

    PubMed

    Chen, Li; Weinmeister, Robert; Kralovicova, Jana; Eperon, Lucy P; Vorechovsky, Igor; Hudson, Andrew J; Eperon, Ian C

    2017-02-28

    The selection of 3΄ splice sites (3΄ss) is an essential early step in mammalian RNA splicing reactions, but the processes involved are unknown. We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-specified site. In the presence of adenosine triphosphate (ATP), all three components bind in a 1:1 stoichiometry with a 3΄ss. Pre-mRNA molecules with two alternative 3΄ss can be bound concurrently by two molecules of U2AF or two U2 snRNPs, so none of the components are restricted. However, concurrent occupancy inhibits splicing. Stoichiometric binding requires conditions consistent with coalescence of the 5΄ and 3΄ sites in a complex (I, initial), but if this cannot form the components show unrestricted and stochastic association. In the absence of ATP, when complex E forms, U2 snRNP association is unrestricted. However, if protein dephosphorylation is prevented, an I-like complex forms with stoichiometric association of U2 snRNPs and the U2 snRNA is base-paired to the pre-mRNA. Complex I differs from complex A in that the formation of complex A is associated with the loss of U2AF65 and 35. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. 27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

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

    27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

  19. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

    Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure proper telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.

  20. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification

    PubMed Central

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; del Carmen Plaza-Calonge, María; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-01-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification. PMID:22212479

  1. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-12-03

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1.

  2. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  3. Innate immune cells express IL-17A/F in acute generalized exanthematous pustulosis and generalized pustular psoriasis.

    PubMed

    Kakeda, M; Schlapbach, Christoph; Danelon, G; Tang, M M; Cecchinato, V; Yawalkar, N; Uguccioni, M

    2014-12-01

    Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.

  4. A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification.

    PubMed

    Bueno, Clara; Montes, Rosa; Melen, Gustavo J; Ramos-Mejia, Verónica; Real, Pedro J; Ayllón, Verónica; Sanchez, Laura; Ligero, Gertrudis; Gutierrez-Aranda, Iván; Fernández, Agustín F; Fraga, Mario F; Moreno-Gimeno, Inmaculada; Burks, Deborah; Plaza-Calonge, María del Carmen; Rodríguez-Manzaneque, Juan C; Menendez, Pablo

    2012-06-01

    The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs but strongly impairs further hematopoietic commitment in favor of an endothelial cell fate. MLL-AF4 hESCs are transcriptionally primed to differentiate towards hemogenic precursors prone to endothelial maturation, as reflected by the marked upregulation of master genes associated to vascular-endothelial functions and early hematopoiesis. Furthermore, we report that MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells. This work illustrates how hESCs may provide unique insights into human development and further our understanding of how leukemic fusion genes, known to arise prenatally, regulate human embryonic hematopoietic specification.

  5. Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT).

    PubMed

    Steuter, J A; Villanueva, M L H; Loberiza, F R; Armitage, J O; Bociek, R G; Ganti, A K; Tarantolo, S R; Vose, J M; Easley, A; Bierman, P J

    2013-07-01

    The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

  6. (/sup 3/H)AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart

    SciTech Connect

    Wang, J.X.; Roeske, W.R.; Gulya, K.; Wang, W.; Yamamura, H.I.

    1987-10-05

    The in vitro binding properties of the novel muscarinic antagonist (/sup 3/H)AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of (/sup 3/H)AF-DX 116 binding were rapid at 25/sup 0/C but 20-40 times slower at 0-4/sup 0/C. Kinetic dissociation constants (K/sub d/s) were estimated to be 31.8 nM and 30.9 nM at 25/sup 0/C; 23.1 nM and 22.9 nM at 0-4/sup 0/C for the cerebral cortex and heart, respectively. In saturation studies, (/sup 3/H)AF-DX 116 labeled 29% of the total (/sup 3/H)(-)QNB binding sites in the cerebral cortical membranes and 87% in the cardiac membranes, with K/sub d/ values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited (/sup 3/H)AF-DX 116 binding in a rank order of potency of atropine > dexetimide > AF-DX 116 > PZ > levetimide in both tissues. Except for PZ/(/sup 3/H)AF-DX 116 and AF-DX 116/(/sup 3/H)AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. 19 references, 2 figures, 4 tables.

  7. Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

    PubMed Central

    Billon-Galés, Audrey; Krust, Andrée; Fontaine, Coralie; Abot, Anne; Flouriot, Gilles; Toutain, Céline; Berges, Hortense; Gadeau, Alain-Pierre; Lenfant, Françoise; Gourdy, Pierre; Chambon, Pierre; Arnal, Jean-François

    2011-01-01

    17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. PMID:21788522

  8. Purification of a new antifungal compound produced by Lactobacillus plantarum AF1 isolated from kimchi.

    PubMed

    Yang, E J; Chang, H C

    2010-04-30

    The aim of this study was to purify and to identify an antifungal compound of Lactobacillus plantarum AF1, which was isolated from kimchi, and to determine if Lb. plantarum AF1 can prevent fungal growth in a particular food model system. The antifungal compound was purified using SPE and recycling prep-HPLC and its structure was elucidated using NMR and ESI-MS. The active compound from Lb. plantarum AF1 is C(12)H(22)N(2)O(2), 3,6-bis(2-methylpropyl)-2,5-piperazinedion has a molecular mass of 226. This is a new antifungal compound produced by lactic acid bacteria (LAB). To investigate the potential application of the antifungal compound to eliminate fungal spoilage in food and feed, soybean was used as a model. White mycelia and dark green spores of Aspergillus flavus ATCC 22546 were observed in the control soybeans after 1 to 2days incubation. However, fungal growth was not observed in the soybeans treated with a 4-fold concentrated supernatant of Lb. plantarum AF1 culture, even after 2days. The end products produced from kimchi LAB, like 3,6-bis(2-methylpropyl)-2,5-piperazinedion identified in this study, may be a promising alternative to chemical preservatives as a potential biopreservative which prevent fungal spoilage and mycotoxin formation in food and feed. Copyright 2010 Elsevier B.V. All rights reserved.

  9. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., refined oil; cotton, undelinted seed. (b) An exemption from the requirement of a tolerance is established... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with...

  10. Genome Sequence of the Native Apiculate Wine Yeast Hanseniaspora vineae T02/19AF

    PubMed Central

    Giorello, Facundo M.; Berná, Luisa; Greif, Gonzalo; Camesasca, Laura; Salzman, Valentina; Medina, Karina; Robello, Carlos; Gaggero, Carina; Aguilar, Pablo S.

    2014-01-01

    The use of novel yeast strains for winemaking improves quality and provides variety including subtle characteristic differences in fine wines. Here we report the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae T02/19AF, which has been shown to positively contribute to aroma and wine quality. PMID:24874663

  11. K-theory of the chair tiling via AF-algebras

    NASA Astrophysics Data System (ADS)

    Julien, Antoine; Savinien, Jean

    2016-08-01

    We compute the K-theory groups of the groupoid C∗-algebra of the chair tiling, using a new method. We use exact sequences of Putnam to compute these groups from the K-theory groups of the AF-algebras of the substitution and the induced lower dimensional substitutions on edges and vertices.

  12. Flow ozonolysis using a semipermeable Teflon AF-2400 membrane to effect gas-liquid contact.

    PubMed

    O'Brien, Matthew; Baxendale, Ian R; Ley, Steven V

    2010-04-02

    A flow-through chemistry apparatus has been developed which allows gases and liquids to contact via a semipermeable Teflon AF-2400 membrane. In this preliminary investigation, the concept was proven by application to the ozonolysis of a series of alkenes.

  13. Genome Sequence of the Native Apiculate Wine Yeast Hanseniaspora vineae T02/19AF.

    PubMed

    Giorello, Facundo M; Berná, Luisa; Greif, Gonzalo; Camesasca, Laura; Salzman, Valentina; Medina, Karina; Robello, Carlos; Gaggero, Carina; Aguilar, Pablo S; Carrau, Francisco

    2014-05-29

    The use of novel yeast strains for winemaking improves quality and provides variety including subtle characteristic differences in fine wines. Here we report the first genome of a yeast strain native to Uruguay, Hanseniaspora vineae T02/19AF, which has been shown to positively contribute to aroma and wine quality. Copyright © 2014 Giorello et al.

  14. Utilizing an Experiential Approach to Teacher Learning about AfL: A Consciousness Raising Opportunity

    ERIC Educational Resources Information Center

    Dixon, Helen; Hawe, Eleanor

    2016-01-01

    In this article we focus on how an experiential based approach to teacher learning about assessment for learning (AfL) provided opportunities for teachers to examine: their deep-seated beliefs about effective learning (and teaching); how these beliefs permeated their day-to-day actions and interactions with students, and the consequence of these…

  15. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when...

  16. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover, when...

  17. Unusual hydrogen bonding patterns in AF (aminofluorene) and AAF (acetylaminofluorene) modified DNA

    SciTech Connect

    Broyde, S.; Hingerty, B.E.; Shapiro, R.; Norman, D.

    1989-01-01

    New structures are presented for AF and AAF modified DNAs that place the carcinogen in the minor groove of a B-DNA helix. These structures employ non-Watson-Crick base pairing schemes with syn guanine at the modification site. 32 refs., 9 figs.

  18. 28. Site Plan: AF Station P67, Fort Custer, Michigan, Plot ...

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

    28. Site Plan: AF Station P-67, Fort Custer, Michigan, Plot Plan (to accompany FY 1956 project planning report), USACOE, 22 July 1954. - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  19. Fracture Mechanics Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, J. W.; Martinez, J.; McLean, C.

    2016-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant on orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent processing flaws will not cause failure during the design life of the tank. Material property inputs for this analysis require testing to determine the stress intensity factor for environment-assisted cracking (KEAC) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched, or SE(B), specimens representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to AF-M315E at 50 C for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor for environment-assisted cracking of the Ti 6Al-4V forged tank material was found to be at least 22 ksivin and at least 31 ksivin for the weld material when exposed to AF-M315E monopropellant.

  20. Energy Harvesting and Storage Systems for Future AF Vehicles

    DTIC Science & Technology

    2012-05-18

    concentration of Li-ions in the electrolyte, ΦLi+ We apply the above model to the analysis of a 3-D unit cell and consider a 3D cube aligned with...coordinate axes. Periodic boundary conditions are imposed in y and z directions. The cube is divided into two subdomains, representing the electrolyte...types of jar and ball were carried out. Various jar and balls can be selected such as alumina, stainless steel , tungsten carbide, agate and zirconium

  1. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.

  2. Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

    PubMed

    Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

    Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

  3. Equalization characteristics of an upflow sludge blanket-aerated biofilter (USB-AF) system.

    PubMed

    Jun, H B; Park, S M; Park, J K; Lee, S H

    2005-01-01

    Equalization characteristics of the upflow sludge blanket-aerated bio-filter (USB-AF) were investigated with the fluctuated raw domestic sewage. Recycle of nitrified effluent from AF to USB triggered the equalization characteristics of the sludge blanket on both soluble and particulate organic matter. Increment of EPS in sludge blanket by nitrate recycle was detected and removal of turbidity and particulates increased at higher recycle ratios by bio-flocculation. Increased TCOD removal in the USB was due to both denitrification of recycled nitrate and entrapment of the particulate organic matter in sludge blanket. Capture of both soluble and particulate organic matter increased sludge blanket layer in the USB, which improved the reactor performances and reduced the organic load on the subsequent AF. Overall TCOD and SS removal efficiencies were about 98% and 96%, respectively in the USB-AF system. Turbidity in the USB effluent was about 44, 20 and 5.5 NTU, at recycle ratios of 0, 100 and 200%, respectively. Particle counts in the range 2-4 microm in the USB effluent were higher than those in influent without nitrate recycle, while particle counts in the range of 0.5-15 microm in the USB effluent decreased 70% at recycle ratio of 200%. The major constituent of EPS extracted from anaerobic sludge was protein and total EPS increased from 109.1 to 165.7 mg/g-VSS with nitrate recycle of 100%. Removal efficiency and concentration of T-N in the UBS-AF effluent was over 70% and below 16 mg/L, respectively.

  4. Properties and transport behavior of perfluorotripentylamine (FC-70)-doped amorphous teflon AF 2400 films.

    PubMed

    Zhang, Hong; Hussam, Abul; Weber, Stephen G

    2010-12-22

    Teflon AF 2400 films are known to imbibe solvents, making films in the presence of solvents less fluorous than they might otherwise be. Herein, we demonstrate that doping films with perfluorotripentylamine (Fluorinert FC-70) maintains the fluorous nature of Teflon AF 2400 and improves transport selectivity for fluorine-containing organic compounds. Density measurements on the FC-70-doped films reveal that free volume decreases dramatically as the dopant concentration increases (0-12 wt %) and then increases to approach that of pure FC-70. Remarkably, films from 0 to 12 wt % FC-70 have the same w/v concentration of Teflon AF 2400, indicating that FC-70 fills the free volume of Teflon AF 2400. This is consistent with the observed increased storage modulus and significant decrease (compared to undoped films) of solute diffusion coefficients in the same range of FC-70 concentrations. In contrast, FC-70 at concentrations greater than 12 wt % dilutes Teflon AF 2400, leading to a decrease of storage modulus and dramatic increase in solute diffusion coefficients. Sorption of chloroform decreases from 11.8 g of chloroform/100 g of film (pure Teflon film) to 3.8 g of chloroform/100 g of film (27 wt % FC-70-doped Teflon film), less than the solubility of chloroform in pure FC-70 (4.06 g of chloroform/100 g of FC-70). Solute partition coefficients from chloroform to FC-70-doped films generally decrease with increased dopant concentration. However, within a series of toluenes and nitrobenzenes, selectivity for F-containing solutes over analogous H-containing solutes increases as dopant concentration increases if the substitution is on the aromatic ring but not if it is on the methyl group (toluene). Transport (partitioning × diffusion) rates, as they involve both thermodynamic and kinetic factors, are not simply related to composition.

  5. CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12.

    PubMed

    Mulaw, M A; Krause, A; Krause, A J; Deshpande, A J; Krause, L F; Rouhi, A; La Starza, R; Borkhardt, A; Buske, C; Mecucci, C; Ludwig, W-D; Lottaz, C; Bohlander, S K

    2012-05-01

    The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125 patients with other types of leukemia and 10 normal bone marrow samples. Based on gene set enrichment analyses, the CALM/AF10-positive samples showed significant upregulation of genes involved in chromatin assembly and maintenance and DNA repair process, and downregulation of angiogenesis and cell communication genes. Interestingly, we observed a striking upregulation of four genes located immediately centromeric to the break point of the t(10;11)(p12;q14) on 10p12 (COMMD3 (COMM domain containing 3), BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), DNAJC1 (DnaJ (Hsp40) homolog subfamily C member 1) and SPAG6 (sperm associated antigen 6)). We also conducted semiquantitative reverse transcriptase-PCR analysis on leukemic blasts from a murine CALM/AF10 transplantation model that does not have the translocation. Commd3, Bmi1 and Dnajc1, but not Spag6 were upregulated in these samples. These results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood.

  6. The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system.

    PubMed

    Di Spiezio Sardo, A; Campo, R; Gordts, S; Spinelli, M; Cosimato, C; Tanos, V; Brucker, S; Li, T C; Gergolet, M; De Angelis, C; Gianaroli, L; Grimbizis, G

    2015-05-01

    How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs and/or segments of Müllerian ducts (complex anomaly) were involved in 27 (69.2%) types. Uterus was the organ most frequently involved (30/39: 76.9%), followed

  7. The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system

    PubMed Central

    Di Spiezio Sardo, A.; Campo, R.; Gordts, S.; Spinelli, M.; Cosimato, C.; Tanos, V.; Brucker, S.; Li, T. C.; Gergolet, M.; De Angelis, C.; Gianaroli, L.; Grimbizis, G.

    2015-01-01

    STUDY QUESTION How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? SUMMARY ANSWER The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. WHAT IS KNOWN ALREADY Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. STUDY DESIGN, SIZE AND DURATION The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. MAIN RESULTS AND THE ROLE OF CHANCE The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs

  8. A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

    PubMed Central

    Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

    2016-01-01

    A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

  9. An Observational, Prospective Survey Assessing the Control of Atrial Fibrillation in Asia Pacific: Rationale and Design of the RecordAF-AP Registry

    PubMed Central

    Amerena, John; Chen, Shih-Ann; Sriratanasathavorn, Charn; Cho, Jeong-Gwan; Dejia, Huang; Omar, Razali; Fat, Tse Hung; King, Anthony

    2011-01-01

    Background: The literature suggests that the prevalence of atrial fibrillation (AF) may be lower in Asian countries than in Western countries. Nevertheless, AF remains a significant public health problem in the region. The burden of AF, the experiences of previous trials and the lack of data on AF and its management in Asia Pacific highlight the need for a comprehensive prospective study of AF management. Methods: The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation Asia Pacific (RecordAF-AP) is a prospective, observational survey of the management of recently diagnosed AF patients with 1-year follow-up in 8 countries across Asia Pacific. Eligible patients presenting with AF, treated or not, will be included in the registry and data will be recorded prospectively during follow-up visits at 6 and 12 months. Results: RecordAF-AP will recruit more than 3000 patients. Study recruitment commenced in April 2009 and the final results anticipated at the end of 2011. Conclusions: RecordAF-AP will assess the real-life management of AF patients in Asia Pacific, including a comparison of clinical outcomes in rhythm versus rate control strategies, providing much needed insight into the costs, treatment choices and clinical outcomes of AF patients in this region. PMID:21344019

  10. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    PubMed Central

    Moghal, N; Neel, B G

    1995-01-01

    Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID:7791800

  11. A prospective, multicenter evaluation of ablating complex fractionated electrograms (CFEs) during atrial fibrillation (AF) identified by an automated mapping algorithm: acute effects on AF and efficacy as an adjuvant strategy.

    PubMed

    Verma, Atul; Novak, Paul; Macle, Laurent; Whaley, Bonnie; Beardsall, Marianne; Wulffhart, Zaev; Khaykin, Yaariv

    2008-02-01

    Complex fractionated electrograms (CFEs) are continuous electrograms (EGMs) of very short cycle length (CL) representing substrate for atrial fibrillation (AF) perpetuation. Ablation of CFEs may result in AF slowing, termination, and prevention, but identifying them can be subjective. The purpose of this study was to prospectively assess (1) whether an automated algorithm can identify CFE regions, (2) the acute effects of ablating these regions on AF, and (3) the long-term efficacy as an adjuvant strategy to pulmonary vein antrum isolation (PVAI). Thirty-five patients (three centers, 61 +/- 9 years, left atrium [LA] 43 +/- 9 mm, ejection fraction 53% +/- 7%) with symptomatic paroxysmal (n = 21) or persistent (n = 14) AF were studied. A decapolar lasso (2-mm spacing) was used for mapping. A three-dimensional shell of the LA and pulmonary veins (PVs) was created. If not already in AF, AF was induced by burst pacing (with or without isoproterenol). Atrial EGMs during AF were mapped/analyzed using an automated CFE algorithm. The algorithm measures the time between discrete deflections in a local EGM over 5 seconds (based on selectable width and peak-to-peak [>0.03 mV] criteria). The mean CL of the local EGM is projected onto the LA shell as a color-coded display. Regions of CL <120 ms (published criteria) were targeted for ablation/elimination. Atrial fibrillation cycle length (AFCL) and regularity were measured from the CS. After CFE ablation, further ablation was done to achieve complete PVAI. AF was spontaneous (n = 20) or induced (n = 15) in all patients. CFEs were most commonly found along the septum (97%), anterior LA (97%), PV antra (83%), base of appendage (83%), and annulus (71%). CFE ablation alone prolonged the AFCL (171 +/- 27 vs. 304 +/- 41 ms; P = .03) and regularized AF to left/right flutter (AFL) in 74% of patients. CFE ablation terminated AF/AFL in 19 patients (54%)-the other 16 were cardioverted-and AF became noninducible in 77%. CFE ablation alone

  12. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.

    PubMed

    Dutta, S; Krause, A; Vosberg, S; Herold, T; Ksienzyk, B; Quintanilla-Martinez, L; Tizazu, B; Chopra, M; Graf, A; Krebs, S; Blum, H; Greif, P A; Vetter, A; Metzeler, K; Rothenberg-Thurley, M; Schneider, M R; Dahlhoff, M; Spiekermann, K; Zimber-Strobl, U; Wolf, E; Bohlander, S K

    2016-05-01

    The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia.

  13. Identification and functional characterization of an afsR homolog regulatory gene from Streptomyces venezuelae ATCC 15439.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2009-02-01

    Sequencing analysis of a 5-kb DNA fragment from Streptomyces venezuelae ATCC 15439 revealed the presence of one 3.1-kb open reading frame (ORF), designated afsRsv. The deduced product of afsR-sv (1,056 aa) was found to have high homology with the global regulatory protein AfsR. Homology-based analysis showed that afsR-sv represents a transcriptional activator belonging to the Streptomyces antibiotic regulatory protein (SARP) family that includes an Nterminal SARP domain containing a bacterial transcriptional activation domain (BTAD), an NB-ARC domain, and a Cterminal tetratricopeptide repeat domain. Gene expression analysis by reverse transcriptase PCR (RT-PCR) demonstrated the activation of transcription of genes belonging to pikromycin production, when afsR-sv was overexpressed in S. venezuelae. Heterologous expression of the afsR-sv in different Streptomyces strains resulted in increased production of the respective antibiotics, suggesting that afsR-sv is a positive regulator of antibiotics biosynthesis.

  14. Identification and characterization of a laminin-binding protein of Aspergillus fumigatus: extracellular thaumatin domain protein (AfCalAp).

    PubMed

    Upadhyay, Santosh Kumar; Mahajan, Lakshna; Ramjee, Sandhya; Singh, Yogendra; Basir, Seemi Farhat; Madan, Taruna

    2009-06-01

    Aspergillus fumigatus, an opportunistic fungal pathogen, infects the human host via inhalation of airborne conidia. Adhesion of fungal conidia, to host cells and extracellular matrix (ECM) components associated with host tissue surfaces, is thought to be the primary step in the pathogenesis and dissemination of infection. To identify novel adhesion proteins (adhesins) of A. fumigatus, we screened its proteome in silico using SPAAN (software program for prediction of adhesins and adhesin-like proteins using neural networks). One of the predicted adhesin-encoding genes with a P(ad) (probability of being adhesin) value >0.9, the gene encoding extracellular thaumatin domain protein (AfCalA), was cloned and expressed in Escherichia coli. Recombinant AfCalAp showed significant binding with laminin and murine lung cells. Anti-AfCalAp antibodies inhibited the binding of AfCalAp to laminin in a dose-dependent manner. Significant binding of anti-AfCalAp antibodies to 2 h swollen conidia suggests the presence of AfCalAp on the conidial surface. AfCalA transcript was not detectable in resting conidia but was detected in conidia incubated with RPMI 1640 medium in the presence and absence of lung epithelial cell line (A539)-derived ECM. Elevated levels of IgE antibodies specific to AfCalAp were observed in the sera of two out of seven patients with allergic bronchopulmonary aspergillosis. The study confirms the relevance of the bioinformatic approach for predicting fungal adhesins and establishes AfCalAp as a novel laminin-binding protein of A. fumigatus.

  15. Hot Isostatic Pressing/Heat Treatment of Cast Superalloy AF2-1DA, Radial Turbine Wheels.

    DTIC Science & Technology

    1980-06-01

    showing typical 19 shrinkage porosity Mag: 400X Etch: Electrolytic oxalic acid 10 Microstructure of HIPped AF2-1DA alloy 29 Mag: 400X Etch...Electrolytic oxalic acid 11 Microstructure of HIPped AF2-1DA alloy note 30 void formations form incipient melting after 2250OF hip Mag: 400X Etch: Electrolytic... oxalic acid V a.w LIST OF ILLUSTRATIONS (Continued) Figure Title Page 12 Microstructure of HIPped AF2-1DA showing effects 31 of solution heat

  16. King Salmon, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-10

    1 .2 - i 121 1b 15 o -- 9 2.4 z 2 22 2 2 2fi 2 13 1ee (X) I me. O.. N.. o Nof " . Tom .eet W .. I T 0 F s 32P IN 67 P 3 FNP -93 P T...I w e Or ulb t...CLIMATOLOGY BRANCHT 2 AkETAHRSRVC/A PSYCHROMETRIC SUMMARY2 I ETE EVC /A 7 3260_ KING SALMON AFS AK 73-82 JAN STAT.Oft STATION NWAI villOAN *PAGE ? 1890...T,,.) .. ." " " , . - . . 1 i. . , ’. . ; : ; .-. A f;: ’ ,- ;. * GLr rA E LMTL~ T AC? PSYCHROMETRIC SUMMARYT2 FAH- EVC /A 7 3267 XING SALM4ON AFS

  17. Nanopatterning of mobile lipid monolayers on electron-beam-sculpted Teflon AF surfaces.

    PubMed

    Shaali, Mehrnaz; Lara-Avila, Samuel; Dommersnes, Paul; Ainla, Alar; Kubatkin, Sergey; Jesorka, Aldo

    2015-02-24

    Direct electron-beam lithography is used to fabricate nanostructured Teflon AF surfaces, which are utilized to pattern surface-supported monolayer phospholipid films with 50 nm lateral feature size. In comparison with unexposed Teflon AF coatings, e-beam-irradiated areas show reduced surface tension and surface potential. For phospholipid monolayer spreading experiments, these areas can be designed to function as barriers that enclose unexposed areas of nanometer dimensions and confine the lipid film within. We show that the effectiveness of the barrier is defined by pattern geometry and radiation dose. This surface preparation technique represents an efficient, yet simple, nanopatterning strategy supporting studies of lipid monolayer behavior in ultraconfined spaces. The generated structures are useful for imaging studies of biomimetic membranes and other specialized surface applications requiring spatially controlled formation of self-assembled, molecularly thin films on optically transparent patterned polymer surfaces with very low autofluorescence.

  18. Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial.

    PubMed

    Shah, Rohan; Hellkamp, Anne; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Fox, Keith A A; Nessel, Christopher C; Mahaffey, Kenneth W; Piccini, Jonathan P; Singer, Daniel E; Patel, Manesh R

    2016-09-01

    We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD). Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009). Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.

    PubMed

    Shah, Rohan; Patel, Manesh R

    2017-03-01

    The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical

  20. Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

    PubMed

    Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

    2017-04-01

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9-driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. Cancer Res; 77(7); 1753-62. ©2017 AACR. ©2017 American Association for Cancer Research.

  1. Oxytrofalcatins A-F, N-benzoylindole analogues from the roots of Oxytropis falcata (Leguminosae).

    PubMed

    Chen, Wen-Hao; Wu, Quan-Xiang; Wang, Rui; Shi, Yan-Ping

    2010-06-01

    Indole alkaloids, oxytrofalcatins A-F (1-6), together with five other known alkaloids (7-11), were isolated from the roots of Oxytropis falcata. Their structures were elucidated by comprehensive spectroscopic analyses, including using 1D and 2D NMR spectroscopy and mass spectrometry. This is the first report of N-benzoylindoles from a natural source. Compounds 1-6 lacked significant cytotoxicity against SGC-7901 and HL-60 tumor cell lines.

  2. Ficusnotins A-F: Rare diarylbutanoids from the leaves of Ficus nota.

    PubMed

    Latayada, Felmer S; Uy, Mylene M; Akihara, Yui; Ohta, Emi; Nehira, Tatsuo; Ômura, Hisashi; Ohta, Shinji

    2017-09-01

    Six diarylbutanoids, designated as ficusnotins A-F, with a rare carbon skeleton consisting of two aromatic rings separated by an unbranched C4-chain have been isolated from the leaves of Ficus nota (Blanco) Merr. (Moraceae). The structures were determined on the basis of spectroscopic data, as well as X-ray crystallographic analysis. The isolated compounds were evaluated for their antibacterial activity against Bacillus subtilis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Evolution of iron speciation during hydration of C{sub 4}AF

    SciTech Connect

    Rose, J.; El Mrabet, S.; Masion, A.; Moulin, I.; Briois, V.; Olivi, L.; Bottero, J.-Y.

    2006-07-01

    It is now well accepted and demonstrated that calcium silicate, calcium aluminate and calcium sulfo aluminate (ettringite, AFm) phases exhibit a good capability to fix metals and metalloids. Unfortunately the role of minor phases and especially calcium-ferric aluminate phase, shorthand C{sub 4}AF is not well defined. In other systems like in soils or sediments iron phases play a key role in the fixation of pollutant. In cement sorption isotherms, indicated that various metals can be retained by the C{sub 4}AF hydrated products. Therefore the capabilities of those phase to retain heavy metal should not be neglected. Previous investigations have shown that the minerals formed during the hydration of C{sub 4}AF are similar to those formed from C3A (pure tri-calcium aluminate) under comparable conditions. Nevertheless no investigation was conducted at the molecular level and there is still a controversy whether Fe substitutes for Al in the hydrated minerals in whole or in part, or if it forms FeOOH clusters scattered throughout the matrix. In this context we have conducted XAS experiments using synchrotron radiation. It was found that the hydration of C{sub 4}AF forms C{sub 3}AH{sub 6} (hydrogarnet) in which Fe randomly substitutes for Al as well as an amorphous FeOOH phase. Intermediate products like AFm (i.e., an ill organized lamellar phase) are also formed but rapidly evolve to C{sub 3}AH{sub 6}; iron does not seem to be incorporated in the AFm structure.

  4. Unciflavones A-F, six novel flavonoids from Selaginella uncinata (Desv.) Spring.

    PubMed

    Zou, Hui; Xu, Kang-Ping; Li, Fu-Shuang; Zou, Zhen-Xing; Liu, Rui; Liu, Rui-Huan; Li, Jing; Tan, Lei-Hong; Tan, Gui-Shan

    2014-12-01

    Six new flavonoids, unciflavones A-F (1-6), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis. All compounds possess exceptional structural features with an aryl substituent at the C-8 position, which are uncommonly encountered in natural resources and firstly reported in genus Selaginella.

  5. Updated Reference Genome Sequence and Annotation of Mycobacterium bovis AF2122/97

    PubMed Central

    Farrell, Damien; Stuber, Tod P.; Schubert, Olga T.; Aebersold, Ruedi; Robbe-Austerman, Suelee

    2017-01-01

    ABSTRACT We report here an update to the reference genome sequence of the bovine tuberculosis bacillus Mycobacterium bovis AF2122/97, generated using an integrative multiomics approach. The update includes 42 new coding sequences (CDSs), 14 modified annotations, 26 single-nucleotide polymorphism (SNP) corrections, and disclosure that the RD900 locus, previously described as absent from the genome, is in fact present. PMID:28385856

  6. AF-TRUST, Air Force Team for Research in Ubiquitous Secure Technology

    DTIC Science & Technology

    2010-07-26

    Live Streaming Systems. PhD. June 2008 • Jeffrey Hartline. Incremental Optimization, PhD, January 2008 AF-TRUST Final Performance Report...Against Intrusion in a Live Streaming Multicast System. Maya Haridasan, Robbert van Renesse. In Proceedings of the 6th IEEE International Conference...Walker White. In Proceedings of SIGMOD 2007 2008 Enforcing Fairness in a Live - Streaming System. Maya Haridasan, Ingrid Jansch-Porto, Kenneth Birman

  7. A comparison of ANB, WITS, AF-BF, and APDI measurements.

    PubMed

    Oktay, H

    1991-02-01

    In the present study, the relationships among ANB, Wits, AF-BF, and APDI measurements used in the assessment of the anteroposterior jaw disorders were examined on the cephalometric radiographs of 63 male and 82 female subjects, and high correlations were found among them. Furthermore, relationships were explored between these parameters and some measurements that were thought to have influenced them. The results of the geometric studies could not be proved on the basis of statistical evaluation.

  8. Air Traffic Control Radar Specialty AFS 303X1. Volume II.

    DTIC Science & Technology

    1981-05-01

    Surveillance Radars, and AN/ MPN -14H Mobile RAPCONs. Typical tasks performed by these incumbents when maintaining these radar systems include: perform PMIs on...document forms (AF Form 264) issue job control numbers maintain status boards, graphs, or charts maintain equipment status reports document equipment...related matters determine work priorities plan work assignments maintain training records, charts , or graphs These incumbents are the most senior of all

  9. Blytheville AFB, Arkansas, Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1987-10-01

    AMOUNTS IN INCfOES .t I I I I I I 9 7 I 13 I 2S I 37 I 19 I 61 I OVER I I DARSI TOTALI IONIHLY...ION 46141 . ItYTIIIVILLC AF P AR FP310 jr EEcopo: 77-Ab MOlNTH: SEF HOuD56Llj: 0600-06(10...VARIA 1I L TO 16 LS I , 35., jr .6 1 .3 .1 .1 Ion., 6.89

  10. Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

    PubMed Central

    Hangai, Mari; Takebe, Noriko; Honma, Hiroyuki; Sasaki, Atsumi; Chida, Ai; Nakano, Rieko; Togashi, Hirobumi; Nakagawa, Riyuki; Oda, Tomoyasu; Matsui, Mizue; Yashiro, Satoshi; Nagasawa, Kan; Kajiwara, Takashi; Takahashi, Kazuma; Takahashi, Yoshihiko; Satoh, Jo

    2016-01-01

    Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects. PMID:26961217

  11. ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation

    PubMed Central

    ElMaghawry, Mohamed

    2015-01-01

    In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.1 The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).2 However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation. A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.3 The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. PMID:26779514

  12. Influence of Environmental Factors on the Production of Penitrems A-F by Penicillium crustosum.

    PubMed

    Kalinina, Svetlana A; Jagels, Annika; Cramer, Benedikt; Geisen, Rolf; Humpf, Hans-Ulrich

    2017-07-01

    Filamentous fungi produce a multitude of secondary metabolites, some of them known as mycotoxins, which are toxic to vertebrates and other animal groups in low concentrations. Among them, penitrems, which belong to the group of indole-diterpene mycotoxins, are synthesized by Penicillium and Aspergillus genera and exhibit potent tremorgenic effects. This is the first complex study of the penitrems A-F production under the influence of different abiotic factors, e.g., media, incubation time, temperature, pH, light, water activity, and carbon and nitrogen source as well as oxidative and salt stress. For this purpose, penitrems A-F were isolated from Penicillium crustosum cultures and used as analytical standards. Among the carbon sources, glucose supplemented to the media at the concentration of 50 g/L, showed the strongest inducing effect on the biosynthesis of penitrems. Among nitrogen sources, glutamate was found to be the most favorable supplement, significantly increasing production of these secondary metabolites. CuSO4-promoted oxidative stress was also shown to remarkably stimulate biosynthesis of all penitrems. In contrast, the salt stress, caused by the elevated concentrations of NaCl, showed an inhibitory effect on the penitrem biosynthesis. Finally, cheese model medium elicited exceptionally high production of all members of the penitrems family. Obtained results give insides into the biosynthesis of toxicologically relevant penitrems A-F under different environmental factors and can be utilized to prevent food contamination.

  13. ROCKET AF adds more concerns about Digoxin safety in patients with atrial fibrillation.

    PubMed

    ElMaghawry, Mohamed

    2015-01-01

    In a recent article in the Journal, we have reviewed the adverse cardiovascular outcomes observed with digoxin use in the PALLAS study.(1) The PALLAS study was designed to determine if dronedarone would reduce major vascular events in patients with permanent atrial fibrillation (AF).(2) However the study was stopped early because of safety reasons, as a significant number of patients on the dronedarone arm reached the co-primary end point composite of stroke, myocardial infarction, systemic embolism, or cardiovascular death. Data sub-analyses suggested that digoxin-dronedarone interaction was responsible for the higher arrhythmic death rate observed in the trial. These observations are consistent with several other studies that demonstrate the potential hazard of the use of digoxin in heart failure and/or atrial fibrillation. A more recent article published in the Lancet studied the use and outcomes of digoxin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism in Atrial Fibrillation (ROCKET AF) trial.(3) The investigators concluded that digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF.

  14. Fracture Growth Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey W.; Martinez, Jonathan; McLean, Christopher

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant in orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent flaws will not cause failure during the design life. Material property inputs for this analysis require testing to determine the stress intensity factor for environmentally-assisted cracking (K (sub EAC)) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched specimens SE(B) representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to the monopropellant at 50 degrees Centigrade for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor of the Ti 6Al-4V forged tank material when exposed to AF-M315E monopropellant was found to be at least 22.0 kilopounds per square inch. The stress intensity factor of the weld material was at least 31.3 kilopounds per square inch.

  15. A strategy for producing refined currents in the Equatorial Atlantic in the context of the search of the AF447 wreckage

    NASA Astrophysics Data System (ADS)

    Drévillon, Marie; Greiner, Eric; Paradis, Denis; Payan, Christophe; Lellouche, Jean-Michel; Reffray, Guillaume; Durand, Edmée; Law-Chune, Stéphane; Cailleau, Sylvain

    2013-01-01

    On the night of 1st June 2009, a Rio-Paris Air France flight (AF447) disappeared in a highly variable and poorly observed part of the western tropical Atlantic Ocean. The first debris was located 5 days after the accident. Several reverse drift computations were conducted in order to define the likely position of the wreckage. Unfortunately, the performance of the operational ocean analyses available in the region of interest ranges from 80 to 100 km of positioning error after 5 days of inverse drift computation. In preparation of the third phase of research of the wreckage at sea, a series of numerical experiments was performed at Météo-France and Mercator Océan in an attempt to better compute the surface currents in the region and for the period of the accident of the AF447 (May and June 2009). Tailored high-resolution atmosphere and ocean reanalyses were first produced respectively at Météo-France and Mercator Océan. Several nested experiments were then performed with a small and flexible ocean model limited to the region of interest. The date of the initial conditions and the type of atmospheric forcing fields were varied in order to produce a small ensemble from which information on the sensitivity to these changes could be derived. Probabilistic and statistical combinations between model and observations were tested and a solution was finally selected by means of a comparison of drift computations with independent surface drift observations.

  16. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  17. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  18. Draft Genome Sequence of Komagataeibacter rhaeticus Strain AF1, a High Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa A; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2014-07-24

    Here, we present the draft genome sequence of Komagatabaeicter rhaeticus strain AF1, which was isolated from Kombucha tea and is capable of producing high levels of cellulose. Copyright © 2014 dos Santos et al.

  19. [Improvement of natamycin production in an industrial strain by heterologous expression of the afsRS(cla) global regulatory genes].

    PubMed

    Tao, Zhengsheng; Wang, Yemin; Zheng, Hualiang; Tao, Meifeng

    2015-05-01

    The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.

  20. Comparison of radiofrequency catheter ablation of drivers and circumferential pulmonary vein isolation in atrial fibrillation: a noninferiority randomized multicenter RADAR-AF trial.

    PubMed

    Atienza, Felipe; Almendral, Jesús; Ormaetxe, José Miguel; Moya, Angel; Martínez-Alday, Jesús Daniel; Hernández-Madrid, Antonio; Castellanos, Eduardo; Arribas, Fernando; Arias, Miguel Ángel; Tercedor, Luis; Peinado, Rafael; Arcocha, Maria Fe; Ortiz, Mercedes; Martínez-Alzamora, Nieves; Arenal, Angel; Fernández-Avilés, Francisco; Jalife, José

    2014-12-16

    Empiric circumferential pulmonary vein isolation (CPVI) has become the therapy of choice for drug-refractory atrial fibrillation (AF). Although results are suboptimal, it is unknown whether mechanistically-based strategies targeting AF drivers are superior. This study sought to determine the efficacy and safety of localized high-frequency source ablation (HFSA) compared with CPVI in patients with drug-refractory AF. This prospective, multicenter, single-blinded study of 232 patients (age 53 ± 10 years, 186 males) randomized those with paroxysmal AF (n = 115) to CPVI or HFSA-only (noninferiority design) and those with persistent AF (n = 117) to CPVI or a combined ablation approach (CPVI + HFSA, superiority design). The primary endpoint was freedom from AF at 6 months post-first ablation procedure. Secondary endpoints included freedom from atrial tachyarrhythmias (AT) at 6 and 12 months, periprocedural complications, overall adverse events, and quality of life. In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months after a single procedure but, after redo procedures, was noninferior to CPVI at 12 months for freedom from AF and AF/AT. Serious adverse events were significantly reduced in the HFSA group versus CPVI patients (p = 0.02). In persistent AF, there were no significant differences between treatment groups for primary and secondary endpoints, but CPVI + HFSA trended toward more serious adverse events. In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months but was noninferior to CPVI at 1 year in achieving freedom of AF/AT and a lower incidence of severe adverse events. In persistent AF, CPVI + HFSA offered no incremental value. (Radiofrequency Ablation of Drivers of Atrial Fibrillation [RADAR-AF]; NCT00674401). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

    2016-02-12

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

  2. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

    PubMed

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2012-01-01

    The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

  3. UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

    SciTech Connect

    Stepanyuk, Galina A.; Serrano, Pedro; Peralta, Eigen; Farr, Carol L.; Axelrod, Herbert L.; Geralt, Michael; Das, Debanu; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Deacon, Ashley M.; Lesley, Scott A.; Elsliger, Marc-André; Godzik, Adam; Wilson, Ian A.; Wüthrich, Kurt; Salomon, Daniel R.; Williamson, James R.

    2016-03-24

    RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional co-activator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein–protein interactions through a short tryptophan-containing peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39–U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35–U2AF65 and RBM39–SF3b155, the RBM39-UHM–U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM–ULM binding interface, providing a rationale for the known specificity of UHM–ULM interactions. This study therefore establishes a structural basis for specific UHM–ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.

  4. Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-mRNA Splicing Factor U2AF65

    SciTech Connect

    Sickmier,E.; Frato, K.; Shen, H.; Paranawithana, S.; Green, M.; Kielkopf, C.

    2006-01-01

    The essential pre-mRNA splicing factor, U2AF{sup 65}, guides the early stages of splice site choice by recognizing a polypyrimidine (Py)-tract consensus sequence near the 3'-splice site. Since Py-tracts are relatively poorly conserved in higher eukaryotes, U2AF{sup 65} is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py-tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF{sup 65} RNA binding domain bound to a Py-tract composed of seven uridines has been determined at 2.5Angstroms resolution. Specific hydrogen bonds between U2AF{sup 65} and the uracil bases provide an explanation for polyuridine recognition. Flexible sidechains and bound water molecules form the majority of the base contacts, and potentially could rearrange when the U2AF{sup 65} structure adapts to different Py-tract sequences. The energetic importance of conserved residues for Py-tract binding is established by analysis of site-directed mutant U2AF{sup 65} proteins using surface plasmon resonance.

  5. Microstructural basis for the effect of chromium on the strength and toughness of AF1410-based high performance steels

    NASA Astrophysics Data System (ADS)

    Ayer, Raghavan; Machmeier, P. M.

    1996-09-01

    The variation in strength and Charpy impact toughness as a function of tempering temperature in the range of 200 ‡C to 650 ‡C was investigated in AF 1410 and AF 1410 + 1 pct Cr steels produced in a laboratory-scale, and a commercially produced AerMet 100 steel. The tensile test results showed that AF 1410 + 1 pct Cr had lower strength compared to AF 1410, while AerMet 100 had the highest strength of the three steels examined. Transmission electron microscopy (TEM) studies demonstrated that the strength variations among the steels can be attributed to differences in the matrix/carbide coherency strain and the volume fraction of the strengthening M2C carbides. The toughness values of the three steels were comparable when tempered up to 424 ‡C. Tempering at and above 454 ‡C resulted in a relative enhancement of toughness in AF 1410 + 1 pct Cr steel compared to AF 1410. This toughening was attributed to the destabilization of cementite at lath and prior austenite boundaries and the formation of reverted austenite.

  6. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-02-27

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata.

  7. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  8. [Biomechanics of AF new 3-d pedical screw system and treatment of 31 patients with unstable thoracolumbar fracture].

    PubMed

    Zou, D; Hai, Y; Ma, H

    1995-04-01

    For anatomic reduction of the spinal frectures, the 3 dimensional multiple correction forces were needed. Several pedical screw systems were designed for reducion and fixation of the spinal fractures as the AO universal joint system and the RF angle screw system. Because of the contradiction of the universal joint and the fixed angle, a new generation of RF was designed and named AF (atlas fixator) system. This is a new concept of 3-D reduction, without complex structure as universal joint, but has truly 3-D adjustment that allowed to reduce the intra-canal compromise. It also provided rigid fixation to maintain the reduction. Comparison with CD, AO, Steffee, and RF, the AF was truly 3-D reduction in XTZ axis. It provided strong symmetric transmitter orthotic force to correct the deformity. 31 patients with unstable thoracolumbar fractures were treated with the new AF system. 17 had partial (15) or complete (2) neurologic deficits. The AF system provided accurate angle to restore the normal thoracic-lumbar lordosis and to maintain it. All patients had a anatomic reduction by AF system. The spinal canal area increased over 33% by CT scan (P < 0.01). All cases were followed up over 8 months. No one deteriorated neurologically after AF fixation.

  9. Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

    PubMed Central

    Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

    2012-01-01

    The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. PMID:22792276

  10. Binding of hnRNP H and U2AF65 to respective G-codes and a poly-uridine tract collaborate in the N50-5'ss selection of the REST N exon in H69 cells.

    PubMed

    Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

    2012-01-01

    The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes.

  11. N-terminal pro-B-type Natriuretic Peptide is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study

    PubMed Central

    Patton, Kristen K.; Ellinor, Patrick T.; Heckbert, Susan R.; Christenson, Robert H.; DeFilippi, Christopher; Gottdiener, John S.; Kronmal, Richard A.

    2014-01-01

    Background Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and health care expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, atrial fibrillation, and mortality. Methods and Results The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5,445 Cardiovascular Health Study participants, using relative risk regression for predicting prevalent AF, and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95%CI 17.9, 913.3, p< 0.001); and adjusted prevalence ratio of 147 for the highest quintile (95% CI 20.4, 1064.3, p<0.001) compared to the lowest. After a median follow up of 10 years (maximum of 16 years), there were 1,126 cases of incident AF (a rate of 2.2 per 100 person years). NT-proBNP was highly predictive of incident AF with an unadjusted hazard ratio of 5.2 (95% CI 4.3, 6.4, p < 0.001) for the development of AF for the highest quintile compared to the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes, and heart failure; with an adjusted hazard ratio of 4.0 (CI 3.2, 5.0, p< 0.001). Conclusions In a community based population of older adults, NT-pro BNP was a remarkable predictor of incident AF, independent of any other previously described risk factor. PMID:19841297

  12. Loss of AF-6/afadin induces cell invasion, suppresses the formation of glandular structures and might be a predictive marker of resistance to chemotherapy in endometrial cancer.

    PubMed

    Yamamoto, Takuro; Mori, Taisuke; Sawada, Morio; Matsushima, Hiroshi; Ito, Fumitake; Akiyama, Makoto; Kitawaki, Jo

    2015-04-12

    AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon cancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in human endometrial cancer. Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional culture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell proliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by AF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were determined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from all patients before the study. The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin showed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA cells-both weakly expressing AF-6/afadin-showed irregular gland-like structures and disorganized colonies with no gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in 3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly AF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656) suppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance to doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed that AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade. AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through the ERK and Src pathway. The inhibitors to these pathways might be

  13. Responsiveness of AF6, a new, short, validated, atrial fibrillation-specific questionnaire—symptomatic benefit of direct current cardioversion

    PubMed Central

    Härdén, Marie; Nyström, Britta; Bengtson, Ann; Medin, Jennie; Frison, Lars

    2010-01-01

    Objectives To measure the effects on symptoms of electrical cardioversion (DC) in patients with atrial fibrillation (AF) by means of a new, short, validated, AF-specific questionnaire, the AF6. Methods One hundred eleven patients (67 ± 12 years, 89 men) were screened before and 12 ± 3 days after DC using AF6, covering ‘breathing difficulties at rest’, ‘breathing difficulties on exertion’, ‘limitations in day-to-day life due to atrial fibrillation’, ‘feeling of discomfort due to atrial fibrillation’, ‘tiredness due to atrial fibrillation’, and ‘worry/anxiety due to atrial fibrillation’. A single global score was calculated. The Toronto AF Symptoms and Severity Check List (AFSS) and the generic SF-36 were also administered. Patients in sinus rhythm at 12 ± 3 days (n = 56) were defined as responders and patients in AF (n = 55) as non-responders. Results The mean single global score decreased in all patients (18 ± 12.4 to 13 ± 11.6, p < 0.0001) and in responders (22 ± 14 vs. 12 ± 12, p < 0.01) but not in non-responders (14 ± 9 vs. 14 ± 11, N.S). The AFSS frequency scores decreased from 14.5 ± 7.7 to 9.5 ± 7.8 in responders, p = 0.001, but not in non-responders. There was a strong correlation between changes in the AF6 and the SF-36 regarding four of the six items. Effect sizes of AF6 ranged from 0 to 0.52 in all patients, in responders from 0.10 to 0.85 and in non-responders from −0.23 to 0.34, the highest figures consistently referring to ‘tiredness due to atrial fibrillation’. Conclusions The symptom scores measured by AF6 decreased significantly, especially in responders. AF6 demonstrated adequate responsiveness to change, and effect sizes were mostly moderate, in responders moderate to high. PMID:20461545

  14. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.

    PubMed

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M; Medeiros, Rodrigo

    2016-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies.

  15. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s disease

    PubMed Central

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A.; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M.; Medeiros, Rodrigo

    2015-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g., AF102B, AF267B, and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (phopho-ERK1/2, phospho-CREB). AF710B (1–30 µg/kg, po) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its anti-amnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice AF710B (10 µg/kg, ip/daily/2 months) – i) mitigated cognitive impairments in Morris water maze; ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1, M1 muscarinic (orthosteric, allosteric or bi-topic) or σ1/muscarinic agonists. These results highlight AF710B as a potential treatment for AD (e.g., improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  16. Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study.

    PubMed

    Turakhia, Mintu P; Santangeli, Pasquale; Winkelmayer, Wolfgang C; Xu, Xiangyan; Ullal, Aditya J; Than, Claire T; Schmitt, Susan; Holmes, Tyson H; Frayne, Susan M; Phibbs, Ciaran S; Yang, Felix; Hoang, Donald D; Ho, P Michael; Heidenreich, Paul A

    2014-08-19

    Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). The goal of this study was to evaluate the association of digoxin with mortality in AF. Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.

    PubMed

    Wong, Ka Sing Lawrence; Hu, Dai Yi; Oomman, Abraham; Tan, Ru-San; Patel, Manesh R; Singer, Daniel E; Breithardt, Günter; Mahaffey, Kenneth W; Becker, Richard C; Califf, Robert; Fox, Keith A A; Berkowitz, Scott D; Hacke, Werner; Hankey, Graeme J

    2014-06-01

    In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. http://www.clinicaltrials.gov. Unique identifier: NCT00123456. © 2014 American Heart Association, Inc.

  18. Monitoring of individual human exposure to aflatoxins (AF) and N-nitrosamines (NNO) by immunoassays

    SciTech Connect

    Wild, C.P.; Umbenhauer, D.; Chapot, B.; Montesano, R.

    1986-01-01

    Highly sensitive immunoassays have been used to quantitate aflatoxins (AF) and N-nitrosamines (NNO) in human body fluids and tissues, respectively. This approach was taken in order to quantitate environmental exposure to these agents at an individual level to facilitate the investigation of their role in the etiology of human cancer. In order to analyse AF in human urine, an immunopurification step has been developed by using AF-specific antibody bound to AH-Sepharose 4B gel in a small (4-ml gel volume) affinity column prior to enzyme-linked immunosorbent assay (ELISA). The ELISA can be used to quantitate aflatoxin B1 (AFB1) over the range 0.01 ng/ml to 10 ng/ml and the assay system has been validated by using human urine samples spiked with AFB1 over this concentration range. In addition, 29 urine samples from the Philippines have been analyzed and found to contain a range of levels from zero to 4.25 ng/ml AFB1 equivalent with a mean of 0.875 ng/ml. This compared with a mean of 0.066 ng/ml AFB1 equivalent in samples from France. Radioimmunoassay of O6-methyldeoxyguanosine (O6-medG) has been performed on human esophageal and cardiac stomach mucosal DNA from tissue samples obtained during surgery in Linxian County, People's Republic of China, an area of high risk for both esophageal and stomach cancer. Using the methodology described and having 1 mg of hydrolyzed DNA allows the detection of approximately 25 fmol O6medG per mg DNA.

  19. Decision making for oral anticoagulants in atrial fibrillation: the ATA-AF study.

    PubMed

    Gussoni, Gualberto; Di Pasquale, Giuseppe; Vescovo, Giorgio; Gulizia, Michele; Mathieu, Giovanni; Scherillo, Marino; Panuccio, Domenico; Lucci, Donata; Nozzoli, Carlo; Fabbri, Gianna; Colombo, Fabrizio; Riva, Letizia; Baldo, Concetta I; Maggioni, Aldo P; Mazzone, Antonino

    2013-06-01

    Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF. 7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED). 63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score<2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS2<2 and bleeding score≥3 were independent predictors of non-use of VKA. Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  20. Involvenflavones A-F, six new flavonoids with 3'-aryl substituent from Selaginella involven.

    PubMed

    Long, Hong-Ping; Zou, Hui; Li, Fu-Shuang; Li, Jing; Luo, Ping; Zou, Zhen-Xing; Hu, Chang-Ping; Xu, Kang-Ping; Tan, Gui-Shan

    2015-09-01

    Six new flavonoids, involvenflavones A-F (1-6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3'-aryl substituent. This is the first report of the apigenin derivatives with 3'-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

  1. Spectral analysis of LBV stars in M31: AF And and Var 15

    NASA Astrophysics Data System (ADS)

    Valeev, A. F.; Sholukhova, O.; Fabrika, S.

    2015-01-01

    We study spectra of two bona fide LBV stars in M31: AF And and Var 15. The spectra were obtained with the 6-m telescope (Russia) from 2005 to 2012. The model spectra were calculated with the CMFGEN code. We have not found strong changes in the spectra of the LBV stars in that time interval, however a certain variability has been detected. We estimate the star and wind parameters, such as luminosity, temperature, raduis, mass loss rate, escape velocity, hydrogen content, and reddening. We study the stars on the Hertzsprung-Russell diagram and find their initial masses using evolutionary tracks by Meynet et al. (1994).

  2. Different image integration modalities to guide AF ablation: impact on procedural and fluoroscopy times.

    PubMed

    Pratola, Claudio; Baldo, Elisa; Artale, Paolo; Marcantoni, Lina; Toselli, Tiziano; Percoco, Gianfranco; Sassone, Biagio; Ferrari, Roberto

    2011-04-01

    Different image integration modalities are available for atrial fibrillation (AF) ablation, but their impact on procedural and fluoroscopy times has not been evaluated yet. Sixty patients (mean age 52.2 ± 12.0 years, 48.3% men, 75% paroxysmal AF) undergoing pulmonary vein (PV) encircling with PV disconnection for symptomatic drug-refractory AF were randomized to ablation with CARTO electroanatomical mapping (Biosense Webster, Diamond Bar, CA, USA) integrated with: (1) preprocedural magnetic resonance imaging (MRI; Group 1); (2) intracardiac echocardiography (ICE; Group 2); (3) preprocedural MRI and ICE (Group 3). PV disconnection was achieved in all patients. Total procedural time (Group 1: 124.7 ± 47.0; Group 2: 112.5 ± 30.4; Group 3: 108.6 ± 34.7 minutes) and total ablation time were similar between groups (P = ns). MRI integration alone required a higher fluoroscopy time (23.8 ± 6.9 in Group 1 vs 11.0 ± 2.3 and 13.9 ± 4.2 minutes in Groups 2 and 3, respectively; P < 0.005) and a longer time spent in the left atrium (109.0 ± 43.5 in Group 1 vs 78.2 ± 29.7 and 74.8 ± 34.3 minutes in Groups 2 and 3, respectively; P = 0.03) in comparison to ICE integration. Addition of MRI to ICE integration showed a tendency for a higher fluoroscopy time in comparison to ICE integration alone (P = 0.06). At a mean follow-up of 9.1 ± 2.2 months, there were no significant differences in AF recurrences among the groups (P = ns). ICE image integration significantly reduces the fluoroscopy time and the time spent in the left atrium in comparison to MRI integration alone. Addition of MRI to ICE integration does not reduce total procedural time and seems to lead to higher fluoroscopy time in comparison to ICE integration alone. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

  3. Alconbury RAF United Kingdom Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-04-01

    AD A746 q13 ALCONBURY RAF UNITED KINGDOM REVISFD UNIFORM SUMMARY OF 1/5SURFACE WEAIER 0..(t0) AIR FORCE ENVIRONMENTAL I CNICAI APPI CATI(NS CENTER...PROCESSING DIVISION USAFETAC Air Weather Service ( MAC) 0SURFACL V, LI’. ILI, I.LRVATIONS F4 ALCOjIwURY RAF UK HSIA #0362 N 52 22 W 000 13 EIEV 16OFIT EGWZ...A RAIWOKUTNMBS Air Force Environmental Technical Appi. Center Scott AFS, IL 62225 1 1 CONTROLLING OFFICE NAME AND ADDRESS OZ. REPORT DATS USAFETAC

  4. Candenatenins A-F, phenolic compounds from the heartwood of Dalbergia candenatensis.

    PubMed

    Cheenpracha, Sarot; Karalai, Chatchanok; Ponglimanont, Chanita; Kanjana-Opas, Akkharawit

    2009-08-01

    Chemical investigation of the CH2Cl2 extract of the heartwood of Dalbergia candenatensis affored six new phenolic compounds, designated candenatenins A-F (1-6), as well as four known compounds, (2R,3R)-3,5-dihydroxy-7-methoxyflavanone (7), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (8), nutiducol (9), and sophoraflavanone A (10). The structures of the new compounds were determined by 1D- and 2D-NMR spectroscopic studies as well as by MS analysis. The cytotoxic activities of the isolated compounds are also reported.

  5. A novel clinical multimodal multiphoton tomograph for AF, SHG, CARS imaging, and FLIM

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; König, Karsten

    2014-02-01

    We report on a flexible nonlinear medical tomograph with multiple miniaturized detectors for simultaneous acquisition of two-photon autofluorescence (AF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) images. The simultaneous visualization of the distribution of endogenous fluorophores NAD(P)H, melanin and elastin, SHG-active collagen and as well as non-fluorescent lipids within human skin in vivo is possible. Furthermore, fluorescence lifetime images (FLIM) can be generated using time-correlated single photon counting.

  6. Dover AFB Delaware. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1974-08-07

    SNOW X OF SMOKE DUST X OF OSS TOTALMONTH T. STORMS AD/OR RAIN &/fOR AND/OR HAIL IObs WITH FOG AND/ORt BOWIG AND/ORt WITH ORST NO. OF( ST )DRIZZLE DRIZZLE...OBSERVATIONS) 13707 DUVEF AF8 DELAWARE 4 Ago4 f!,SL 55 AR STATION STATION RA50 01055 MONTH ALL WEATHER ALL CLASS NOVAS ( ST .) ( CONDITION SPE MEAN (NT...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 1.3707 )0VEIc AFB 0ELAwAIRE 43-46251-72 JAN4 ALL WEATHEV, 0600-0800 Cuss x05o5 ILL ST .) SIPEED i MEAN (KNTS

  7. A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

    PubMed Central

    Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

    2017-01-01

    Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination

  8. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.

    PubMed

    Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Breithardt, Günter

    2013-05-14

    This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin

  9. Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

    PubMed

    Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

    2017-08-26

    Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT2R2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support,education, and patient

  10. Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'.

    PubMed

    Kirchhof, Paulus; Bax, Jeroen; Blomstrom-Lundquist, Carina; Calkins, Hugh; Camm, A John; Cappato, Ricardo; Cosio, Francisco; Crijns, Harry; Diener, Hans-Christian; Goette, Andreas; Israel, Carsten W; Kuck, Karl-Heinz; Lip, Gregory Y H; Nattel, Stanley; Page, Richard L; Ravens, Ursula; Schotten, Ulrich; Steinbeck, Gerhard; Vardas, Panos; Waldo, Albert; Wegscheider, Karl; Willems, Stephan; Breithardt, Günter

    2009-12-01

    Atrial fibrillation (AF) causes important mortality and morbidity on a population-level. So far, we do not have the means to prevent AF or AF-related complications adequately. Therefore, over 70 experts on atrial fibrillation convened for the 2nd AFNET/EHRA consensus conference to suggest directions for research to improve management of AF patients (Appendix 1). The group defined three main areas in need for research in AF: 1. better understanding of the mechanisms of AF; 2. Improving rhythm control monitoring and management; and 3. comprehensive cardiovascular risk management in AF patients. The group put forward the hypothesis that successful therapy of AF and its associated complications will require comprehensive therapy. This applies e.g. to the "old" debate of "rate versus rhythm control", since rhythm control is generally added to underlying (continued) rate control therapy, but also to the emerging debate of "antiarrhythmic drugs versus catheter ablation", of which both may be needed in most patients to maintain sinus rhythm, but also to therapy of conditions that predispose to AF and contribute to cardiovascular complications such as stroke, cognitive decline, heart failure, and acute coronary syndromes. We call for research initiatives aiming at a better understanding of the different causes of AF and its complications, and at development and validation of mechanism-based therapies. The future of AF therapy may require a combination of management of underlying and concomitant conditions, early and comprehensive rhythm control therapy, adequate control of ventricular rate and cardiac function, and continuous therapy to prevent AF-associated complications (e.g. antithrombotic therapy). The reasons for these suggestions are detailed in this paper.

  11. Relationship between Af temperature and load changes in Ni-Ti orthodontic wire under different thermomechanical conditions.

    PubMed

    Kawashima, I; Ohno, H; Sachdeva, R

    1999-12-01

    Simple three point bending tests were performed on Ni-Ti wires with three different Af points (1 degree C, 13 degrees C and 34 degrees C) to clarify the relationship between Af temperature and load changes under constant deformation. Each wire was deformed at 37 degrees C and then thermal changes were imposed by temperatures of 2 degrees C or 60 degrees C. The load changes with thermal changes from 37 degrees C to 2 degrees C or 60 degrees C showed the same tendency on the wires with different Af points: In the loading stage, the load became lower than the initial level at 37 degrees C and in the unloading stage, the load became higher than the initial load. The largest load change in the unloading stage was measured with the 13 degrees C Af point wire. Care must be taken when handling Ni-Ti wire with an Af point of less than 1 degree C in order to prevent it from reaching the limit of critical stress of slip deformation when the temperature in the mouth rises to above 40 degrees C.

  12. An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

    PubMed Central

    Agrawal, Anant A.; Salsi, Enea; Chatrikhi, Rakesh; Henderson, Steven; Jenkins, Jermaine L.; Green, Michael R.; Ermolenko, Dmitri N.; Kielkopf, Clara L.

    2016-01-01

    How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals. PMID:26952537

  13. Response of Nitrosospira sp. Strain AF-Like Ammonia Oxidizers to Changes in Temperature, Soil Moisture Content, and Fertilizer Concentration▿

    PubMed Central

    Avrahami, Sharon; Bohannan, Brendan J. M.

    2007-01-01

    Very little is known regarding the ecology of Nitrosospira sp. strain AF-like bacteria, a unique group of ammonia oxidizers within the Betaproteobacteria. We studied the response of Nitrosospira sp. strain AF-like ammonia oxidizers to changing environmental conditions by applying molecular methods and physiological measurements to Californian grassland soil manipulated in the laboratory. This soil is naturally high in Nitrosospira sp. strain AF-like bacteria relative to the much-better-studied Nitrosospira multiformis-like ammonia-oxidizing bacteria. Increases in temperature, soil moisture, and fertilizer interacted to reduce the relative abundance of Nitrosospira sp. strain AF-like bacteria, although they remained numerically dominant. The overall abundance of ammonia-oxidizing bacteria increased with increasing soil moisture and decreased with increasing temperature. Potential nitrification activity was altered by interactions among temperature, soil moisture, and fertilizer, with activity tending to be higher when soil moisture and temperature were increased. The increase in potential nitrification activity with increased temperature was surprising, given that the overall abundance of ammonia-oxidizing bacteria decreased significantly under these conditions. This observation suggests that (i) Nitrosospira sp. strain AF-like bacteria may respond to increased temperature with an increase in activity, despite a decrease in abundance, or (ii) that potential nitrification activity in these soils may be due to organisms other than bacteria (e.g., archaeal ammonia oxidizers), at least under conditions of increased temperature. PMID:17158615

  14. The splicing factor U2AF65 is functionally conserved in the thermotolerant deep-sea worm Alvinella pompejana.

    PubMed

    Henscheid, Kristy L; Shin, David S; Cary, S Craig; Berglund, J Andrew

    2005-03-10

    Due to their inherent stability, thermophilic bacteria and archaea serve as important resources for biochemical and biophysical analyses of many biological processes. Unfortunately, scientists characterizing eukaryote-specific processes, such as nuclear pre-mRNA splicing, are unable to take advantage of these sources of thermostable proteins. To identify and provide a source of thermostable eukaryotic proteins, we are characterizing splicing factors in the thermotolerant deep-sea vent polychaete, Alvinella pompejana. This worm, also known as the Pompeii worm, is found in the extreme environment of deep-sea hydrothermal vents, and is one of the most thermotolerant eukaryotic organisms known. We report on detailed analyses of U2AF65, the large subunit of the U2 small nuclear ribonucleoprotein auxiliary factor, an essential splicing factor important for intron definition and alternative splicing. The cloning and characterization of Pompeii U2AF65 show it is highly similar to human U2AF65 in sequence and function and is more thermostable than the human protein when bound to RNA in vitro. Notably, Pompeii U2AF65 can restore splicing in a human extract depleted of human U2AF. We also determine that the general splicing mechanisms and signal sequences are conserved in the Pompeii worm, an annelid which has previously been uncharacterized in terms of splicing factors and signals.

  15. Type 2 diabetes, glucose homeostasis and incident atrial fibrillation: the Atherosclerosis Risk in Communities Study

    PubMed Central

    Huxley, Rachel R.; Alonso, Alvaro; Lopez, Faye L.; Filion, Kristian B.; Agarwal, Sunil K.; Loehr, Laura R.; Soliman, Elsayed Z.; Pankow, James S.; Selvin, Elizabeth

    2011-01-01

    Objective Type 2 diabetes has been inconsistently associated with risk of atrial fibrillation (AF) in previous studies that have frequently been beset by methodological challenges. Design Prospective cohort study. Setting The Atherosclerosis Risk in Communities Study. Participants Detailed medical histories were obtained on 13025 participants. Individuals were categorized as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990–92). Main Outcome Measures Diagnoses of incident AF were obtained through 2007. Associations between type 2 diabetes and markers of glucose homeostasis with the incidence of AF were estimated using Cox proportional hazards models after adjusting for possible confounders. Results Type 2 diabetes was associated with a significant increase in risk of AF (HR 1.35, 95% confidence interval [CI]: 1.14–1.60) after adjustment for confounders. There was no indication that individuals with pre-diabetes or those with undiagnosed diabetes were at increased risk of AF compared to those without diabetes. We observed a positive linear association between HbA1c and risk of AF in those with and without diabetes: 1.13 (1.07–1.20) and 1.05 (0.96–1.15) per 1% point increase, respectively. There was no association between fasting glucose or insulin (p>0.05) in those without diabetes but a significant association with fasting glucose in those with the condition (p=0.0002). Results were similar in whites and African Americans. Conclusions Diabetes, HbA1c level and poor glycemic control are independently associated with increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation. PMID:21930722

  16. Impact of Intensive Glycemic Control on the Incidence of Atrial Fibrillation and Associated Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus (from the ACCORD Study)

    PubMed Central

    Fatemi, Omid; Yuriditsky, Eugene; Tsioufis, Costas; Tsachris, Demetrios; Morgan, Timothy; Basile, Jan; Bigger, Thomas; Cushman, William; Goff, David; Soliman, Elsayed Z.; Thomas, Abraham; Papademetriou, Vasilios

    2014-01-01

    Atrial fibrillation (AF) is prevalent among individuals with type 2 diabetes mellitus (DM), and is associated with markers of poor glycemic control; however the impact of glycemic control on incident AF and outcomes is unknown. We sought to prospectively evaluate if intensive glycemic control in individuals with DM impacts incident AF, and to evaluate morbidity and mortality among individuals with DM and incident AF. We studied 10,082 individuals with DM from the ACCORD cohort in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0%, or a standard strategy targeting a glycated hemoglobin of 7.0-7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period at a rate of 5.9/1,000 person-years in the intensive-therapy group, and a rate of 6.37/1,000 person-years in the standard-therapy group (p=0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a HR of 2.65 for all-cause mortality (95% CI 1.8-3.86, p<0.0001), HR of 2.1 for myocardial infarction (95% CI 1.33-3.31, p=0.0015), and HR of 3.80 for development of heart failure (95% CI 2.48-5.84, p<0.0001). In conclusion, intensive glycemic control did not impact rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality as compared to those without AF. PMID:25159234

  17. Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo

    PubMed Central

    Rudner, David Z.; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential role in 3′ splice site selection. U2AF binds the intron pyrimidine tract between the branchpoint and the 3′ splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain enriched in arginine–serine dipeptide repeats termed an RS domain. The two U2AF RS domains have been assigned essential and independent roles in spliceosome assembly in vitro—the hU2AF65 RS domain is required to target U2 snRNP to the branch site and the hU2AF35 RS domain is necessary for protein–protein interactions with constitutive and alternative splicing factors. We have investigated the functional requirements for the RS domains on the Drosophila U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result, we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38). Despite its requirement for enhancer-dependent splicing activity in vitro, the dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the small and large subunits could not be rescued by dU2AF50ΔRS and dU2AF38ΔRS transgenes. Therefore, in contrast to the separate roles assigned to the U2AF RS domains in vitro, our genetic data suggest that they may have redundant functions in vivo. PMID:9531538

  18. Substrate specificity and gene expression of two Penicillium chrysogenum α-L-arabinofuranosidases (AFQ1 and AFS1) belonging to glycoside hydrolase families 51 and 54.

    PubMed

    Sakamoto, Tatsuji; Inui, Misako; Yasui, Kana; Hosokawa, Sachiko; Ihara, Hideshi

    2013-02-01

    We previously isolated two α-L-arabinofuranosidases (ABFs), termed AFQ1 and AFS1, from the culture filtrate of Penicillium chrysogenum 31B. afq1 and afs1 complementary DNAs encoding AFQ1 and AFS1 were isolated by in vitro cloning. The deduced amino acid sequences of AFQ1 and AFS1 are highly similar to those of Penicillium purpurogenum ABF 2 and ABF 1, respectively, which belong to glycoside hydrolase (GH) families 51 and 54, respectively. Pfam analysis revealed an "Alpha-L-AF_C" domain in AFQ1 and "ArabFuran-catal" and "AbfB" domains in AFS1. Semi-quantitative RT-PCR analysis indicated that the afq1 gene was constitutively expressed in P. chrysogenum 31B at a low level, although the expression was slightly induced with arabinose, arabinitol, arabinan, and arabinoxylan. In contrast, expression of the afs1 gene was strongly expressed by the above four carbohydrates and less strongly induced by galactan. Recombinant enzymes (rAFQ1 and rAFS1) expressed in Escherichia coli were active against both p-nitrophenyl α-L-arabinofuranoside and polysaccharides with different specificities. (1)H-NMR analysis revealed that rAFS1 degraded arabinofuranosyl side chains that were both singly and doubly linked to the backbones of arabinoxylan and L-arabinan. On the other hand, rAFQ1 preferentially released arabinose linked to C-3 of single-substituted xylose or arabinose residues in the two polysaccharides.

  19. Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

    NASA Technical Reports Server (NTRS)

    McClure, Mark B.; Greene, Benjamin

    2014-01-01

    All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

  20. Intracardiac impedance response during acute AF internal cardioversion using novel rectilinear and capacitor-discharge waveforms.

    PubMed

    Rababah, A S; Walsh, S J; Manoharan, G; Walsh, P R; Escalona, O J

    2016-07-01

    Intracardiac impedance (ICI) is a major determinant of success during internal cardioversion of atrial fibrillation (AF). However, there have been few studies that have examined the dynamic behaviour of atrial impedance during internal cardioversion in relation to clinical outcome. In this study, voltage and current waveforms captured during internal cardioversion of acute AF in ovine models using novel radiofrequency (RF) generated low-tilt rectilinear and conventional capacitor-discharge based shock waveforms were retrospectively analysed using a digital signal processing algorithm to investigate the dynamic behaviour of atrial impedance during cardioversion. The algorithm was specifically designed to facilitate the simultaneous analysis of multiple impedance parameters, including: mean intracardiac impedance (Z M), intracardiac impedance variance (ICIV) and impedance amplitude spectrum area (IAMSA) for each cardioversion event. A significant reduction in ICI was observed when comparing two successive shocks of increasing energy where cardioversion outcome was successful. In addition, ICIV and IAMSA variables were found to inversely correlate to the magnitude of energy delivered; with a stronger correlation found to the former parameter. In conclusion, ICIV and IAMSA have been evidenced as two key dynamic intracardiac impedance variables that may prove useful in better understanding of the cardioversion process and that could potentially act as prognostic markers with respect to clinical outcome.

  1. Loss of Dnmt3b accelerates MLL-AF9 leukemia progression.

    PubMed

    Zheng, Y; Zhang, H; Wang, Y; Li, X; Lu, P; Dong, F; Pang, Y; Ma, S; Cheng, H; Hao, S; Tang, F; Yuan, W; Zhang, X; Cheng, T

    2016-12-01

    Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. Abnormal DNA methylation is involved in the initiation and progression of AML. The de novo methyltransferases Dnmt3a and Dnmt3b are responsible for the generation of genomic methylation patterns. While DNMT3A is frequently mutated in hematological malignancies, DNMT3B is rarely mutated. Although it has been previously reported that Dnmt3b functions as a tumor suppressor in a mouse model of Myc-induced lymphomagenesis, its function in AML is yet to be determined. In this study, we demonstrated that deletion of Dnmt3b accelerated the progression of MLL-AF9 leukemia by increasing stemness and enhancing cell cycle progression. Gene profiling analysis revealed upregulation of the oncogenic gene set and downregulation of the cell differentiation gene set. Furthermore, loss of Dnmt3b was able to synergize with Dnmt3a deficiency in leukemia development. Taken together, these results demonstrate that Dnmt3b plays a tumor suppressive role in MLL-AF9 AML progression, thereby providing new insights into the roles of DNA methylation in leukemia development.

  2. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection.

    PubMed

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-07-17

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes' status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors' detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability.

  3. Multiple-image-depth modeling for hotspot and AF printing detections

    NASA Astrophysics Data System (ADS)

    Tang, Y. P.; Chou, C. S.; Huang, W. C.; Liu, R. G.; Gau, T. S.

    2012-03-01

    Typical OPC models focus on predicting wafer contour or CD; therefore, the modeling approach emphasizes careful determination of feature and edge locations in the photo-resist (PR) as well as the exposure threshold, so that the 'cut' model image matches the wafer SEM contours or cut-line CDs most closely. This is an exquisite approach with regard to the contour-based OPC, for the model is calibrated directly from wafer CDs. However, for other applications such as hotspot detection or assist feature (AF) printing prediction that might occur at the top or the bottom of the PR, the typical OPC model approach may not be accurate enough. Usually, these kinds of phenomenon can only be properly described by rigorous simulation, which is very time-consuming and hence not suitable for OPC. In this paper, the approach of building the OPC model with multiple image depths will be discussed. This approach references the images at the bottom and/or the top of the PR. This way, the behavior of the images which are not shown at the normal image depth can be predicted more accurately without distorting the optical model. This compromised OPC modeling approach is beneficial for runtime reduction compared to the rigorous simulation, and for better accuracy compared to conventional model. The applications for AF printing and hotspot predictions using the multiple image depth approach will be demonstrated.

  4. EPA Region 2 AIRS FACILITY SUBSYSTEM (AIRS-AFS) GIS Layer

    EPA Pesticide Factsheets

    This ArcGIS 10.2 point feature class contains identification, location and status information for EPA Region 2 facilities (NYS, NJ, Puerto Rico and the US Virgin Islands) registered in the Aerometric Information Retrieval System - Air Facility Subsystem. (AIRS/AFS). The AFS subsystem contains emissions, compliance, and permit data for stationary sources regulated by the U.S. EPA and state and local air pollution agencies. This information is used by states in preparation of State Implementation Plans (SIPs), to track the compliance status of point sources with various regulatory programs, and report emissions estimates for pollutants regulated under the Clean Air Act.All data for EPA Region 2 Regulated Facility GIS layers are extracted from the Facility Registry System (FRS) of Envirofacts on a monthly basis using R2GIS SQL procedures and Linked Server definitions. The attributes for each media specific R2GIS Regulated Facility layer provides the ID, name, address and environmental interest (permit designation or regulated activity) from the parent media program system and the best available coordinates from the FRS Geospatial Tables except for the Region 2 CERLIS layers were all locational data is from the CERCLIS database only. There are a small percentage of EPA Regulated Facilities for which no coordinate information has been registered in any of the related EPA or State Program System Databases. These facilities will have attribute table records in the Fa

  5. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

    PubMed Central

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  6. Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

    NASA Astrophysics Data System (ADS)

    Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

    2013-11-01

    In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

  7. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  8. [Mutational analysis of RNA splicing machinery genes SF3B1, U2AF1 and SRSF2 in 118 patients with myelodysplastic syndromes and related diseases].

    PubMed

    Wang, J Y; Ma, J; Lin, Y N; Wang, J; Shen, H; Gui, F M; Han, C; Li, Q H; Song, Z; Wang, X J

    2017-03-14

    Objective: To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases. Methods: Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis. Results: Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) years vs 51 (13-84) years, z=-1.981, P=0.048], lower HGB level[63 (40-95) g/L vs 77 (34-144) g/L, z=-3.192, P=0.001], higher platelet counts[121 (22-888) ×10(9)/L vs 59 (6-1 561) ×10(9)/L, z=-3.305, P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122) vs 0.017 (0-0.268) , z=-2.885, P=0.004], higher ring sideroblasts percent [0 (0-64%) vs 0 (0-58%) , z=-4.664, P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients. Conclusion: Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.

  9. MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia.

    PubMed

    Monroe, Sara C; Jo, Stephanie Y; Sanders, Daniel S; Basrur, Venkatesha; Elenitoba-Johnson, Kojo S; Slany, Robert K; Hess, Jay L

    2011-01-01

    The aim of this study was to better understand how mixed lineage leukemia (MLL) fusion proteins deregulate the expression of genes critical for leukemia. The transforming domain of one of the most common MLL fusion partners, AF9, was immunopurified after expression in myeloblastic M1 cells, and associating proteins were identified by mass spectrometric analysis. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction was used to determine how binding of associating proteins compare across Hoxa9 and Meis1 in cell lines with and without MLL fusion proteins and how binding is altered during gene down-regulation and differentiation. Consistent with earlier purifications of ENL and AF4 from 293 cells, the 90 amino acid C-terminal domain of AF9 associates with many other MLL translocation partners including Enl, Af4, Laf4, Af5q31, Ell, and Af10. This complex, termed elongation assisting proteins (EAPs), also contains the RNA polymerase II C-terminal domain kinase Cdk9/Cyclin T1/T2 (pTEFb) and the histone H3 lysine 79 methyltransferase Dot1L. Myeloid cells transformed by MLL fusions show higher levels and a broader distribution of EAP components at genes critical for leukemia. Inhibition of EAP components pTEFb and Dot1l show that both contribute significantly to activation of Hoxa9 and Meis1 expression. EAP is dynamically associated with the Hoxa9 and Meis1 loci in hematopoietic cells and rapidly dissociates during induction of differentiation. In the presence of MLL fusion proteins, its dissociation is prevented. The findings suggest that MLL fusion proteins deregulate genes critical for leukemia by excessive recruitment and impaired dissociation of EAP from target loci. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  10. MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia

    PubMed Central

    Monroe, Sara C.; Jo, Stephanie Y.; Sanders, Daniel S.; Basrur, Venkatesha; Elenitoba-Johnson, Kojo S.; Slany, Robert K.; Hess, Jay L.

    2011-01-01

    Objective The aim of this study was to better understand how MLL fusion proteins deregulate the expression of genes critical for leukemia. Materials and Methods The transforming domain of one of the most common MLL fusion partners, AF9, was immuno-purified after expression in myeloblastic M1 cells and associating proteins were identified by mass spectrometric analysis. Chromatin immunoprecipitation followed by quantitative PCR was used to determine how binding of associating proteins compare across Hoxa9 and Meis1 in cell lines with and without MLL fusion proteins and how binding is altered during gene down-regulation and differentiation. Results Consistent with earlier purifications of ENL and AF4 from 293 cells, the 90 amino acid C- terminal domain of AF9 associates with many other MLL translocation partners including Enl, Af4, Laf4, Af5q31, Ell, and Af10. This complex termed EAP for Elongation Assisting Proteins, also contains the RNA polymerase II C terminal domain kinase Cdk9/Cyclin T1/T2 (pTEFb) and the histone H3 lysine 79 methyltransferase Dot1L. Myeloid cells transformed by MLL fusions show higher levels and a broader distribution of EAP components at genes critical for leukemia. Inhibition of EAP components pTEFb and Dot1l show that both contribute significantly to activation of Hoxa9 and Meis1 expression. EAP is dynamically associated with the Hoxa9 and Meis1 loci in hematopoietic cells and rapidly dissociates during induction of differentiation. In the presence of MLL fusion proteins, its dissociation is prevented. Conclusion The findings suggest that MLL fusion proteins deregulate genes critical for leukemia by excessive recruitment and impaired dissociation of EAP from target loci. PMID:20854876

  11. A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

    PubMed

    Choe, William C; Passman, Rod S; Brachmann, Johannes; Morillo, Carlos A; Sanna, Tommaso; Bernstein, Richard A; Di Lazzaro, Vincenzo; Diener, Hans-Christoph; Rymer, Marilyn M; Beckers, Frank; Koehler, Jodi; Ziegler, Paul D

    2015-09-15

    Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke.

  12. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  13. AF03, an alternative squalene emulsion-based vaccine adjuvant prepared by a phase inversion temperature method.

    PubMed

    Klucker, Marie-Françoise; Dalençon, François; Probeck, Patricia; Haensler, Jean

    2012-12-01

    AF03 is a squalene-based emulsion adjuvant that is present in the adjuvanted pandemic influenza vaccine, Humenza™. In this report, we describe the design and development of this novel adjuvant formulation from the selection of the oil and surfactant system used in the adjuvant composition to the phase inversion temperature emulsification process that afforded AF03 as a long-term stable and well calibrated oil-in-water emulsion. The emulsion was characterized by its particle sizes, surface and interfacial tensions, viscosity, and long-term stability. Copyright © 2012 Wiley Periodicals, Inc.

  14. USAF Bioenvironmental Noise Data Handbook. Volume 166. AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft,

    DTIC Science & Technology

    1982-07-01

    OPERATOR NOISE MEASUREMENTS AF/M32T-1 Tester, Pressurized Cabin Leakage, Aircraft Tyndall AFB, 19 June 1980 NSN 4920-00- 347 -9455, Field * J108...a- a a o a af .4a a0 1 P ,? o4 o1 01 ao aD Nh s 1AA a ~ ~ a naaa .4 a aif CL O va I am wEj r .M PO -ODM.a)a D aa CDo NW)N 4 % ma a a. . 9 w ao N~ a I

  15. The Atrial Fibrillation Therapies after ER visit: Outpatient Care for Patients with Acute AF - The AFTER3 Study.

    PubMed

    Angaran, Paul; Mariano, Zara; Dragan, Vlad; Zou, Lily; Atzema, Clare L; Mangat, Iqwal; Dorian, Paul

    2015-01-01

    Visits to the emergency room (ER) for atrial fibrillation/flutter (AF) are common, but follow-up care is rarely systematically organized and is often delayed. We conducted a pilot program to develop a systematic, protocol-based system of care for patients presenting to the ER with a primary diagnosis of AF. Consecutive patients presenting to the ER with ECG-documented AF at an urban teaching hospital were treated according to a guideline-based care protocol, including a patient toolkit at ER discharge, and systematic referral to a rapid access AF clinic. Consenting patients received questionnaires on AF knowledge, patient satisfaction, and the AFEQT questionnaire at first visit and three-month follow-up. Of the 321 patients with AF, 244 (76%) were discharged from the ER and 166 (68%) were referred to the AF clinic for urgent follow-up. Among 166 referred, 144 (87%) were seen, within a median 10.5 days (IQR 6-16.5 days); 128 (89%) patients agreed to participate in the study and 81% received a toolkit in the ER. The mean age of patients seen in AF clinic was 63.6±13.2 years and 59% were male. Eighty-seven percent were aware of their diagnosis, stroke risk (82%), possible complications (90%), treatment options (86%) and benefits of adherence (86%). Severity of Atrial Fibrillation class was > 2 in 51% at baseline; AFEQT scores increased from baseline (56.4±25.5) to three months post-ER visit (76.4±20.0), a moderately large improvement in QOL (p<0.0001). Seventy eight percent of patients with CHA2DS2-VASc score > 1 were treated with an oral anticoagulant. A systematic program to improve patient transition of care from the ER to community clinic was associated with prompt, guideline-based care, and high levels of patient disease awareness. Quality of life scores improved substantially between the index ER visit and 3 months post-visit.

  16. Improved outcomes with European Society of Cardiology guideline-adherent antithrombotic treatment in high-risk patients with atrial fibrillation: a report from the EORP-AF General Pilot Registry.

    PubMed

    Lip, Gregory Y H; Laroche, Cécile; Popescu, Mircea Iaochim; Rasmussen, Lars Hvilsted; Vitali-Serdoz, Laura; Dan, Gheorghe-Andrei; Kalarus, Zbigniew; Crijns, Harry J G M; Oliveira, Mario Martins; Tavazzi, Luigi; Maggioni, Aldo P; Boriani, Giuseppe

    2015-12-01

    Guideline-adherent therapy for stroke prevention in atrial fibrillation has been associated with better outcomes, in terms of thromboembolism (TE) and bleeding. In this report from the EuroObservational Research Programme-Atrial Fibrillation (EORP-AF) Pilot General Registry, we describe the associated baseline features of 'high risk' AF patients in relation to guideline-adherent antithrombotic treatment, i.e. whether they were adherent, over-treated, or under-treated based on the 2012 European Society of Cardiology (ESC) guidelines. Secondly, we assessed the predictors of guideline-adherent antithrombotic treatment. Thirdly, we evaluated outcomes for all-cause mortality, TE, bleeding, and the composite endpoint of 'any TE, cardiovascular death or bleeding' in relation to whether they were ESC guideline-adherent treatment. From the EORP-AF cohort, the follow-up dataset of 2634 subjects was used to assess the impact of guideline adherence or non-adherence. Of these, 1602 (60.6%) were guideline adherent, whilst 458 (17.3%) were under-treated, and 574 (21.7%) were over-treated. Non-guideline-adherent treatment can be related to region of Europe as well as associated clinical features, but not age, AF type, symptoms, or echocardiography indices. Over-treatment per se was associated with symptoms, using the EHRA score, as well as other comorbidities. Guideline-adherent antithrombotic management based on the ESC guidelines is associated with significantly better outcomes. Specifically, the endpoint of 'all cause death and any TE' is increased by >60% by undertreatment [hazard ratio (HR) 1.679 (95% confidence interval (CI) 1.202-2.347)] or over-treatment [HR 1.622 (95% CI 1.173-2.23)]. For the composite endpoint of 'cardiovascular death, any TE or bleeding', over-treatment increased risk by >70% [HR 1.722 (95% CI 1.200-2.470)]. Even in this cohort with high overall rates of oral anticoagulation use, ESC guideline-adherent antithrombotic management is associated with

  17. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    PubMed

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Antiarrhythmic strategies in patients with atrial fibrillation managed by cardiologists and internists: Antithrombotic Agents in Atrial Fibrillation (ATA-AF) survey.

    PubMed

    Berisso, Massimo Zoni; Fabbri, Gianna; Gonzini, Lucio; Caruso, Davide; Fontanella, Andrea; Pellegrini, Francesco; Silvestri, Nunzia; Vincenti, Antonio; Mathieu, Giovanni; Di Pasquale, Giuseppe

    2014-08-01

    To provide insights on the antiarrhythmic management of atrial fibrillation among patients enrolled in the Antithrombotic Agents in Atrial Fibrillation (ATA-AF) study, and to assess the adherence of the Italian cardiologists and internists to guidelines recommendations. The ATA-AF study is a multicenter, observational study with prospective data collection on the management and treatment of patients with atrial fibrillation. From March to July 2010, 6910 patients with atrial fibrillation were recruited in 164 Italian Cardiology (Card) and 196 Internal Medicine (IMed) centers. Permanent atrial fibrillation was diagnosed in 50.8%, persistent atrial fibrillation in 24.4%, paroxysmal in 15.5%, and first-detected atrial fibrillation in 9.3% of the patients. Rhythm control (rhyC) strategy was pursued in 27.5% (39.6% Card vs. 12.9% IMed; P < 0.0001) and rate control (raC) in 51.4% (43.7% Card vs. 60.7% IMed; P < 0.0001); in 21.1% the antiarrhythmic strategy was not defined. Patients assigned to rhyC were younger and with less comorbidities than those assigned to raC. Adjusted multivariable analysis showed that atrial fibrillation type, setting of management, age and site of patient discharge were the most important independent predictors of rhyC assignment. The severity of atrial fibrillation-related symptoms was not associated with rhyC assignment. At discharge, beta-blockers, amiodarone and class 1c antiarrhythmic drugs were the drugs mainly used in the Card centers; and beta-blockers, digitalis, amiodarone and diltiazem/verapamil were used in the IMed centers. Amiodarone was overused in both Card and IMed centers. In the present study, rhyC was the strategy mainly pursued by cardiologists and raC by internists; treatment strategy assignment and antiarrhythmic therapy often do not agree with the guideline recommendations.

  19. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD.

    PubMed

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-06-01

    Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs.Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs.Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels.Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population.

  20. A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

    PubMed Central

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Yuan, Ruozhen; Tang, Hehan; Liu, Ming

    2016-01-01

    Abstract Calcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs. Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs. Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (≤2.15 mmol/L) than in patients with higher serum calcium levels. Lower serum calcium levels (≤2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population. PMID:27368027

  1. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry: How Inert is Teflon AF?

    PubMed Central

    Lai, Chun-Ze; Koseoglu, Secil S.; Lugert, Elizabeth C.; Boswell, Paul G.; Rábai, József; Lodge, Timothy P.; Bühlmann, Philippe

    2011-01-01

    Fluorous media are the least polar and polarizable condensed phases known. Their use as membrane materials considerably increases the selectivity and robustness of ion-selective electrodes (ISEs). In this research, a fluorous amorphous perfluoropolymer was used for the first time as a matrix for an ISE membrane. Electrodes for pH measurements with membranes composed of poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene) (87% dioxole monomer content; known as Teflon AF2400) as polymer matrix, a linear perfluorooligoether as plasticizer, sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate providing for ionic sites, and bis[(perfluorooctyl)propyl]-2,2,2-trifluoroethylamine as H+-ionophore were investigated. All electrodes had excellent potentiometric selectivities, showed Nernstian responses to H+ over a wide pH range, exhibited enhanced mechanical stability and maintained their selectivity over at least four weeks. For membranes of low ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations exceeding 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations, which cannot be explained by the Mackie–Meares obstruction model. The selectivities and resistances depend on the polymer concentration because of a functional group associated with Teflon AF2400, with a concentration of one functional group per 854 monomer units of the polymer. In the fluorous environment of these membranes, this functional group binds to Na+, K+, Ca2+, and the unprotonated ionophore with binding constants of 103.5, 101.8, 106.8 and 104.4 M−1, respectively. Potentiometric and spectroscopic evidence indicates that these functional groups are COOH groups formed by the hydrolysis of carboxylic acid fluoride (COF) groups originally present in Teflon AF2400. The use of higher ionophore concentrations removes the undesirable effect of these COOH groups almost completely

  2. Fatigue life estimation program for Part 23 airplanes, `AFS.FOR`

    SciTech Connect

    Kaul, S.K.

    1993-12-31

    The purpose of this paper is to introduce to the general aviation industry a computer program which estimates the safe fatigue life of any Federal Aviation Regulation (FAR) Part 23 airplane. The algorithm uses the methodology (Miner`s Linear Cumulative Damage Theory) and the various data presented in the Federal Aviation Administration (FAA) Report No. AFS-120-73-2, dated May 1973. The program is written in FORTRAN 77 language and is executable on a desk top personal computer. The program prompts the user for the input data needed and provides a variety of options for its intended use. The program is envisaged to be released through issuance of a FAA report, which will contain the appropriate comments, instructions, warnings and limitations.

  3. Adak NAS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1983-08-24

    operated by the U. S. Ser- vices aoi some foreig;n stations .silim, similar reporting prscticei. UiJesu otlherwise noted the Co ~luwilof suianries are...34 TRNSITERVEoRE .iF Oct 3.94 Longviev hAl Weather Sot available NA N/ N/A statin (Jo~Unit hAP & Navy) 2. 2 2/31/13 Ad~k(Joint’Unit) AF & Not available N/A I/A N/A...641214.15 2.18 cO 4 18.1 7.2 17. 9 .1.4421 FES 5 . 18.1 5.4 17.2 1 .5 19.1 17.4 L. 4 2.1 .1 76.Z IIG2 4 .7 _9.57) 1.97 MAN 5 5.5 19.5 13.3 1I.3 12. 9

  4. AF-GEOSpace Version 2.0: Space Environment Software Products for 2002

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Tautz, M.

    2002-05-01

    AF-GEOSpace Version 2.0 (release 2002 on WindowsNT/2000/XP) is a graphics-intensive software program developed by AFRL with space environment models and applications. It has grown steadily to become a development tool for automated space weather visualization products and helps with a variety of tasks: orbit specification for radiation hazard avoidance; satellite design assessment and post-event analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; and physics research and education. The object-oriented C++ code is divided into five module classes. Science Modules control science models to give output data on user-specified grids. Application Modules manipulate these data and provide orbit generation and magnetic field line tracing capabilities. Data Modules read and assist with the analysis of user-generated data sets. Graphics Modules enable the display of features such as plane slices, magnetic field lines, line plots, axes, the Earth, stars, and satellites. Worksheet Modules provide commonly requested coordinate transformations and calendar conversion tools. Common input data archive sets, application modules, and 1-, 2-, and 3-D visualization tools are provided to all models. The code documentation includes detailed examples with click-by-click instructions for investigating phenomena that have well known effects on communications and spacecraft systems. AF-GEOSpace Version 2.0 builds on the success of its predecessors. The first release (Version 1.21, 1996/IRIX on SGI) contained radiation belt particle flux and dose models derived from CRRES satellite data, an aurora model, an ionosphere model, and ionospheric HF ray tracing capabilities. Next (Version 1.4, 1999/IRIX on SGI) science modules were added related to cosmic rays and solar protons, low-Earth orbit radiation dosages, single event effects probability maps, ionospheric

  5. Pope AFB, North Carolina Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1985-03-01

    OL.A IRE.IOA$ E0.T10S 01.S T 04. RtU ASP OOtE)U 6 *L’-AL .LI"!ATCL)GY i %A %Cm 2_T SURFACE WINDS .AT-Fd 1.RV1CL’?1AC PERCENTAGE FREQUENCY OF WIND...DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 72V~ -JP AF-!_~ _________ 7-L_________ tot ST A-T 0 k.I IsA .;T. A .L .LAT" E-’ •_ _-_ SPEED MEAN KNTS 1...0 , T ._ . _ * ,... . K . --- .. j , ,.. ’ . .. , m E¢ 800 1 ,00 2! 6100 9 . t 1200- ___? .. ..00 . . . : 100 2! goo EXAMPLE # 1 lHead ceiling

  6. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  7. RAF Lakenheath, United Kingdom. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1988-02-01

    3: 1 ... . 2 . . jb -3VI SO I 7.27b 6 . ( 5.764 5.103 4.571 4.47 1 4.367 .47 5.244 b.712 7.717 7.3< 7 5.4.7 1333 osJ 915 a37 91 ’ɘ 911 645 0. 92’ 1...LA II WE17,rY uSAFLTAC fqL" LUlLy CFS[kVATO.V AIR .LA IHfP SERVICC/MAC STATIO, NUMPER: 75 3- STAIIOf, NAME : R AF LAKtNI-ATH L91[EU KINGf0CM L CIEC

  8. Hill AFB, Utah Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-09-01

    GLCqAL CLIMATOLOGY QRANCN b AX EAT,.C PSYCHROMETRIC SUMMARY AIP WE THER+ SEPICE /CPNIAC ?9 𔃿’ HILL AF- uT 14-81 ST" e~- STA?1010 1M1 VIA STN PAGE2 yeP...1 *, * 1-,* . 1 1 . I ! I i !9 -./ ., 1. 4 ,; ? , j : .. 7, dc L_ 1 I_ ’ I a AA I 6 if / "i - IT 𔃾 _ _"_ __. i ./ 2 . , 2 ., 921 ,- ’ 7 3 7.3...SEP. OCT NOV. DC ANNUAL MEAN ’’’ 7 *L 𔃾.3 23. .8 7.7 𔃽.3 4C.8 34.8 79.3 23.4 14.9 9.s SO 5D *143 7 4 7.128 7 . 94 6 .8g4 7.2;5 7 9 ;3 9.2 42 8 .632

  9. Slurry sampling in serum blood for mercury determination by CV-AFS.

    PubMed

    Aranda, Pedro R; Gil, Raúl A; Moyano, Susana; De Vito, Irma; Martinez, Luis D

    2009-01-30

    The heavy metal mercury (Hg) is a neurotoxin known to have a serious health impact even at relatively low concentrations. A slurry method was developed for the sensitive and precise determination of mercury in human serum blood samples by cold vapor generation coupled to atomic fluorescence spectrometry (CV-AFS). All variables related to the slurry formation were studied. The optimal hydrochloric concentration and tin(II) chloride concentration for CV generation were evaluated. Calibration within the range 0.1-10 microg L(-1) Hg was performed with the standard addition method, and compared with an external calibration. Additionally, the reliability of the results obtained was evaluated by analyzing mercury in the same samples, but submitted to microwave-assisted digestion method. The limit of detection was calculated as 25 ng L(-1) and the relative standard deviation was 3.9% at levels around of 0.4 microg L(-1)Hg.

  10. RNA structure replaces the need for U2AF2 in splicing.

    PubMed

    Lin, Chien-Ling; Taggart, Allison J; Lim, Kian Huat; Cygan, Kamil J; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes.

  11. Installation Restoration Program. Technical Support Document for Record of Decision, Cape Newenham, AFS.

    DTIC Science & Technology

    1988-01-18

    Clyde Consultants 701 Sesame Street Anchorage, AK 99503 71/46/2 71/21/1 RECORD OF DECISION Installation: The Cape Newenham AFS, is located in the...Q S-0 .- ( L to ea a -- 0 a) eoS -r-cc M A -( /5 W 4-) M 0 W) (0 4-.0 ’a - )4- -- -- 0 .0 CU E )) 0 > D. > 0 L W( ’ t’aS u to o4- E ’A W) (a( (a-a0 410...0- L4- 4-) U) to ~ Cl L EO LO. 41~ 0x - 4) 0 ) 0 0) 4-) LA- 4) 04-) a:) L/ Lu a) C Lu 0 L. +.) ~z .4-’ 41.0 0 L&i -LIi LIi JL ) Lf) 2E Li- V) L t J

  12. Hot-Fire Testing of a 1N AF-M315E Thruster

    NASA Technical Reports Server (NTRS)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  13. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  14. Model-based estimation of the attributable fraction for cross-sectional, case-control and cohort studies using the R package AF.

    PubMed

    Dahlqwist, Elisabeth; Zetterqvist, Johan; Pawitan, Yudi; Sjölander, Arvid

    2016-06-01

    The attributable fraction (or attributable risk) is a widely used measure that quantifies the public health impact of an exposure on an outcome. Even though the theory for AF estimation is well developed, there has been a lack of up-to-date software implementations. The aim of this article is to present a new R package for AF estimation with binary exposures. The package AF allows for confounder-adjusted estimation of the AF for the three major study designs: cross-sectional, (possibly matched) case-control and cohort. The article is divided into theoretical sections and applied sections. In the theoretical sections we describe how the confounder-adjusted AF is estimated for each specific study design. These sections serve as a brief but self-consistent tutorial in AF estimation. In the applied sections we use real data examples to illustrate how the AF package is used. All datasets in these examples are publicly available and included in the AF package, so readers can easily replicate all analyses.

  15. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities. The...

  16. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  17. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients.

    PubMed

    Woodley, David T; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M Peter; Keene, Douglas; Chen, Mei

    2017-08-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti-type VII collagen autoantibodies in patients' blood or skin. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. ClinicalTrials.gov NCT02698735. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH, and VA Merit Award.

  18. Detection of atrial fibrillation by permanent pacemakers: observations from the STOP AF trial.

    PubMed

    Plummer, C J; McComb, J M

    2003-12-01

    Pacemaker telemetry is increasingly being used to infer the presence or absence of arrhythmias in clinical practice. To evaluate the reliability of these data in patients with sick-sinus syndrome, a sub-study of eighteen consecutive patients in the Systematic Trial of Pacing to prevent Atrial Fibrillation (STOP AF) implanted with dual-chamber pacemakers had simultaneous 24-hour Holter recordings and pacemaker telemetry down-loaded. Whilst heart rate data were very similar, telemetry data achieved only 57% sensitivity with 64% specificity for the presence of atrial fibrillation on Holter recording over 24 hours. False-positive results were due to far-field sensing while false-negatives were seen with very short episodes of atrial fibrillation. The pacemaker's anti-tachycardia responses were not specific for the detection of atrial fibrillation. There are very few published reports correlating pacemaker diagnostic data and stored electrograms with external Holter monitoring. We believe that more validation studies of are needed before pacemaker diagnostic data can be used with confidence in clinical practice. It is unlikely that current devices with sophisticated detection algorithms will fail to detect prolonged episodes of arrhythmia and their capacity to confirm events with stored electrograms, intervals and markers reduces the possibility of false-positives, but care must be taken in the interpretation of stored data from devices without these capabilities. Equally, it cannot be assumed that if intracardiac electrograms from one episode confirm the presence of an arrhythmia, that all recorded events have been similarly correctly interpreted. We have shown in a sub-study of STOP-AF that simple mathematical models using heart rate bin analysis are not reliable for detection of arrhythmias with short durations. Despite these limitations, the potential of implanted pacemakers to record cardiac rhythm and trends, such as heart-rate variability, over time remains an

  19. Plateau waveform shape allows a much higher patient shock energy tolerance in AF patients.

    PubMed

    Boriani, Giuseppe; Edvardsson, Nils; Biffi, Mauro; Silvestri, Paolo; Martignani, Cristian; Valzania, Cinzia; Diemberger, Igor; Moulder, J Christopher; Mouchawar, Gabriel; Poci, Dritan; Branzi, Angelo; Kroll, Mark W

    2007-07-01

    To evaluate the possible pain reduction of the plateau waveform in atrial fibrillation (AF) patients. Previous studies have indicated that reduced amplitude waveforms would be less painful than a conventional (65/65% tilt) biphasic waveform. Computer modeling suggested that a moderately long (10-12 msec) plateau (flat topped) shock waveform would deliver equivalent effectiveness with the lowest possible peak amplitude. We enrolled 27 patients at two sites with persistent AF with a total of 220 shocks delivered during internal atrial cardioversion using an interleaved crossover design. Patient response was scored in three ways: (1) a verbally reported discomfort score, (2) visual analog scale (VAS), and (3) a blinded observer reporting a contraction score. All scores were significantly reduced (P < 0.0001) by the plateau waveform with impressive statistics: Verbal discomfort (3.51 +/- 0.13 to 2.89 +/- 0.12), VAS (7.00 +/- 0.56 to 5.91 +/- 0.36), and contraction scores (1.94 +/- 0.12 to 1.62 +/- 0.12). The average pain threshold shift (TS) for the Verbal score was 2.34, while that for the VAS score was 2.30. (This means that the patient typically could tolerate 2.34 times as much energy with the plateau waveform for the same level of verbally reported discomfort.) The contraction TS was less at 1.57. Response scores were also corrected for the shock sequence number to control for the sensitization effect from multiple shocks. This increased the TS for the Verbal score to 3.58, but the shock number was not significant for the VAS. A pulmonary artery electrode return was associated with lower pain compared with a coronary sinus position. A plateau shaped biphasic waveform resulted in significantly increased shock energy pain tolerances. Controlling for session sensitization, patients tolerated over three times as much energy for the same verbally reported discomfort score.

  20. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF

    PubMed Central

    Bassand, Jean-Pierre; Accetta, Gabriele; Camm, Alan John; Cools, Frank; Fitzmaurice, David A.; Fox, Keith A.A.; Goldhaber, Samuel Z.; Goto, Shinya; Haas, Sylvia; Hacke, Werner; Kayani, Gloria; Mantovani, Lorenzo G.; Misselwitz, Frank; ten Cate, Hugo; Turpie, Alexander G.G.; Verheugt, Freek W.A.; Kakkar, Ajay K.

    2016-01-01

    Aims The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. Methods and results GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. Conclusion The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01090362. PMID:27357359

  1. AF printability check with a full-chip 3D resist profile model

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En R.; Chang, Jason; Song, Hua; Shiely, James

    2013-09-01

    A single compact resist model capable of predicting 3D resist profile is strongly demanded for the advanced technology nodes to avoid the potential hotspots due to imperfect resist pattern shape and its lack of resistance in the subsequent etch process. In this work, we propose a resist 3D (R3D) compact model that takes acidz-diffusion effect into account. The chemical reaction between acid and base along z-direction is treated as second order effect that is absorbed into the anisotropic diffusion length as a fitting parameter. Meanwhile, the resist model in the x-y wafer plane is still kept in general by applying the compact solution of 2D reaction-diffusion equation. In order to have the 2D contour predictability at arbitrary resist height, calibration from entire 3D data (CDs at several heights) areconducted simultaneously witha single cost function so that the R3D compact model is described by a common set of resist free parameters and threshold for all resist heights. With the low energy approximation, the acid z-diffusion effect is equivalent to a z-diffused TCC that takes the form of linear combination of pure optical TCCs sampled at discrete image-depth which can be pre-calculated. With this benefit, the R3D compact model offers a more physical approach but adds no runtime concern on the OPC and verification applications. The predicted resist cross-section profiles from our test patterns are compared those computed with rigorous lithography simulator SLITHO and show very good matching results between them. The demonstration of the AF printability check from the predicted cross-section profile at AF indicates the success of our R3D compact model.

  2. Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

    PubMed

    Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

    2014-08-01

    Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF. © 2014, The American College of Clinical Pharmacology.

  3. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    USDA-ARS?s Scientific Manuscript database

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  4. Modulation of the metabolic response to an endotoxin challenge in Brahman heifers through OmniGen-AF supplementation

    USDA-ARS?s Scientific Manuscript database

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the metabolic response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton, TX, were separated into 2...

  5. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis

    PubMed Central

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy te; Basso, Giuseppe

    2016-01-01

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations. PMID:27698462

  6. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    PubMed

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  7. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

  8. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

  9. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 419A(f)(6) is based on the totality of the arrangement and all related facts and circumstances, including any related insurance contracts. Accordingly, all agreements and understandings (including... the participating employers, and those differences are not merely reflective of differences in current...

  10. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  11. Distribution of muscarinic receptor subtypes in rat brain as determined in binding studies with AF-DX 116 and pirenzepine

    SciTech Connect

    Giraldo, E.; Hammer, R.; Ladinsky, H.

    1987-03-02

    In vitro competition binding experiments with the selective muscarinic antagonists AF-DX 116 and pirenzepine (PZ) vs /sup 3/H-N-methylscopolamine as radioligand revealed a characteristic distribution of muscarinic receptor subtypes in different regions of rat brain. Based on nonlinear least squares analysis, the binding data were compatible with the presence of three different subtypes: the M/sub 1/ receptor (high affinity for PZ), the cardiac M/sub 2/ receptor (high affinity for AF-DX 116) and the glandular M/sub 2/ receptor (low affinity for PZ and AF-DX 116). The highest proportion of M/sub 1/ receptors was found in the hippocampus, while the cerebellum and the hypothalamus were the regions with the largest fraction of the cardiac M/sub 2/ and glandular M/sub 2/ receptors, respectively. In certain brain areas, depending on the relative proportions of the subtypes, flat binding curves were seen for AF-DX 116 and PZ. Based on these data, an approximate distribution pattern of the subtypes in the various brain regions is presented. 19 references, 1 figure, 2 tables.

  12. Rhein-Main Apt, Germany/Franfurt. Revised Uniform Summary of Surface Weather Observations. Parts A-F

    DTIC Science & Technology

    1977-08-01

    DATA PROCESSING BRANCH usAF E’ C CEILING, VERSUS VISIBILITY AIR WEATHER SERVICE/MAC 0 RHEINMAIN APT GERMANY/FRAtKFURT...SERVICE/MAC RHEINMAIN APT GENMANY/FRANKFURT 67-7o OEZ U. PERCENTAGE FREQUENCY OF OCCURRENCE 0000-.)200 , (FROM HOURLY OBSERVATIONS) o , - VISIBILITY

  13. 26 CFR 1.419A(f)(6)-1 - Exception for 10 or more employer plan.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... by the recipient. (c) Characteristics indicating a plan is not a 10 or more employer plan—(1) In general. The presence of any of the characteristics described in paragraphs (c)(2) through (c)(6) of this... requirements of section 419A(f)(6) and this section, a plan having any of the following characteristics is not...

  14. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  15. Ultrasound body composition traits response to an endotoxin challenge in Brahman heifers supplemented with Omnigen-AF

    USDA-ARS?s Scientific Manuscript database

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the body composition traits response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183 ± 5 kg) from the Texas AgriLife Research Center in Overton, TX, were separat...

  16. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  17. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  18. The Implementation of Collaborative Learning Using AfL through Giving Feedback Strategy for Improving Students’ Attention to Mathematics Lesson

    NASA Astrophysics Data System (ADS)

    Kurniasih, R.; Sujadi, I.; Pramesti, G.

    2016-02-01

    This research aims to describe the process of implementation collaborative learning with AfL through giving feedback strategy for improving students’ attention to mathematics lesson. Data which is collected in this research are students’ attention towards learning and students’ achievement. The result of this research showed that the learning steps by using collaborative learning with AfL through giving feedback strategy which can improve students’ attention are: 1) pre activity: the teacher delivers the purpose of the learning, successful criteria, apperception, and motivation. 2) main activity: the teacher gives the background of learning activity, explains learning materials at a glance, divides students discuss, the teacher observes and guides students to the problem solving, present their discussion result, gives feedback, the students do AfL problem and the answer is collected and result will be given before next meeting. 3) post activity: the teacher with students concludes the material. Test result, the percentage of students who complete the examination in the second cycle is 77.27%. Based on those results can be concluded that the implementation of collaborative learning using AfL through giving feedback can improve students’ attention towards learning and students’ achievement of XI IPA Students MA Al-Islam Jamsaren Surakarta academic year 2013/2014.

  19. Binding-folding induced regulation of AF1 transactivation domain of the glucocorticoid receptor by a cofactor that binds to its DNA binding domain.

    PubMed

    Garza, Anna S; Khan, Shagufta H; Moure, Carmen M; Edwards, Dean P; Kumar, Raj

    2011-01-01

    Intrinsically disordered (ID) regions of proteins commonly exist within transcription factors, including the N-terminal domain (NTD) of steroid hormone receptors (SHRs) that possesses a powerful activation function, AF1 region. The mechanisms by which SHRs pass signals from a steroid hormone to control gene expression remain a central unresolved problem. The role of N-terminal activation function AF1, which exists in an intrinsically disordered (ID) conformation, in this process is of immense importance. It is hypothesized that under physiological conditions, ID AF1 undergoes disorder/order transition via inter- and intra-molecular communications, which allows AF1 surfaces to interact with specific co-regulatory proteins, critical for the final outcome of target gene expression regulated by SHRs. However, the means by which AF1 acquires functionally folded conformations is not well understood. In this study, we tested whether binding of jun dimerization protein 2 (JDP2) within the DNA binding domain (DBD) of the glucocorticoid receptor (GR) leads to acquisition of functionally active structure in its AF1/NTD. Our results show that signals mediated from GR DBD:JDP2 interactions in a two domain GR fragment, consisting of the entire NTD and little beyond DBD, significantly increased secondary/tertiary structure formation in the NTD/AF1. This increased structure formation facilitated AF1's interaction with specific co-regulatory proteins and subsequent glucocorticoid response element-mediated AF1 promoter:reporter activity. These results support the hypothesis that inter- and intra-molecular signals give a functionally active structure(s) to the GR AF1, which is important for its transcriptional activity.

  20. Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation.

    PubMed

    Conen, David; Rodondi, Nicolas; Mueller, Andreas; Beer, Juerg; Auricchio, Angelo; Ammann, Peter; Hayoz, Daniel; Kobza, Richard; Moschovitis, Giorgio; Shah, Dipen; Schlaepfer, Juerg; Novak, Jan; di Valentino, Marcello; Erne, Paul; Sticherling, Christian; Bonati, Leo; Ehret, Georg; Roten, Laurent; Fischer, Urs; Monsch, Andreas; Stippich, Christoph; Wuerfel, Jens; Schwenkglenks, Matthias; Kuehne, Michael; Osswald, Stefan

    2017-07-11

    Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits. Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017. Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters.

  1. Complementary DNA cloning, sequence analysis, and tissue transcription profile of a novel U2AF2 gene from the Chinese Banna mini-pig inbred line.

    PubMed

    Wang, S Y; Huo, J L; Miao, Y W; Cheng, W M; Zeng, Y Z

    2013-04-02

    U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an important gene for pre-messenger RNA splicing in higher eukaryotes. In this study, the Banna mini-pig inbred line (BMI) U2AF2 coding sequence (CDS) was cloned, sequenced, and characterized. The U2AF2 complete CDS was amplified using the reverse transcription-polymerase chain reaction (RT-PCR) technique based on the conserved sequence information of cattle and known highly homologous swine expressed sequence tags. This novel gene was deposited into the National Center for Biotechnology Information database (Accession No. JQ839267). Sequence analysis revealed that the BMI U2AF2 coding sequence consisted of 1416 bp and encoded 471 amino acids with a molecular weight of 53.12 kDa. The protein sequence has high sequence homology with U2AF65 of 6 species - Homo sapiens (100%), Equus caballus (100%), Canis lupus (100%), Macaca mulatta (99.8%), Bos taurus (74.4%), and Mus musculus (74.4%). The phylogenetic tree analysis revealed that BMI U2AF65 has a closer genetic relationship with B. taurus U2AF65 than with U2AF65 of E. caballus, C. lupus, M. mulatta, H. sapiens, and M. musculus. RT-PCR analysis showed that BMI U2AF2 was most highly expressed in the brain; moderately expressed in the spleen, lung, muscle, and skin; and weakly expressed in the liver, kidney, and ovary. Its expression was nearly silent in the spinal cord, nerve fiber, heart, stomach, pancreas, and intestine. Three microRNA target sites were predicted in the CDS of BMI U2AF2 messenger RNA. Our results establish a foundation for further insight into this swine gene.

  2. The elongation complex components BRD4 and MLLT3/AF9 are transcriptional coactivators of nuclear retinoid receptors.

    PubMed

    Flajollet, Sébastien; Rachez, Christophe; Ploton, Maheul; Schulz, Céline; Gallais, Rozenn; Métivier, Raphaël; Pawlak, Michal; Leray, Aymeric; Issulahi, Al Amine; Héliot, Laurent; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2013-01-01

    Nuclear all-trans retinoic acid receptors (RARs) initiate early transcriptional events which engage pluripotent cells to differentiate into specific lineages. RAR-controlled transactivation depends mostly on agonist-induced structural transitions in RAR C-terminus (AF-2), thus bridging coactivators or corepressors to chromatin, hence controlling preinitiation complex assembly. However, the contribution of other domains of RAR to its overall transcriptional activity remains poorly defined. A proteomic characterization of nuclear proteins interacting with RAR regions distinct from the AF-2 revealed unsuspected functional properties of the RAR N-terminus. Indeed, mass spectrometry fingerprinting identified the Bromodomain-containing protein 4 (BRD4) and ALL1-fused gene from chromosome 9 (AF9/MLLT3), known to associate with and regulates the activity of Positive Transcription Elongation Factor b (P-TEFb), as novel RAR coactivators. In addition to promoter sequences, RAR binds to genomic, transcribed regions of retinoid-regulated genes, in association with RNA polymerase II and as a function of P-TEFb activity. Knockdown of either AF9 or BRD4 expression affected differentially the neural differentiation of stem cell-like P19 cells. Clusters of retinoid-regulated genes were selectively dependent on BRD4 and/or AF9 expression, which correlated with RAR association to transcribed regions. Thus RAR establishes physical and functional links with components of the elongation complex, enabling the rapid retinoid-induced induction of genes required for neuronal differentiation. Our data thereby extends the previously known RAR interactome from classical transcriptional modulators to components of the elongation machinery, and unravel a functional role of RAR in transcriptional elongation.

  3. The Elongation Complex Components BRD4 and MLLT3/AF9 Are Transcriptional Coactivators of Nuclear Retinoid Receptors

    PubMed Central

    Flajollet, Sébastien; Rachez, Christophe; Ploton, Maheul; Schulz, Céline; Gallais, Rozenn; Métivier, Raphaël; Pawlak, Michal; Leray, Aymeric; Issulahi, Al Amine; Héliot, Laurent; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2013-01-01

    Nuclear all-trans retinoic acid receptors (RARs) initiate early transcriptional events which engage pluripotent cells to differentiate into specific lineages. RAR-controlled transactivation depends mostly on agonist-induced structural transitions in RAR C-terminus (AF-2), thus bridging coactivators or corepressors to chromatin, hence controlling preinitiation complex assembly. However, the contribution of other domains of RAR to its overall transcriptional activity remains poorly defined. A proteomic characterization of nuclear proteins interacting with RAR regions distinct from the AF-2 revealed unsuspected functional properties of the RAR N-terminus. Indeed, mass spectrometry fingerprinting identified the Bromodomain-containing protein 4 (BRD4) and ALL1-fused gene from chromosome 9 (AF9/MLLT3), known to associate with and regulates the activity of Positive Transcription Elongation Factor b (P-TEFb), as novel RAR coactivators. In addition to promoter sequences, RAR binds to genomic, transcribed regions of retinoid-regulated genes, in association with RNA polymerase II and as a function of P-TEFb activity. Knockdown of either AF9 or BRD4 expression affected differentially the neural differentiation of stem cell-like P19 cells. Clusters of retinoid-regulated genes were selectively dependent on BRD4 and/or AF9 expression, which correlated with RAR association to transcribed regions. Thus RAR establishes physical and functional links with components of the elongation complex, enabling the rapid retinoid-induced induction of genes required for neuronal differentiation. Our data thereby extends the previously known RAR interactome from classical transcriptional modulators to components of the elongation machinery, and unravel a functional role of RAR in transcriptional elongation. PMID:23762261

  4. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  5. Implementation of AF-CBT by community practitioners serving child welfare and mental health: a randomized trial.

    PubMed

    Kolko, David J; Baumann, Barbara L; Herschell, Amy D; Hart, Jonathan A; Holden, Elizabeth A; Wisniewski, Stephen R

    2012-02-01

    The Partnerships for Families project is a randomized clinical trial designed to evaluate the implementation of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT), an evidence-based treatment for family conflict, coercion, and aggression, including child physical abuse. To evaluate the effectiveness of a training program in this model, 182 community practitioners from 10 agencies were randomized to receive AF-CBT training (n = 90) using a learning community model (workshops, consultation visits) or Training as Usual (TAU; n = 92) which provided trainings per agency routine. Practitioners completed self-report measures at four time points (0, 6, 12, and 18 months following baseline). Of those assigned to AF-CBT, 89% participated in at least one training activity and 68% met a "training completion" definition. A total of 80 (44%) practitioners were still active clinicians in the study by 18-month assessment in that they had not met our staff turnover or study withdrawal criteria. Using an intent-to-train design, hierarchical linear modeling analyses revealed significantly greater initial improvements for those in the AF-CBT training condition (vs. TAU condition) in CBT-related knowledge and use of AF-CBT teaching processes, abuse-specific skills, and general psychological skills. In addition, practitioners in both groups reported significantly more negative perceptions of organizational climate through the intervention phase. These significant, albeit modest, findings are discussed in the context of treatment training, research, and work force issues as they relate to the diverse backgrounds, settings, and populations served by community practitioners.

  6. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4–MLL Fusion Protein

    PubMed Central

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-01-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  8. Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C

    PubMed Central

    Sabry, Dina; Elamir, Azza; Mahmoud, Rania Hosny; Abdelaziz, Ahmed Ali; Fathy, Wael

    2017-01-01

    Background The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients. Methods Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR. Results Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed. Conclusion LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C. PMID:28392862

  9. Impact of intensive glycemic control on the incidence of atrial fibrillation and associated cardiovascular outcomes in patients with type 2 diabetes mellitus (from the Action to Control Cardiovascular Risk in Diabetes Study).

    PubMed

    Fatemi, Omid; Yuriditsky, Eugene; Tsioufis, Costas; Tsachris, Demetrios; Morgan, Timothy; Basile, Jan; Bigger, Thomas; Cushman, William; Goff, David; Soliman, Elsayed Z; Thomas, Abraham; Papademetriou, Vasilios

    2014-10-15

    Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF.

  10. Clathrin assembly lymphoid myeloid leukemia-AF10-positive acute leukemias: a report of 2 cases with a review of the literature.

    PubMed

    Huh, Ji Young; Chung, Soie; Oh, Doyeun; Kang, Myung Seo; Eom, Hyeon Seok; Cho, Eun Hae; Han, Mi Hwa; Kong, Sun Young

    2010-04-01

    The translocation t(10;11)(p13;q14q21) has been found to be recurrent in acute lymphoblastic and myeloid leukemias, and results in the fusion of the clathrin assembly lymphoid myeloid leukemia (CALM) gene with the AF10 gene; these genes are present on chromosomes 11 and 10, respectively. Because the CALM-AF10 rearrangement is a rare chromosomal abnormality, it is not included in routine molecular tests for acute leukemia. Here, we describe the cases of 2 patients with the CALM-AF10 fusion gene. The first patient (case 1) was diagnosed with T-cell ALL, and the second patient (case 2) was diagnosed with AML. Both patient samples showed expression of the homeobox A gene cluster and the histone methyltransferase hDOT1L, which suggests that they mediate leukemic transformation in CALM-AF10-positive and mixed-lineage leukemia-AF10-positive leukemias. Both patients achieved complete remission after induction chemotherapy. The first patient (case 1) relapsed after double-unit cord blood transplantation; there was no evidence of relapse in the second patient (case 2) after allogenic peripheral blood stem cell transplantation. Since CALM-AF10- positive leukemias have been shown to have poor prognosis with conventional therapy, molecular tests for CALM-AF10 rearrangement would be necessary to detect minimal residual disease during follow-up.

  11. Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells.

    PubMed

    Sudan, Sudhanshu; Rupasinghe, H P Vasantha

    2014-01-01

    Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer.

  12. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  13. Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.

    PubMed

    Sherwood, Matthew W; Nessel, Christopher C; Hellkamp, Anne S; Mahaffey, Kenneth W; Piccini, Jonathan P; Suh, Eun-Young; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hankey, Graeme J; Berkowitz, Scott D; Fox, Keith A A; Patel, Manesh R

    2015-12-01

    Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. Copyright © 2015 American College of Cardiology Foundation. Published by

  14. Impact of chronic obstructive pulmonary disease on prognosis in atrial fibrillation: A report from the EURObservational Research Programme Pilot Survey on Atrial Fibrillation (EORP-AF) General Registry.

    PubMed

    Proietti, Marco; Laroche, Cécile; Drozd, Marcin; Vijgen, Johan; Cozma, Dragos C; Drozdz, Jaroslaw; Maggioni, Aldo P; Boriani, Giuseppe; Lip, Gregory Y H

    2016-11-01

    Chronic obstructive pulmonary disease (COPD) is a common chronic disease, being associated with both high rates of morbidity and mortality. Similarly, atrial fibrillation (AF) is associated with a higher risk of both cardiovascular (CV) events and overall mortality. The AF and COPD often coexist, but the impact of COPD on prognosis in European AF patients is unknown. We evaluated COPD prevalence in patients enrolled in the EURObservational Research Programme Pilot Survey on Atrial Fibrillation Registry Pilot Phase. Clinical factors associated with COPD and adverse outcomes at 1-year follow-up were determined. In the overall cohort, a diagnosis of COPD was recorded in 339 (11.0%) of AF patients. The AF patients with COPD were more burdened with risk factors and comorbidities, including diabetes mellitus (P < .0001) and chronic heart failure (P < .0001). β-Blockers were less likely to be prescribed to patients with COPD (P = .0007). On follow-up, AF patients with COPD had a higher risk of both CV death and all-cause death (both P < .0001), as well as for the composite outcome of any thromboembolic event/bleeding /CV death (P = .0003). Cox regression analysis found that COPD was independently associated with an increase in all-cause death (hazard ratio, 1.55; 95% CI 1.05-2.28; P = .0269). Chronic obstructive pulmonary disease is highly prevalent in European AF patients, and is associated with higher rates of CV death, all-cause death, and the composite outcome of any thromboembolic event/bleeding/CV death. The presence of COPD in AF patients was independently associated with all-cause death in AF patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry.

    PubMed

    Lip, Gregory Y H; Laroche, Cécile; Dan, Gheorghe-Andrei; Santini, Massimo; Kalarus, Zbigniew; Rasmussen, Lars Hvilsted; Oliveira, Mário Martins; Mairesse, Georges; Crijns, Harry J G M; Simantirakis, Emmanouil; Atar, Dan; Kirchhof, Paulus; Vardas, Panos; Tavazzi, Luigi; Maggioni, Aldo P

    2014-03-01

    Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (∼20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal.

  16. Diabetes Type 1 - Multiple Languages: MedlinePlus

    MedlinePlus

    ... of All Topics All Diabetes Type 1 - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) Chinese - Simplified (简体中文) French (français) Russian (Русский) Somali (af Soomaali) Spanish (español) Arabic (العربية) ...

  17. Carotid-femoral pulse wave velocity is associated with N-terminal pro-B-type natriuretic peptide level in patients with atrial fibrillation.

    PubMed

    Chen, Lin Y; Tai, Bee C; Foo, David C; Wong, Raymond C; Adabag, A Selcuk; Benditt, David G; Ling, Lieng H

    2011-01-01

    To determine the extent to which conduit artery stiffness is associated with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF). Cross-sectional study. National University Hospital, Singapore. Cases (n=117) were patients with AF onset <65 years of age without heart failure or structural heart disease. Controls (n=274) were patients without AF who were seen at the general cardiology clinic. Transthoracic echocardiography, carotid-femoral pulse wave velocity (CFPWV) measured using applanation tonometry and blood draw for plasma NT-proBNP at enrolment for all patients. Plasma NT-proBNP. In patients with AF, CFPWV was associated with NT-proBNP after adjusting for hypertension and factors that were univariately associated with NT-proBNP: age at enrolment, type of AF, body mass index, left ventricular mass index, left atrial volume index, mitral E/E', mitral deceleration time and use of β-blockers (β=0.234; 95% CI 0.100 to 0.367; p=0.001). In contrast, CFPWV was not associated with NT-proBNP in controls. In patients with AF, the adjusted mean NT-proBNP level in the highest quartile of CFPWV (350 pg/ml; 95% CI 237 to 517 pg/ml) was fivefold higher than the lowest quartile (69 pg/ml; 95% CI 47 to 103 pg/ml) (p=0.001). CFPWV is associated with NT-proBNP level in AF. Since elevated NT-proBNP is a marker of adverse cardiovascular outcomes, arterial stiffness may be associated with worse prognosis in patients with AF.

  18. Insecticidal activity of Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af from Bacillus thuringiensis against lepidopteran corn pests.

    PubMed

    Hernández-Martínez, Patricia; Hernández-Rodríguez, Carmen Sara; Rie, Jeroen Van; Escriche, Baltasar; Ferré, Juan

    2013-05-01

    Vip3Aa, Vip3Ad, Vip3Ae, and Vip3Af proteins from Bacillus thuringiensis were tested for their toxicity against Spodoptera frugiperda and Agrotis ipsilon. Vip3Ad was non-toxic to the two species. Vip3Ae and Vip3Af were significantly more toxic than Vip3Aa against S. frugiperda, both as protoxins and as toxins. Against A. ipsilon, Vip3Ae protoxin was more toxic than Vip3Aa and Vip3Af protoxins. Purification by metal-chelate affinity chromatography significantly affected Vip3Ae toxicity against the two insect species.

  19. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

    PubMed

    Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

    2014-06-01

    Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

  20. Protective effect of niacinamide on interleukin-1beta-induced annulus fibrosus type II collagen degeneration in vitro.

    PubMed

    Duan, Deyu; Yang, Shuhua; Shao, Zengwu; Wang, Hong; Xiong, Xiaoqian

    2007-02-01

    The protective effect of niacinamide on interleukin-1beta (IL-1beta)-induced annulus fibrosus (AF) type II collagen degeneration in vitro and the mechanism were investigated. Chiba's intervertebral disc (IVD) culture models in rabbits were established and 48 IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups: normal control group, niacinamide-treated group, type II collagen degneration group (IL-1beta) and treatment group (niacinamide+IL-1beta). After culture for one week, AFs were collected for inducible nitric oxide synthase (iNOS), cysteine containing aspartate specific protease-3 (Caspase-3) and type II collagen immunohistochemical examination, and type II collagen reverse transcription polymerase chain reaction (RT-PCR). The results showed that rate of iNOS positive staining AF cells in the 4 groups was 17.6%, 10.9%, 73.9% and 19.3% respectively. The positive rate in treatment group was significantly lower than in the type II collagen degeneration group (P<0.01). Rate of Caspase-3 positive staining AF cells in the 4 groups was 3.4%, 4.2%, 17.6% and 10.3% respectively. The positive rate in treatment group was lower than in the type II collagen degeneration group (P<0.01). Type II collagen staining demonstrated that lamellar structure and continuity of collagen in treatment group was better reversed than in the degeneration group. RT-PCR revealed that the expression of type II collagen in treatment group was significantly stronger than that in type II collagen degeneration group (P<0.01). It was concluded that niacinamide could effectively inhibit IL-1beta stimulated increase of iNOS and Caspase-3 in AF, and alleviate IL-1beta-caused destruction and synthesis inhibition of type II collagen. Niacinamide is of potential for clinical treatment of IVD degeneration.

  1. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  2. Semi-empirical seismic relations of A-F stars from COROT and Kepler legacy data

    NASA Astrophysics Data System (ADS)

    Moya, A.; Suárez, J. C.; García Hernández, A.; Mendoza, M. A.

    2017-10-01

    Asteroseismology is witnessing a revolution, thanks to high-precise asteroseismic space data (MOST, COROT, Kepler, BRITE) and their large ground-based follow-up programs. Those instruments have provided an unprecedented large amount of information, which allows us to scrutinize its statistical properties in the quest for hidden relations among pulsational and/or physical observables. This approach might be particularly useful for stars whose pulsation content is difficult to interpret. This is the case of intermediate-mass classical pulsating stars (i.e. γ Dor, δ Scuti, hybrids) for which current theories do not properly predict the observed oscillation spectra. Here, we establish a first step in finding such hidden relations from data mining techniques for these stars. We searched for those hidden relations in a sample of δ Scuti and hybrid stars observed by COROT and Kepler (74 and 153, respectively). No significant correlations between pairs of observables were found. However, two statistically significant correlations emerged from multivariable correlations in the observed seismic data, which describe the total number of observed frequencies and the largest one, respectively. Moreover, three different sets of stars were found to cluster according to their frequency density distribution. Such sets are in apparent agreement with the asteroseismic properties commonly accepted for A-F pulsating stars.

  3. La Crosse MAP, Wisconsin. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1982-07-30

    091U 15A 66 T9 PAWIS A-F 5Aso PQtI nFM NOUN.! = JAN 73 - mHO8 PoRn , FMs DAB.! MU JAN 48 - WNC 81 TD K CO PIIVU WIC 6 T O L =1 -6’S L 30 I ’em ~cu...Cosa 00.0100.0 p000 400 8693 99.8 97.0 96.3 99.1 99.9 99.8 99.6 99* 99.91 99.9 99*9w 0.0 00.000 00 30 803 4T 970 gais 99.1 99.9 99.6k 99.6 99.8199.9...bS 1 9 9 ltd 9 So&*! lid 9 Lt aL. I~ i Gai 350 $c 2.3 56.1 59.9 50.5 50.5 61.0 61.1 61.2 51.2 1.2 51.2 51.2 61.21 51.2 51.2.1.13 300S4*2 s09s 62.5 53.2

  4. Chemically peculiar A/F stars in open clusters of the Milky Way

    NASA Astrophysics Data System (ADS)

    Gebran, M.; Monier, R.

    2010-12-01

    Abundance anomalies have been determined at the surface of many field and open cluster A and F dwarfs. These abundance anomalies are most likely caused by microscopic diffusion at work within the stable envelopes of A stars. However diffusion can be counteracted by several other mixing processes such as convection, rotational mixing and mass loss. We present a short review of the surface abundance patterns of A/F stars in the Pleiades (100 Myr), Coma Berenices (450 Myr) and Hyades (650 Myr) open clusters. Real star-to-star variations of the abundances were found for several chemical elements in the A dwarfs in these clusters. The derived abundances are then compared to evolutionary models from the Montreal group. These comparisons strongly suggest the occurence of hydrodynamical processes at play within the radiative zones of these stars and hindering the effects of microscopic diffusion (mixing processes/mass loss). In the frame of Gaia mission, simulations are presented that predict the number of A stars and open clusters that Gaia will observe in the Galaxy.

  5. Performance Analysis of Beamforming in Fixed-gain AF Relay Networks with Asymmetric Correlated Fading Channels

    NASA Astrophysics Data System (ADS)

    Li, Min

    2014-07-01

    In this paper, the performance of beamforming (BF) for a dual-hop amplify-and-forward (AF) relay network, where the source and destination are each equipped with multiple antennas, is investigated. It is assumed that the source-relay and relay-destination channels experience mixed fading distributions, namely, correlated Nakagami-m/Rician and correlated Rician/Nakagami-m, respectively. By considering fixed-gain relaying, analytical expressions for outage probability (OP) and average symbol error rate (ASER) are derived in closed-form. Numerical results are presented to demonstrate the efficacy of our performance analysis, also illustrate the impact of channel correlation, fading severity, Rician factor and antenna configuration on the performance of the system. It is shown that the correlated Nakagami-m/Rician fading channel can achieve better performance than the correlated Rician/Nakagami-m fading channel with the increase of fading severity parameter, and the correlated Rician/Nakagami-m fading channel may outperform the correlated Nakagami-m/Rician fading channel by enlarging the Rician factor.

  6. Perturbative magnetoresistance technique used to investigate FM/AF coupled bilayers

    NASA Astrophysics Data System (ADS)

    Oliveira, Alexandre; da Costa, Ricardo; Melo, Abner; Chesman, Carlos

    2014-03-01

    In this study we introduced modifications to a collinear four probe magnetoresistance set-up in order to measure magnetic properties that can only be sensed by techniques based on magnetization perturbation. In addition to the applied DC magnetic field (Hdc) , in magnetoresistance experiments, a small and quasi-static alternating magnetic field (hac, less than 10 Oe and around 800 Hz) is applied perpendicularly, both parallel to the sample plane. Due to Zeeman interaction, hac drives sample magnetization to oscillate slightly around its equilibrium position. Although we apply only DC current (few mA), the detected voltage carries DC and AC components. The DC voltage component provides information on magnetoresistance (MR) and the AC component is called perturbative magnetoresistance (PMR). We successfully demonstrated that the PMR signal is proportional to the first derivative of resistance with respect to hac. Using this technique and a phenomenological model that takes into account the relevant free energy terms of FM/AF coupled bilayers, we were able to study reversible and irreversible magnetization rotation processes in these magnetic systems. With respect to magnetic anisotropy, we investigated rotatable anisotropy, proposed by McMichael et al and Geshev et al. Financial support: CNPq, FAPERN and CAPES (Brazilian agencies).

  7. Dover AFB, Delaware Revised Uniform Summary of Surface Weather Observations (RUSSWO) Parts A-F.

    DTIC Science & Technology

    1981-10-16

    90. 92. 93.8 94.4 94 7 9497 94o8 94.9 95.0 95.0 95.0 95.1 95.* >oo 11. 75.1 86, 91.2 93.6 94* 95.3 95.6 95.6 95.7 95.8 95.9 95.9 95.9 95, 9 95.9...BRANCH uI AUFTAC PSYCHROMETRIC SUMMARY ! A. EATHCR SERVICE/MAC 1 7 7 LOVER AF3 Or 70,73-81 FEE STATION STATION NAkE Ytms MONTe PAGE I nb ~iJ-CS( ~OtAS 4L...30 31(IN.H;) B AR OMET R I C P RE S S URE ( NB ) 100 150 600 650 900 950 1000 1050 (O1) II -I’ g 5 1 I I F P R E S 5 U R E A L T I T U D E (10 0 O’S FT

  8. High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

    NASA Technical Reports Server (NTRS)

    Hammoud, A. N.; Baumann, E. D.; Overton, E.; Myers, I. T.; Suthar, J. L.; Khachen, W.; Laghari, J. R.

    1992-01-01

    Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments.

  9. Joint Source-Relay Design for Full-Duplex MIMO AF Relay Systems

    NASA Astrophysics Data System (ADS)

    Shi, Qingjiang; Hong, Mingyi; Gao, Xiqi; Song, Enbin; Cai, Yunlong; Xu, Weiqiang

    2016-12-01

    The performance of full-duplex (FD) relay systems can be greatly impacted by the self-interference (SI) at relays. By exploiting multi-antenna in FD relay systems, the spectral efficiency of FD relay systems can be enhanced through spatial SI mitigation. This paper studies joint source transmit beamforming and relay processing to achieve rate maximization for FD MIMO amplify-and-forward (AF) relay systems with consideration of relay processing delay. The problem is difficult to solve due mainly to the SI constraint induced by the relay processing delay. In this paper, we first present a sufficient condition under which the relay amplification matrix has rank one structure. Then, for the case of rank one amplification matrix, the rate maximization problem is equivalently simplified into an unconstrained problem which can be locally solved using gradient ascent method. Next, we propose a penalty-based algorithmic framework, called P-BSUM, for a class of constrained optimization problems which have difficult equality constraints in addition to some convex constraints. By rewriting the rate maximization problem with a set of auxiliary variables, we apply the P-BSUM algorithm to the rate maximization problem in the general case. Finally, numerical results validate the efficiency of the proposed algorithms and show that the joint source-relay design approach under the rank one assumption could be strictly suboptimal as compared to the P-BSUM-based joint source-relay design approach.

  10. Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.

    PubMed Central

    Durand, B; Saunders, M; Gaudon, C; Roy, B; Losson, R; Chambon, P

    1994-01-01

    A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-cis retinoic acid receptor (RXR) alpha has been characterized as an amphipathic alpha-helix whose main features are conserved between transcriptionally active members of the nuclear receptor superfamily. This conserved motif, which can activate autonomously in the absence of ligand in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcription, thus indicating that a ligand-dependent conformational change is necessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers are bound can affect the activity of the AF-2s of the heterodimeric partners, as well as the relative efficiency with which all-trans and 9-cis retinoic acids activate the RAR partner. Images PMID:7957103

  11. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

    PubMed Central

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-01-01

    Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL–AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL–AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation. PMID:26593443

  12. Raman sensitivity enhancement for aqueous absorbing sample using Teflon-AF 2400 liquid core optical fibre cell.

    PubMed

    Tian, Yanjie; Zhang, Liuyang; Zuo, Jian; Li, Zuowei; Gao, Shuqin; Lu, Guohui

    2007-01-02

    The compatibility Teflon-AF 2400 liquid core optical fibre with resonance Raman spectroscopy (RRS-LCOF) was used to detect aqueous biomolecules. The maximum sensitivity enhancement factor for concentrations greater than the detection limit in a conventional cell was 10, and detection limit reduction of about 1000-fold have been achieved for the measurement of aqueous absorbing sample using Teflon-AF 2400 fibre Raman cell compared to the conventional cell. We were able to collect spectra of 2.5 x 10(-9) and 2.5 x 10(-10) M aqueous beta-carotene using 16.2 mW of laser power and 10s integration time. This volume of a 2.5 x 10(-10) M aqueous solution corresponds to only 1.5 fmol or 830 fg of beta-carotene. The results of this preliminary study indicate that RRS-LCOF has potential in bioanalytical and biomedical applications.

  13. Blood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: Results from the ROCKET AF Trial.

    PubMed

    Vemulapalli, Sreekanth; Hellkamp, Anne S; Jones, W Schuyler; Piccini, Jonathan P; Mahaffey, Kenneth W; Becker, Richard C; Hankey, Graeme J; Berkowitz, Scott D; Nessel, Christopher C; Breithardt, Günter; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R

    2016-08-01

    We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF). The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP. In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10-mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P = .06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69). In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

    PubMed

    Singer, Daniel E; Hellkamp, Anne S; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R; Piccini, Jonathan P; Hankey, Graeme J; Breithardt, Günter; Halperin, Jonathan L; Becker, Richard C; Hacke, Werner; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

    2015-03-03

    In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  16. An Updated Version of the U.S. Air Force Multi-Attribute Task Battery (AF-MATB)

    DTIC Science & Technology

    2014-08-01

    assessing human performance in a controlled multitask environment. The most recent release of AF-MATB contains numerous improvements and additions...Strategic Behavior, MATB, Multitasking , Task Battery, Simulator, Multi-Attribute Task Battery, Automation 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...performance and multitasking strategy. As a result, a specific Information Throughput (IT) Mode was designed to customize the task to fit the Human

  17. Current Status and Outcomes of Direct Oral Anticoagulant Use in Real-World Atrial Fibrillation Patients - Fushimi AF Registry.

    PubMed

    Yamashita, Yugo; Uozumi, Ryuji; Hamatani, Yasuhiro; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Ogawa, Hisashi; Abe, Mitsuru; Morita, Satoshi; Akao, Masaharu

    2017-08-25

    The current status and outcomes of direct oral anticoagulant (DOAC) use have not been widely evaluated in unselected patients with atrial fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up data with oral anticoagulant (OAC) status were available for 3,731 patients by the end of November 2015. We evaluated OAC status and clinical outcomes according to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and major bleeding events during the median follow-up of 3.0 years was 224 (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the prevalence of DOAC use increased gradually and steadily, and that of warfarin, DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional hazards modeling incorporating change in OAC status as a time-dependent covariate for stroke/SE and major bleeding events, use of DOAC compared with warfarin was not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45). In real-world clinical practice, there were no significant differences in stroke/SE events or major bleeding events for DOAC compared with warfarin in patients with AF.

  18. KI Sawyer AFB, Gwinn, Michigan. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1979-04-26

    WID DIRECTION AND SPEED (FROM HOURLY OBSERVAlIONS) 9483’, K I SA-YFk AF6 ti1 ____, _____;______78____ _______ STATION STATiSm KAME YEAS ST ALL rf.TTlf...94816~ K I SAWYFRC AFB 1I 1A STA-1,O, STAMMO kAME YERS4M ( PAGE 2 iboo-2p00Q "OUAS (L. S.T. WET BULB TEMPERATURE DEPRESSION (F) TOTAL I TOTAL IF) 1 0

  19. An illness-specific version of the Revised Illness Perception Questionnaire in patients with atrial fibrillation (AF IPQ-R): Unpacking beliefs about treatment control, personal control and symptom triggers.

    PubMed

    Taylor, Elaina C; O'Neill, Mark; Hughes, Lyndsay D; Moss-Morris, Rona

    2017-09-11

    This study modified the Revised Illness Perception Questionnaire (IPQ-R) in patients with persistent atrial fibrillation (AF). Qualitative interviews and think-aloud techniques informed modification of the IPQ-R to be specific to AF patients. Confirmatory Factor Analysis (CFA) (n = 198) examined the validity of the modified IPQ-R (AF-IPQ-R). Exploratory factor analysis (EFA) examined the new AF-triggers scale. Construct validity examined associations between the AF-IPQ-R, quality of life (QoL) and beliefs about medicines. Test-retest and internal reliability were examined. Interviews indicated that patients viewed triggers of AF rather than initial causes of illness as more applicable. Patients believed specific behaviours such as rest could control AF. Treatment control beliefs related to pharmacological and procedural treatments. These data were used to modify the IPQ-R subscales and to develop a triggers of AF scale. CFA indicated good model fit. EFA of the triggers scale indicated three factors: emotional; health behaviours; and over-exertion triggers. Expected correlations were found between the AF-IPQ-R, QoL and treatment beliefs, evidencing good construct validity. The AF-IPQ-R showed sound psychometric properties. It provides more detailed specification than the IPQ-R of beliefs that may help to understand poor QoL in AF patients, and guidance for future interventions in this area.

  20. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably. © 2016 John Wiley & Sons Ltd.

  1. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  2. Self-assembly of amphiphilic peptide (AF)6H5K15 derivatives: roles of hydrophilic and hydrophobic residues.

    PubMed

    Thota, Naresh; Jiang, Jianwen

    2014-03-13

    A molecular dynamics simulation study is reported to investigate the roles of hydrophilic and hydrophobic residues in the self-assembly of (AF)6H5K15 peptide derivatives. The peptide, as well as water and counterions, are represented by the MARTINI coarse-grained model. The assembly is observed to follow a three-step process: formation of small clusters, large clusters, and micelles. With increasing length of hydrophilic Lys residues in (AF)6H5Kn (n = 10, 15, 20, and 25), assembly capability is found to be reduced with the formation of smaller micelles or the presence of individual peptide chains. Upon replacing Ala by more hydrophobic Phe in AmFnH5K15 (m + n = 12), larger micelles are formed. With increasing length of hydrophobic Phe residues in FnH5K15 (n = 4, 8, 12, and 16), micelle size increases and the morphology shifts from spherical to fiber-like. The simulation study provides mechanistic insight into the crucial roles of hydrophilicity and hydrophobicity in the assembly of (AF)6H5K15 derivatives; it reveals that assembly capability is reduced by increasing hydrophilicity, whereas increasing hydrophobicity leads to morphology transition.

  3. A spent SRB used on STS-87 is lifted in a hoisting slip in Hangar AF at CCAS

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is lifted in a hoisting slip in the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  4. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  5. ZFP521 regulates murine hematopoietic stem cell function and facilitates MLL-AF9 leukemogenesis in mouse and human cells.

    PubMed

    Garrison, Brian S; Rybak, Adrian P; Beerman, Isabel; Heesters, Balthasar; Mercier, Francois E; Scadden, David T; Bryder, David; Baron, Roland; Rossi, Derrick J

    2017-08-03

    The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521/Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis whose function in HSC biology remains elusive. Competitive serial transplantation assays using Zfp521-deficient mice revealed that ZFP521 regulates HSC self-renewal and differentiation. In contrast, ectopic expression of ZFP521 in HSCs led to a robust maintenance of progenitor activity in vitro. Transcriptional analysis of human acute myeloid leukemia (AML) patient samples revealed that ZNF521 is highly and specifically upregulated in AMLs with MLL translocations. Using an MLL-AF9 murine leukemia model and serial transplantation studies, we show that ZFP521 is not required for leukemogenesis, although its absence leads to a significant delay in leukemia onset. Furthermore, knockdown of ZNF521 reduced proliferation in human leukemia cell lines possessing MLL-AF9 translocations. Taken together, these results identify ZNF521/ZFP521 as a critical regulator of HSC function, which facilitates MLL-AF9-mediated leukemic disease in mice.

  6. A comparative study on the effects of tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF) and basic fibroblast growth factor (bFGF) on the chorioallantoic membrane of the chick embryo.

    PubMed

    Olivo, M; Bhardwaj, R; Schulze-Osthoff, K; Sorg, C; Jacob, H J; Flamme, I

    1992-09-01

    The chorioallantoic membrane (CAM) assay is a widely used bioassay for testing angiogenic activities. In the present study we compared the gross and micromorphological effects of three angiogenic factors applied in Elvax carriers on the CAM: Tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h-AF), and basic fibroblast growth factor (bFGF). Our question was whether the CAM responds to these factors which have very different actions with a stereotype or with a factor specific reaction. By microangiography and light microscopy, all positive reactions appeared as a spoke-wheel vascular pattern with a bundle of small capillary blood vessels in the center. These vessels were predominantly of a distended type in h-AF and TNF experiments, while narrower capillary vessels followed bFGF application. Chorioallantoic ectoderm and endoderm were thickened by cell accumulation and the mesenchymal stroma of the CAM was edematous and infiltrated with leucocytes in all three reactions. Additionally, bFGF experiments showed areas of densely arranged fibroblasts. Observations in vivo showed chorioallantoic tissue movements as a possible mechanism for the spokewheel vascular pattern. As compared with our results from studies of cytokinetics with bromodeoxyuridine, these current findings indicate that chemotaxis is responsible for the chorioallantoic angiogenic reaction rather than cellular proliferation.

  7. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Accellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2015-09-01

    Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest ...NUMBER: Wake Forest University Health Sciences Medical Center Boulevard Winston-Salem, NC 27157 9. SPONSORING / MONITORING AGENCY NAME(S) AND

  8. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    DTIC Science & Technology

    2016-09-01

    equivalent to those repaired using nerve autograph, the current gold standard for tension-free repair of transected peripheral nerves. Axon counts and neuromuscular junction morphology were equivalent between the AFS seeded ANA.

  9. Stroke prevention in atrial fibrillation and ‘real world’ adherence to guidelines in the Balkan Region: The BALKAN-AF Survey

    PubMed Central

    Potpara, Tatjana S.; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S.; Polovina, Marija M.; Petranov, Stanislav L.; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y. H.; Potpara, Tatjana S.; Polovina, Marija; Milanov, Srdjan; Pavlovic, Marija; Petrovic, Marijana; Simovic, Stefan; Mitic, Gorana; Milanov, Marko; Savic, Jelena; Gnip, Sanja; Radovic, Pavica; Markovic, Snezana; Koncarevic, Ivana; Gavrilovic, Jelena; Acimovic, Tijana; Djikic, Dijana; Malic, Semir; Hodzic, Jusuf; Stojanovic, Milovan; Ilic, Marina Deljanin; Zlatar, Milan; Matic, Dragan; Lazic, Snezana; Peric, Vladan; Markovic, Sanja; Kovacevic, Snezana; Arandjelovic, Aleksandra; Asanin, Milika; Zdravkovic, Marija; Dan, Gheorghe-Andrei; Breha, Anca; Dan, Anca Rodica; Musetescu, Rodica; Popescu, Mircea Ioachim; Badila, Elisabeta; Georgescu, Catalina Arsenescu; Pop, Sorina; Popescu, Raluca; Neamtu, Simina; Oancea, Floriana; Trendafilova, Elina; Dimitrova, Elena; Goshev, Evgenii; Velichkova, Anna; Petranov, Stanislav; Kamenova, Delyana; Kamenova, Penka; Elefterova, Svetoslava; Shterev, Valentin; Zekova, Maria; Diukiandzhieva, Stela; Dimitrov, Boiko; Sotirov, Tihomir; Simeonova, Valentina; Drianovska, Dimitrina; Boiadzhieva, Liliya Ivanova Vasileva; Buchukova, Darina; Goda, Artan; Paparisto, Vilma; Gjergo, Hortensia; Mijo, Alma; Shirka, Ervina; Gjini, Viktor; Ekmekciu, Uliks; Refatllari, Ina; Kusljugic, Zumreta; Loncar, Daniela; Mrsic, Denis; Tulumovic, Hazim; Pojskic, Belma; Sijamija, Alma; Bijedic, Amira; Karamujic, Indira; Bijedic, Irma; Halilovic, Sanela; Sokolovic, Sekib; Manola, Sime; Zeljkovic, Ivan; Pavlovic, Nikola; Radeljic, Vjekoslav; Brusich, Sandro; Anic, Ante; Jeric, Melita; Pekic, Petar; Milas, Kresimir; Music, Ljilja; Bulatovic, Nebojsa; Nenezic, Ana; Asanovic, Dijana

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary ‘real-world’ AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the ‘truly low-risk’ patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  10. Cardiac Remodeling, Circulating Biomarkers and Clinical Events in Patients with a History of Atrial Fibrillation. Data from the GISSI-AF Trial.

    PubMed

    Staszewsky, Lidia; Masson, Serge; Barlera, Simona; Disertori, Marcello; Boni, Silvana; Bertoli, Daniele; Vriz, Olga; Pasotti, Elena; Zeni, Prisca; Vago, Tarcisio; Maggioni, Aldo P; Tognoni, Gianni; Latini, Roberto

    2015-12-01

    Atrial fibrillation (AF) is the most common arrhythmia and has an increasing impact on public health because of its morbidity and mortality. Clinical and diagnostic tests to predict the recurrence of arrhythmia and clinical events before AF becomes permanent are still an open issue. 307 out of 1442 patients in sinus rhythm, at high risk of recurrence of AF enrolled in the GISSI-AF study, participated in a substudy with echocardiographic and biohumoral evaluation at baseline and at 12-month follow-up. The relations between biomarker concentrations and echocardiographic parameters with study endpoints in 1 year, were analysed by a stepwise multivariable Cox model (entry criteria p < 0.5 and stay criteria p < 0.2). The echocardiographic variables, cardiac markers and clinical variables considered in the statistical model indicated a higher concentration of NT-proBNP at baseline as the strongest factor related to time of first AF recurrence (HR 1.42; 95 %CI 1.23-1.46), first CV hospitalization (HR 1.58; 95 %CI 1.31-1.92) and increasing duration of recurrent AF (OR 2.16; 95 %CI 1.52-3.08). Valsartan treatment was not related to clinical events. In patients in sinus rhythm with a history of AF a higher concentration of NT-proBNP at baseline was the strongest independent risk factor for first AF recurrence and its duration, and for the first hospital admission for cardiovascular reasons.

  11. The effect of atrial preference pacing on atrial fibrillation electrophysiological substrate in Myotonic Dystrophy type 1 population.

    PubMed

    Russo, Vincenzo; Nigro, Gerardo; DI Meo, Federica; Papa, Andrea Antonio; Cioppa, Nadia Della; Proietti, Riccardo; Russo, Maria Giovanna; Calabrò, Raffaele; Politano, Luisa

    2014-12-01

    P-wave dispersion is a non invasive indicator of intra-atrial conduction heterogeneity producing substrate for reentry, which is a pathophysiological mechanism of atrial fibrillation. The relationship between P-wave dispersion (PD) and atrial fibrillation (AF) in Myotonic dystrophy type 1 (DM1) patients is still unclear. Atrial Preference Pacing (APP) is an efficient algorithm to prevent paroxysmal AF in patients implanted with dual-chamber pacemaker. Aim of our study was to evaluate the possible correlation between atrial preference pacing algorithm, P-wave dispersion and AF burden in DM1 patients with normal cardiac function underwent permanent dual-chamber pacemaker implantation. We enrolled 50 patients with DM1 (age 50.3 ± 7.3; 11 F) underwent dual-chamber pacemaker implantation for various degree of atrioventricula block. The study population was randomized following 1 months stabilization period to APP algorithm features programmed OFF or ON. Patients were assessed every 3 months for the first year, and every 6 months thereafter up to 3 years. At each follow-up visit, we counted: the number of premature atrial beats, the number and the mean duration of AF episodes, AF burden and the percentage of atrial and ventricular pacing. APP ON Group showed lower number of AF episodes (117 ± 25 vs. 143 ± 37; p = 0.03) and AF burden (3059 ± 275 vs. 9010 ± 630 min; p < 0.04) than APP OFF Group. Atrial premature beats count (44903 ± 30689 vs. 13720 ± 7717 beats; p = 0.005) and Pwave dispersion values (42,1 ± 11 ms vs. 29,1 ± 4,2 ms, p = 0,003) were decreased in APP ON Group. We found a significant positive correlation between PD and AF burden (R = 0,8, p = 0.007). Atrial preference pacing algorithm, decreasing the number of atrial premature beats and the P-wave dispersion, reduces the onset and perpetuator factors of AF episodes and decreases the AF burden in DM1 patients underwent dual chamber pacemaker implantation for various degree of atrioventricular blocks

  12. Mutations in the Caenorhabditis elegans U2AF Large Subunit UAF-1 Alter the Choice of a 3′ Splice Site In Vivo

    PubMed Central

    Ma, Long; Horvitz, H. Robert

    2009-01-01

    The removal of introns from eukaryotic RNA transcripts requires the activities of five multi-component ribonucleoprotein complexes and numerous associated proteins. The lack of mutations affecting splicing factors essential for animal survival has limited the study of the in vivo regulation of splicing. From a screen for suppressors of the Caenorhabditis elegans unc-93(e1500) rubberband Unc phenotype, we identified mutations in genes that encode the C. elegans orthologs of two splicing factors, the U2AF large subunit (UAF-1) and SF1/BBP (SFA-1). The uaf-1(n4588) mutation resulted in temperature-sensitive lethality and caused the unc-93 RNA transcript to be spliced using a cryptic 3′ splice site generated by the unc-93(e1500) missense mutation. The sfa-1(n4562) mutation did not cause the utilization of this cryptic 3′ splice site. We isolated four uaf-1(n4588) intragenic suppressors that restored the viability of uaf-1 mutants at 25°C. These suppressors differentially affected the recognition of the cryptic 3′ splice site and implicated a small region of UAF-1 between the U2AF small subunit-interaction domain and the first RNA recognition motif in affecting the choice of 3′ splice site. We constructed a reporter for unc-93 splicing and using site-directed mutagenesis found that the position of the cryptic splice site affects its recognition. We also identified nucleotides of the endogenous 3′ splice site important for recognition by wild-type UAF-1. Our genetic and molecular analyses suggested that the phenotypic suppression of the unc-93(e1500) Unc phenotype by uaf-1(n4588) and sfa-1(n4562) was likely caused by altered splicing of an unknown gene. Our observations provide in vivo evidence that UAF-1 can act in regulating 3′ splice-site choice and establish a system that can be used to investigate the in vivo regulation of RNA splicing in C. elegans. PMID:19893607

  13. Structure of the Archaeoglobus fulgidus orphan ORF AF1382 determined by sulfur SAD from a moderately diffracting crystal

    PubMed Central

    Zhu, Jin-Yi; Fu, Zheng-Qing; Chen, Lirong; Xu, Hao; Chrzas, John; Rose, John; Wang, Bi-Cheng

    2012-01-01

    The crystal structure of the 11.14 kDa orphan ORF 1382 from Archaeoglobus fulgidus (AF1382) has been determined by sulfur SAD phasing using a moderately diffracting crystal and 1.9 Å wavelength synchrotron X-rays. AF1382 was selected as a structural genomics target by the Southeast Collaboratory for Structural Genomics (SECSG) since sequence analyses showed that it did not belong to the Pfam-A database and thus could represent a novel fold. The structure was determined by exploiting longer wavelength X-rays and data redundancy to increase the anomalous signal in the data. AF1382 is a 95-­residue protein containing five S atoms associated with four methionine residues and a single cysteine residue that yields a calculated Bijvoet ratio (ΔF anom/F) of 1.39% for 1.9 Å wavelength X-rays. Coupled with an average Bijvoet redundancy of 25 (two 360° data sets), this produced an excellent electron-density map that allowed 69 of the 95 residues to be automatically fitted. The S-SAD model was then manually completed and refined (R = 23.2%, R free = 26.8%) to 2.3 Å resolution (PDB entry 3o3k). High-resolution data were subsequently collected from a better diffracting crystal using 0.97 Å wavelength synchrotron X-rays and the S-SAD model was refined (R = 17.9%, R free = 21.4%) to 1.85 Å resolution (PDB entry 3ov8). AF1382 has a winged-helix–turn–helix structure common to many DNA-binding proteins and most closely resembles the N-terminal domain (residues 1–82) of the Rio2 kinase from A. fulgidus, which has been shown to bind DNA, and a number of MarR-family transcriptional regulators, suggesting a similar DNA-binding function for AF1382. The analysis also points out the advantage gained from carrying out data reduction and structure determination on-site while the crystal is still available for further data collection. PMID:22948926

  14. Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

    PubMed Central

    Hamatani, Yasuhiro; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru

    2015-01-01

    Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID:26540107

  15. Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.

    PubMed

    Chen, Xiaoyi; Clark, Jason; Wunderlich, Mark; Fan, Cuiqing; Davis, Ashley; Chen, Song; Guan, Jun-Lin; Mulloy, James C; Kumar, Ashish; Zheng, Yi

    2017-02-15

    Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.

  16. Characterization of the molar mass distribution of macromolecules in beer for different mashing processes using asymmetric flow field-flow fractionation (AF4) coupled with multiple detectors.

    PubMed

    Choi, Jaeyeong; Zielke, Claudia; Nilsson, Lars; Lee, Seungho

    2017-07-01

    The macromolecular composition of beer is largely determined by the brewing and the mashing process. It is known that the physico-chemical properties of proteinaceous and polysaccharide molecules are closely related to the mechanism of foam stability. Three types of "American pale ale" style beer were prepared using different mashing protocols. The foam stability of the beers was assessed using the Derek Rudin standard method. Asymmetric flow field-flow fractionation (AF4) in combination with ultraviolet (UV), multiangle light scattering (MALS) and differential refractive index (dRI) detectors was used to separate the macromolecules present in the beers and the molar mass (M) and molar mass distributions (MD) were determined. Macromolecular components were identified by enzymatic treatments with β-glucanase and proteinase K. The MD of β-glucan ranged from 10(6) to 10(8) g/mol. In addition, correlation between the beer's composition and foam stability was investigated (increased concentration of protein and β-glucan was associated with increased foam stability).

  17. Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry.

    PubMed

    Boriani, Giuseppe; Laroche, Cecile; Diemberger, Igor; Fantecchi, Elisa; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Sinagra, Gianfranco; Petrescu, Lucian; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

    2015-05-01

    Atrial fibrillation is often asymptomatic, but outcomes require further characterization. The study objective was to investigate the clinical presentation, management, and outcomes in asymptomatic and symptomatic patients with atrial fibrillation who were prospectively enrolled in the EurObservational Research Programme - Atrial Fibrillation (EORP-AF) Pilot General Registry. A total of 3119 patients were enrolled, and 1237 (39.7%) were asymptomatic (European Heart Rhythm Association [EHRA] score I). Among symptomatic patients, 963 (51.2%) had mild symptoms (EHRA score II) and 919 (48.8%) had severe or disabling symptoms (EHRA III-IV). Permanent atrial fibrillation was 3-fold more common in asymptomatic patients than in symptomatic patients. On multivariate analysis, male gender (odds ratio [OR], 1.630; 95% confidence interval [CI], 1.384-1.921), older age (OR, 1.019; 95% CI, 1.012-1.026), previous myocardial infarction (OR, 1.681; 95% CI, 1.350-2.093), and limited physical activity (OR, 1.757; 95% CI, 1.495-2.064) were associated significantly with asymptomatic (EHRA I) atrial fibrillation. Fully asymptomatic atrial fibrillation (absence of current and previous symptoms) was present in 520 patients (16.7%) and was associated independently with male gender, age, and previous myocardial infarction. Appropriate guideline-based prescription of oral anticoagulants was lower in these patients, and aspirin was prescribed more frequently. Mortality at 1 year was more than 2-fold higher in asymptomatic patients compared with symptomatic patients (9.4% vs 4.2%, P < .0001) and was associated independently with older age and comorbidities, including chronic kidney disease and chronic heart failure. Asymptomatic atrial fibrillation is common in daily cardiology practice and is associated with elderly age, more comorbidities, and high thromboembolic risks. A higher 1-year mortality was found in asymptomatic patients compared with symptomatic patients. Copyright © 2015 Elsevier

  18. Mobile phones in cryptogenic strOke patients Bringing sIngle Lead ECGs for Atrial Fibrillation detection (MOBILE-AF): study protocol for a randomised controlled trial.

    PubMed

    Treskes, Roderick W; Gielen, Willem; Wermer, Marieke J; Grauss, Robert W; van Alem, Anouk P; Dehnavi, Reza Alizadeh; Kirchhof, Charles J; van der Velde, Enno T; Maan, Arie C; Wolterbeek, Ron; Overbeek, Onno M; Schalij, Martin J; Trines, Serge A

    2017-08-29

    Recently published randomised clinical trials indicate that prolonged electrocardiom (ECG) monitoring might enhance the detection of paroxysmal atrial fibrillation (AF) in cryptogenic stroke or transient ischaemic attack (TIA) patients. A device that might be suitable for prolonged ECG monitoring is a smartphone-compatible ECG device (Kardia Mobile, Alivecor, San Francisco, CA, USA) that allows the patient to record a single-lead ECG without the presence of trained health care staff. The MOBILE-AF trial will investigate the effectiveness of the ECG device for AF detection in patients with cryptogenic stroke or TIA. In this paper, the rationale and design of the MOBILE-AF trial is presented. For this international, multicentre trial, 200 patients with cryptogenic stroke or TIA will be randomised. One hundred patients will receive the ECG device and will be asked to record their ECG twice daily during a period of 1 year. One hundred patients will receive a 7-day Holter monitor. The primary outcome of this study is the percentage of patients in which AF is detected in the first year after the index ischaemic stroke or TIA. Secondary outcomes include markers for AF prediction, orally administered anticoagulation therapy changes, as well as the incidence of recurrent stroke and major bleeds. First results can be expected in mid-2019. ClinicalTrials.gov, ID: NCT02507986 . Registered on 15 July 2015.

  19. U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3' End Formation.

    PubMed

    Park, Sung Mi; Ou, Jianhong; Chamberlain, Lynn; Simone, Tessa M; Yang, Huan; Virbasius, Ching-Man; Ali, Abdullah M; Zhu, Lihua Julie; Mukherjee, Siddhartha; Raza, Azra; Green, Michael R

    2016-05-19

    Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy-related factor 7 (Atg7) pre-mRNA is abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity.

  20. Letter to the Editor: H-1, C-13 and N-15 Assignments for the Archaeglobus fulgidis Protein AF2095.

    SciTech Connect

    Powers, Robert; Acton, Thomas; Chiang, Yiwen; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Ma, LiChung; Rost, Burkhard; Montelione, Gaetano

    2004-09-01

    The Human genome project promises to provide an unprecedented wealth of information on cell biology, development, evolution and physiology. Translating this immense increase in genomic information into advances in medicine and human health requires a concerted effort to explore and investigate the structure and molecular activity for the vast amount of proteins in the Human proteome that lack any such explicit experimental information. Structural genomics is providing a means to determine the molecular and cellular function of these proteins by characterizing the complete range of protein folds (Montelione, 2001). By annotating sequence information with a protein structure, it is sometimes possible to decipher the biochemical activity of hypothetical proteins from structural similarity and the conservation of spatial arrangement of active site residues. Homology can often be inferred by structural similarity even in the absence of recognizable sequence similarity, and can sometimes be used to identify functional relationships between distantly related proteins. Determining an experimental structure for each protein in a proteome is currently impractical because of the significant time commitment and resources required by X-ray and NMR. Therefore, the current paradigm of structural genomics is to determine a representative structure for each cluster of homologous protein domain sequences that lack similarity to a protein domain with a known structure. In this manner, comparative modeling using a single experimental structure can provide approximate but useful 3D structural information for an entire protein domain family. The Northeast Structural Genomics Consortium (NESG; www.nesg.org) is a pilot project funded by the National Institutes of Health Protein Structure Initiative, focusing on proteins from eukaryotic model organisms including humans. The thermophillic archaea Archaeglobus fulgidis AF2095 protein is an example of a protein of unknown biological function

  1. Hyperuricemia is associated with an increased prevalence of paroxysmal atrial fibrillation in patients with type 2 diabetes referred for clinically indicated 24-h Holter monitoring.

    PubMed

    Mantovani, A; Rigolon, R; Civettini, A; Bolzan, B; Morani, G; Bonapace, S; Dugo, C; Zoppini, G; Bonora, E; Targher, G

    2017-07-15

    Several studies have reported an association between hyperuricemia and increased risk of permanent atrial fibrillation (AF) in patients with and without type 2 diabetes mellitus (T2DM). Currently, no published data are available on the relationship between hyperuricemia and risk of paroxysmal AF. We retrospectively evaluated 245 T2DM outpatients without pre-existing AF, cancer, cirrhosis and end-stage renal disease, who underwent a 24-h ECG-Holter monitoring for various clinical indications. Hyperuricemia was defined as a serum uric acid level >7 mg/dl for men and >6 mg/dl for women or allopurinol use. The diagnosis of paroxysmal AF was confirmed in affected individuals on the basis of 24-h ECG-Holter monitoring by experienced cardiologists. Hyperuricemia was observed in 59 (24.1%) patients, whereas paroxysmal AF was found in 11 (4.5%) patients. The prevalence of paroxysmal AF was higher in patients with hyperuricemia than in those without hyperuricemia (10.2 vs. 2.7%, p = 0.026). Logistic regression analysis showed that hyperuricemia was associated with an increased risk of prevalent paroxysmal AF. This association remained significant even after adjustment for age, metabolic syndrome and chronic kidney disease (adjusted-odds ratio 4.01, 95% CI 1.08-14.9; p = 0.039). Similar results were found when we used serum uric acid levels as a continuous measure. This study shows for the first time that hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM. These findings may partly explain the increased risk of permanent atrial fibrillation and cardiovascular death observed among patients with hyperuricemia.

  2. Assessment of Remote Heart Rhythm Sampling Using the AliveCor Heart Monitor to Screen for Atrial Fibrillation: The REHEARSE-AF Study.

    PubMed

    Halcox, Julian P J; Wareham, Kathie; Cardew, Antonia; Gilmore, Mark; Barry, James P; Phillips, Ceri; Gravenor, Michael B

    2017-08-28

    Background -Asymptomatic atrial fibrillation (AF) is increasingly common in the aging population and implicated in many ischemic strokes. Earlier identification of AF with appropriate anticoagulation may decrease stroke morbidity and mortality. Methods -We conducted a randomized controlled trial of AF screening using an AliveCor Kardia monitor attached to a WiFi-enabled iPod to obtain ECGs (iECGs) in ambulatory patients. Patients ≥65 years of age with a CHADS-VASc score ≥2 free from AF were randomized to the iECG arm or routine care (RC). iECG participants acquired iECGs twice weekly over 12 months (plus additional iECGs if symptomatic) onto a secure study server with overread by an automated AF detection algorithm and by a cardiac physiologist and/or consultant cardiologist. Time to diagnosis of AF was the primary outcome measure. The overall cost of the devices, ECG interpretation, and patient management were captured and used to generate the cost per AF diagnosis in iECG patients. Clinical events and patient attitudes/experience were also evaluated. Results -We studied 1001 patients (500 iECG, 501 RC) who were 72.6±5.4 years of age; 534 were female. Mean CHADS-VASc score was 3.0 (heart failure, 1.4%; hypertension, 54%; diabetes mellitus, 30%; prior stroke/transient ischemic attack, 6.5%; arterial disease, 15.9%; all CHADS-VASc risk factors were evenly distributed between groups). Nineteen patients in the iECG group were diagnosed with AF over the 12-month study period versus 5 in the RC arm (hazard ratio, 3.9; 95% confidence interval=1.4-10.4; P=0.007) at a cost per AF diagnosis of $10780 (£8255). There was a similar number of stroke/transient ischemic attack/systemic embolic events (6 versus 10, iECG versus RC; hazard ratio=0.61; 95% confidence interval=0.22-1.69; P=0.34). The majority of iECG patients were satisfied with the device, finding it easy to use without restricting activities or causing anxiety. Conclusion - Screening with twice-weekly single

  3. Identifying the relationship between the non-PV triggers and the critical CFAE sites post-PVAI to curtail the extent of atrial ablation in longstanding persistent AF.

    PubMed

    Elayi, Claude S; DI Biase, Luigi; Bai, Rong; Burkhardt, J David; Mohanty, Prasant; Sanchez, Javier; Santangeli, Pasquale; Hongo, Richard; Gallinghouse, G Joseph; Horton, Rodney; Bailey, Shane; Zagrodzky, Jason; Beheiry, Salwa; Natale, Andrea

    2011-11-01

    Complex fractionated atrial electrograms (CFAE) ablation has been performed in addition to pulmonary veins (PV) isolation to increase the success rate of atrial fibrillation (AF) ablation in patients with longstanding (LS) persistent AF. The mechanism underlying the clinical benefit of CFAE ablation remains, however, poorly understood. We compared the impact of CFAE ablation on the prevalence of non-PV atrial triggers inducing AF in 2 groups of patients with LS persistent AF. One group underwent PVAI alone, and the other group underwent PVAI plus CFAE ablation. In addition, we correlated the site of non-PV triggers with the presence of CFAE. A total of 98 consecutive patients with symptomatic drug refractory LS persistent AF presenting for ablation had a preablation electroanatomic CFAE map. Patients randomized to either isolation of the PVs and posterior wall (PVAI) (group I, n = 48 pts) or PVAI and biatrial ablation of CFAEs (group II, 50 pts). After ablation, infusion of isoproterenol up to 30 mcg/min was given to reveal non PV foci inducing AF. Those foci were mapped and correlated with CFAE regions and ablated. A total of 19 patients (76%) with PV foci inducing AF were associated with either stable or transient CFAE after PVAI, respectively, in 12 patients (48%) and 7 patients (28%). A total of 20 (42%) non-PV triggers were observed in group I versus 5 (10%) in group II (P < 0.001) in 18 and 5 patients, respectively. After a mean f/u of 17.2 ± 5.2 months, 33 (69%) patients in group I and 36 (72%) patients in group II were in SR (P = NS). Non-PV triggers inducing AF post-PVAI were associated with the presence of stable or transient CFAE in 48% and 28% of cases, respectively, in LS persistent AF. CFAE ablation after PVAI was associated with a significantly higher elimination of those non-PV triggers. This suggests that at least part of the beneficial effect achieved by CFAE ablation reflects elimination of non-PV AF triggers. © 2011 Wiley Periodicals, Inc.

  4. Blood Types

    MedlinePlus

    ... FIND A BLOOD DRIVE Blood Types and the Population O positive is the most common blood type. ... of the different blood types in the U.S. population is: Caucasian African- American Latino-American Asian O + ...

  5. Hydrogen Transport Conditions and Effects in Cathodically Polarized AF1410 Steel

    NASA Astrophysics Data System (ADS)

    Charca, Samuel M.; Uwakweh, Oswald N. C.; Agarwala, Vinod S.

    2007-10-01

    Hydrogen permeation of AF1410 steel membranes due to cathodic polarization using the Devanathan and Starchurski double cell (DSDC) with 0.1M H2SO4 + 1 g/L Na2HAsO4·7H2O, and 0.1M NaOH media in the input and exit cells, respectively, under Galvanostatic conditions depended on the polarization current density, membrane thickness, and surface roughness. For a 0.35-mm-thick membrane, the steady-state hydrogen permeated using increasing polarization currents from 1.00 to 10.00 mA varied correspondingly from 0.6 × 10-5 (mol H/m2s) to 1.03 × 10-5 mol H/m2s, with accompanying transient rates or permeation rates of 1.07 × 10-4 A/m2s to 4.40 × 10-4 A/m2s. With a constant polarization current density of 20 A/m2, the steady-state permeated hydrogen was in the range of 1.00 × 10-5 (mol H/m2s) to 3.50 × 10-5 (mol H/m2s), for 0.30-mm and 0.09-mm-thick membranes, respectively. The breakthrough times decreased from 2130 to 300 seconds with decreasing membranes thickness from 0.30 to 0.09 mm. The formation of blisters was observed more on the input side surface than on the exit-side surface and occurred for polarization charging current densities greater than 30.0 A/m2. The tendency for blister formation increased with decreasing material’s surface roughness. Cracks accompanying blisters tended to form on both the input and exit-side surfaces only with continued charging following the attainment of steady-state permeation, though they were generally lower on the potentiostated exit side. The average effective permeation coefficient of hydrogen was determined to be 2.89 × 10-12 m2/s for membrane thicknesses ranging from 0.09 to 0.30 mm based on the slope method.

  6. Development of a Magnetic-Core, Transverse-Field AF Demagnetizer

    NASA Astrophysics Data System (ADS)

    Schillinger, W. E.; Morris, E. R.; Coe, R. S.; Finn, D. R.

    2016-12-01

    A standard cleaning technique in the study of a rock's natural remanent magnetization (NRM) is progressive Alternating Field Demagnetization (AFD). However, for a significant fraction of samples, demagnetization is not completed by the maximum field of 200 mT or less available in commercial instruments; a field at least two or three times higher is needed. The data from 0 to 160 mT for a resistant red bed sample from Tibet is shown below. It just starts to reveal the sample's characteristic component, but this interpretation would have been tenuous, since 85% of the NRM remained untouched. Continued demagnetization to 500 mT helps a great deal, reducing the NRM to just 30% of its initial value and proving that the segment from 160 to 500 mT indeed trends toward the origin. We have constructed an alternating field (AF) demagnetizer that can routinely operate at fields of up to 0.6 Tesla. It uses a magnetic core in an air-cooled coil and is compatible with our existing sample handler for automated demagnetization and measurement experiments. Nonlinearities of the magnetic core are not a significant problem; even harmonics of the magnetic field are ≤1 ppm of the fundamental and so generate negligible anhysteretic remanence. A surprising result during the testing was that the coil's inductance changed with magnetic field. This made it necessary to add an auto-tuning feature, to keep the drive's frequency on the coil's resonance. We have recently added the ability to include a DC field of up to 0.5 mT, parallel to the alternating field, to perform Anhysteretic Remanent Magnetization (ARM), partial ARM experiments and anisotropy of ARM. We will report on these ARM results at the AGU meeting. Currently the maximum field we can obtain is 600 mT, but by reshaping the core to minimize flux leakage, significantly higher fields should be attainable, since the saturation flux density of the core material is 1.5T.

  7. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

  8. Intranasal Administration of the Antisecretory Peptide AF-16 Reduces Edema and Improves Cognitive Function Following Diffuse Traumatic Brain Injury in the Rat

    PubMed Central

    Clausen, Fredrik; Hansson, Hans-Arne; Raud, Johan; Marklund, Niklas

    2017-01-01

    A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls. The rats survived for either 48 h or 15 days post-injury. At 48 h, the animals were tested in the Morris water maze (MWM) for memory function and their brains analyzed for cerebral edema. Here, mFPI-induced brain edema compared to sham or naïve controls that was significantly reduced by AF-16 treatment (p < 0.05) although MWM performance was not altered. In the 15-day survival groups, the MWM learning and memory abilities as well as histological changes were analyzed. AF-16-treated brain-injured animals shortened both MWM latency and swim path in the learning trials (p < 0.05) and improved probe trial performance compared to brain-injured controls treated with the inactive reference peptide. A modest decrease by AF-16 on TBI-induced changes in hippocampal glial acidic fibrillary protein (GFAP) staining (p = 0.11) was observed. AF-16 treatment did not alter any other immunohistochemical analyses (degenerating neurons, beta-amyloid precursor protein (β-APP), and Olig2). In conclusion, intranasal AF-16-attenuated brain edema and enhanced visuospatial learning and memory following diffuse TBI in the rat. Intranasal administration early post-injury of a promising neuroprotective substance offers a novel treatment approach for TBI. PMID:28261150

  9. Bioreductive metabolism of AF-2[2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide] combined with 2-nitroimidazoles. Implications for use as hypoxic cell markers.

    PubMed

    Koch, C J; Giandomenico, A R; Iyengar, C W

    1993-09-14

    Metabolism of misonidazole under hypoxic conditions depletes the parent drug and causes about 4% of the reduced-drug-products to form adducts with cellular macromolecules (binding), and this process has been used to detect hypoxia in cells and tissues. The nitrofuran, AF-2 [2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide] has been shown to increase both the metabolic depletion of misonidazole and its binding. In the present study, factors which might affect this process have been examined, in an in vitro system, to test the hypothesis that metabolic depletion of misonidazole could limit its ability to diffuse freely to the hypoxic cell population. Drastic reductions in glucose concentrations from their normal value of 5-10 mM to less than 0.5 mM had no significant effect on the metabolism of either misonidazole or AF-2. Similarly, glucose concentration did not influence the binding of misonidazole, even when concentrations of both oxygen (extreme hypoxia) and glucose were near zero--a very toxic biochemical environment. Similarly, the metabolism of the nitroheterocyclics had no effect on glucose consumption. The bioreductive depletion of misonidazole in extreme hypoxia appeared to be independent of drug concentration between 25 and 100 microM: this nearly zero-order rate of drug metabolism prevented the possibility of working at constant drug concentration. AF-2 exacerbated this effect by greatly enhancing the metabolic depletion of misonidazole. AF-2 was found to increase both the metabolic depletion and binding of misonidazole by the same factor. An unexpected finding was that metabolism of etanidazole, a 2-nitroimidazole closely related to misonidazole, was not enhanced by AF-2. Micromolar amounts of oxygen inhibited the reductive activation of AF-2, and also the interaction between AF-2 and misonidazole. Our results suggest that metabolic depletion of nitroheterocyclics could influence their ability to diffuse adequately to hypoxic tissues, particularly at the low

  10. Evaluation of the sustainability and clinical outcome of alternatives for families: A cognitive-behavioral therapy (AF-CBT) in a child protection center

    PubMed Central

    Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for child physical abuse and family aggression/conflict that was included in the National Child Traumatic Stress Network’s initial EBT dissemination efforts in 2002. Seven practitioners participated in a year-long Learning Collaborative in AF-CBT and in similar training programs for 4 other EBTs. The agency’s routine data collection system was used to document the clinical and adjustment outcomes of 52 families presenting with a physically abused child who received their services between 2 and 5 years after the AF-CBT training had ended. Measures of the use of all 5 EBTs documented their frequency, internal consistency, and intercorrelations. Controlling for the unique content of the other four EBTs, the amount of AF-CBT Abuse-specific content delivered was related to improvements on standardized parent rating scales (i.e., child externalizing behavior, anger, anxiety, social competence) and both parent and clinician ratings of the child’s adjustment at discharge (i.e., child more safe, less scared/sad, more appropriate with peers). The amount of AF-CBT General content was related to a few discharge ratings (better child prognosis, helpfulness to parents). These novel data provide suggestive evidence for the sustainability and clinical benefits of AF-CBT in an existing community clinic serving physically abused children and their families, and are discussed in the context of key developments in the treatment model and dissemination literature. PMID:21354619

  11. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited.

    PubMed

    Gué, Michaël; Sun, Jian-Sheng; Boudier, Thomas

    2006-01-24

    Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation.

  12. Adsorption/desorption phenomena on pure and Teflon AF-coated titania surfaces studied by dynamic contact angle analysis.

    PubMed

    Rupp, F; Axmann, D; Ziegler, C; Geis-Gerstorfer, J

    2002-12-15

    As a result of inflammatory processes, plaque formation on dental titanium implants often leads to clinically pathogenic situations. This special biofilm formation on (bio)materials in contact with saliva is initiated by ionic and protein interactions. In this interfacial process, albumin becomes a main constituent of dental pellicle. Interfacial reactions change the surface characteristics. They determine the following steps of macromolecular adsorption and bacterial adhesion. This work focuses on the dynamic contact angle analysis (DCA), which is a tool for online measurements of dynamic changes of wettability without disturbing the interface during detection. Repeatability of the DCA method has been assessed according to the Bland and Altman method. The kinetics and equilibrium data of shifts in the wetting tension hysteresis indicate ionic influences at the titanium/bovine serum albumin (BSA) interface: the Ca-mediated increase of the BSA adsorption on titanium and the adsorption maximum at the isoelectric point (IEP) of BSA. Ti was surface modified by Teflon AF polymeric coatings. The result of the assessment gives reason to consider Teflon AF as a reference material for DCA repeatability studies. This surface modification caused drastic changes in the dynamic interfacial reactions. Shifts in the wetting tensions during DCA adsorption-desorption experiments clearly demonstrated the partially irreversible adsorption of BSA on Teflon AF. In contrast, reversible adsorption behavior was detected on pure Ti surfaces. These findings strengthen the hypothesis that the analysis of dynamic changes in wetting tension and wetting tension hysteresis is a sensitive analytical method for the detection of dynamic interfacial changes at biomaterial/biosystem interfaces during the initial steps of biofilm formation.

  13. Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

    PubMed Central

    Gué, Michaël; Sun, Jian-Sheng; Boudier, Thomas

    2006-01-01

    Background Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. Methods Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. Results In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. Conclusion The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation. PMID:16433901

  14. SAfety of Fondaparinux in transoesophageal echocardiography-guided Electric cardioversion of Atrial Fibrillation (SAFE-AF) study: a pilot study.

    PubMed

    Cohen, Ariel; Stellbrink, Christoph; Le Heuzey, Jean-Yves; Faber, Thomas; Aliot, Etienne; Banik, Norbert; Kropff, Stefan; Omran, Heyder

    2015-02-01

    Current guidelines recommend unfractionated heparin (UFH) or low-molecular-weight heparin plus an oral anticoagulant for the prevention of thromboembolism in patients undergoing electric cardioversion of atrial fibrillation (AF). Selective factor Xa inhibitors, such as fondaparinux, which has a favourable benefit-risk profile in the prevention and treatment of venous thromboembolism and the management of acute coronary syndromes, have not been systematically evaluated in this setting. To evaluate the efficacy and safety of fondaparinux versus standard treatment in patients undergoing echocardiographically-guided cardioversion of AF. In this multicentre, randomized, open-label, controlled, two-parallel-group, phase II pilot study, patients with AF undergoing electric cardioversion following transoesophageal echocardiography (TEE) were randomized to fondaparinux or standard therapy (UFH plus vitamin K antagonist [VKA]). Patients showing an atrial thrombus in the first TEE (clot-positive) were randomized to treatment with fondaparinux or standard care for 4 weeks before cardioversion. The primary endpoint (combined rate of cerebral neurological events, systemic thromboembolism, all-cause death and major bleeding events) occurred in 3 of 174 (1.7%) patients on fondaparinux and 2 of 170 (1.2%) patients on UFH+VKA. The rate of thrombus disappearance among clot-positive patients was higher in the fondaparinux arm (11 of 14; 78.6%) than in the UFH+VKA arm (7 of 14; 50.0%). Incidences of adverse events were similar (45.4% with fondaparinux and 46.5% with UFH+VKA). In this pilot study in patients with TEE-guided cardioversion, the use of fondaparinux appeared to be well tolerated, with similar efficacy to UFH+VKA. Furthermore, a trend to greater thrombus resolution was observed. Copyright © 2015. Published by Elsevier Masson SAS.

  15. Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

    PubMed Central

    Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

    2016-01-01

    Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

  16. Single-unit activity during natural vision: diversity, consistency, and spatial sensitivity among AF face patch neurons.

    PubMed

    McMahon, David B T; Russ, Brian E; Elnaiem, Heba D; Kurnikova, Anastasia I; Leopold, David A

    2015-04-08

    Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene.

  17. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293

    PubMed Central

    Kanhayuwa, Lakkhana; Coutts, Robert H. A.

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4–14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140–493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3’-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50–65% and 60–75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259–343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity. PMID:27736869

  18. Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial.

    PubMed

    Sherwood, Matthew W; Cyr, Derek D; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Washam, Jeffrey B; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Singer, Daniel E; Piccini, Jonathan P; Nessel, Christopher C; Mahaffey, Kenneth W; Patel, Manesh R

    2016-08-22

    The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown. The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial. Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups. In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Gray AAF/Fort Lewis, Washington. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1982-12-14

    NR4RR4wfIfm ’oOF A 6uV ---- --- ’-- - - Lp -L. -AL CLTMATOLOY QPANCH ,-P-,AC . WEATHER CONDITIONS V:- rTAH-R SERVICL/AC 7- JAT ’ AF/FT LEi.TS hA 73-Bl...3.836 3.695 3.611 41002 59002 7.186 7%230 8.507 TOTAL 822 762 837 810 837 810 837 837 810 837 810 81 Q 81 r MEAN310IIo2 fl V11 . All 8 918 69227

  20. O’Hare International Airport, Chicago Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    DTIC Science & Technology

    1984-10-01

    O’h6RE IAP IL p STATImN 6.4411 vAlls u WIT BULS TEMPERATURE DEPRESION (P) TOTAL TOTAL 0 1.2 3.4 5.4 7.8 It.0 )@ll.12113.1d 115-1617-11 -~.22 .42 .4 ?.lt...SCRMT jS 1ATCIIYHO RC SUMMARY ATk -F>AT,, S i~JlrMfAf 72 L1 iJCA’IJ-CltAiL IAP IL I. ) AL.E 1 "Tlf ________________ WIT BULB TEMPERATURE DEPRESION (P

  1. Lockheed NC-130B (AF58-712) Aircraft. A Study of STOL Operational Techniques; landing approach.

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Lockheed NC-130B (AF58-712) Aircraft. A Study of STOL Operational Techniques; landing approach. Nose-low pitch attitude of the aircraft was required in wave-off (or go-around) at 85 knots with flaps 70 degrees. An increase in stall-speed margin could be required to produce a more positive climb angle. (Nov 1962) Note: Used in publication in Flight Research at Ames; 57 Years of Development and Validation of Aeronautical Technology NASA SP-1998-3300 fig. 104; 60yrs at Ames, Atmosphere of Freedom NASA SP-2000-4314

  2. Progress Report on Activities in Support of Composite Repair Engineering Development Program Tasks AF, AH and AI

    DTIC Science & Technology

    2006-11-01

    Task AF Designation Aluminium Alloy Surface Preparation GBSP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy...silane, BR-127 prime GBSNP 7075T76UC Bare 7075-T76 Scotchbrite abrade, solvent clean, grit-blast, 1% aqueous epoxy silane GBSP 7075T6C Clad 7075-T76...Cohesive Failure (%) Specimen 1 2 3 4 5 Average GBSP 7075T76UC 100 85 90 90 95 92.0 GBSNP 7075T76UC 94 94 98 100 100 97.2 GBSP 7075T6C 30 40 50 35 20 35

  3. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293.

    PubMed

    Kanhayuwa, Lakkhana; Coutts, Robert H A

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4-14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140-493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3'-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50-65% and 60-75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259-343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity.

  4. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  5. Continued ultraviolet studies of some Be stars of later type

    NASA Technical Reports Server (NTRS)

    Slettebak, A.

    1985-01-01

    Anomalous ionization (C IV and Si IV) is seen in IUE spectra of Be stars as late as B8, and occurs also in standard stars of similar spectral type. Asymmetrical lines suggesting mass loss are present in all the Be stars and several of the standard stars as well, with no obvious correlation with v sin i. Emission shoulders are present in the Mg II lines of two B5e stars but not in Be stars of later type. Again there is no correlation with v sin i. The A-F shell stars show rich Fe II absorption spectra in the ultraviolet, in one case with velocity structure.

  6. Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model

    PubMed Central

    Kirubakaran, Senthil; Chowdhury, Rasheda A.; Hall, Mark C.S.; Patel, Pravina M.; Garratt, Clifford J.; Peters, Nicholas S.

    2015-01-01

    Background Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear. Objective The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change. Methods Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue. Results Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity. Conclusion Electrogram fractionation with increasing persistence of AF results from slow localized conduction or block

  7. Fractionation of electrograms is caused by colocalized conduction block and connexin disorganization in the absence of fibrosis as AF becomes persistent in the goat model.

    PubMed

    Kirubakaran, Senthil; Chowdhury, Rasheda A; Hall, Mark C S; Patel, Pravina M; Garratt, Clifford J; Peters, Nicholas S

    2015-02-01

    Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear. The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change. Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue. Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity. Electrogram fractionation with increasing persistence of AF results from slow localized conduction or block associated with changes in atrial connexin

  8. Neuroprotective and Anti-Inflammatory Effects of the Flavonoid-Enriched Fraction AF4 in a Mouse Model of Hypoxic-Ischemic Brain Injury

    PubMed Central

    Keddy, Paul G. W.; Dunlop, Kate; Warford, Jordan; Samson, Michel L.; Jones, Quinton R. D.; Rupasinghe, H. P. Vasantha; Robertson, George S.

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling. PMID:23251498

  9. Neuroprotective and anti-inflammatory effects of the flavonoid-enriched fraction AF4 in a mouse model of hypoxic-ischemic brain injury.

    PubMed

    Keddy, Paul G W; Dunlop, Kate; Warford, Jordan; Samson, Michel L; Jones, Quinton R D; Rupasinghe, H P Vasantha; Robertson, George S

    2012-01-01

    We report here neuroprotective and anti-inflammatory effects of a flavonoid-enriched fraction isolated from the peel of Northern Spy apples (AF4) in a mouse of model of hypoxic-ischemic (HI) brain damage. Oral administration of AF4 (50 mg/kg, once daily for 3 days) prior to 50 min of HI completely prevented motor performance deficits assessed 14 days later that were associated with marked reductions in neuronal cell loss in the dorsal hippocampus and striatum. Pre-treatment with AF4 (5, 10, 25 or 50 mg/kg, p.o.; once daily for 3 days) produced a dose-dependent reduction in HI-induced hippocampal and striatal neuron cell loss, with 25 mg/kg being the lowest dose that achieved maximal neuroprotection. Comparison of the effects of 1, 3 or 7 doses of AF4 (25 mg/kg; p.o.) prior to HI revealed that at least 3 doses of AF4 were required before HI to reduce neuronal cell loss in both the dorsal hippocampus and striatum. Quantitative RT-PCR measurements revealed that the neuroprotective effects of AF4 (25 mg/kg; p.o.; once daily for 3 days) in the dorsal hippocampus were associated with a suppression of HI-induced increases in the expression of IL-1β, TNF-α and IL-6. AF4 pre-treatment enhanced mRNA levels for pro-survival proteins such as X-linked inhibitor of apoptosis and erythropoietin following HI in the dorsal hippocampus and striatum, respectively. Primary cultures of mouse cortical neurons incubated with AF4 (1 µg/ml), but not the same concentrations of either quercetin or quercetin-3-O-glucose or its metabolites, were resistant to cell death induced by oxygen glucose deprivation. These findings suggest that the inhibition of HI-induced brain injury produced by AF4 likely involves a transcriptional mechanism resulting from the co-operative actions of various phenolics in this fraction which not only reduce the expression of pro-inflammatory mediators but also enhance pro-survival gene signalling.

  10. Skin advanced glycation end product accumulation is poorly reflected by glycemic control in type 2 diabetic patients (ZODIAC-9).

    PubMed

    Gerrits, Esther G; Lutgers, Helen L; Kleefstra, Nanne; Groenier, Klaas H; Smit, Andries J; Gans, Rijk O B; Bilo, Henk J G

    2008-07-01

    Glycemic memory can be reflected by tissue accumulation of advanced glycation end products (AGEs). In type 1 diabetes mellitus (T1DM) patients, hemoglobin A1c (HbA1c) levels over various time periods poorly predicted the accumulation of different AGEs in skin biopsies. Our aim was to investigate whether HbA1c assessments can predict the change in skin AGEs during time in type 2 diabetes mellitus (T2DM). We included 452 T2DM patients participating in a shared-care setting, who are screened annually for HbA1c and diabetic complications. Baseline and follow-up levels of skin AGEs were assessed with a validated noninvasive autofluorescence (AF) method, which is based on the fluorescence characteristics of certain AGEs. Our study population had a mean age of 65 years and 54% were female. After a mean follow-up duration of 3.3 years, linear regression analyses showed weak relationships among different assessments of HbA1c (baseline, maximum, mean, and variance of HbA1c) and skin AF at follow-up. Baseline skin AF and age were predictors of skin AF at follow-up, but diabetes duration, smoking, and creatinine were of less or no predictive value for skin AF at follow-up. In our T2DM population, integrated HbA1c assessments over years poorly predict the change in skin AGE level measured by skin AF. These findings agree with results in patients with T1DM. This suggests either the need for longer exposure to glucose disturbances to change tissue AGEs or other mechanisms, such as oxidative stress, leading to AGE accumulation.

  11. Skin Advanced Glycation End Product Accumulation Is Poorly Reflected by Glycemic Control in Type 2 Diabetic Patients (ZODIAC-9)

    PubMed Central

    Gerrits, Esther G.; Lutgers, Helen L.; Kleefstra, Nanne; Groenier, Klaas H.; Smit, Andries J.; Gans, Rijk O. B.; Bilo, Henk J. G.

    2008-01-01

    Background Glycemic memory can be reflected by tissue accumulation of advanced glycation end products (AGEs). In type 1 diabetes mellitus (T1DM) patients, hemoglobin A1c (HbA1c) levels over various time periods poorly predicted the accumulation of different AGEs in skin biopsies. Our aim was to investigate whether HbA1c assessments can predict the change in skin AGEs during time in type 2 diabetes mellitus (T2DM). Methods We included 452 T2DM patients participating in a shared-care setting, who are screened annually for HbA1c and diabetic complications. Baseline and follow-up levels of skin AGEs were assessed with a validated noninvasive autofluorescence (AF) method, which is based on the fluorescence characteristics of certain AGEs. Results Our study population had a mean age of 65 years and 54% were female. After a mean follow-up duration of 3.3 years, linear regression analyses showed weak relationships among different assessments of HbA1c (baseline, maximum, mean, and variance of HbA1c) and skin AF at follow-up. Baseline skin AF and age were predictors of skin AF at follow-up, but diabetes duration, smoking, and creatinine were of less or no predictive value for skin AF at follow-up. Conclusions In our T2DM population, integrated HbA1c assessments over years poorly predict the change in skin AGE level measured by skin AF. These findings agree with results in patients with T1DM. This suggests either the need for longer exposure to glucose disturbances to change tissue AGEs or other mechanisms, such as oxidative stress, leading to AGE accumulation. PMID:19885232

  12. Immunogenicity, Efficacy, Safety, and Mechanism of Action of Epitope Vaccine (Lu AF20513) for Alzheimer’s Disease: Prelude to a Clinical Trial

    PubMed Central

    Davtyan, Hayk; Ghochikyan, Anahit; Petrushina, Irina; Hovakimyan, Armine; Davtyan, Arpine; Poghosyan, Anna; Marleau, Annette M.; Movsesyan, Nina; Kiyatkin, Anatoly; Rasool, Suhail; Larsen, Anna Kirstine; Madsen, Peter Juul; Wegener, Karen Malene; Ditlevsen, Dorte Kornerup; Cribbs, David H.; Pedersen, Lars Ostergaard; Agadjanyan, Michael G.

    2013-01-01

    Alzheimer’s disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain. However, attempts at targeting the main culprits, neurotoxic Aβ peptides, have thus far proven unsuccessful for improving cognitive function. Recent clinical trials with passively administrated anti-Aβ antibodies failed to slow cognitive decline in mild-moderate AD patients, but suggest that an immunotherapeutic approach could be effective in patients with mild AD. In an AD mouse model (Tg2576) we tested the immunogenicity (cellular and humoral immune responses) and efficacy (AD-like pathology) of clinical grade Lu AF20513 vaccine. Lu AF20513 induces robust “non-self” T cell responses and production of anti-Aβ antibodies that reduce AD-like pathology in the brains of Tg2576 mice without inducing microglial activation and enhancing astrocytosis or CAA. Importantly, a single immunization with Lu AF20513 induces strong humoral immunity in mice with pre-existing memory Th cells. In addition, Lu AF20513 induces strong humoral responses in guinea pigs and monkeys. Collectively, these data suggest translation of Lu AF20513 to clinical setting with aims to (i) induce therapeutically potent anti-Aβ antibody responses in patients with mild AD, particularly if they have memory Th cells generated after immunizations with conventional Tetanus Toxoid vaccine; (ii) exclude likely pathological autoreactive T cell responses. PMID:23486963

  13. DNA-Mediated Transfer of an RNA Polymerase II Gene: Reversion of the Temperature-Sensitive Hamster Cell Cycle Mutant TsAF8 by Mammalian DNA

    PubMed Central

    Ingles, C. James; Shales, Michael

    1982-01-01

    Treatment of the TsAF8 temperature-sensitive (TS) mutant of Syrian hamster BHK-21 cells, with calcium phosphate precipitates of genomic TS+ DNAs from a variety of mammalian cell lines permitted the selection of TS+ colonies at 40°C. TS+ transformation events were distinguished from spontaneous TS+ reversions in experiments in which α-amanitin-sensitive (AmaS) TS+ DNA was used to transform an AmaR derivative of TsAF8 cells and AmaR TS+ DNA was used to transform AmaS TsAF8 cells. In each case it was possible to demonstrate the unselected acquisition of the appropriate AmaS or AmaR phenotype with the selected TS+ allele. Each of these TS+ transformed cell lines when grown at 40°C contained an RNA polymerase II activity with a sensitivity to inhibition by α-amanitin characteristic of the particular DNA used to transform the TS cells, whereas at 34°C the same cells contained a mixture of AmaR and AmaS polymerase II activities. Together, these data provide convincing evidence that the RNA polymerase II gene determining sensitivity to inhibition by α-amanitin can be transferred to TsAF8 cells and that the TS defect in TsAF8 is a polymerase II mutation. PMID:14582161

  14. Determination of stereochemistry of bacteriochlorophyll gF and 8(1)-hydroxy-chlorophyll aF from Heliobacterium modesticaldum.

    PubMed

    Mizoguchi, Tadashi; Oh-oka, Hirozo; Tamiaki, Hitoshi

    2005-01-01

    The reaction center complex of heliobacteria contains three kinds of chlorophyll pigments, bacteriochlorophyll gF (BChl gF), its 13(2)-epimer BChl gF' and 8(1)-hydroxy-chlorophyll aF (8(1)-OH-Chl aF). Because the full stereochemistry of these naturally occurring chlorophyllous pigments has remained unknown, we determined the stereochemistry of both BChl gF and 8(1)-OH-Chl aF extracted from Heliobacterium modesticaldum. The configurations of the specific functional groups at ring-B as well as those at ring-D and -E were investigated by use of nuclear Overhauser effect correlations in their 1H-NMR spectra and circular dichroism spectra, as well as by modified Mosher's method in their chemical modification: (1) E-configuration was confirmed for the 8-ethylidene group at ring-B in BChl gF, (2) R-configuration was identified for the 1-hydroxyethyl group at ring-B in 8(1)-OH-Chl aF and (3) 13(2)-(R)-, 17-(S)- and 18-(S)-configurations at ring-D and -E in both BChl gF and 8(1)-OH-Chl aF were confirmed. These stereochemistries enabled us to discuss their biosynthesis and to propose possible routes for preparation of ethylidene and 1-hydroxyethyl groups at the 8-position.

  15. Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)

    PubMed Central

    Lian, Wei; Jayapal, Karthik P; Charaniya, Salim; Mehra, Sarika; Glod, Frank; Kyung, Yun-Seung; Sherman, David H; Hu, Wei-Shou

    2008-01-01

    Background A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear. Results In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an afsS disruption mutant that is completely deficient in the production of actinorhodin, a major S. coelicolor antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of afsS disruption was not observed until the onset of stationary phase. Conclusion Our data suggests a comprehensive role for S. coelicolor AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria. PMID:18230178

  16. Callyaerins A-F and H, new cytotoxic cyclic peptides from the Indonesian marine sponge Callyspongia aerizusa.

    PubMed

    Ibrahim, Sabrin R M; Min, Cho Cho; Teuscher, Franka; Ebel, Rainer; Kakoschke, Christel; Lin, Wenhan; Wray, Victor; Edrada-Ebel, RuAngelie; Proksch, Peter

    2010-07-15

    Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the l form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 microM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  17. Comparison of the exact thermodynamics of the AF Blume-Emery-Grifiths and of the spin-1 ferromagnetic Ising models

    NASA Astrophysics Data System (ADS)

    Corrêa Silva, E. V.; Thomaz, M. T.

    2016-11-01

    We study in detail the thermodynamics of the anti-ferromagnetic Blume-Emery-Griffiths (AF BEG) model in the presence of a longitudinal magnetic field. Its thermodynamics is derived from the exact Helmholtz free energy (HFE) of the model, valid for T > 0. Numerical simulations of this model on a periodic space chain with 10 sites (N=10) yield the energy spectra of the model at K/J = 2 for D/J = 1 and D/J = 2, thus helping us compare, for a broad range of temperature, how some (per site) thermodynamic functions with the same value of K/J but distinct values of D/J behave, namely: the z-component of the magnetization, the specific heat and the entropy. These thermodynamic functions of the AF BEG model at K/|J| = 2 are compared to those of the spin-1 ferromagnetic Ising model with D/|J| > 1.5, for which the T=0 phase diagrams of both models are identical. This comparison is done in a large interval of temperature.

  18. Linear quadratic game and non-cooperative predictive methods for potential application to modelling driver-AFS interactive steering control

    NASA Astrophysics Data System (ADS)

    Na, Xiaoxiang; Cole, David J.

    2013-02-01

    This paper is concerned with the modelling of strategic interactions between the human driver and the vehicle active front steering (AFS) controller in a path-following task where the two controllers hold different target paths. The work is aimed at extending the use of mathematical models in representing driver steering behaviour in complicated driving situations. Two game theoretic approaches, namely linear quadratic game and non-cooperative model predictive control (non-cooperative MPC), are used for developing the driver-AFS interactive steering control model. For each approach, the open-loop Nash steering control solution is derived; the influences of the path-following weights, preview and control horizons, driver time delay and arm neuromuscular system (NMS) dynamics are investigated, and the CPU time consumed is recorded. It is found that the two approaches give identical time histories as well as control gains, while the non-cooperative MPC method uses much less CPU time. Specifically, it is observed that the introduction of weight on the integral of vehicle lateral displacement error helps to eliminate the steady-state path-following error; the increase in preview horizon and NMS natural frequency and the decline in time delay and NMS damping ratio improve the path-following accuracy.

  19. Comparison of the ferromagnetic Blume-Emery-Griffiths model and the AF spin-1 longitudinal Ising model at low temperature

    NASA Astrophysics Data System (ADS)

    Thomaz, M. T.; Corrêa Silva, E. V.

    2016-03-01

    We derive the exact Helmholtz free energy (HFE) of the standard and staggered one-dimensional Blume-Emery-Griffiths (BEG) model in the presence of an external longitudinal magnetic field. We discuss in detail the thermodynamic behavior of the ferromagnetic version of the model, which exhibits magnetic field-dependent plateaux in the z-component of its magnetization at low temperatures. We also study the behavior of its specific heat and entropy, both per site, at finite temperature. The degeneracy of the ground state, at T=0, along the lines that separate distinct phases in the phase diagram of the ferromagnetic BEG model is calculated, extending the study of the phase diagram of the spin-1 antiferromagnetic (AF) Ising model in S.M. de Souza and M.T. Thomaz, J. Magn. and Magn. Mater. 354 (2014) 205 [5]. We explore the implications of the equality of phase diagrams, at T=0, of the ferromagnetic BEG model with K/|J| = - 2 and of the spin-1 AF Ising model for D/|J| > 1/2.

  20. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin.

    PubMed

    Maharjan, Sushila; Oh, Tae-Jin; Lee, Hei Chan; Sohng, Jae Kyung

    2008-09-01

    Two regulator genes, metK1-sp and afsR-sp, from Streptomyces peucetius ATCC 27952 were heterologously expressed in S. venezuelae ATCC 15439, to produce 14-membered pikromycin antibiotics. The production of pikromycin was increased by 1.6-fold and 2.6-fold by the expression of metK1-sp and afsR-sp, respectively. The overexpression of metK1-sp and afsR-sp in S. venezuelae stimulated the expression of the pathway-specific regulatory genes, pikD and ketosynthase, as demonstrated by RT-PCR. The elevated transcripts of the pikD and ketosynthase genes were consistent with the enhanced production of pikromycin.

  1. High temperature NMR study of the local structure of molten LaF3-AF (A = Li, Na, K and Rb) mixtures.

    PubMed

    Rollet, Anne-Laure; Godier, Stéphanie; Bessada, Catherine

    2008-06-14

    The local structures of molten lanthanum alkali fluoride binaries have been studied using HT NMR technique. The chemical shifts of (19)F, (23)Na and (139)La in solid and in liquid have been compared for AF (A = alkali) and LaF(3). In pure molten alkali fluorides, the polarisability of anion-cation pairs appears to be a key parameter to depict the observed evolution of (19)F chemical shifts. The influence of the composition has also been studied by measuring the chemical shifts in molten LaF(3)-AF as a function of LaF(3) concentration. A strong influence of the alkali influence is observed. The coordination number of lanthanum is decreased versus AF amount all the more since the alkali atomic number is high. Moreover, the more polarisable the alkali, the less bridging fluorines between the LaF(x) units.

  2. The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

    DTIC Science & Technology

    2014-10-01

    measured by Annexin V (F) and phosphorylated H2AX (G). PB, peripheral blood. BM, bone marrow. ). rtTA, reverse tetracycline -controlled...reverse tetracycline - controlled transactivator . WT, wild- type. MUT, S34F mutant. * pɘ.05, ** p≤0.01, ***p≤0.001 2 (Figure 1). In...and tertiary recipients (C). rtTA, reverse tetracycline -controlled transactivator . WT, wild-type. MUT, S34F mutant. * pɘ.05, ** p≤0.01, ***p

  3. Blood typing

    MedlinePlus

    A blood sample is needed. The test to determine your blood group is called ABO typing. Your blood sample is mixed with antibodies against type A and B blood. Then, the sample is checked to see whether ...

  4. The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain.

    PubMed

    Li, X; Lynn, B D; Nagy, J I

    2012-01-01

    Electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36) occur in most major structures in the mammalian central nervous system. These synapses link ensembles of neurons and influence their network properties. Little is known about the macromolecular constituents of neuronal gap junctions or how transmission through electrical synapses is regulated at the level of channel conductance or gap junction assembly/disassembly. Such knowledge is a prerequisite to understanding the roles of gap junctions in neuronal circuitry. Gap junctions share similarities with tight and adhesion junctions in that all three reside at close plasma membrane appositions, and therefore may associate with similar structural and regulatory proteins. Previously, we reported that the tight junction-associated protein zonula occludens-1 (ZO-1) interacts with Cx36 and is localized at gap junctions. Here, we demonstrate that two proteins known to be associated with tight and adherens junctions, namely AF6 and MUPP1, are components of neuronal gap junctions in rodent brain. By immunofluorescence, AF6 and MUPP1 were co-localized with Cx36 in many brain areas. Co-immunoprecipitation and pull-down approaches revealed an association of Cx36 with AF6 and MUPP1, which required the C-terminus PDZ domain interaction motif of Cx36 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MUPP1. As AF6 is a target of the cAMP/Epac/Rap1 signalling pathway and MUPP1 is a scaffolding protein that interacts with CaMKII, the present results suggest that AF6 may be a target for cAMP/Epac/Rap1 signalling at electrical synapses, and that MUPP1 may contribute to anchoring CaMKII at these synapses. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors