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.

Effects of interaction strength, doping, and frustration on the antiferromagnetic phase of the two-dimensional Hubbard model

DOE PAGES

Fratino, L.; Charlebois, M.; Sémon, P.; ...

2017-12-19

Recent quantum-gas microscopy of ultracold atoms and scanning tunneling microscopy of the cuprates reveal new detailed information about doped Mott antiferromagnets, which can be compared with calculations. Using cellular dynamical mean-field theory, we map out the antiferromagnetic (AF) phase of the two-dimensional Hubbard model as a function of interaction strength U, hole doping δ, and temperature T . The Néel phase boundary is nonmonotonic as a function of U and δ. Frustration induced by second-neighbor hopping reduces Néel order more effectively at small U. The doped AF is stabilized at large U by kinetic energy and at small U bymore » potential energy. The transition between the AF insulator and the doped metallic AF is continuous. At large U, we find in-gap states similar to those observed in scanning tunneling microscopy. Finally, we predict that, contrary to the Hubbard bands, these states are only slightly spin polarized.« less

Effects of interaction strength, doping, and frustration on the antiferromagnetic phase of the two-dimensional Hubbard model

NASA Astrophysics Data System (ADS)

Fratino, L.; Charlebois, M.; Sémon, P.; Sordi, G.; Tremblay, A.-M. S.

2017-12-01

Recent quantum-gas microscopy of ultracold atoms and scanning tunneling microscopy of the cuprates reveal new detailed information about doped Mott antiferromagnets, which can be compared with calculations. Using cellular dynamical mean-field theory, we map out the antiferromagnetic (AF) phase of the two-dimensional Hubbard model as a function of interaction strength U , hole doping δ , and temperature T . The Néel phase boundary is nonmonotonic as a function of U and δ . Frustration induced by second-neighbor hopping reduces Néel order more effectively at small U . The doped AF is stabilized at large U by kinetic energy and at small U by potential energy. The transition between the AF insulator and the doped metallic AF is continuous. At large U , we find in-gap states similar to those observed in scanning tunneling microscopy. We predict that, contrary to the Hubbard bands, these states are only slightly spin polarized.

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

Stepanyuk, Galina A.; Serrano, Pedro; Peralta, Eigen

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 chemicalmore » 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.« less

Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells.

PubMed

Ye, Dongping; Liang, Weiguo; Dai, Libing; Zhou, Longqiang; Yao, Yicun; Zhong, Xin; Chen, Honghui; Xu, Jiake

2015-05-01

Degeneration of the intervertebral disc (IVD) is a major chronic medical condition associated with back pain. To better understand the pathogenesis of IVD degeneration, we performed comparative and quantitative proteomic analyses of normal and degenerated human annulus fibrosus (AF) cells and identified proteins that are differentially expressed between them. Annulus fibrosus cells were isolated and cultured from patients with lumbar disc herniation (the experimental group, degenerated AF cells) and scoliosis patients who underwent orthopaedic surgery (the control group, normal AF cells). Comparative proteomic analyses of normal and degenerated cultured AF cells were carried out using 2-D electrophoresis, mass spectrometric analyses, and database searching. Quantitative analyses of silver-stained 2-D electrophoresis gels of normal and degenerated cultured AF cells identified 10 protein spots that showed the most altered differential expression levels between the two groups. Among these, three proteins were decreased, including heat shock cognate 71-kDa protein, glucose-6-phosphate 1-dehydrogenase, and protocadherin-23, whereas seven proteins were increased, including guanine nucleotide-binding protein G(i) subunit α-2, superoxide dismutase, transmembrane protein 51, adenosine receptor A3, 26S protease regulatory subunit 8, lipid phosphate phosphatase-related protein, and fatty acyl-crotonic acid reductase 1. These differentially expressed proteins might be involved in the pathophysiological process of IVD degeneration and have potential values as biomarkers of the degeneration of IVD. © 2015 Wiley Publishing Asia Pty Ltd.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

PubMed

Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

PubMed Central

Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation. PMID:26641092

The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

DTIC Science & Technology

2016-12-01

U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for public release...ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S...induction, U2AF1(S34F) mice have reduced WBCs, increased hematopoietic stem /progenitor cells, and increased HSC cell cycling compared to U2AF1(WT) mice

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

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Delivery of Iron-Sulfur Clusters to the Hydrogen-Oxidizing [NiFe]-Hydrogenases in Escherichia coli Requires the A-Type Carrier Proteins ErpA and IscA

PubMed Central

Pinske, Constanze; Sawers, R. Gary

2012-01-01

During anaerobic growth Escherichia coli synthesizes two membrane-associated hydrogen-oxidizing [NiFe]-hydrogenases, termed hydrogenase 1 and hydrogenase 2. Each enzyme comprises a catalytic subunit containing the [NiFe] cofactor, an electron-transferring small subunit with a particular complement of [Fe-S] (iron-sulfur) clusters and a membrane-anchor subunit. How the [Fe-S] clusters are delivered to the small subunit of these enzymes is unclear. A-type carrier (ATC) proteins of the Isc (iron-sulfur-cluster) and Suf (sulfur mobilization) [Fe-S] cluster biogenesis pathways are proposed to traffic pre-formed [Fe-S] clusters to apoprotein targets. Mutants that could not synthesize SufA had active hydrogenase 1 and hydrogenase 2 enzymes, thus demonstrating that the Suf machinery is not required for hydrogenase maturation. In contrast, mutants devoid of the IscA, ErpA or IscU proteins of the Isc machinery had no detectable hydrogenase 1 or 2 activities. Lack of activity of both enzymes correlated with the absence of the respective [Fe-S]-cluster-containing small subunit, which was apparently rapidly degraded. During biosynthesis the hydrogenase large subunits receive their [NiFe] cofactor from the Hyp maturation machinery. Subsequent to cofactor insertion a specific C-terminal processing step occurs before association of the large subunit with the small subunit. This processing step is independent of small subunit maturation. Using western blotting experiments it could be shown that although the amount of each hydrogenase large subunit was strongly reduced in the iscA and erpA mutants, some maturation of the large subunit still occurred. Moreover, in contrast to the situation in Isc-proficient strains, these processed large subunits were not membrane-associated. Taken together, our findings demonstrate that both IscA and ErpA are required for [Fe-S] cluster delivery to the small subunits of the hydrogen-oxidizing hydrogenases; however, delivery of the Fe atom to the active site might have different requirements. PMID:22363723

Feasibility of Screening for Antibiotic Resistance - Part I

DTIC Science & Technology

2005-09-01

Klebsiella pneumonia (AF052258), Providencia stuartii (AF052259), Serratia marcescens (AF052260). After alignment of the sequences of the various...intracellular targets of fluoroquinolones , the type II DNA topoisomerases gyrase and topoisomerase IV [Balas et al., 1998; Weigel et al., 1998]. Mutations in...the quinolones resistant determining region (QRDR) of the parC gene, which encodes the A subunit of topoisomerase , and the gyrA gene, which encodes

JPRS Report, Science & Technology, USSR: Computers

DTIC Science & Technology

1987-09-10

O H V 01 Ü C Q) ö H n) in u At A2 Af A2 SC-S5SI A3 A4...At A2 20 Af A2 At 42 -55" A4 ) A3 A4 -555e i Ü .■•; sj <, .^ ^ u o ca to <u u o u CM cfl u u C dJ u u to O i-l 4J tii... O C Q) ß l-l tfl !Z> O Key: A. Multiplex channel. The input of subchannel A of the YeS-5568 disk controller is connected to the first

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

PubMed

Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

2015-12-01

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

Cwf16p Associating with the Nineteen Complex Ensures Ordered Exon Joining in Constitutive Pre-mRNA Splicing in Fission Yeast

PubMed Central

Sasaki-Haraguchi, Noriko; Ikuyama, Takeshi; Yoshii, Shogo; Takeuchi-Andoh, Tomoko; Frendewey, David; Tani, Tokio

2015-01-01

Exons are ligated in an ordered manner without the skipping of exons in the constitutive splicing of pre-mRNAs with multiple introns. To identify factors ensuring ordered exon joining in constitutive pre-mRNA splicing, we previously screened for exon skipping mutants in Schizosaccharomyces pombe using a reporter plasmid, and characterized three exon skipping mutants named ods1 (ordered splicing 1), ods2, and ods3, the responsible genes of which encode Prp2/U2AF59, U2AF23, and SF1, respectively. They form an SF1-U2AF59-U2AF23 complex involved in recognition of the branch and 3′ splice sites in pre-mRNA. In the present study, we identified a fourth ods mutant, ods4, which was isolated in an exon-skipping screen. The ods4 + gene encodes Cwf16p, which interacts with the NineTeen Complex (NTC), a complex thought to be involved in the first catalytic step of the splicing reaction. We isolated two multi-copy suppressors for the ods4-1 mutation, Srp2p, an SR protein essential for pre-mRNA splicing, and Tif213p, a translation initiation factor, in S. pombe. The overexpression of Srp2p suppressed the exon-skipping phenotype of all ods mutants, whereas Tif213p suppressed only ods4-1, which has a mutation in the translational start codon of the cwf16 gene. We also showed that the decrease in the transcriptional elongation rate induced by drug treatment suppressed exon skipping in ods4-1. We propose that Cwf16p/NTC participates in the early recognition of the branch and 3′ splice sites and cooperates with the SF1-U2AF59-U2AF23 complex to maintain ordered exon joining. PMID:26302002

Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.

PubMed

Schmidt, Constanze; Wiedmann, Felix; Voigt, Niels; Zhou, Xiao-Bo; Heijman, Jordi; Lang, Siegfried; Albert, Virginia; Kallenberger, Stefan; Ruhparwar, Arjang; Szabó, Gábor; Kallenbach, Klaus; Karck, Matthias; Borggrefe, Martin; Biliczki, Peter; Ehrlich, Joachim R; Baczkó, István; Lugenbiel, Patrick; Schweizer, Patrick A; Donner, Birgit C; Katus, Hugo A; Dobrev, Dobromir; Thomas, Dierk

2015-07-14

Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited predominantly atrial expression, and atrial K(2P)3.1 transcript levels were highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug target for mechanism-based AF therapy. © 2015 American Heart Association, Inc.

Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease

PubMed Central

Dou, Xiaobing; Xia, Yongliang; Chen, Jing; Qian, Ying; Li, Songtao; Zhang, Ximei; Song, Zhenyuan

2014-01-01

Background and Purpose Overactive lipolysis in adipose tissue contributes to the pathogenesis of alcoholic liver disease (ALD); however, the mechanisms involved have not been elucidated. We previously reported that chronic alcohol consumption produces a hypomethylation state in adipose tissue. In this study we investigated the role of hypomethylation in adipose tissue in alcohol-induced lipolysis and whether its correction contributes to the well-established hepatoprotective effect of betaine in ALD. Experimental Approach Male C57BL/6 mice were divided into four groups and started on one of four treatments for 5 weeks: isocaloric pair-fed (PF), alcohol-fed (AF), PF supplemented with betaine (BT/AF) and AF supplemented with betaine (BT/AF). Betaine, 0.5% (w v−1), was added to the liquid diet. Both primary adipocytes and mature 3T3-L1 adipocytes were exposed to demethylation reagents and their lipolytic responses determined. Key Results Betaine alleviated alcohol-induced pathological changes in the liver and rectified the impaired methylation status in adipose tissue, concomitant with attenuating lipolysis. In adipocytes, inducing hypomethylation activated lipolysis through a mechanism involving suppression of protein phosphatase 2A (PP2A), due to hypomethylation of its catalytic subunit, leading to increased activation of hormone-sensitive lipase (HSL). In line with in vitro observations, reduced PP2A catalytic subunit methylation and activity, and enhanced HSL activation, were observed in adipose tissue of alcohol-fed mice. Betaine attenuated this alcohol-induced PP2A suppression and HSL activation. Conclusions and Implications In adipose tissue, a hypomethylation state contributes to its alcohol-induced dysfunction and an improvement in its function may contribute to the hepatoprotective effects of betaine in ALD. PMID:24819676

Triplex DNA-binding proteins are associated with clinical outcomes revealed by proteomic measurements in patients with colorectal cancer

PubMed Central

2012-01-01

Background Tri- and tetra-nucleotide repeats in mammalian genomes can induce formation of alternative non-B DNA structures such as triplexes and guanine (G)-quadruplexes. These structures can induce mutagenesis, chromosomal translocations and genomic instability. We wanted to determine if proteins that bind triplex DNA structures are quantitatively or qualitatively different between colorectal tumor and adjacent normal tissue and if this binding activity correlates with patient clinical characteristics. Methods Extracts from 63 human colorectal tumor and adjacent normal tissues were examined by gel shifts (EMSA) for triplex DNA-binding proteins, which were correlated with clinicopathological tumor characteristics using the Mann-Whitney U, Spearman’s rho, Kaplan-Meier and Mantel-Cox log-rank tests. Biotinylated triplex DNA and streptavidin agarose affinity binding were used to purify triplex-binding proteins in RKO cells. Western blotting and reverse-phase protein array were used to measure protein expression in tissue extracts. Results Increased triplex DNA-binding activity in tumor extracts correlated significantly with lymphatic disease, metastasis, and reduced overall survival. We identified three multifunctional splicing factors with biotinylated triplex DNA affinity: U2AF65 in cytoplasmic extracts, and PSF and p54nrb in nuclear extracts. Super-shift EMSA with anti-U2AF65 antibodies produced a shifted band of the major EMSA H3 complex, identifying U2AF65 as the protein present in the major EMSA band. U2AF65 expression correlated significantly with EMSA H3 values in all extracts and was higher in extracts from Stage III/IV vs. Stage I/II colon tumors (p = 0.024). EMSA H3 values and U2AF65 expression also correlated significantly with GSK3 beta, beta-catenin, and NF- B p65 expression, whereas p54nrb and PSF expression correlated with c-Myc, cyclin D1, and CDK4. EMSA values and expression of all three splicing factors correlated with ErbB1, mTOR, PTEN, and Stat5. Western blots confirmed that full-length and truncated beta-catenin expression correlated with U2AF65 expression in tumor extracts. Conclusions Increased triplex DNA-binding activity in vitro correlates with lymph node disease, metastasis, and reduced overall survival in colorectal cancer, and increased U2AF65 expression is associated with total and truncated beta-catenin expression in high-stage colorectal tumors. PMID:22682314

Adiabatic Compression Sensitivity of AF-M315E

DTIC Science & Technology

2015-07-01

the current work is to expand the knowledge base from previous experiments completed at AFRL for AF-M315E in stainless steel U-tubes at room...addressed, to some degree, with the use of clamps and a large stainless steel plate to dissipate any major vibrations. A large preheated bath of 50:50 v/v...autocatalytic chain decomposition in the propellant. This exothermic decomposition decreases the fume -off initiation temperature of the propellant and its

Thermophilic Ferritin: Versatile Nanohost

NASA Astrophysics Data System (ADS)

Pulsipher, Katherine W.

Thermophilic ferritin from Archaeoglobus fulgidus (AfFtn) is a 24meric, hollow, cage-like protein, whose native function is the oxidation, mineralization, and storage of iron. Unique among ferritins, its self-assembly is dependent on high ionic strength, reflecting the deep sea thermal vent environment where A. fulgidus is found. This ionic strength dependence can be used to encapsulate charged cargo within the AfFtn cavity. Its subunits self-assemble into tetrahedral symmetry, resulting in four, large (4.5 nm), triangular pores, not found in other ferritins. Due to its size (12 nm outer diameter, 8 nm inner diameter), self-assembly properties, and potential for both genetic and chemical modification, AfFtn is an ideal nanocontainer for a variety of cargo, including inorganic nanoparticles and proteins. We have sought to better understand the self-assembly of AfFtn and its encapsulation of various cargo. Guided by computational analysis and through mutagenesis, we have investigated the role of electrostatics along the AfFtn trimeric interface in self-assembly. We have developed a series of single point mutants with increasingly favorable cage assembly. One specific mutation, E65R, has a dramatic effect on AfFtn, almost entirely preventing disassembly and enhancing thermal stability by 14°C. By using a novel graphene-based microelectrode, we have determined that AfFtn maintains its quaternary structure upon encapsulation of a gold nanoparticle, developing a new tool for investigating protein-nanomaterial interactions. We have also shown that AfFtn can be used to template seeded gold nanoparticle growth and have explored two often neglected factors in ferritin-nanoparticle templating: the charge of the gold salt used, and the size of the protein pores. Our results demonstrate that the open, porous structure of AfFtn allows more efficient particle growth than typical closed-pore ferritins. Finally, we have expanded the cargo uptake of AfFtn beyond nanoparticles to include proteins, encapsulating supercharged GFP. The AfFtn-cargo complexes developed here have application in catalysis, nanomaterials synthesis, and targeted delivery.

Prime Contract Awards of $100,000 or More by Federal Supply Classification or Service Category and Purchasing Office. Part 2 (5450-9999)

DTIC Science & Technology

1989-01-01

af a>o - o CL -4 0-u< m - CLO. -4 0 WC -4 M b c CLC 0 )U"aCV C 0L > 4 .t 0 0L 0 " .0." ID0ZW W4 .0 04q 4- I- H 00CL1 0 CC, 0U) 0L >-1 ~3 CL EU ) ɜ...E0 0 E E U a 4-43H ~ U 0 MO 000 af ) H) o 00W 00 0 U) 0 00000 0 w -J f-L U- 0’ O () 00 a) Z -J cl -4 0) -1 (n <-0 40 0 -j -4 4 -l000-4 000N1 -AC 4- -4 L...uL )L)U :fL- _ L CLO CL𔃾--- CL C - 0. L1- - LUUC C CA oO0ooCL -. Cl0 C-. Ovcn0 WUC -j L0_0 $1 >L)0 U -4 Ec - 0)( ( o( af 0. CL M 2u )(1) L c ) L L

Antiferromagnetism and superconductivity in layered organic conductors: Variational cluster approach.

PubMed

Sahebsara, P; Sénéchal, D

2006-12-22

The kappa-(ET)2X layered conductors (where ET stands for BEDT-TTF) are studied within the dimer model as a function of the diagonal hopping t' and Hubbard repulsion U. Antiferromagnetism and d-wave superconductivity are investigated at zero temperature using variational cluster perturbation theory (VCPT). For large U, Néel antiferromagnetism exists for t' < t(c2)', with t(c2)' approximately 0.9. For fixed t', as U is decreased (or pressure increased), a d(x2-y2) superconducting phase appears. When U is decreased further, then a d(xy) order takes over. There is a critical value of t(c1)' approximately 0.8 of t' beyond which the AF and dSC phases are separated by the Mott disordered phase.

Type III interferon is a critical regulator of innate antifungal immunity.

PubMed

Espinosa, Vanessa; Dutta, Orchi; McElrath, Constance; Du, Peicheng; Chang, Yun-Juan; Cicciarelli, Bryan; Pitler, Amy; Whitehead, Ian; Obar, Joshua J; Durbin, Joan E; Kotenko, Sergei V; Rivera, Amariliz

2017-10-06

Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus ( Af ) as a model to study antifungal immune responses, we found that depletion of CCR2 + monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2 + monocytes are an important early source of type I IFNs that prime optimal expression of IFN-λ. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2 + monocytes or by exogenous administration of IFN-α and IFN-λ. Thus, CCR2 + monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-λ expression. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Antiferromagnetic vs. non-magnetic ε phase of solid oxygen. Periodic density functional theory studies using a localized atomic basis set and the role of exact exchange.

PubMed

Ramírez-Solís, A; Zicovich-Wilson, C M; Hernández-Lamoneda, R; Ochoa-Calle, A J

2017-01-25

The question of the non-magnetic (NM) vs. antiferromagnetic (AF) nature of the ε phase of solid oxygen is a matter of great interest and continuing debate. In particular, it has been proposed that the ε phase is actually composed of two phases, a low-pressure AF ε 1 phase and a higher pressure NM ε 0 phase [Crespo et al., Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 10427]. We address this problem through periodic spin-restricted and spin-polarized Kohn-Sham density functional theory calculations at pressures from 10 to 50 GPa using calibrated GGA and hybrid exchange-correlation functionals with Gaussian atomic basis sets. The two possible configurations for the antiferromagnetic (AF1 and AF2) coupling of the 0 ≤ S ≤ 1 O 2 molecules in the (O 2 ) 4 unit cell were studied. Full enthalpy-driven geometry optimizations of the (O 2 ) 4 unit cells were done to study the pressure evolution of the enthalpy difference between the non-magnetic and both antiferromagnetic structures. We also address the evolution of structural parameters and the spin-per-molecule vs. pressure. We find that the spin-less solution becomes more stable than both AF structures above 50 GPa and, crucially, the spin-less solution yields lattice parameters in much better agreement with experimental data at all pressures than the AF structures. The optimized AF2 broken-symmetry structures lead to large errors of the a and b lattice parameters when compared with experiments. The results for the NM model are in much better agreement with the experimental data than those found for both AF models and are consistent with a completely non-magnetic (O 2 ) 4 unit cell for the low-pressure regime of the ε phase.

Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice

PubMed Central

Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

2015-01-01

Abstract Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca2+ transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. Key points Acute inhibition of purinergic receptors with a selective P2X3 antagonist prevents transmission of information from taste buds to sensory nerves. The P2X3 antagonist has no effect on taste-evoked release of ATP, confirming the effect is postsynaptic. The results confirm previous results with P2X2/3 double knockout mice that ATP is required for transmission of all taste qualities, including sour and salty. Previously, ATP was confirmed to be required for bitter, sweet and umami tastes, but was questioned for salty and sour tastes due to pleomorphic deficits in the double knockout mice. The geniculate ganglion in mouse contains two populations of ganglion cells with different subunit composition of P2X2 and P2X3 receptors making them differently susceptible to pharmacological block and, presumably, desensitization. PMID:25524179

Three moving groups detected in the LAMOST DR1 archive

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

Zhao, J. K.; Zhao, G.; Chen, Y. Q.

2014-05-20

We analyze the kinematics of thick disk and halo stars observed by the Large Sky Area Multi-Object Fiber Spectroscopic Telescope. We have constructed a sample of 7993 F, G, and K nearby main-sequence stars (d < 2 kpc) with estimates of position (x, y, z) and space velocity (U, V, W) based on color and proper motion from the Sloan Digital Sky Survey DR9 catalog. Three 'phase-space overdensities' are identified in (V, √(U{sup 2}+2V{sup 2})) with significance levels of σ > 3. Two of them (the Hyades-Pleiades stream and the Arcturus-AF06 stream) have been identified previously. We also find evidencemore » for a new stream (centered at V ∼ –180 km s{sup –1}) in the halo. The formation mechanisms of these three streams are analyzed. Our results support the hypothesis that the Arcturus-AF06 stream and the new stream originated from the debris of a disrupted satellite, while the Hyades-Pleiades stream has a dynamical origin.« less

Sequential recognition of the pre-mRNA branch point by U2AF65 and a novel spliceosome-associated 28-kDa protein.

PubMed Central

Gaur, R K; Valcárcel, J; Green, M R

1995-01-01

Splicing of pre-mRNAs occurs via a lariat intermediate in which an intronic adenosine, embedded within a branch point sequence, forms a 2',5'-phosphodiester bond (RNA branch) with the 5' end of the intron. How the branch point is recognized and activated remains largely unknown. Using site-specific photochemical cross-linking, we have identified two proteins that specifically interact with the branch point during the splicing reaction. U2AF65, an essential splicing factor that binds to the adjacent polypyrimidine tract, crosslinks to the branch point at the earliest stage of spliceosome formation in an ATP-independent manner. A novel 28-kDa protein, which is a constituent of the mature spliceosome, contacts the branch point after the first catalytic step. Our results indicate that the branch point is sequentially recognized by distinct splicing factors in the course of the splicing reaction. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 PMID:7493318

Plant RuBisCo assembly in E. coli with five chloroplast chaperones including BSD2.

PubMed

Aigner, H; Wilson, R H; Bracher, A; Calisse, L; Bhat, J Y; Hartl, F U; Hayer-Hartl, M

2017-12-08

Plant RuBisCo, a complex of eight large and eight small subunits, catalyzes the fixation of CO 2 in photosynthesis. The low catalytic efficiency of RuBisCo provides strong motivation to reengineer the enzyme with the goal of increasing crop yields. However, genetic manipulation has been hampered by the failure to express plant RuBisCo in a bacterial host. We achieved the functional expression of Arabidopsis thaliana RuBisCo in Escherichia coli by coexpressing multiple chloroplast chaperones. These include the chaperonins Cpn60/Cpn20, RuBisCo accumulation factors 1 and 2, RbcX, and bundle-sheath defective-2 (BSD2). Our structural and functional analysis revealed the role of BSD2 in stabilizing an end-state assembly intermediate of eight RuBisCo large subunits until the small subunits become available. The ability to produce plant RuBisCo recombinantly will facilitate efforts to improve the enzyme through mutagenesis. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Counseling patients with succinate dehydrogenase subunit defects: genetics, preventive guidelines, and dealing with uncertainty

PubMed Central

Raygada, Margarita; King, Kathryn S.; Adams, Karen T.; Stratakis, Constantine A.; Pacak, Karel

2016-01-01

The discovery that mutations in the succinate dehydrogenase (SDH) complex subunit (SDHA, B/C/D/AF2) genes predispose patients to the development of tumors has led to the identification of a large population of patients and relatives at risk for developing malignancies. The most frequent conditions associated with these mutations are the familial paraganglioma syndromes. Other tumors that are frequently associated with SDH mutations (SDHx) are gastrointestinal stromal tumors and renal cell carcinomas. A number of other rare associations have also been described. SDHx mutations are often clinically silent and metastatic, but they may also be aggressive in their presentation. The penetrance of these mutations is beginning to be understood, and the characteristics of the phenotype are being elucidated. However, the inability to accurately predict the appearance, nature, and location of tumors as well as their tendency to recur or metastasize pose challenges to those who counsel and manage patients with SDHx mutations. In this work, we present our approach for counseling these families in the context of the current uncertainties, while striving to maintain patient autonomy. PMID:24854530

Department of the Army Justification of Estimates for FY 1991 Submitted to Congress January 1990. Operation and Maintenance, Army Justification Book. Volume 1

DTIC Science & Technology

1990-01-01

8217 - ’"I Si _ Cr ~J-1 IL tJ -4; 4* V -) a- Nii :1-1 N - *~- ~ - - Flh 31 - ’,- I - , - 241 m -18 ’TNJN V _, ZA- E -t 4 3R 2 u : aF - - *>- -- Lj 0 00...0J~ . -4 4. C C rn~ 00. m * a ) ca Z4 :) af -4 4j Z. Ci o a) rn C.) to ~L C"W.o ) ) u) /3 0 MJ 0 r_4-4- 4-j go u 0 a0 W >to-44L-Ui 4-CJ J4 4J u) u~ E...t J m w-0~ w ~ 0 Z z~ 0 to u wm D m. -X 00’> Q) -~ U cn .- 1~. - 0 Uf.- 0> u0 -j t >C - cn uu 4z vC*-4J mu4- w v Ř-J W~c w w w wCCu ’ Af ~-a ju 0 0 z

Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.

PubMed

Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula

2014-03-01

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

Measures of Body Size and Composition and Risk of Incident Atrial Fibrillation in Older People

PubMed Central

Karas, Maria G.; Yee, Laura M.; Biggs, Mary L.; Djoussé, Luc; Mukamal, Kenneth J.; Ix, Joachim H.; Zieman, Susan J.; Siscovick, David S.; Gottdiener, John S.; Rosenberg, Michael A.; Kronmal, Richard A.; Heckbert, Susan R.; Kizer, Jorge R.

2016-01-01

Various anthropometric measures, including height, have been associated with atrial fibrillation (AF). This raises questions about the appropriateness of using ratio measures such as body mass index (BMI), which contains height squared in its denominator, in the evaluation of AF risk. Among older adults, the optimal anthropometric approach to risk stratification of AF remains uncertain. Anthropometric and bioelectrical impedance measures were obtained from 4,276 participants (mean age = 72.4 years) free of cardiovascular disease in the Cardiovascular Health Study. During follow-up (1989–2008), 1,050 cases of AF occurred. BMI showed a U-shaped association, whereas height, weight, waist circumference, hip circumference, fat mass, and fat-free mass were linearly related to incident AF. The strongest adjusted association occurred for height (per each 1-standard-deviation increment, hazard ratio = 1.38, 95% confidence interval: 1.25, 1.51), which exceeded all other measures, including weight (hazard ratio = 1.21, 95% confidence interval: 1.13, 1.29). Combined assessment of log-transformed weight and height showed regression coefficients that departed from the 1 to −2 ratio inherent in BMI, indicating a loss of predictive information. Risk estimates for AF tended to be stronger for hip circumference than for waist circumference and for fat-free mass than for fat mass, which was explained largely by height. These findings highlight the prominent role of body size and the inadequacy of BMI as determinants of AF in older adults. PMID:27188936

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number. Part 6 (KYOWA DENGYO CORP-N D S INC)

DTIC Science & Technology

1990-01-01

czt a.r 1= Lme mi.). L).) 6 A N...U3 aa a a 0 1a a 0 Ca a =0 a 0 a2 1.2 a a ama 4 a 9 aaAU91 z a a a u a UU a ; t Z a U 2 cc aF - 2 -1. : . R. Ra a, Z .4 a I,2 g il a9a a90 a - 12...N 04a 00s 0o 0000 0 ŘW0 -. CW40 41.0 0 W to c 0 (D~4 OW v s C~C.) rii CO.) U3U 9z Di C.) C. .4 cc .4.4 .4 . ZZE ~ E to 40 ) C’) NtD a) M af . )

Postsynaptic P2X3-containing receptors in gustatory nerve fibres mediate responses to all taste qualities in mice.

PubMed

Vandenbeuch, Aurelie; Larson, Eric D; Anderson, Catherine B; Smith, Steven A; Ford, Anthony P; Finger, Thomas E; Kinnamon, Sue C

2015-03-01

Taste buds release ATP to activate ionotropic purinoceptors composed of P2X2 and P2X3 subunits, present on the taste nerves. Mice with genetic deletion of P2X2 and P2X3 receptors (double knockout mice) lack responses to all taste stimuli presumably due to the absence of ATP-gated receptors on the afferent nerves. Recent experiments on the double knockout mice showed, however, that their taste buds fail to release ATP, suggesting the possibility of pleiotropic deficits in these global knockouts. To test further the role of postsynaptic P2X receptors in afferent signalling, we used AF-353, a selective antagonist of P2X3-containing receptors to inhibit the receptors acutely during taste nerve recording and behaviour. The specificity of AF-353 for P2X3-containing receptors was tested by recording Ca(2+) transients to exogenously applied ATP in fura-2 loaded isolated geniculate ganglion neurons from wild-type and P2X3 knockout mice. ATP responses were completely inhibited by 10 μm or 100 μm AF-353, but neither concentration blocked responses in P2X3 single knockout mice wherein the ganglion cells express only P2X2-containing receptors. Furthermore, AF-353 had no effect on taste-evoked ATP release from taste buds. In wild-type mice, i.p. injection of AF-353 or simple application of the drug directly to the tongue, inhibited taste nerve responses to all taste qualities in a dose-dependent fashion. A brief access behavioural assay confirmed the electrophysiological results and showed that preference for a synthetic sweetener, SC-45647, was abolished following i.p. injection of AF-353. These data indicate that activation of P2X3-containing receptors is required for transmission of all taste qualities. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Defining essential elements and genetic interactions of the yeast Lsm2-8 ring and demonstration that essentiality of Lsm2-8 is bypassed via overexpression of U6 snRNA or the U6 snRNP subunit Prp24.

PubMed

Roth, Allen J; Shuman, Stewart; Schwer, Beate

2018-06-01

A seven-subunit Lsm2-8 protein ring assembles on the U-rich 3' end of the U6 snRNA. A structure-guided mutational analysis of the Saccharomyces cerevisiae Lsm2-8 ring affords new insights to structure-function relations and genetic interactions of the Lsm subunits. Alanine scanning of 39 amino acids comprising the RNA-binding sites or intersubunit interfaces of Lsm2, Lsm3, Lsm4, Lsm5, and Lsm8 identified only one instance of lethality (Lsm3-R69A) and one severe growth defect (Lsm2-R63A), both involving amino acids that bind the 3'-terminal UUU trinucleotide. All other Ala mutations were benign with respect to vegetative growth. Tests of 235 pairwise combinations of benign Lsm mutants identified six instances of inter-Lsm synthetic lethality and 45 cases of nonlethal synthetic growth defects. Thus, Lsm2-8 ring function is buffered by a network of internal genetic redundancies. A salient finding was that otherwise lethal single-gene deletions lsm2 Δ, lsm3 Δ, lsm4 Δ, lsm5 , and lsm8 Δ were rescued by overexpression of U6 snRNA from a high-copy plasmid. Moreover, U6 overexpression rescued myriad lsm Δ lsm Δ double-deletions and lsm Δ lsm Δ lsm Δ triple-deletions. We find that U6 overexpression also rescues a lethal deletion of the U6 snRNP protein subunit Prp24 and that Prp24 overexpression bypasses the essentiality of the U6-associated Lsm subunits. Our results indicate that abetting U6 snRNA is the only essential function of the yeast Lsm2-8 proteins. © 2018 Roth et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans.

PubMed

Chowdhury, Nilanjan Pal; Mowafy, Amr M; Demmer, Julius K; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-02-21

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD(+) complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH(-) is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH(-) by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH(•), immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH(-) that converts crotonyl-CoA to butyryl-CoA.

Studies on the Mechanism of Electron Bifurcation Catalyzed by Electron Transferring Flavoprotein (Etf) and Butyryl-CoA Dehydrogenase (Bcd) of Acidaminococcus fermentans*

PubMed Central

Chowdhury, Nilanjan Pal; Mowafy, Amr M.; Demmer, Julius K.; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-01-01

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD+ complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH− is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH− by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD⨪, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH•, immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH− that converts crotonyl-CoA to butyryl-CoA. PMID:24379410

A Bibliography of Selected Publications: Project Air Force, 5th Edition

DTIC Science & Technology

1989-05-01

Dyna - R-3028-AF. A Dynamic Retention Model for Air Force Officers: METRIC’s DL and and Pipeilne Variability. M. J. Carrillo. Theory and Estimates. G...Theorem and Dyna - and Support. METRIC’s Demand and Pipeline Variability. R-3255-AF. Aircraft Airframe Cost Estimating Relationships: N-2283/1-AF...U). 1970-1985. N-2409-AF. Tanker Splitting Across the SlOP Bomber Force R-3389-AF. Dyna -METRIC Version 4: Modeling Worldwide (U). Logistics Support of

Saturation mutagenesis reveals manifold determinants of exon definition.

PubMed

Ke, Shengdong; Anquetil, Vincent; Zamalloa, Jorge Rojas; Maity, Alisha; Yang, Anthony; Arias, Mauricio A; Kalachikov, Sergey; Russo, James J; Ju, Jingyue; Chasin, Lawrence A

2018-01-01

To illuminate the extent and roles of exonic sequences in the splicing of human RNA transcripts, we conducted saturation mutagenesis of a 51-nt internal exon in a three-exon minigene. All possible single and tandem dinucleotide substitutions were surveyed. Using high-throughput genetics, 5560 minigene molecules were assayed for splicing in human HEK293 cells. Up to 70% of mutations produced substantial (greater than twofold) phenotypes of either increased or decreased splicing. Of all predicted secondary structural elements, only a single 15-nt stem-loop showed a strong correlation with splicing, acting negatively. The in vitro formation of exon-protein complexes between the mutant molecules and proteins associated with spliceosome formation (U2AF35, U2AF65, U1A, and U1-70K) correlated with splicing efficiencies, suggesting exon definition as the step affected by most mutations. The measured relative binding affinities of dozens of human RNA binding protein domains as reported in the CISBP-RNA database were found to correlate either positively or negatively with splicing efficiency, more than could fit on the 51-nt test exon simultaneously. The large number of these functional protein binding correlations point to a dynamic and heterogeneous population of pre-mRNA molecules, each responding to a particular collection of binding proteins. © 2018 Ke et al.; Published by Cold Spring Harbor Laboratory Press.

Rule modification in junior sport: Does it create differences in player movement?

PubMed

Gastin, Paul B; Allan, Matthew D; Bellesini, Kylie; Spittle, Michael

2017-10-01

To determine the effects of rule modification on player movement during matchplay in junior Australian football (AF). Quasi-experimental study design. Time-motion analysis was used to record variables pertaining to player movement including total distance covered, high-speed running (HSR) distance (>14.4km/h) and HSR efforts. GPS data obtained from 145 players (7-12 years) were analysed across four junior AF leagues and three age group combinations (U8/U9, U9/U10 and U11/U12). The four leagues were collapsed into two separate conditions (compliant and non-compliant) based on their adherence to a modified junior sport policy. To control for the influence of age and physical maturity, a secondary analysis was performed on an adequately matched U8 subset of data (n=48). Significant differences (p<0.05) were found between compliant and non-compliant leagues for age and all player movement variables, with participants in the compliant leagues achieving less player movement. Significant differences were also evident between conditions in the U8 subset in total and relative distance and HSR efforts, with moderate to very large differences (29-60%) observed for all player movement variables. Rule modifications limits the extent and intensity of player movement in junior AF compared to standard playing conditions. The unintended effect of reduced physical activity with rule modifications should be compensated for with additional activities wherever possible. League administrators and policy makers should consider the objectives of rule modifications and weigh up both positive and negative outcomes. Copyright © 2017. Published by Elsevier Ltd.

Towards enhanced and interpretable clustering/classification in integrative genomics

PubMed Central

Lu, Yang Young; Lv, Jinchi; Fuhrman, Jed A.

2017-01-01

Abstract High-throughput technologies have led to large collections of different types of biological data that provide unprecedented opportunities to unravel molecular heterogeneity of biological processes. Nevertheless, how to jointly explore data from multiple sources into a holistic, biologically meaningful interpretation remains challenging. In this work, we propose a scalable and tuning-free preprocessing framework, Heterogeneity Rescaling Pursuit (Hetero-RP), which weighs important features more highly than less important ones in accord with implicitly existing auxiliary knowledge. Finally, we demonstrate effectiveness of Hetero-RP in diverse clustering and classification applications. More importantly, Hetero-RP offers an interpretation of feature importance, shedding light on the driving forces of the underlying biology. In metagenomic contig binning, Hetero-RP automatically weighs abundance and composition profiles according to the varying number of samples, resulting in markedly improved performance of contig binning. In RNA-binding protein (RBP) binding site prediction, Hetero-RP not only improves the prediction performance measured by the area under the receiver operating characteristic curves (AUC), but also uncovers the evidence supported by independent studies, including the distribution of the binding sites of IGF2BP and PUM2, the binding competition between hnRNPC and U2AF2, and the intron–exon boundary of U2AF2 [availability: https://github.com/younglululu/Hetero-RP]. PMID:28977511

The Official Home Page of the U.S. Air Force

Science.gov Websites

: May 24 Air Force directs one-day operational safety review SecAF LOI SecAF LOI Letter of Intent AF and members using two C-130 and one C-17 training airframes. (U.S. Air Force photo by Richard Eldridge) The Transport Team crew members using two C-130 and one C-17 training airframes. (U.S. Air Force photo by

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

Cui Xiangshun; Li Xingyu; Kim, Nam-Hyung

To gain insights into the roles the paternal genome and chromosome number play in pre-implantation development, we cultured fertilized embryos and diploid and haploid parthenotes (DPs and HPs, respectively), and compared their development and gene expression patterns. The DPs and fertilized embryos did not differ in developmental ability but HPs development was slower and characterized by impaired compaction and blastocoel formation. Microarray analysis revealed that fertilized blastocysts expressed several genes at higher levels than DP blastocysts; these included the Y-chromosome-specific gene eukaryotic translation initiation factor 2, subunit 3, structural gene Y-linked (Eif2s3y) and the imprinting gene U2 small nuclear ribonucleoproteinmore » auxiliary factor 1, related sequence 1 (U2af1-rs1). We also found that when DPs and HPs were both harvested at 44 and 58 h of culture, they differed in the expression of 38 and 665 genes, respectively. However, when DPs and HPs were harvested at the midpoints of 4-cell stage (44 and 49 h, respectively), no differences in expression was observed. Similarly, when the DPs and HPs were harvested when they became blastocysts (102 and 138 h, respectively), only 15 genes showed disparate expression. These results suggest that while transcripts needed for early development are delayed in HPs, it does progress sufficiently for the generation of the various developmental stages despite the lack of genetic components.« less

Effects of clay after an aflatoxin challenge on aflatoxin clearance, milk production, and metabolism of Holstein cows.

PubMed

Sulzberger, S A; Melnichenko, S; Cardoso, F C

2017-03-01

Oral supplementation of clay to dairy cattle has been reported to reduce toxicity of aflatoxin (AF) in contaminated feed. The objective of this study was to determine the effects of 3 concentrations of dietary clay supplementation in response to an AF challenge. Ten multiparous rumen-cannulated Holstein cows [body weight (mean ± SD) = 669 ± 20 kg and 146 ± 69 d in milk], were assigned to 1 of 5 treatments in a randomized replicated 5 × 5 Latin square design balanced to measure carryover effects. Periods (21 d) were divided in an adaptation phase (d 1 to 14) and a measurement phase (d 15 to 21). From d 15 to 17, cows received an AF challenge. The challenge consisted of 100 μg of aflatoxin B 1 (AFB 1 )/kg of dietary dry matter intake (DMI). The material was fitted into 10-mL gelatin capsules and administered into the rumen through a rumen-cannula based on the average DMI obtained on d 12 to 14. Treatments were no clay plus an AF challenge (POS); 3 different concentrations of clay (0.5, 1, or 2% of dietary DMI) plus an AF challenge; and a control consisting of no clay and no AF challenge (C). Statistical analysis was performed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). Two contrasts, CONT1 (POS vs. C) and CONT2 (POS vs. the average of 0.5, 1, and 2% clay), were compared along with the linear and quadratic treatment effects (POS, 0.5%, 1%, 2%). Cows supplemented with clay had lower AF excretion in milk as aflatoxin M 1 (AFM 1 ; 0.5% = 20.83 μg/d, 1% = 22.82 μg/d, and 2% = 16.51 μg/d) and AF transfer from rumen fluid to milk (AFM 1; 0.5% = 1.01%, 1% = 0.98%, and 2% = 0.74%) compared with cows in POS (AFM 1 = 27.81 μg/d and AF transfer = 1.37%, CONT2). Similarly, concentrations of AFM 1 in milk (0.5% = 0.35 μg/kg, 1% = 0.30 μg/kg, 2% = 0.25 μg/kg), AFB 1 in feces (0.5% = 1.79 μg/g, 1% = 1.52 μg/kg, 2% = 1.48 μg/kg), and AFB 1 in rumen fluid (0.5% = 0.05 μg/kg, 1% = 0.02 μg/kg, 2% = 0.02 μg/kg) were reduced in cows fed clay compared with POS (0.43 μg/kg, 2.78 μg/kg, and 0.10 μg/kg, respectively, CONT2). Cows supplemented with clay tended to have lower 3.5% fat-corrected milk [0.5% = 38.2 kg, 1% = 39.3 kg, 2% = 38.4 kg, standard error of the mean (SEM) = 1.8] than cows in POS (41.3 kg; SEM = 1.8; CONT2). Plasma superoxide dismutase (SOD) concentration tended to be lower for cows fed clay in the diet (0.5% = 2.16 U/mL, 1% = 1.90 U/mL, 2% = 2.3 U/mL; SEM = 0.3) than for cows in POS (2.72 U/mL; CONT2). Additionally, when cows were exposed to AF without clay in the diet, plasma concentrations of aspartate aminotransferase (AST) decreased from 84.23 (C) to 79.17 (POS) and glutamate dehydrogenase (GLDH) decreased from 91.02 (C) to 75.81 (POS). In conclusion, oral supplementation of clay reduced the transfer of AF from the rumen to milk and feces. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Uranium from Seawater Marine Testing Program at the University of Miami’s Broad Key Island Research Station

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

Gill, Gary A.; Kuo, Li-Jung; Strivens, Jonathan E.

Marine testing at Broad Key Island (BKI), Florida was conducted to validate adsorption capacity and adsorption kinetics results obtained for several formulations of the ORNL amidoxime-based polymeric adsorbents in Sequim Bay, Washington in another location with different oceanographic and water quality conditions (e.g. temperature, dissolved organic carbon, salinity and trace element content). Broad Key is a small island off the southeast coast of Florida at the southern end of Biscayne Bay. Flow-through column and recirculating flume experiments were conducted at BKI using ambient filtered seawater and identical exposure systems as were used at the Pacific Northwest National Laboratory’s (PNNL) Marinemore » Sciences laboratory (MSL). Testing was conducted in two periods in FY 2015 and FY 2016 with five different amidoxime-based adsorbent materials, four produced by ORNL (AF1, AI8, AF8, and AF1-DMSO) and one by LCW technologies (LCW-10). All exposures were conducted at ambient seawater temperatures, with moderate temperature control on the ambient seawater to mitigate large daily swings in the seawater temperature. The ORNL adsorbents AF1, AI8 and AF1-AO-DMSO all had fairly similar adsorption capacities (6.0 to 6.6 g U/ kg adsorbent) after 56 days of exposure at ambient temperature (26 to 31 °C) and salinity (35.7 to 37.4), but the AF8 adsorbent was considerably lower at 4.4 g U/kg adsorbent. All the adsorbents tested at BKI had higher capacities than was observed at PNNL, with the higher temperatures likely a major factor contributing to this difference. In general, the elemental distribution (expressed as a relative percentage) on all the adsorbents agreed well, including good agreement with the elemental distribution pattern for AF1 adsorbent exposed at PNNL. The most notable exception to a uniform elemental distributional pattern across the various adsorbents occurs with vanadium. The relative mass percentage for vanadium retained by the adsorbents ranged from a minimum of 13% for the AF8 formulation to a maximum of 29% for the AI8 formulation. All the V/U mass ratios at BKI are lower than observed for the AF1 adsorbent at PNNL (3.0). Temperature likely plays a significant role in the V/U mass ratio difference between BKI and PNNL. Because uranium has a higher adsorption capacity at higher temperatures, one would expect that warmer exposures would favor a lower V/U mass ratio, which could explain why the V/U mass ratio for the PNNL exposures are higher than observed for the BKI exposures. Marine Testing at BKI offers the opportunity to test adsorbent performance under warmer ambient and more saline conditions than exist at the marine test site on Sequim Bay. This is particularly important since the amidoxime-based adsorbents respond strongly to temperature. In addition, since salinities are about 15% higher at BKI compared to Sequim Bay (36 vs. 31), uranium adsorption capacities are about 15% higher at the BKI site compared to Sequim Bay.« less

A comparison of the physical and anthropometric qualities explanatory of talent in the elite junior Australian football development pathway.

PubMed

Woods, Carl T; Cripps, Ashley; Hopper, Luke; Joyce, Christopher

2017-07-01

To compare the physical and anthropometric qualities explanatory of talent at two developmental levels in junior Australian football (AF). Cross-sectional observational. From a total of 134 juniors, two developmental levels were categorised; U16 (n=50; 15.6±0.3 y), U18 (n=84; 17.4±0.5 y). Within these levels, two groups were a priori defined; talent identified (U16; n=25; 15.7±0.2 y; U18 n=42; 17.5±0.4 y), non-talent identified (U16; n=25; 15.6±0.4 y; U18; n=42; 17.3±0.6 y). Players completed seven physical and anthropometric assessments commonly utilised for talent identification in AF. Binary logistic regression models were built to identify the qualities most explanatory of talent at each level. A combination of standing height, dominant leg dynamic vertical jump height and 20m sprint time provided the most parsimonious explanation of talent at the U16 level (AICc=60.05). At the U18 level, it was a combination of body mass and 20m sprint time that provided the most parsimonious explanation of talent (AICc=111.27). Despite similarities, there appears to be distinctive differences in physical and anthropometric qualities explanatory of talent at the U16 and U18 level. Coaches may view physical and anthropometric qualities more (or less) favourably at different levels of the AF developmental pathway. Given these results, future work should implement a longitudinal design, as physical and/or anthropometric qualities may deteriorate (or emerge) as junior AF players develop. Copyright © 2016 Sports Medicine Australia. All rights reserved.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Global regulation of alternative RNA splicing by the SR-rich protein RBM39.

PubMed

Mai, Sanyue; Qu, Xiuhua; Li, Ping; Ma, Qingjun; Cao, Cheng; Liu, Xuan

2016-08-01

RBM39 is a serine/arginine-rich RNA-binding protein that is highly homologous to the splicing factor U2AF65. However, the role of RBM39 in alternative splicing is poorly understood. In this study, RBM39-mediated global alternative splicing was investigated using RNA-Seq and genome-wide RBM39-RNA interactions were mapped via cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq) in wild-type and RBM39-knockdown MCF-7 cells. RBM39 was involved in the up- or down-regulation of the transcript levels of various genes. Hundreds of alternative splicing events regulated by endogenous RBM39 were identified. The majority of these events were cassette exons. Genes containing RBM39-regulated alternative exons were found to be linked to G2/M transition, cellular response to DNA damage, adherens junctions and endocytosis. CLIP-Seq analysis showed that the binding site of RBM39 was mainly in proximity to 5' and 3' splicing sites. Considerable RBM39 binding to mRNAs encoding proteins involved in translation was observed. Of particular importance, ~20% of the alternative splicing events that were significantly regulated by RBM39 were similarly regulated by U2AF65. RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65. The current study offers a genome-wide view of RBM39's regulatory function in alternative splicing. RBM39 may play important roles in multiple cellular processes by regulating both alternative splicing of RNA molecules and transcript levels. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel protein-protein interaction in the RES (REtention and Splicing) complex.

PubMed

Tripsianes, Konstantinos; Friberg, Anders; Barrandon, Charlotte; Brooks, Mark; van Tilbeurgh, Herman; Seraphin, Bertrand; Sattler, Michael

2014-10-10

The retention and splicing (RES) complex is a conserved spliceosome-associated module that was shown to enhance splicing of a subset of transcripts and promote the nuclear retention of unspliced pre-mRNAs in yeast. The heterotrimeric RES complex is organized around the Snu17p protein that binds to both the Bud13p and Pml1p subunits. Snu17p exhibits an RRM domain that resembles a U2AF homology motif (UHM) and Bud13p harbors a Trp residue reminiscent of an UHM-ligand motif (ULM). It has therefore been proposed that the interaction between Snu17p and Bud13p resembles canonical UHM-ULM complexes. Here, we have used biochemical and NMR structural analysis to characterize the structure of the yeast Snu17p-Bud13p complex. Unlike known UHMs that sequester the Trp residue of the ULM ligand in a hydrophobic pocket, Snu17p and Bud13p utilize a large interaction surface formed around the two helices of the Snu17p domain. In total 18 residues of the Bud13p ligand wrap around the Snu17p helical surface in an U-turn-like arrangement. The invariant Trp(232) in Bud13p is located in the center of the turn, and contacts surface residues of Snu17p. The structural data are supported by mutational analysis and indicate that Snu17p provides an extended binding surface with Bud13p that is notably distinct from canonical UHM-ULM interactions. Our data highlight structural diversity in RRM-protein interactions, analogous to the one seen for nucleic acid interactions. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Subunit association of gamma-glutamyltranspeptidase of Escherichia coli K-12.

PubMed

Hashimoto, W; Suzuki, H; Nohara, S; Tachi, H; Yamamoto, K; Kumagai, H

1995-12-01

gamma-Glutamyltranspeptidase [EC 2.3.2.2] of Escherichia coli K-12 consists of one large subunit and one small subunit, which can be separated from each other by high-performance liquid chromatography. Using ion spray mass spectrometry, the masses of the large and the small subunit were determined to be 39,207 and 20,015, respectively. The large subunit exhibited no gamma-glutamyltranspeptidase activity and the small subunit had little enzymatic activity, but a mixture of the two subunits showed partial recovery of the enzymatic activity. The results of native-polyacrylamide gel electrophoresis suggested that they could partially recombine, and that the recombined dimer exhibited enzymatic activity. The gene of gamma-glutamyltranspeptidase encoded a signal peptide, and the large and small subunits in a single open reading frame in that order. Two kinds of plasmid were constructed encoding the signal peptide and either the large or the small subunit. A gamma-glutamyltranspeptidase-less mutant of E. coli K-12 was transformed with each plasmid or with both of them. The strain harboring the plasmid encoding each subunit produced a small amount of the corresponding subunit protein in the periplasmic space but exhibited no enzymatic activity. The strain transformed with both plasmids together exhibited the enzymatic activity, but its specific activity was approximately 3% of that of a strain harboring a plasmid encoding the intact structural gene. These results indicate that a portion of the separated large and small subunits can be reconstituted in vitro and exhibit the enzymatic activity, and that the expressed large and small subunits independently are able to associate in vivo and be folded into an active structure, though the specific activity of the associated subunits was much lower than that of native enzyme. This suggests that the synthesis of gamma-glutamyltranspeptidase in a single precursor polypeptide and subsequent processing are more effective to construct the intact structure of gamma-glutamyltranspeptidase than the association of the separated large and small subunits.

Involvement of the orphan nuclear estrogen receptor-related receptor α in osteoclast adhesion and transmigration

PubMed Central

Bonnelye, Edith; Saltel, Frédéric; Chabadel, Anne; Zirngibl, Ralph A; Aubin, Jane E; Jurdic, Pierre

2010-01-01

The orphan nuclear receptor, estrogen receptor-related receptor α (ERRα) is expressed in osteoblasts and osteoclasts (OCs) and has been proposed to be a modulator of estrogen signaling. To determine the role of ERRα in OC biology, we knocked down ERRα activity by transient transfection of an siRNA directed against ERRα in the RAW264.7 monocyte–macrophage cell line that differentiates into OCs in the presence of receptor activator of nuclear factor κB-ligands and macrophage colony-stimulating factor. In parallel, stable RAW cell lines expressing a dominant-negative form of ERRα and green fluorescent protein (RAW-GFP-ERRαΔAF2) were used. Expression of OC markers was assessed by real-time PCR, and adhesion and transmigration tests were performed. Actin cytoskeletal organization was visualized using confocal microscopy. We found that RAW264.7 cells expressing siRNA directed against ERRα and RAW-GFP-ERRαΔAF2 OCs displayed abnormal spreading, and decreased osteopontin and β3 integrin subunit expression compared with the corresponding control cells. Decreased adhesion and the absence of podosome belts concomitant with abnormal localization of c-src were also observed in RAW-GFP-ERRαΔAF2-derived OCs. In addition, RAW-GFP-ERRαΔAF2-derived OCs failed to transmigrate through osteoblast cell layers. Our data show that the impairment of ERRα function does not alter OC precursor proliferation and differentiation but does alter the adhesion/spreading and migration capacities of mature OCs. PMID:20841427

Digital Doppler Radial Velocity Data Compared Objectively with Digital Reflectivity Radar Data.

DTIC Science & Technology

1980-05-01

AD-A092 318 AIR FORCE INST OF TECH WRIGHT-PATTERSON AFS OH F/6 17/9 DI6ITAL DOPPLER RADIAL VELOCITY DATA COMPARED OBJECTIVELY WITH --ETC(UMAY G0 T F...Technology (ATCQ D.:rp’: ofWbi fcr. rlght-Paterson AfS OH _45433.- . 19. KEY WORDS (Continue on reverse side it necessary anld Identify by block number) 8...14I 4J ZUi 0 0’ ~0 MWiLi )0( InO 011C4-. ɜ l- W OW o. .4 w U CZt ( - 3 a p-N a M 0 .LtW a X 0N- W U W XOL :) DWuUvN CY Z- O It 0% toI a C-~z 10- 2: J 3

Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population: a register-based study from Sweden.

PubMed

Bengtsson, Karin; Forsblad-d'Elia, Helena; Lie, Elisabeth; Klingberg, Eva; Dehlin, Mats; Exarchou, Sofia; Lindström, Ulf; Askling, Johan; Jacobsson, Lennart T H

2018-04-01

To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Allelic variation at high-molecular-weight glutenin subunit loci in Aegilops biuncialis Vis].

PubMed

Kozub, N A; Sozinov, I A; Ksinias, I N; Sozinov, A A

2011-09-01

Alleles at the high-molecular-weight glutenin subunit loci Glu-U1 and Glu-M(b)1 were analyzed in the tetraploid species Aegilops biuncialis (UUM(b)M(b)). The material for the investigation included the collection of 39 accessions of Ae. biuncialis from Ukraine (the Crimea), one Hellenic accession, one accession of unknown origin, F2 seeds from different crosses, as well as samples from natural populations from the Crimea. Ae. umbellulata and Ae. comosa accessions were used to allocate components of the HMW glutenin subunit patterns of Ae. biuncialis to U or M(b) genomes. Eight alleles were identified at the Glu-U1 locus and ten alleles were revealed at the Glu-M(b) 1 locus. Among alleles at the Glu-M(b) 1 locus ofAe. biuncialis there were two alleles controlling the y-type subunit only and one allele encoding the x-subunit only.

The Long and Short Term Impact of Elevated Body Mass Index on Risk of New Atrial Fibrillation in the Women’s Health Study

PubMed Central

Tedrow, Usha B; Conen, David; Ridker, Paul M; Cook, Nancy R; Koplan, Bruce A; Manson, JoAnn E; Buring, Julie E; Albert, Christine M

2010-01-01

Objectives To characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Background Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Methods Cases of AF were confirmed by medical record review in 34,309 participants in the Women’s Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. Results Over 12.9 +/− 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% CI 3.4, 6.1, p<0.0001) increase in risk with each kg/m2. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were utilized to estimate dynamic risk, overweight (HR 1.22 95%CI 1.02, 1.45, p=0.03) and obesity (HR 1.65 95%CI 1.36, 2.00, p<0.0001) were associated with adjusted short term elevations in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of developing AF (p=0.02) compared to those maintaining BMI <30 kg/m2. The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short term elevations in BMI was substantial (18.3%). Conclusions In this population of apparently healthy women, BMI was associated with short and long term elevations in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. PMID:20488302

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

PubMed Central

Siontis, Konstantinos C.; Geske, Jeffrey B.; Ong, Kevin; Nishimura, Rick A.; Ommen, Steve R.; Gersh, Bernard J.

2014-01-01

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors. PMID:24965028

Resonance energy transfer between the active sites of creatine kinase from rabbit brain.

PubMed

Grossman, S H

1990-09-03

Resonance energy transfer was measured between the active site domains of the brain isozyme of creatine kinase (CK-BB). The reactive thiol near the active sites, one on each subunit of the dimeric protein, was derivatized using 5-[2-[iodoacetyl)amino)ethyl]aminonaphthalene-1-sulfonic acid (AED), 2-[4'-iodoacetamidoanilino]naphthalene-6-sulfonic acid (AANS) and 5-iodoacetamidofluorescein (AF). Suitable donor/acceptor protein conjugated hybrids were prepared by controlled kinetics producing CK-BB-AED/AF and CK-BB-AANS/AF. Transfer efficiencies, measured from the quenching of the donor lifetime and steady-state sensitized acceptor emission, ranged from 0.10 to 0.17. From determination of the donor/acceptor overlap integrals, donor quantum yields and attempts to delimit the orientation factor using steady-state and phase-resolved anisotropy measurements, it was found that a suitable estimate of the range between the active sites was between 45 and 57 A. This range is similar to that reported previously for the muscle isozyme of creatine kinase (Grossman, S.H. (1989) Biochemistry 28, 4894-4902) but is a significantly greater distance than detected for the hybrid, myocardial specific isozyme (Grossman, S.H. (1983) Biochemistry 22, 5369-5375).

Low-molecular-weight glutenin subunits from the 1U genome of Aegilops umbellulata confer superior dough rheological properties and improve breadmaking quality of bread wheat.

PubMed

Wang, Jian; Wang, Chang; Zhen, Shoumin; Li, Xiaohui; Yan, Yueming

2018-04-01

Wheat-related genomes may carry new glutenin genes with the potential for quality improvement of breadmaking. In this study, we estimated the gluten quality properties of the wheat line CNU609 derived from crossing between Chinese Spring (CS, Triticum aestivum L., 2n = 6x = 42, AABBDD) and the wheat Aegilops umbellulata (2n = 2x = 14, UU) 1U(1B) substitution line, and investigated the function of 1U-encoded low-molecular-weight glutenin subunits (LMW-GS). The main quality parameters of CNU609 were significantly improved due to introgression of the 1U genome, including dough development time, stability time, farinograph quality number, gluten index, loaf size and inner structure. Glutenin analysis showed that CNU609 and CS had the same high-molecular-weight glutenin subunit (HMW-GS) composition, but CNU609 carried eight specific 1U genome-encoded LMW-GS. The introgression of the 1U-encoded LMW-GS led to more and larger protein body formation in the CNU609 endosperm. Two new LMW-m type genes from the 1U genome, designated Glu-U3a and Glu-U3b, were cloned and characterized. Secondary structure prediction implied that both Glu-U3a and Glu-U3b encode subunits with high α-helix and β-strand content that could benefit the formation of superior gluten structure. Our results indicate that the 1U genome has superior LMW-GS that can be used as new gene resources for wheat gluten quality improvement. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Effects of Mn and Al on the Intragranular Acicular Ferrite Formation in Rare Earth Treated C-Mn Steel

NASA Astrophysics Data System (ADS)

Song, Mingming; Song, Bo; Yang, Zhanbing; Zhang, Shenghua; Hu, Chunlin

2017-07-01

The influence of Al, Mn and rare earth (RE) on microstructure of C-Mn steel was investigated. The capacities of different RE inclusions to induce intragranular acicular ferrite (AF) formation were compared. Result shows that RE treatment could make C-Mn steel from large amounts of intragranular AF. Al killed is detrimental to the formation of intragranular AF in RE-treated C-Mn steel. An upper bainite structure would replace the AF when Al content increased to 0.027 mass %. The optimal Mn content to form AF is about 0.75-1.31 mass %. The effective RE inclusion which could induce AF nucleation is La2O2S. When patches of MnS are attached on the surface of La2O2S inclusion, AF nucleation capacity of RE-containing inclusion could enlarge obviously. The existence of manganese-depleted zone and low lattice misfit would be the main reason of La-containing inclusion inducing AF nucleation in C-Mn steel.

Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation.

PubMed

Cao, Wenguang; Razanau, Aleh; Feng, Dairong; Lobo, Vincent G; Xie, Jiuyong

2012-09-01

The molecular basis of cell signal-regulated alternative splicing at the 3' splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3' splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3' splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3' splice site usage.

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

PubMed Central

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

2016-01-01

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. PMID:27488468

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.

Organic Compounds in the Exhaust of a J85-5 Turbine Engine

DTIC Science & Technology

1980-09-01

8217 rcoe E)a•se, Teyxes uno r job vrder 79?31D-11-1H ilhen J.. averegt , spe: i czt ~ 1 -s , oir r=the data are used -’) an 7,rx~se oither than 2: rei...the USAFSAM sorption tube atmospheric sample system ( AF Invention No. 12,052; U.S. Patent No. 4,170,901). The collected samples were analyzed with a...f ’a- @1. 06 a C L v M~~I w ,a!j 1 ’l l .1 cNm l c0 w EL In c , .0 0 ) d’ 3 G)I’ c af a c. I%0 111 , 3 >1u w z w" r ojn 3..c N m enj m L. Nuw X >- 12

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

Extracting uranium from seawater: Promising AF series adsorbents

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

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

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

Structure–function analysis and genetic interactions of the SmG, SmE, and SmF subunits of the yeast Sm protein ring

PubMed Central

Schwer, Beate; Kruchten, Joshua; Shuman, Stewart

2016-01-01

A seven-subunit Sm protein ring forms a core scaffold of the U1, U2, U4, and U5 snRNPs that direct pre-mRNA splicing. Using human snRNP structures to guide mutagenesis in Saccharomyces cerevisiae, we gained new insights into structure–function relationships of the SmG, SmE, and SmF subunits. An alanine scan of 19 conserved amino acids of these three proteins, comprising the Sm RNA binding sites or inter-subunit interfaces, revealed that, with the exception of Arg74 in SmF, none are essential for yeast growth. Yet, for SmG, SmE, and SmF, as for many components of the yeast spliceosome, the effects of perturbing protein–RNA and protein–protein interactions are masked by built-in functional redundancies of the splicing machine. For example, tests for genetic interactions with non-Sm splicing factors showed that many benign mutations of SmG, SmE, and SmF (and of SmB and SmD3) were synthetically lethal with null alleles of U2 snRNP subunits Lea1 and Msl1. Tests of pairwise combinations of SmG, SmE, SmF, SmB, and SmD3 alleles highlighted the inherent redundancies within the Sm ring, whereby simultaneous mutations of the RNA binding sites of any two of the Sm subunits are lethal. Our results suggest that six intact RNA binding sites in the Sm ring suffice for function but five sites may not. PMID:27417296

DNA sensors to assess the effect of VKORC1 and CYP2C9 gene polymorphisms on warfarin dose requirement in Chinese patients with atrial fibrillation.

PubMed

Huang, Tao-Sheng; Zhang, Ling; He, Qiong; Li, Yu-Bin; Dai, Zhong-Li; Zheng, Jian-Rui; Cheng, Pei-Qi; He, Yun-Shao

2017-03-01

The optimal dose of warfarin depends on polymorphisms in the VKORC1 (the vitamin K epoxide reductase complex subunit (1) and CYP2C9 (cytochrome P450 2C9) genes. To minimize the risk of adverse reactions, warfarin dosages should be adjusted according to results from rapid and simple monitoring methods. However, there are few pharmacogenetic-guided warfarin dosing algorithms that are based on large cohorts from the Chinese population, especially patients with atrial fibrillation. This study aimed to validate a pharmacogenetic-guided warfarin dosing algorithm based on results from a new rapid electrochemical detection method used in a multicenter study. Three SNPs (CYP2C9 *2, *3 and VKORC1 c.-1639G > A) were genotyped by electrochemical detection using a sandwich-type format that included a 3' short thiol capture probe and a 5' ferrocene-labeled signal probe. A total of 1285 samples from four clinical hospitals were evaluated. Concordance rates between the results from the electrochemical DNA biosensor and the sequencing test were 99.8%. The results for gene distribution showed that most Chinese patients had higher warfarin susceptibility because mutant-type and heterozygotes were present in the majority of subjects (99.4%) at locus c.-1639G > A. When the International Warfarin Pharmacogenetics Consortium algorithm was used to estimate therapeutic dosages for 362 patients with AF and the values were compared with their actual dosages, the results revealed that 56.9% were similar to actual dosages (within the 20% range). A novel electrochemical detection method of CYP2C9 *2, *3and VKORC1 c.-1639G > A alleles was evaluated. The warfarin dosing algorithm based on data gathered from a large patient cohort can facilitate the reasonable and effective use of warfarin in Chinese patients with AF.

Description of Kuraishia piskuri f.a., sp. nov., a new methanol assimilating yeast and transfer of phylogenetically related Candida species to the genera Kuraishia and Nakazawaea as new combinations.

PubMed

Kurtzman, Cletus P; Robnett, Christie J

2014-11-01

The new anamorphic yeast Kuraishia piskuri, f.a., sp. nov. is described for three strains that were isolated from insect frass from trees growing in Florida, USA (type strain, NRRL YB-2544, CBS 13714). Species placement was based on phylogenetic analysis of nuclear gene sequences for the D1/D2 domains of large subunit rRNA, small subunit rRNA, translation elongation factor-1α, and subunits B1 and B2 of RNA polymerase II B. From this analysis, the anamorphic species Candida borneana, Candida cidri, Candida floccosa, Candida hungarica, and Candida ogatae were transferred to the genus Kuraishia as new combinations and Candida anatomiae, Candida ernobii, Candida ishiwadae, Candida laoshanensis, Candida molendini-olei, Candida peltata, Candida pomicola, Candida populi, Candida wickerhamii, and Candida wyomingensis were transferred to the genus Nakazawaea. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

USAF Bioenvironmental Noise Data Handbook. Volume 130. A-7 Aircraft in the AF32A-19 and the AF32A-24 Noise Suppressors, Near and Far-Field Noise.

DTIC Science & Technology

1980-07-01

C2 w C3 0 . . . . 0 0 0 0 1 CO Cl UJI ty . . I. . . . . . . . . . I. . . . . U, Z 91 Is . . . 0 0 0 0 r U z ce tD z us z m z woe z 0 00 CL ti) 0 Z 6...I( x O~ tD .)Z ,ll . . .P .. . . .. . .o 0 z : :• (Y -, 11-4 I •••••• It; rl L-l ulC z co i’Li u 11 1 gr - - - -- -.... .... ....... ..U3U% A, z oc ao...II 𔃻 3 - - 3 - 33 - -a z 0 jAj " 7 nu ~ fu j( ~ : .. \\./ : * a a a32 m 4’ . 4t... U 0 10,0 r,,_ I,. co CD 1,4 Z c a 0 -- -- 64 "*" o :) € go e ° o

Survey of Antithrombotic Treatment in Rural Patients (>60 years) with Atrial Fibrillation in East China.

PubMed

Wei, Yong; Xu, Juan; Wu, Haiqing; Zhou, Genqing; Chen, Songwen; Wang, Caihong; Shen, Yahong; Yang, Shunhong; Wang, Bin; He, Zheng; Sun, Jianping; Sun, Weidong; Ouyang, Ping; Liu, Shaowen

2018-05-01

The prevalence and antithrombotic treatment of atrial fibrillation (AF) in Chinese rural population is not well known. The aim of this study was to investigate the extent to which antithrombotic treatment was prescribed for rural AF patients >60 years. We identified 828 AF patients from 36734 rural residents >60 years in Shanghai China. Our data indicated the overall prevalence rate of AF was 2.3% in rural population >60 years in East China and 38.9% of AF patients underwent antithrombotic therapy, including warfarin (5.9%), aspirin (29.6%), clopidogrel (2.9%) and aspirin combined with clopidogrel (0.5%). Of enrolled subjects, 98.4% had CHA 2 DS 2 -VASc score ≥1, 72.0% had HAS-BLED score <3 and 59.2% had CHA 2 DS 2 -VASc score ≥2 with HAS-BLED score <3. Missing early detection (34.9%), delay in seeking treatment for asymptomatic AF (25.5%) and doctors's incomplete inform of AF-related risk of stroke to patients (21.7%) were three dominant causes for failing anticoagulant usage. In conclusion, most AF patients were with a high risk of thrombosis and a low risk of bleeding in China, but a large majority of them failed to take anticoagulants mainly for missing an early screening of AF and lack of awareness on AF for both patients and primary care physicians.

A KCNQ1 mutation causes age-dependant bradycardia and persistent atrial fibrillation.

PubMed

Ki, Chang-Seok; Jung, Chae Lim; Kim, Hyun-ji; Baek, Kwan-Hyuck; Park, Seung Jung; On, Young Keun; Kim, Ki-Suk; Noh, Su Jin; Youm, Jae Boum; Kim, June Soo; Cho, Hana

2014-03-01

Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.

Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart.

PubMed

Li, Ning; Csepe, Thomas A; Hansen, Brian J; Sul, Lidiya V; Kalyanasundaram, Anuradha; Zakharkin, Stanislav O; Zhao, Jichao; Guha, Avirup; Van Wagoner, David R; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Biesiadecki, Brandon J; Hummel, John D; Weiss, Raul; Fedorov, Vadim V

2016-08-09

Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor and its downstream GIRK (G protein-coupled inwardly rectifying potassium channels) channels (IK,Ado). We applied biatrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and nonfailing human hearts (n=37). Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10-100 µmol/L) produced more significant shortening of action potential durations in RA (from 290±45 to 239±41 ms, 17.3±10.4%; P<0.01) than LA (from 307±24 to 286±23 ms, 6.7±6.6%; P<0.01). In 10 hearts, adenosine induced AF (317±116 s) that, when sustained (≥2 minutes), was primarily maintained by 1 to 2 localized reentrant drivers in lateral RA. Tertiapin (10-100 nmol/L), a selective GIRK channel blocker, counteracted adenosine-induced action potential duration shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher adenosine A1 receptor (2.7±1.7-fold; P<0.01) and GIRK4 (1.7±0.8-fold; P<0.05) protein expression than lateral/posterior LA. This study revealed a 3-fold RA-to-LA adenosine A1 receptor protein expression gradient in the human heart, leading to significantly greater RA versus LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest adenosine A1 receptor/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine. © 2016 American Heart Association, Inc.

Analysis of Advanced CI Applications

DTIC Science & Technology

1981-03-01

rner Street Boston, ,/iA 021 10 Atcn« L,r. Fred Quelle AF^L/Of (ianscum AHB, MA 01/31 Atun « ./r. John Oanny AF..L/AL0 Kirtiand AHB...M d/11 / Atun « .jr. J. d. Hoyye ArJC/OL Andrew^ Ar’d, DO 20.334 Atv,n« oapt Oyole AFdC/X^rU Andrews Af-d, ÜO 20334 8 10 II...8217’■ ..:., ■■ . >. ■ — Ini Mil/Li;icoin Lab H. ). üux l-i Le ; in ji-on, MA U^l /.j Atun » iJr. ü. üreenwooj 4U Naval

Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

PubMed

Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times/day + Taurine 175mg x 3 times/day, with or without EPA 180 mg & DHA 120 mg, to avoid serious current limitations in the use of Doxycycline 100 mg 2 times/day, for 4 weeks.

Extracting Uranium from Seawater: Promising AF Series Adsorbents

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

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

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 withmore » 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.« less

Structure-function analysis and genetic interactions of the SmG, SmE, and SmF subunits of the yeast Sm protein ring.

PubMed

Schwer, Beate; Kruchten, Joshua; Shuman, Stewart

2016-09-01

A seven-subunit Sm protein ring forms a core scaffold of the U1, U2, U4, and U5 snRNPs that direct pre-mRNA splicing. Using human snRNP structures to guide mutagenesis in Saccharomyces cerevisiae, we gained new insights into structure-function relationships of the SmG, SmE, and SmF subunits. An alanine scan of 19 conserved amino acids of these three proteins, comprising the Sm RNA binding sites or inter-subunit interfaces, revealed that, with the exception of Arg74 in SmF, none are essential for yeast growth. Yet, for SmG, SmE, and SmF, as for many components of the yeast spliceosome, the effects of perturbing protein-RNA and protein-protein interactions are masked by built-in functional redundancies of the splicing machine. For example, tests for genetic interactions with non-Sm splicing factors showed that many benign mutations of SmG, SmE, and SmF (and of SmB and SmD3) were synthetically lethal with null alleles of U2 snRNP subunits Lea1 and Msl1. Tests of pairwise combinations of SmG, SmE, SmF, SmB, and SmD3 alleles highlighted the inherent redundancies within the Sm ring, whereby simultaneous mutations of the RNA binding sites of any two of the Sm subunits are lethal. Our results suggest that six intact RNA binding sites in the Sm ring suffice for function but five sites may not. © 2016 Schwer et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Optical probes of symmetry breaking in magnetic and superconducting BaFe2(As1-xPx)2

NASA Astrophysics Data System (ADS)

Orenstein, Joseph

The discovery of iron pnictide superconductors has opened promising new directions in the effort to fully understand the phenomenon of high-Tc, with a focus on the connections between superconductivity, magnetism, and electronic nematicity. The BaFe2(As1-xPx)2 (P:Ba122) system in particular has received attention because isovalent substitution of As for P generates less disorder than doping on the Fe site. The phase diagram of P:Ba122 is characterized by a line of simultaneous antiferromagnetic (AF) and tetragonal-to-orthorhombic transitions, Ts (x) , that penetrates the superconducting dome at x =0.28, just below optimal doping (xopt = 0.30). In this work, we use spatially-resolved optical polarimetry and photomodulated reflectance to detect linear birefringence and therefore breaking of 4-fold rotational (C4) symmetry. In underdoped (x<0.28) samples, birefringence appears at T>Tsand grows continuously with decreasing T . The birefringence is unidirectional in a large (300 μm x300 μm) field of view, suggesting that C4 breaking in this range of T is caused by residual strain that couples to a diverging nematic susceptibility. Birefringence maps just below Ts (x) show the appearance of domains, indicating the onset of spontaneous symmetry breaking to an AF ground state. Surprisingly, in samples with x>0.28, in which the low T phase is superconducting/ tetragonal rather than AF/orthorhombic, C4 breaking is observed as well, with an abrupt onset and domain formation at 55 K. We tentatively associate these features with a transition to an AF phase induced by residual strain, as previously proposed [H.-H. Kuo et al. Phys. Rev. B86, 134507 (2012)] to account for structure in resistivity vs. T. Time-resolved photomodulation allow us to follow the amplitude of the AF order with time following pulsed photoexcitation. Below Tc the AF order at first weakens , but then strengthens in response to the photoinduced weakening of superconductivity. This complex time evolution is accounted for quantitatively by a model based on the coexistence and competition of AF and superconducting order. We gratefully acknowledge support by the U.S. Department of Energy, Office of Science, Materials Sciences and Engineering Division, and the Gordon and Betty Moore Foundation's EPiQS Initiative through Grant GBMF4537.

12 CFR 509.103 - Civil money penalties.

Code of Federal Regulations, 2010 CFR

2010-01-01

...,500 12 U.S.C. 1467a(r)(3) Late/Inaccurate Reports—3rd Tier 1,375,000 12 U.S.C. 1817(j)(16)(A) Change in Control—1st Tier 7,500 12 U.S.C. 1817(j)(16)(B) Change in Control—2nd Tier 37,500 12 U.S.C. 1817(j.... 4012a(f) Flood Insurance 1 385 2 135,000 1 Per day. 2 Per year. [56 FR 38306, Aug. 12, 1991, as amended...

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

Dual Production Sources in the Procurement of Weapon Systems: A Policy Analysis

DTIC Science & Technology

1983-11-01

Competitive Aspects of the AIM-9B Seeker Assembly Procurement, memorandum to Carl Wilbourn , U.S. Navy OP-96D, December 16, 1977. 3 sARINC Report, p...Corporation, R-2706-DR&E, February 1981. Carroll, Frank, Competitive Aspects of the AIM-9B Seeker Assembly Procurement, Memorandum to Carl Wilbourn , U.S...David J., and Joseph P. Large, Estimated Costs of Extended Low Rate Airframe Production, The Rand Corporation, R-2243-AF, March 1978, Fisher, Gene H

Control of alternative splicing by forskolin through hnRNP K during neuronal differentiation

PubMed Central

Cao, Wenguang; Razanau, Aleh; Feng, Dairong; Lobo, Vincent G.; Xie, Jiuyong

2012-01-01

The molecular basis of cell signal-regulated alternative splicing at the 3′ splice site remains largely unknown. We isolated a protein kinase A-responsive ribonucleic acid (RNA) element from a 3′ splice site of the synaptosomal-associated protein 25 (Snap25) gene for forskolin-inhibited splicing during neuronal differentiation of rat pheochromocytoma PC12 cells. The element binds specifically to heterogeneous nuclear ribonucleo protein (hnRNP) K in a phosphatase-sensitive way, which directly competes with the U2 auxiliary factor U2AF65, an essential component of early spliceosomes. Transcripts with similarly localized hnRNP K target motifs upstream of alternative exons are enriched in genes often associated with neurological diseases. We show that such motifs upstream of the Runx1 exon 6 also bind hnRNP K, and importantly, hnRNP K is required for forskolin-induced repression of the exon. Interestingly, this exon encodes the peptide domain that determines the switch of the transcriptional repressor/activator activity of Runx1, a change known to be critical in specifying neuron lineages. Consistent with an important role of the target genes in neurons, knocking down hnRNP K severely disrupts forskolin-induced neurite growth. Thus, through hnRNP K, the neuronal differentiation stimulus forskolin targets a critical 3′ splice site component of the splicing machinery to control alternative splicing of crucial genes. This also provides a regulated direct competitor of U2AF65 for cell signal control of 3′ splice site usage. PMID:22684629

Highly conserved small subunit residues influence rubisco large subunit catalysis.

PubMed

Genkov, Todor; Spreitzer, Robert J

2009-10-30

The chloroplast enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of photosynthetic CO(2) fixation. With a deeper understanding of its structure-function relationships and competitive inhibition by O(2), it may be possible to engineer an increase in agricultural productivity and renewable energy. The chloroplast-encoded large subunits form the active site, but the nuclear-encoded small subunits can also influence catalytic efficiency and CO(2)/O(2) specificity. To further define the role of the small subunit in Rubisco function, the 10 most conserved residues in all small subunits were substituted with alanine by transformation of a Chlamydomonas reinhardtii mutant that lacks the small subunit gene family. All the mutant strains were able to grow photosynthetically, indicating that none of the residues is essential for function. Three of the substitutions have little or no effect (S16A, P19A, and E92A), one primarily affects holoenzyme stability (L18A), and the remainder affect catalysis with or without some level of associated structural instability (Y32A, E43A, W73A, L78A, P79A, and F81A). Y32A and E43A cause decreases in CO(2)/O(2) specificity. Based on the x-ray crystal structure of Chlamydomonas Rubisco, all but one (Glu-92) of the conserved residues are in contact with large subunits and cluster near the amino- or carboxyl-terminal ends of large subunit alpha-helix 8, which is a structural element of the alpha/beta-barrel active site. Small subunit residues Glu-43 and Trp-73 identify a possible structural connection between active site alpha-helix 8 and the highly variable small subunit loop between beta-strands A and B, which can also influence Rubisco CO(2)/O(2) specificity.

Synthesis and Characterization of Ferromagnetic/Antiferromagnetic Perovskite Oxide Superlattices

NASA Astrophysics Data System (ADS)

Jia, Yue

Perovskite oxides span a diverse range of functional properties such as ferromagnetism, superconductivity, and ferroelectricity, which makes them promising candidate materials for applications such as sensors, energy conversion and data storage devices. With recent advances in thin film deposition techniques, the precise manipulation of atomic layers on the unit cell level make it possible to synthesize epitaxial thin film heterostructures consisting of layers with different properties. The structural compatibility of perovskite oxides allows them to be epitaxially grown in complex heterostructures such as superlattices with a large density of interfaces where the interplay between spin, charge, orbital, and lattice degrees of freedom gives rise to new behaviors. The ferromagnetic (FM)/antiferromagnetic (AF) interface is particularly interesting due to exchange coupling which is not only of interest for fundamental research but also is of great significance for industrial applications. Unlike metallic systems that have been studied for decades with wide ranges of applications in devices such as hard disk drives, thin films of complex metal oxides is a relatively new field. Perovskite oxides show much more diverse functional properties than metals and open new pathways for tailoring propertiestowards specific device applications. Epitaxial La0.7Sr0.3MnO3 (LSMO)/La 0.7Sr0.3FeO3 (LSFO) superlattices serve as model systems to explore the magnetic structure and exchange coupling at perovskite oxide interfaces. Earlier work suggested that (001)-oriented LSMO/LSFO superlattices with compensated AF spins at the interface display spin-flop coupling characterized by perpendicular alignment between the AF spin axes and the FM moments at a sublayer thickness of 6 unit cells (u.c.). Changing the crystallographic orientation of the interface from (001) to (111) introduces changes to factors such as the charge density of each stacking layer, the magnetic iiistructure of the AF layer at the interface, the symmetry of the lattice, and the orbital degeneracy. Therefore, different properties and exchange coupling mechanisms are expected. (111)-oriented LSMO/LSFO superlattices with sublayer thicknesses ranging from 3 to 60 u.c. were synthesized and characterized. Detailed analysis of their structural, electronic, and magnetic properties were performed using synchrotron radiation based resonant x-ray reflectivity, soft x-ray magnetic spectroscopy, and photoemission electron microscopy to explore the effect of sublayer thickness on the magnetic structure and exchange coupling at (111)-oriented perovskite oxide interfaces. Interfacial effects and ultrathin superlattice sublayers can stabilize orientations of the LSFO AF spin axis which differ from that of LSFO films and LSMO/LSFO bilayers. In the ultrathin limit (3 to 6 u.c.), it was found that the AF properties of the LSFO sublayers are preserved with an out-of-plane canting of the AF spin axis, while the FM properties of the LSMO sublayers are significantly depressed. For thicker LSFO layers (> 9 u.c.), the out-of-plane canting of the AF spin axis is only present in superlattices with thick LSMO sublayers. As a result, exchange coupling in the form of spin-flop coupling exists only in superlattices which display both robust ferromagnetism and out-of-plane canting of the AF spin axis. A portion of the AF moments can be reoriented by a moderate external magnetic field through spin-flop coupling with the FM LSMO sublayers that have low magnetocrystalline anisotropy in the (111) plane. The AF order in the spin-flop coupled superlattices was studied using angle-dependent x-ray magnetic linear dichroism. The AF order can be categorized into two types: majority of the AF moments cant out-of-the-plane of the film along the or directions depending on the LSFO layer thickness, while a minority portion lies within the (111) plane in different AF domains. The energy difference between domains with their spin axes along the in-plane or out-of-plane directions is small, and the magnetic order of AF thin films is far ivmore complex than in bulk LSFO. The complex AF structure in these (111)-oriented LSMO/LSFO superlattices illustrates that complex metal oxide heterostructures can serve as fertile ground for discovery of new magnetic phases, which have potential applications in next generation information technology devices.

Meta-analysis of efficacy and safety of apixaban and uninterrupted apixaban therapy compared to vitamin K antagonists in patients undergoing catheter ablation for atrial fibrillation.

PubMed

Ukaigwe, Anene; Shrestha, Pragya; Karmacharya, Paras; Hussain, Sarah K; Samii, Soraya; Gonzalez, Mario D; Wolbrette, Deborah; Naccarrelli, Gerald V

2017-03-01

Apixaban is a Factor Xa inhibitor increasingly being used for stroke prevention in atrial fibrillation (AF). Although several studies have been done, the efficacy and safety of apixaban during the peri-procedural period of AF ablation remains unclear. We sought to systematically review pooled data from these various studies to evaluate thromboembolic and bleeding risks in patients undergoing catheter ablation for AF who are treated with apixaban (interrupted and uninterrupted). Studies comparing anticoagulation with apixaban or vitamin K antagonists (VKA) in patients undergoing ablation for AF were identified via an electronic search of MEDLINE, EMBASE, clinical trials.gov, and Cochrane Library from inception to January 2016. Study-specific risk ratios were calculated and combined with a fixed-effects model meta-analysis. In the analysis of 2100 pooled patients, thromboembolic complications (TE) occurred in 14/778 (1.80 %) patients in the apixaban group (AG) compared to 20/1322 patients in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2  = 0 %). Major bleeding occurred in 9/778 (1.2 %) of the AG compared to 20/1322 (1.51 %) in the VKA group (RR 1.03, 95 % CI 0.55-1.90, p = 0.93, I 2  = 0 %). In uninterrupted apixaban group (uAG), TE occurred in 4/585 (0.68 %) patients in the uAG compared to 6/910 (0.66 %) in VKA group (RR 0.86, 95 % CI 0.25-2.95, p = 0.81, I 2  = 0 %). Major bleeding occurred in 5/585 (0.85 %) in uAG compared to 7/910 (0.77 %) in the VKA group (RR 1.20, 95 % CI 0.37-3.88, p = 0.76, I 2  = 0 %). Our study demonstrates patients treated with apixaban and VKA during the peri-procedural period for AF ablation have similar rates of TE and bleeding complications. Interrupted and uninterrupted apixaban strategies were associated with similar outcomes.

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Mechanistic Comparison of "Nearly Missed" Versus "On-Target" Rotor Ablation.

PubMed

Yamazaki, Masatoshi; Avula, Uma Mahesh R; Berenfeld, Omer; Kalifa, Jérôme

2015-08-01

This study used advanced optical mapping techniques to examine atrial fibrillation (AF) dynamics before and after 2 distinct electrogram-based ablation strategies: complex fractionated atrial electrograms (CFAEs) and DFmax/rotor ablation. Among the electrogram analytical features proposed to unravel the atrial regions that perpetuate AF, CFAEs, highest dominant frequency sites (DFmax), and, more recently, phase analysis-enabled rotor mapping have received the largest attention. Still, the mechanisms by which these approaches modulate AF dynamics and lead to AF termination are unknown. In Langendorff-perfused sheep hearts, AF was maintained by the continuous perfusion of acetylcholine and high-resolution endocardial-epicardial optical videos were recorded from the left atrial free wall and the posterior left atrium. Then, DFmax/rotor regions (n = 7), or CFAE regions harboring the highest wavebreak density (HWD) (n = 5), were targeted with a 4F ablation catheter (5 to 15 W, 30 to 60 s/point). Thereafter, we examined the changes in AF dynamics and whether AF terminated. DFmax/rotor point ablation resulted in a significant decrease in DFmax values. In 2 animals AF terminated, whereas in the remaining 5 animals the post-ablation DFmax domain remained in the vicinity of its pre-ablation location. However, after HWD/CFAEs density ablation, DFmax values did not change, AF did not terminate, and post-ablation DFmax domains relocated from the left atrial free wall to the pulmonary vein-posterior left atrium region. In another group of hearts (n = 12), we observed that upon a progressive increase in acetylcholine concentration-mimicking the acute electrophysiological changes occurring after ablation-3-dimensional rotors drifted from one atrial region to another along large gradients of myocardial thickness. "On-target" DFmax/rotor ablation leads to the annihilation of the fibrillation-driving rotor. This translates into large decreases in AF frequency or AF termination. In contrast, "nearly missed" HWD/CFAEs ablation spares the fibrillation-driving rotor, and set the stage for rotor drift along large myocardial thickness gradients. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart

PubMed Central

Li, Ning; Csepe, Thomas A.; Hansen, Brian J.; Sul, Lidiya V.; Kalyanasundaram, Anuradha; Zakharkin, Stanislav O.; Zhao, Jichao; Guha, Avirup; Van Wagoner, David R.; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul ML; Biesiadecki, Brandon; Hummel, John D; Weiss, Raul; Fedorov, Vadim V.

2016-01-01

Background Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor (A1R) and its downstream GIRK channels (IK,Ado). Methods We applied bi-atrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and non-failing human hearts (n=37). Results Optical mapping of coronary-perfused atria (n=24) revealed that adenosine perfusion (10–100μM) produced more significant shortening of action potential durations (APD80) in RA (from 290±45ms to 239±41ms, 17.3±10.4%; p<0.01) than LA (from 307±24ms to 286±23ms, 6.7±6.6%; p<0.01). In ten hearts, adenosine induced AF (317±116 sec) that, when sustained (≥2 min), was primarily maintained by one/two localized reentrant drivers in lateral RA. Tertiapin (10–100nM), a selective GIRK channel blocker, counteracted adenosine-induced APD shortening and prevented AF induction. Immunoblotting showed that the superior/middle lateral RA had significantly higher A1R (2.7±1.7 fold; p<0.01) and GIRK4 (1.7±0.8 fold; p<0.05) protein expression than lateral/posterior LA. Conclusions This study revealed a three-fold RA-to-LA A1R protein expression gradient in the human heart, leading to significantly greater RA vs. LA repolarization sensitivity in response to adenosine. Sustained adenosine-induced AF is maintained by reentrant drivers localized in lateral RA regions with the highest A1R/GIRK4 expression. Selective atrial GIRK channel blockade may effectively treat AF during conditions with increased endogenous adenosine. PMID:27462069

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

Jack Preiss

Conversion of the Potato tuber ADP-glucose Pyrophopshorylase Regulatory Subunit into a Catalytic Subunit. ADP-glucose synthesis, a rate-limiting reaction in starch synthesis, is catalyzed by ADP-glucose pyrophosphorylase (ADPGlc PPase). The enzyme in plants is allosterically activated by 3-phosphoglycerate (3PGA) and inhibited by inorganic phosphate (Pi) and is composed of two subunits as a heterotetramer, a2b2. Subunit a is the catalytic subunit and subunit b is designated as the regulatory subunit.The b subunit increases the affinty of the activator for the catalytic subunit. Recent results have shown that the subunits are derived from the same ancestor subunit as the regulatory subunit canmore » be converted to a catalytically subunit via mutation of just two amino acids. Lys44 and Thr54 in the large subunit from potato tuber were converted to the homologous catalytic subunit residues, Arg33 and Lys43. The activity of the large subunit mutants cannot be readily tested with a co-expressed wild-type small (catalytic) subunit because of the intrinsic activity of the latter. We co-expressed the regulatory-subunit mutants with SmallD145N, an inactive S subunit in which the catalytic Asp145 was mutated. The activity of the small (catalytic) subunit was reduced more than three orders of magnitude. Coexpression of the L subunit double mutant LargeK44R/T54K with SmallD145N generated an enzyme with considerable activity, 10% and 18% of the wildtype enzyme, in the ADP-glucose synthetic and pyrophosphorolytic direction, respectively. Replacement of those two residues in the small subunit by the homologous amino acids in the L subunits (mutations R33K and K43T) decreased the activity one and two orders of magnitude. The wild-type enzyme and SmallD145NLargeK44R/T54K had very similar kinetic properties indicating that the substrate site has been conserved. The fact that only two mutations in the L subunit restored enzyme activity is very strong evidence that the large subunit is derived from the catalytic ancestor. Previous results showed that Asp145 in the small subunit of the wild-type is essential for catalysis, whereas the homologous Asp160 in the Large WT subunit is not. However, in this study, mutation D160N or D160E in the LK44R/T54K subunit abolished the activity, which shows the ancestral essential role of this residue and confirms that the catalysis of SmallD145NLarge K44R/T54K occurs in the L(b) subunit. A phylogenetic tree of the ADP-Glc PPases present in photosynthetic eukaryotes also sheds information about the origin of the subunits. The tree showed that plant Small and Large subunits can be divided into two and four distinct groups, respectively. The two main groups of S subunits are from dicot and monocot plants, whereas Large subunit groups correlate better with their documented tissue expression. The first Large-subunit group is generally expressed in photosynthetic tissues and comprises Large subunits from dicots and monocots. Group II displays a broader expression pattern, whereas groups III and IV are expressed in storage organs (roots, stems, tubers, seeds). Subunits from group III are only from dicot plants, whereas group IV are seed-specific subunits from monocots. These last two groups stem from the same branch of the phylogenetic tree and split before monocot and dicot separation. Thus few as two mutations turned the L subunit from Solanum tuberosum catalytic, showing that L and S subunits share a common catalytic ancestor, rather than a non-catalytic one. The L subunit evolved to have a regulatory role, lost catalytic residues more than 130 million years ago before monocots and dicots diverged, and preserved, possibly as a byproduct, the active site domain.« less

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.

PubMed

Brown, Jennifer R; Moslehi, Javid; O'Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D; Fraser, Graeme; Rule, Simon; Kipps, Thomas J; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A

2017-10-01

The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation ( clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021 ). Copyright© 2017 Ferrata Storti Foundation.

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials

PubMed Central

Brown, Jennifer R.; Moslehi, Javid; O’Brien, Susan; Ghia, Paolo; Hillmen, Peter; Cymbalista, Florence; Shanafelt, Tait D.; Fraser, Graeme; Rule, Simon; Kipps, Thomas J.; Coutre, Steven; Dilhuydy, Marie-Sarah; Cramer, Paula; Tedeschi, Alessandra; Jaeger, Ulrich; Dreyling, Martin; Byrd, John C.; Howes, Angela; Todd, Michael; Vermeulen, Jessica; James, Danelle F.; Clow, Fong; Styles, Lori; Valentino, Rudy; Wildgust, Mark; Mahler, Michelle; Burger, Jan A.

2017-01-01

The first-in-class Bruton’s tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6–16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021). PMID:28751558

Chemistry of 1,1,2,2,9,9,10,10-octafluoro-[2,2]-paracyclophane: Its synthesis and reactions

NASA Astrophysics Data System (ADS)

Duan, Jian-Xin

This dissertation describes the first example of the synthesis of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) under non-high-dilution conditions. Under very mild reaction conditions, bis-p-(chlorodifluoromethyl)benzene (TFPX dichloride) and its derivatives reacted with Zn dust in N,N-dimethyl acetamide (DMA) (Zinc method) affording the corresponding AF4 and its derivatives in moderate to good yields. Purification of products was also studied and an efficient purification process was developed. A new and very cheap method for preparation of TFPX dichloride is also disclosed. Using the very cheap fluorinating reagent, anhydrous hydrogen fluoride (AHF), 1,4-bis(trichloromethyl)benezene or its derivatives were converted to TFPX and its derivatives in high yields (F/Cl exchange reaction). With the success of the Zinc method and F/Cl exchange reaction, highly pure AF4 thus can be provided to the semiconductor industry and academy research scientists in large quantity and at a very low price. Starting from AF4, numerous AF4 derivatives were synthesized using convenient reaction conditions. Reaction of AF4 with fuming nitric acid at room temperature gave mono-nitroAF4 in almost quantitative yield. Reduction of the mono-nitroAF4 with iron powder in the presence of HCl in alcoholic solvent gave the aminoAF4 in 90% yield. Via the diazonium salt intermediate, iodoAF4 was also obtained in good yield. Under similar reaction conditions, disubstituted AF4 derivatives were also prepared in good yields. Heating a mixture of AF4, trifluoroacetyl peroxide and dichloromethane gave the trifluoromethylated dimeric AF4 as a mixture of diastereomers. When these products were heated to 170--180°C in the presence of I 2, 4-trifluoromethyl-AF4 was obtained in almost 87% yield. X-ray structural analysis showed that the C-C bond connecting the two cyclophane moieties to be longer than the normal C-C bond. Kinetic studies, conducted in the presence of excess amount of hydrogen donor, showed this bond to be quite weak. Oxidation of AF4 with HIO3 in the presence of catalytic amount of H2SO4 in trifluoroacetic acid gave AF4 quinone in one step. AF4 quinone can be easily reduced to the hydroquinone by Na 2S2O4 aqueous solution.

Characterization of the Genetic Program Linked to the Development of Atrial Fibrillation in CREM-IbΔC-X Mice.

PubMed

Seidl, Matthias D; Stein, Juliane; Hamer, Sabine; Pluteanu, Florentina; Scholz, Beatrix; Wardelmann, Eva; Huge, Andreas; Witten, Anika; Stoll, Monika; Hammer, Elke; Völker, Uwe; Müller, Frank U

2017-08-01

Reduced expression of genes regulated by the transcription factors CREB/CREM (cAMP response element-binding protein/modulator) is linked to atrial fibrillation (AF) susceptibility in patients. Cardiomyocyte-directed expression of the inhibitory CREM isoform CREM-IbΔC-X in transgenic mice (TG) leads to spontaneous-onset AF preceded by atrial dilatation and conduction abnormalities. Here, we characterized the altered gene program linked to atrial remodeling and development of AF in CREM-TG mice. Atria of young (TGy, before AF onset) and old (TGo, after AF onset) TG mice were investigated by mRNA microarray profiling in comparison with age-matched wild-type controls (WTy/WTo). Proteomic alterations were profiled in young mice (8 TGy versus 8 WTy). Annotation of differentially expressed genes revealed distinct differences in biological functions and pathways before and after onset of AF. Alterations in metabolic pathways, some linked to altered peroxisome proliferator-activated receptor signaling, muscle contraction, and ion transport were already present in TGy. Electron microscopy revealed significant loss of sarcomeres and mitochondria and increased collagen and glycogen deposition in TG mice. Alterations in electrophysiological pathways became prominent in TGo, concomitant with altered gene expression of K + -channel subunits and ion channel modulators, relevant in human AF. The most prominent alterations of the gene program linked to CREM-induced atrial remodeling were identified in the expression of genes related to structure, metabolism, contractility, and electric activity regulation, suggesting that CREM transgenic mice are a valuable experimental model for human AF pathophysiology. © 2017 American Heart Association, Inc.

Identifying the Physical Fitness, Anthropometric and Athletic Movement Qualities Discriminant of Developmental Level in Elite Junior Australian Football: Implications for the Development of Talent.

PubMed

Gaudion, Sarah L; Doma, Kenji; Sinclair, Wade; Banyard, Harry G; Woods, Carl T

2017-07-01

Gaudion, SL, Doma, K, Sinclair, W, Banyard, HG, and Woods, CT. Identifying the physical fitness, anthropometric and athletic movement qualities discriminant of developmental level in elite junior Australian football: implications for the development of talent. J Strength Cond Res 31(7): 1830-1839, 2017-This study aimed to identify the physical fitness, anthropometric and athletic movement qualities discriminant of developmental level in elite junior Australian football (AF). From a total of 77 players, 2 groups were defined according to their developmental level; under 16 (U16) (n = 40, 15.6 to 15.9 years), and U18 (n = 37, 17.1 to 17.9 years). Players performed a test battery consisting of 7 physical fitness assessments, 2 anthropometric measurements, and a fundamental athletic movement assessment. A multivariate analysis of variance tested the main effect of developmental level (2 levels: U16 and U18) on the assessment criterions, whilst binary logistic regression models and receiver operating characteristic (ROC) curves were built to identify the qualities most discriminant of developmental level. A significant effect of developmental level was evident on 9 of the assessments (d = 0.27-0.88; p ≤ 0.05). However, it was a combination of body mass, dynamic vertical jump height (nondominant leg), repeat sprint time, and the score on the 20-m multistage fitness test that provided the greatest association with developmental level (Akaike's information criterion = 80.84). The ROC curve was maximized with a combined score of 180.7, successfully discriminating 89 and 60% of the U18 and U16 players, respectively (area under the curve = 79.3%). These results indicate that there are distinctive physical fitness and anthropometric qualities discriminant of developmental level within the junior AF talent pathway. Coaches should consider these differences when designing training interventions at the U16 level to assist with the development of prospective U18 AF players.

Identification of nucleotides in E. coli 16S rRNA essential for ribosome subunit association.

PubMed

Pulk, Arto; Maiväli, Ulo; Remme, Jaanus

2006-05-01

The ribosome consists of two unequal subunits, which associate via numerous intersubunit contacts. Medium-resolution structural studies have led to grouping of the intersubunit contacts into 12 directly visualizable intersubunit bridges. Most of the intersubunit interactions involve RNA. We have used an RNA modification interference approach to determine Escherichia coli 16S rRNA positions that are essential for the association of functionally active 70S ribosomes. Modification of the N1 position of A702, A1418, and A1483 with DMS, and of the N3 position of U793, U1414, and U1495 with CMCT in 30S subunits strongly interferes with 70S ribosome formation. Five of these positions localize into previously recognized intersubunit bridges, namely, B2a (U1495), B2b (U793), B3 (A1483), B5 (A1418), and B7a (A702). The remaining position displaying interference, U1414, forms a base pair with G1486, which is a part of bridge B3. We contend that these five intersubunit bridges are essential for reassociation of the 70S ribosome, thus forming the functional core of the intersubunit contacts.

Identification of nucleotides in E. coli 16S rRNA essential for ribosome subunit association

PubMed Central

Pulk, Arto; Maiväli, Ülo; Remme, Jaanus

2006-01-01

The ribosome consists of two unequal subunits, which associate via numerous intersubunit contacts. Medium-resolution structural studies have led to grouping of the intersubunit contacts into 12 directly visualizable intersubunit bridges. Most of the intersubunit interactions involve RNA. We have used an RNA modification interference approach to determine Escherichia coli 16S rRNA positions that are essential for the association of functionally active 70S ribosomes. Modification of the N1 position of A702, A1418, and A1483 with DMS, and of the N3 position of U793, U1414, and U1495 with CMCT in 30S subunits strongly interferes with 70S ribosome formation. Five of these positions localize into previously recognized intersubunit bridges, namely, B2a (U1495), B2b (U793), B3 (A1483), B5 (A1418), and B7a (A702). The remaining position displaying interference, U1414, forms a base pair with G1486, which is a part of bridge B3. We contend that these five intersubunit bridges are essential for reassociation of the 70S ribosome, thus forming the functional core of the intersubunit contacts. PMID:16556933

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Healthcare Resource Utilization and Costs Associated with Recurrent Episodes of Atrial Fibrillation: The FRACTAL Registry

PubMed Central

REYNOLDS, MATTHEW R.; ESSEBAG, VIDAL; ZIMETBAUM, PETER; COHEN, DAVID J.

2007-01-01

Cost of Recurrent AF Introduction Drivers of cost in the atrial fibrillation (AF) population are not fully understood. We sought to characterize the resource utilization and costs of treating new-onset AF, with emphasis on the incremental costs associated with recurrent episodes of AF over time. Methods and Results An inception cohort of 973 AF patients was followed at 3–6 month intervals in an observational registry over a mean of 24 ± 9 months. AF therapies, clinical outcomes, and both inpatient and outpatient medical resource utilization were tracked at each follow-up interval. Registry patients were managed primarily with cardioversion and pharmacological therapy. Direct healthcare costs were calculated from a U.S. perspective by multiplying measures of resource utilization by representative price weights. Costs were compared among patients in whom the initial episode of AF became permanent and patients who initially achieved sinus rhythm and had either 0, 1–2, or ≥3 documented recurrences during follow-up. Mean annual costs for these four groups were $2,372, $3,385, $6,331, and $10,312 per patient per year, respectively (P < 0.001 for trend), with the largest variation related to hospital costs. In multivariable analysis controlling for demographic characteristics and baseline cardiac and comorbid conditions, each documented recurrence of AF was found to increase annual healthcare costs by ∼$1,600. Conclusion Following initial diagnosis, patients with AF treated with traditional therapies incur $4,000–$5,000 in annual direct healthcare costs. Costs are markedly higher in patients with multiple AF recurrences. These data may be helpful in evaluating the economic impact of new technologies for treating AF. PMID:17451468

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.

PubMed

Wu, J; Liu, P; Zhu, J L; Maddukuri, S; Zern, M A

1998-03-01

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.

Subunit Conformations and Assembly States of a DNA Translocating Motor: The Terminase of Bacteriophage P22

PubMed Central

Němeček, Daniel; Gilcrease, Eddie B.; Kang, Sebyung; Prevelige, Peter E.; Casjens, Sherwood; Thomas, George J.

2007-01-01

Bacteriophage P22, a podovirus infecting strains of Salmonella typhimurium, packages a 42 kbp genome using a headful mechanism. DNA translocation is accomplished by the phage terminase, a powerful molecular motor consisting of large and small subunits. Although many of the structural proteins of the P22 virion have been well characterized, little is known about the terminase subunits and their molecular mechanism of DNA translocation. We report here structural and assembly properties of ectopically expressed and highly purified terminase large and small subunits. The large subunit (gp2), which contains the nuclease and ATPase activities of terminase, exists as a stable monomer with an α/β fold. The small subunit (gp3), which recognizes DNA for packaging and may regulate gp2 activity, exhibits a highly α-helical secondary structure and self-associates to form a stable oligomeric ring in solution. For wildtype gp3, the ring contains nine subunits, as demonstrated by hydrodynamic measurements, electron microscopy and native mass spectrometry. We have also characterized a gp3 mutant (Ala 112 → Thr) that forms a ten subunit ring, despite a subunit fold indistinguishable from wildtype. Both the nonameric and decameric gp3 rings exhibit nonspecific DNA binding activity, and gp2 is able to bind strongly to the DNA/gp3 complex but not to DNA alone. We propose a scheme for the roles of P22 terminase large and small subunits in the recruitment and packaging of viral DNA and discuss the model in relation to proposals for terminase-driven DNA translocation in other phages. PMID:17945256

Functioning of the Drosophila Wilms'-Tumor-1-Associated Protein Homolog, Fl(2)d, in Sex-Lethal-Dependent Alternative Splicing

PubMed Central

Penn, Jill K. M.; Graham, Patricia; Deshpande, Girish; Calhoun, Gretchen; Chaouki, Ahmad Sami; Salz, Helen K.; Schedl, Paul

2008-01-01

fl(2)d, the Drosophila homolog of Wilms'-tumor-1-associated protein (WTAP), regulates the alternative splicing of Sex-lethal (Sxl), transformer (tra), and Ultrabithorax (Ubx). Although WTAP has been found in functional human spliceosomes, exactly how it contributes to the splicing process remains unknown. Here we attempt to identify factors that interact genetically and physically with fl(2)d. We begin by analyzing the Sxl-Fl(2)d protein–protein interaction in detail and present evidence suggesting that the female-specific fl(2)d1 allele is antimorphic with respect to the process of sex determination. Next we show that fl(2)d interacts genetically with early acting general splicing regulators and that Fl(2)d is present in immunoprecipitable complexes with Snf, U2AF50, U2AF38, and U1-70K. By contrast, we could not detect Fl(2)d complexes containing the U5 snRNP protein U5-40K or with a protein that associates with the activated B spliceosomal complex SKIP. Significantly, the genetic and molecular interactions observed for Sxl are quite similar to those detected for fl(2)d. Taken together, our findings suggest that Sxl and fl(2)d function to alter splice-site selection at an early step in spliceosome assembly. PMID:18245840

CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor.

PubMed

Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Docheva, Nikolina; Dong, Zhong; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S; Erez, Offer; Korzeniewski, Steven J

2017-07-01

To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.

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

Spreitzer, Robert Joseph

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of CO 2 fixation in photosynthesis. However, it is a slow enzyme, and O 2 competes with CO 2 at the active site. Oxygenation initiates the photorespiratory pathway, which also results in the loss of CO 2. If carboxylation could be increased or oxygenation decreased, an increase in net CO 2 fixation would be realized. Because Rubisco provides the primary means by which carbon enters all life on earth, there is much interest in engineering Rubisco to increase the production of food and renewable energy. Rubisco is located in the chloroplasts of plants,more » and it is comprised of two subunits. Much is known about the chloroplast-gene-encoded large subunit (rbcL gene), which contains the active site, but much less is known about the role of the nuclear-gene-encoded small subunit in Rubisco function (rbcS gene). Both subunits are coded by multiple genes in plants, which makes genetic engineering difficult. In the eukaryotic, green alga Chlamydomonas reinhardtii, it has been possible to eliminate all the Rubisco genes. These Rubisco-less mutants can be maintained by providing acetate as an alternative carbon source. In this project, focus has been placed on determining whether the small subunit might be a better genetic-engineering target for improving Rubisco. Analysis of a variable-loop structure (βA-βB loop) of the small subunit by genetic selection, directed mutagenesis, and construction of chimeras has shown that the small subunit can influence CO 2/O 2 specificity. X-ray crystal structures of engineered chimeric-loop enzymes have indicated that additional residues and regions of the small subunit may also contribute to Rubisco function. Structural dynamics of the small-subunit carboxyl terminus was also investigated. Alanine-scanning mutagenesis of the most-conserved small-subunit residues has identified a possible structural pathway between the small-subunit βA-βB loop and alpha-helix 8 of the large-subunit α/β-barrel active site. Hybrid enzymes were also created comprised of plant small subunits and Chlamydomonas large subunits, and these enzymes have increases in CO 2/O 2 specificity, further indicating that small subunits may be the key for ultimately engineering an improved Rubisco enzyme.« less

Charts for Helicopter-Performance Estimation

DTIC Science & Technology

1945-08-01

tilerelatlons among the design parameters. Tinerasults should theref~r~ he af practical assistance in comparative performance studies. The accuracy with...page facing the figure, Ihxnerlcal appllcatton.- In order to calculate the maximum value af the rata-of-climb parameter” Ym It is necessary first to find...values of A\\~ and ~ when Czt ~ as 01, snd k have been selected. For Khe values c~ = 1.5 snd a = 6, curves 2 t of uYt Qgatnst h\\v for several values of

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

AWARD NUMBER: W811XWH-13-1-0310 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...REPORT DATE September 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Sep2015 - 31Aug2016 4. TITLE AND SUBTITLE Acceleration of Regeneration of Large

An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China.

PubMed

Zhou, Ziqiang; Hu, Dayi

2008-01-01

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Since only limited data on the Chinese population, which is the largest in the world, is available, we conducted an epidemiological study on the prevalence and risk factors of AF in mainland China. This population-based study conducted by cluster sampling comprised 29079 participants forming 14 cohorts from 13 provinces across China, where the population was nearly 1 billion. Every participant underwent electrocardiogram and physical examinations and responded to the interviewer-led questionnaire(s). Univariate and multiple statistical analyses were conducted to explore the relationship between AF prevalence and risk factors. The age-standardized prevalence of AF in China (>or=30 y) was 0.65%, and it increased with age. Men showed a higher prevalence of AF than women (0.91% [age-standardized, 0.66%] vs. 0.65% [0.63%], P = 0.013); several significant risk factors (age, hyperthyroidism, coronary heart disease, and rheumatic heart disease) were identified for AF in the general population. Stroke prevalence was much higher in AF patients than in non-AF people (12.95% vs. 2.28%, P < 0.001). AF was confirmed to be a significant independent risk factor for stroke prevalence in the studied population (OR = 2.776, [1.814, 4.248], P < 0.001). We found that AF patients received poor treatment (2.7%, warfarin; 39.7%, aspirin). This study conducted on a large sample size demonstrates that AF prevalence in mainland China is slightly lower than that in Western countries and similar to that in Asian areas, and confirms that AF is a serious public health problem in China. We identified several potential risk factors, but their associations with AF still need to be further studied.

The Hydrophobicity and Adhesion of Heterogeneous Surfaces of Dual Nanometer and Micron Scale Structures

DTIC Science & Technology

2011-04-11

scale post geometry. superhydrophobic , surface modification, adhesion, contact angle, Cassie, Wenzel, PDMS, CYTOP, Teflon AF, roll-off angle U U U U SAR...width > 1, the micro-scale features dominated the wetting state regardless of the nano-scale post geometry., KEYWORDS superhydrophobic , surface... superhydrophobicity can be routinely found in nature. Fo~ example, many plant leaves1.2, bird feathers3, insect wings and insect legs4 take advantage of

12 CFR 222.71 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... 1681a(r)(2). (k) Credit card issuer has the same meaning as in 15 U.S.C. 1681a(r)(1)(A). (l) Credit... as in 15 U.S.C. 1681a(k)(1)(A). (b) Annual percentage rate has the same meaning as in 12 CFR 226.14(b... as in 15 U.S.C. 1681a(f). (h) Credit has the same meaning as in 15 U.S.C. 1681a(r)(5). (i) Creditor...

12 CFR 222.71 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... 1681a(r)(2). (k) Credit card issuer has the same meaning as in 15 U.S.C. 1681a(r)(1)(A). (l) Credit... as in 15 U.S.C. 1681a(k)(1)(A). (b) Annual percentage rate has the same meaning as in 12 CFR 226.14(b... as in 15 U.S.C. 1681a(f). (h) Credit has the same meaning as in 15 U.S.C. 1681a(r)(5). (i) Creditor...

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

PubMed

Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

2013-03-19

Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

PubMed Central

Wongpalee, Somsakul Pop; Vashisht, Ajay; Sharma, Shalini; Chui, Darryl; Wohlschlegel, James A; Black, Douglas L

2016-01-01

Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest. DOI: http://dx.doi.org/10.7554/eLife.19743.001 PMID:27882870

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Installation Restoration Program. Phase 2. Confirmation Quantification. Stage 2 for MacDill Air Force Base, Florida. Volume 2

DTIC Science & Technology

1988-07-22

Inc. of Savannah, Georgia and Tallahassee, Florida provided analytical services. Michael Newberry, Captain USAF, and Jeff Mason, 2d LT., USAF, from...2803-19 AG AP6 ST;- ES Ci eit 2803-20 A? APC S -2 ES 23033-23 AG .AF6 SD-S 2803-22 AC AP6 SD-4 E.> PARAMIETER 280u- .y 2&u r 23-2: 2803-22 Bezo (g.h.1

Assessment of anticoagulation treatments in non-valvular atrial fibrillation patients diagnosed in a basic health area.

PubMed

Aguilera Alcaraz, Beatriz M; Abellán Huerta, José; Carbayo Herencia, Julio Antonio; Ariza Copado, Consuelo; Hernández Menárguez, Fernando; Abellán Alemán, José

Atrial fibrillation (AF) is the most common cardiac arrhythmia. To assess the need for anticoagulation is essential for its management. Our objective was to investigate whether the indication of anticoagulation was adequate in patients diagnosed with non-valvular AF, given the CHA2-DS2-VASc scale, measuring the International Normalizad Ratio range (INR) in patients treated with anti-vitamin K drugs. This is an observational and cross sectional study. 232 patients with atrial fibrillation were included. We analyzed demographic, the CHA2-DS2-VASc and HAS-BLED variables, the treatment and INR values for 6 consequentive months. The confrontation of variables was performed using chi-square and Mantel-Haenzel test. The prevalence of AF was 1.05%. The 88.4% had CHA2-DS2-VASc ≥ 2. The 71.1% were taking anticoagulants, of which 58.2% were under antivitamin k. The 46.7% of patients taking antivitamin K, presented inadequate range of INR. There was a greater prescription of antivitamin k in patients with persistent or permanent AF compared to the paroxysmal form (62.8 vs. 37.2% p<.001). The use of drugs that increase bleeding was associated with a worse control of INR after adjustment for the main variables of clinical relevance (odds ratio 2.17 [1.02-4.59], p=.043). The level of anticoagulation with antivitamin K was inadequate in our sample, despite a proper follow up and adherence to treatment. Patients with paroxysmal AF received less antivitamin K than those with persistent/permanent AF. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Petrographic Analysis of Cores from Plant 42

DTIC Science & Technology

2016-10-01

ER D C TR -X X- D R AF T Petrographic Analysis of Cores from Plant 42 E n gi n ee r R es ea rc h a n d D ev el op m en t C en te r...E. Rae Reed-Gore, Kyle Klaus, and Robert D. Moser October 2016 Approved for public release; distribution is unlimited. The U.S. Army...ORIGINATOR. ii Figures and Tables Figures Figure 1. Test location map of AF Plant 42 with core number locations. ............................. 2

Quality of life, activity impairment, and healthcare resource utilization associated with atrial fibrillation in the US National Health and Wellness Survey.

PubMed

Goren, Amir; Liu, Xianchen; Gupta, Shaloo; Simon, Teresa A; Phatak, Hemant

2013-01-01

This study builds upon current studies of atrial fibrillation (AF) and health outcomes by examining more comprehensively the humanistic burden of illness (quality of life, activity impairment, and healthcare resource utilization) among adult patients with AF, using a large, nationally representative sample and matched controls. Data were analyzed from the Internet-based 2009 US National Health and Wellness Survey. Outcomes were Mental and Physical Component Summary (MCS and PCS) and health utility scores from the SF-12, activity impairment, hospitalizations, and healthcare provider and emergency room (ER) visits. Patients with self-reported diagnosis of AF were matched randomly on age and gender with an equal number of respondents without AF. Generalized linear models examined outcomes as a function of AF vs. non-AF status, controlling for CHADS2 score, comorbidity counts, demographics, and clinical variables. Exploratory structural equation modeling assessed the above in an integrated model of humanistic burden. Mean age of AF patients (1,296 from a total sample of 75,000) was 64.9 years and 65.1% were male. Adjusting for covariates, compared with non-AF patients, AF patients had lower MCS, PCS, and utility scores, greater activity impairment (rate ratio = 1.26), more traditional provider visits (rate ratio = 1.43), and increased odds of ER visits (OR = 2.53) and hospitalizations (OR = 2.71). Exploratory structural equation modeling analyses revealed that persons with AF experienced a significantly higher overall humanistic burden. This study highlights and clarifies the substantial burden of AF and its implications for preparing efficacious AF management plans to address the imminent rise in prevalence.

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.

U2504 Determines the Species Specificity of the A-site Cleft Antibiotics: The sStructures of Tiamulin, Homoharringtonine and Bruceantin Bound to the Ribosome

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

Gurel, G.; Blaha, G; Moore, P

2009-01-01

Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 {angstrom}. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the A-site cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In themore » ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.« less

U2504 Determines the Species Specificity of the A-Site Cleft Antibiotics: The Structures of Tiamulin, Homoharringtonine, and Bruceantin Bound to the Ribosome

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

Gürel, Güliz; Blaha, Gregor; Moore, Peter B.

2009-06-30

Structures have been obtained for the complexes that tiamulin, homoharringtonine, and bruceantin form with the large ribosomal subunit of Haloarcula marismortui at resolutions ranging from 2.65 to 3.2 {angstrom}. They show that all these inhibitors block protein synthesis by competing with the amino acid side chains of incoming aminoacyl-tRNAs for binding in the Asite cleft in the peptidyl-transferase center, which is universally conserved. In addition, these structures support the hypothesis that the species specificity exhibited by the A-site cleft inhibitors is determined by the interactions they make, or fail to make, with a single nucleotide, U2504 (Escherichia coli). In themore » ribosome, the position of U2504 is controlled by its interactions with neighboring nucleotides, whose identities vary among kingdoms.« less

Panorama, section 2 of 3, note the Operations Building (Facility ...

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

Panorama, section 2 of 3, note the Operations Building (Facility 294) in the center of facility, view facing west - U.S. Naval Base, Pearl Harbor, Naval Radio Station, AF/FRD-10 Circularly Disposed Antenna Array, Wahiawa, Honolulu County, HI

γ-Aminobutyric Acid Type A α4, β2, and δ Subunits Assemble to Produce More Than One Functionally Distinct Receptor Type

PubMed Central

Eaton, Megan M.; Bracamontes, John; Shu, Hong-Jin; Li, Ping; Mennerick, Steven; Steinbach, Joe Henry

2014-01-01

Native γ-aminobutyric acid (GABA)A receptors consisting of α4, β1–3, and δ subunits mediate responses to the low, tonic concentration of GABA present in the extracellular milieu. Previous studies on heterologously expressed α4βδ receptors have shown a large degree of variability in functional properties, including sensitivity to the transmitter. We studied properties of α4β2δ receptors employing free subunits and concatemeric constructs, expressed in Xenopus oocytes, HEK 293 cells, and cultured hippocampal neurons. The expression system had a strong effect on the properties of receptors containing free subunits. The midpoint of GABA activation curve was 10 nM for receptors in oocytes versus 2300 nM in HEK cells. Receptors activated by the steroid alfaxalone had an estimated maximal open probability of 0.6 in oocytes and 0.01 in HEK cells. Irrespective of the expression system, receptors resulting from combining the tandem construct β2-δ and a free α4 subunit exhibited large steroid responses. We propose that free α4, β2, and δ subunits assemble in different configurations with distinct properties in oocytes and HEK cells, and that subunit linkage can overcome the expression system-dependent preferential assembly of free subunits. Hippocampal neurons transfected with α4 and the picrotoxin-resistant δ(T269Y) subunit showed large responses to alfaxalone in the presence of picrotoxin, suggesting that α4βδ receptors may assemble in a similar configuration in neurons and oocytes. PMID:25238745

Air Mobility Command > Home

Science.gov Websites

U.S. Air Force AF Week in Photos Senior leaders meet with industry to discuss utilizing artificial intelligence and quantum science throughout the Air Force AF announces 2018 Blacks in Government Meritorious

Maternal pomegranate juice attenuates maternal inflammation-induced fetal brain injury by inhibition of apoptosis, neural nitric oxide synthase and NF-κB in a rat model.

PubMed

Ginsberg, Yuval; Khatib, Nizar; Saadi, Noor; Ross, Michael G; Weinr, Zeev; Beloosesky, Ron

2018-04-27

Maternal inflammation is a risk factor for neonatal brain injury and future neurological deficits. Pomegranates have been shown to exhibit anti-inflammatory, anti-apoptotic and anti-oxidant activities. We hypothesized that pomegranate juice (POM) may attenuate fetal brain injury in a rat model of maternal inflammation. Pregnant rats (24 total) were randomized for i.p. LPS (100 ug/kg) or saline at time 0 at 18 days of gestation. From day 11 of gestation, 12 dams were provided ad libitum access to drinking water, and 12 dams were provided ad libitum access to drinking water with pomegranate juice (5cc per day), resulting in 4 groups of 6 dams (SAL/SAL, POM/SAL, SAL/LPS, POM/LPS). All dams were sacrificed 4 hours following the injection and maternal blood and fetal brains were collected from the 4 treatment groups. Maternal IL-6 serum levels and fetal brain caspase 3 active form (af), NF-kB p65, neuronal nitric oxide synthase (phospho-nNOS) and pro-inflammatory cytokine levels were determined by ELISA and western blot. Maternal LPS significantly increased maternal serum IL-6 levels (6039 ± 1039 vs 66 ± 46pg/ml; p < 0.05) and fetal brain caspase 3 af, NF-kB p65, phospho-nNOS and the pro-inflammatory cytokines compared to the control group (caspase 3 af 0.26 ± 0.01 vs. 0.20 ± 0.01 u; NF-κB p65 0.24 ± 0.01 vs. 0.1 ± 0.01 u; phospho-nNOS 0.23 ± 0.01 vs. 0.11 ± 0.01 u; IL-6 0.25 ± 0.01 vs. 0.09 ± 0.01 u; TNFα 0.26 ± 0.01 vs. 0.12 ± 0.01 u; CCL2 0.23 ± 0.01 vs. 0.1 ± 0.01 u). Maternal supplementation of POM to LPS exposed dams (POM/LPS) significantly reduced maternal serum IL-6 levels (3059± 1121pg/ml, fetal brain: caspase 3 af (0.2 ± 0.01 u), NF-κB p65 (0.22 ± 0.01 u), phospho-nNOS (0.19 ± 0.01 u) as well as the brain pro-inflammatory cytokines (IL-6, TNFα and CCL2) compared to LPS group. Maternal POM supplementation may attenuate maternal-inflammation-induced fetal brain injury. POM neuroprotective effects might be secondary to the suppression of both the maternal inflammatory response and inhibition of fetal brain apoptosis, neuronal nitric oxide synthase and NF-kB activation. Copyright © 2018. Published by Elsevier Inc.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Trends in U.S. Hospitalizations Rates and Rhythm Control Therapies Following Publication of the AFFIRM and RACE Trials

PubMed Central

Martin-Doyle, William; Essebag, Vidal; Zimetbaum, Peter; Reynolds, Matthew R.

2010-01-01

Introduction The impact of trials comparing rate vs. rhythm control for AF on subsequent use of rhythm control therapies and hospitalizations at a national level has not been described. Methods and Results We queried the Healthcare Cost & Utilization Project on the frequency of hospital admissions and performance of specific rhythm control procedures from 1998–2006. We analyzed trends in hospitalization for AF as principal diagnosis before and after the publication of key rate vs. rhythm trials in 2002. We also reviewed the use of electrical cardioversion and catheter ablation as principal procedures during hospital admissions for any cause and for AF as principal diagnosis. We additionally appraised the overall outpatient utilization of antiarrhythmic drugs during this same time frame using IMS Health’s National Prescription Audit.™ Admissions for AF as a principal diagnosis increased at 5%/year from 1998–2002. Following publication of the AFFIRM and RACE trials in 2002, admissions declined by 2%/year from 2002–2004, before rising again from 2004–06. In-hospital electrical cardioversion followed a similar pattern. National prescription volumes for antiarrhythmic drugs grew at <1%/yr from 2002–06, with a marked decline in the use of Class I-A agents, while catheter ablations during admissions for AF as the principal diagnosis increased at 30%/year. Conclusion The use of rhythm control therapies in the U.S. declined significantly in the first few years after publication of AFFIRM and RACE. This trend reversed by 2005, at which time rapid growth in the use of catheter ablation for AF was observed. PMID:21087329

Prp43p Is a DEAH-Box Spliceosome Disassembly Factor Essential for Ribosome Biogenesis

PubMed Central

Combs, D. Joshua; Nagel, Roland J.; Ares, Manuel; Stevens, Scott W.

2006-01-01

The known function of the DEXH/D-box protein Prp43p is the removal of the U2, U5, and U6 snRNPs from the postsplicing lariat-intron ribonucleoprotein complex. We demonstrate that affinity-purified Prp43p-associated material includes the expected spliceosomal components; however, we also identify several preribosomal complexes that are specifically purified with Prp43p. Conditional prp43 mutant alleles confer a 35S pre-rRNA processing defect, with subsequent depletion of 27S and 20S precursors. Upon a shift to a nonpermissive temperature, both large and small-ribosomal-subunit proteins accumulate in the nucleolus of prp43 mutants. Pulse-chase analysis demonstrates delayed kinetics of 35S, 27S, and 20S pre-rRNA processing with turnover of these intermediates. Microarray analysis of pre-mRNA splicing defects in prp43 mutants shows a very mild effect, similar to that of nonessential pre-mRNA splicing factors. Prp43p is the first DEXH/D-box protein shown to function in both RNA polymerase I and polymerase II transcript metabolism. Its essential function is in its newly characterized role in ribosome biogenesis of both ribosomal subunits, positioning Prp43p to regulate both pre-mRNA splicing and ribosome biogenesis. PMID:16382144

A Novel Strategy to Inhibit Hedgehog Signaling and Control Growth of Androgen-Independent Prostate Cancer Cells

DTIC Science & Technology

2013-12-01

M TIME PPC1 Volume of Spheroid Ctrl (respective media) .2% DMSO 10 uM Free Curcumin 20 uM Free Curcumin 10 uM Tagged Curcumin 20 uM Tagged... Curcumin FIGURE 6 Ctrl media 10uM FC 20uM FC 20uM TC 10uM TC 2% DMSO PC3 t0 Div 8 FIGURE 7 Phospho-p65 NFκB subunit expression decreased In

A 33 kyr Paleomagnetic Secular Variation Record from Fish Lake, Utah

NASA Astrophysics Data System (ADS)

Reilly, B. T.; Stoner, J. S.; Hatfield, R. G.; Ziegler, L. B.; Abbott, M. B.; Larsen, D. J.; Hillman, A. L.

2014-12-01

We present a new North American lacustrine PSV record spanning the last ~ 33 ka from Fish Lake, Utah. Eleven meters of sediment were recovered from three holes with overlapping drives using a UWITECH coring system. Magnetic susceptibility was measured in the field to ensure stratigraphic completeness and to provide real time information on the material recovered. The recovered lake stratigraphy includes three distinct facies, interpreted to represent the post-glacial (0.75-6.75 m), last glacial maximum (LGM)/deglaciation (6.75-9.5 m), and pre-LGM period (9.5-11.75 m), with an initial chronology constrained by ten radiocarbon dates. CT scans were made on each section and used to monitor for coring deformation and establish precise stratigraphic correlation. Magnetic remanence was studied using AF demagnetization of u-channel samples measured on the OSU 2-G Enterprises u-channel magnetometer. The NRM is characterized by a viscous remanent magnetization (VRM), present throughout the core but successfully removed by 20 mT AF demagnetization. Weak NRM intensities in the post-glacial interval (3-6 x 10-4 A/m before AF demagnetization and 1-3 x 10-4 A/m following 20 mT AF demagnetization) approach the sensitivity of the u-channel magnetometer with increasing demagnetization and result in high MAD values during PCA analysis. Accordingly, we choose to use the NRM measured after 20 mT AF demagnetization for the post-glacial sediments to avoid both the VRM overprint and noise introduced due to week intensities at higher demagnetization steps. Major inclination features are consistent with other western North American PSV records providing confidence in this approach. NRM intensities are significantly higher below 6.75 m, reflecting increased terrigenous input during the LGM/deglaciation and pre LGM periods. A stable magnetization is isolated using a PCA over the 20-60 mT AF demagnetization steps, yielding MAD values of <1 and ~2, respectively. Declination is rotated to a mean of zero and inclinations vary around geocentric axial dipole predictions for the site's location further suggesting that a reliable PSV record is preserved. The continuous PSV record reveals higher amplitude swings during the late Pleistocene. Here we assess the reliability and implications of these observations.

The fabrication and characterization of a multi-laminate, angle-ply collagen patch for annulus fibrosus repair.

PubMed

McGuire, Rachel; Borem, Ryan; Mercuri, Jeremy

2017-12-01

One major limitation of intervertebral disc (IVD) repair is that no ideal biomaterial has been developed that effectively mimics the angle-ply collagen architecture and mechanical properties of the native annulus fibrosus (AF). Furthermore, it would be beneficial to devise a simple, scalable process by which to manufacture a biomimetic biomaterial that could function as a mechanical repair patch to be secured over a large defect in the outer AF that will support AF tissue regeneration. Such a biomaterial would: (1) enable the employment of early-stage interventional strategies to treat IVD degeneration (i.e. nucleus pulposus arthroplasty); (2) prevent IVD re-herniation in patients with large AF defects; and (3) serve as a platform to develop full-thickness AF and whole IVD tissue engineering strategies. Due to the innate collagen fibre alignment and mechanical strength of pericardium, a procedure was developed to assemble multi-laminate angle-ply AF patches derived from decellularized pericardial tissue. Patches were subsequently assessed histologically to confirm angle-ply microarchitecture, and mechanically assessed for biaxial burst strength and tensile properties. Additionally, patch cytocompatibility was evaluated following seeding with bovine AF cells. This study demonstrated the effective removal of porcine cell remnants from the pericardium, and the ability to reliably produce multi-laminate patches with angle-ply architecture using a simple assembly technique. Resultant patches demonstrated their inherent ability to resist biaxial burst pressures reminiscent of intradiscal pressures commonly borne by the AF, and exhibited tensile strength and modulus values reported for native human AF. Furthermore, the biomaterial supported AF cell viability, infiltration and proliferation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Kangnung ROK AFS, K18, Korea. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1968-02-26

0ooo 33.7 6C.1 OC .7 61.1 61.2 61.2 61.2 61.2 61.2 61.2 61.2 61.2 61.2 61.2 61.2 I.-- > A500 33. 62.4 6Z.G 63:41 63 . 5 3.5 635 63.563 63.5 631 63. 63.5...uZ BZhS5 856 61. 68. 68: 1 6a. 6a . 6". 6, >0 2500 24 3 -637 T 77 5172 W87 W57 . T1t87 -a5 187bk$.!) at$7 . 17 f 1 6 .1 18. bI8 2 2000 C5.2 69.6 70.8

The morphological and chemical characteristics of striatal neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the rat.

PubMed

Waldvogel, H J; Kubota, Y; Trevallyan, S C; Kawaguchi, Y; Fritschy, J M; Mohler, H; Faull, R L

1997-10-01

The distribution, morphology and chemical characteristics of neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of the basal ganglia in the rat brain were investigated at the light, confocal and electron microscope levels using single, double and triple immunohistochemical labelling techniques. The results showed that alpha1-subunit immunoreactive neurons were sparsely distributed throughout the rat striatum. Double and triple labelling results showed that all the alpha1-subunit-immunoreactive neurons were positive for glutamate decarboxylase and immunoreactive for the beta2,3 and gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit-immunoreactive neurons were identified in the striatum on the basis of cellular morphology and chemical characteristics. The most numerous alpha1-subunit-immunoreactive neurons were medium-sized, aspiny neurons with a widely branching dendritic tree. They were parvalbumin-negative and were located mainly in the dorsolateral regions of the striatum. Electron microscopy showed that these neurons had an indented nuclear membrane, typical of striatal interneurons, and were surrounded by small numbers of axon terminals which established alpha1-subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75% of the total population of alpha1-subunit-immunoreactive neurons in the striatum. The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous population of large-sized neurons localized in the ventral and medial regions of the striatum. The most numerous large-sized cells were parvalbumin-negative, had two to three relatively short branching dendrites and were designated type 2 alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2 neurons were characterized by a highly convoluted nuclear membrane and were sparsely covered with small axon terminals. The type 2 neurons comprised 20% of the total population of alpha1-subunit-immunoreactive neurons. The remaining large-sized alpha1-immunoreactive cells were designated type 3 cells; they were positive for parvalbumin and were distinguished by long branching dendrites extending dorsally for 600-800 microm into the striatum. These neurons comprised 5% of the total population of alpha1-subunit-immunoreactive neurons and were surrounded by enkephalin-immunoreactive terminals. Electron microscopy showed that the alpha1-subunit type 3 neurons had an indented nuclear membrane and were densely covered with small axon terminals which established alpha1-subunit-immunoreactive symmetrical synaptic contacts with the soma and dendrites. These results provide a detailed characterization of the distribution, morphology and chemical characteristics of the alpha1-subunit-immunoreactive neurons in the rat striatum and suggest that the type 1 and type 2 neurons comprise of separate populations of striatal interneurons while the type 3 neurons may represent the large striatonigral projection neurons described by Bolam et al. [Bolam J. P., Somogyi P., Totterdell S. and Smith A. D. (1981) Neuroscience 6, 2141-2157.].

Department of the Navy Supporting Data for FY 1992/1993 Budget Estimates Submitted to Congress February 1991. Operating Appropriations Navy and Marine Corps

DTIC Science & Technology

1991-02-01

CL a . 0. a.I CL 97C. -4 . =- mW~ = m- r. :v V) r-4cvcvcv o w 0 cd 0 0 m Voo 0, C4 0 E .* 0 czt cv 0"’ cv -o 0 ed bCa ~ O cv wc w cv bo m- c 0. m. cv...C)C - -44 Un % $4, W.. C) )C 4 CL 0 1-4 CD co co C>0 r- 00 ++ W af .~). 4-)4 ~4 ~ nEnS4X I- Q) ED Lo~ - 0 a) r- 41 0) u c 0 -P ua 0 -4 0 ’a r ( - - a...va 6, 48 .- ,0.0 00 000 0 0 O - 00 00 0 0 .0 0 0 00 10 oa U vi I a ’ o 1 1 40 a W-, o0 -a- o 4 .O c 8u oA 44 l*2. 4 * a c u u " : Cl n. a. 00 1 Af Im

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus

PubMed Central

van den Akker, Guus G. H.; Surtel, Don A. M.; Cremers, Andy; Richardson, Stephen M.; Hoyland, Judith A.; van Rhijn, Lodewijk W.

2016-01-01

Introduction Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Methods Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). Results The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. Conclusion We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair. PMID:26794306

Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus.

PubMed

van den Akker, Guus G H; Surtel, Don A M; Cremers, Andy; Richardson, Stephen M; Hoyland, Judith A; van Rhijn, Lodewijk W; Voncken, Jan Willem; Welting, Tim J M

2016-01-01

Loss of annulus fibrosus (AF) integrity predisposes to disc herniation and is associated with IVD degeneration. Successful implementation of biomedical intervention therapy requires in-depth knowledge of IVD cell biology. We recently generated unique clonal human nucleus pulposus (NP) cell lines. Recurring functional cellular phenotypes from independent donors provided pivotal evidence for cell heterogeneity in the mature human NP. In this study we aimed to generate and characterize immortal cell lines for the human AF from matched donors. Non-degenerate healthy disc material was obtained as surplus surgical material. AF cells were immortalized by simian virus Large T antigen (SV40LTAg) and human telomerase (hTERT) expression. Early passage cells and immortalized cell clones were characterized based on marker gene expression under standardized culturing and in the presence of Transforming Growth factor β (TGFβ). The AF-specific expression signature included COL1A1, COL5A1, COL12A1, SFRP2 and was largely maintained in immortal AF cell lines. Remarkably, TGFβ induced rapid 3D sheet formation in a subgroup of AF clones. This phenotype was associated with inherent differences in Procollagen type I processing and maturation, and correlated with differential mRNA expression of Prolyl 4-hydroxylase alpha polypeptide 1 and 3 (P4HA1,3) and Lysyl oxidase (LOX) between clones and differential P4HA3 protein expression between AF cells in histological sections. We report for the first time the generation of representative human AF cell lines. Gene expression profile analysis and functional comparison of AF clones revealed variation between immortalized cells and suggests phenotypic heterogeneity in the human AF. Future characterization of AF cellular (sub-)populations aims to combine identification of additional specific AF marker genes and their biological relevance. Ultimately this knowledge will contribute to clinical application of cell-based technology in IVD repair.

Dental Laboratory Career Ladder AFS 982X0.

DTIC Science & Technology

1982-09-01

7ADA120 102 AIR FORCE OCCUPATIONAL MEASUREMENT CENTER RANDOLPH AFB TX F/6 Ri9 DENTAL LABORATORY CAREER LADDER AFS 982XO.(U) UNCLASSIFIED NLEEEili E...Eli E~lllllllllEEE EEEEEIIIEEEEEE EIEEEEIIEEEEEE IIIIIIIIIIIIIIlLZ UNITED STATES AIR FORCE 0! DENTAL LABORATORY CAREER LADDER DTlC AFS 982X0 ELEr.L_...LADDER STRUCTURE GROUPS ----------------------------------- 57 APPENDIX B - JOB DESCRIPTIONS FOR BASE AND AREA DENTAL LABORATORY PERSONNEL

12 CFR 222.71 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

....C. 1681a(f). (h) Credit has the same meaning as in 15 U.S.C. 1681a(r)(5). (i) Creditor has the same meaning as in 15 U.S.C. 1681a(r)(5). (j) Credit card has the same meaning as in 15 U.S.C. 1681a(r)(2). (k.... 1681a(k)(1)(A). (b) Annual percentage rate has the same meaning as in 12 CFR 226.14(b) with respect to...

12 CFR 222.71 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

....C. 1681a(f). (h) Credit has the same meaning as in 15 U.S.C. 1681a(r)(5). (i) Creditor has the same meaning as in 15 U.S.C. 1681a(r)(5). (j) Credit card has the same meaning as in 15 U.S.C. 1681a(r)(2). (k.... 1681a(k)(1)(A). (b) Annual percentage rate has the same meaning as in 12 CFR 226.14(b) with respect to...

Conformational characteristics of dimeric subunits of RNA from energy minimization studies. Mixed sugar-puckered ApG, ApU, CpG, and CpU.

PubMed

Thiyagarajan, P; Ponnuswamy, P K

1981-09-01

Following the procedure described in the preceding article, the low energy conformations located for the four dimeric subunits of RNA, ApG, ApU, CpG, and CpU are presented. The A-RNA type and Watson-Crick type helical conformations and a number of different kinds of loop promoting ones were identified as low energy in all the units. The 3E-3E and 3E-2E pucker sequences are found to be more or less equally preferred; the 2E-2E sequence is occasionally preferred, while the 2E-3E is highly prohibited in all the units. A conformation similar to the one observed in the drug-dinucleoside monophosphate complex crystals becomes a low energy case only for the CpG unit. The low energy conformations obtained for the four model units were used to assess the stability of the conformational states of the dinucleotide segments in the four crystal models of the tRNAPhe molecule. Information on the occurrence of the less preferred sugar-pucker sequences in the various loop regions in the tRNAPhe molecule has been obtained. A detailed comparison of the conformational characteristics of DNA and RNA subunits at the dimeric level is presented on the basis of the results.

Conformational characteristics of dimeric subunits of RNA from energy minimization studies. Mixed sugar-puckered ApG, ApU, CpG, and CpU.

PubMed Central

Thiyagarajan, P; Ponnuswamy, P K

1981-01-01

Following the procedure described in the preceding article, the low energy conformations located for the four dimeric subunits of RNA, ApG, ApU, CpG, and CpU are presented. The A-RNA type and Watson-Crick type helical conformations and a number of different kinds of loop promoting ones were identified as low energy in all the units. The 3E-3E and 3E-2E pucker sequences are found to be more or less equally preferred; the 2E-2E sequence is occasionally preferred, while the 2E-3E is highly prohibited in all the units. A conformation similar to the one observed in the drug-dinucleoside monophosphate complex crystals becomes a low energy case only for the CpG unit. The low energy conformations obtained for the four model units were used to assess the stability of the conformational states of the dinucleotide segments in the four crystal models of the tRNAPhe molecule. Information on the occurrence of the less preferred sugar-pucker sequences in the various loop regions in the tRNAPhe molecule has been obtained. A detailed comparison of the conformational characteristics of DNA and RNA subunits at the dimeric level is presented on the basis of the results. PMID:6168312

Prime Contractors with Awards Over $25,000 by Name, Location, and Contract Number. Part 2 (BAIN MXRARY BAIN-CONSOLIDATED PRODUCTS CORP)

DTIC Science & Technology

1990-01-01

5’ -DOF t’- -- F 0 M C)0 co loc. ’m toF mN NO NO F o w r-44( cu 4) 04- F00 0FO0F 0 0 F 3: u) F.F I >z zL)L UL CL F C’ CFF 0 F FO F CC . ~~FF ’-F aF ...0 ot 0 I-L o oL 0~~ It<A1 tII <( , Ca 4 .,wt u m 0 z Hmm m0 IMP 4m o z 0 .1 o a)O 0 1 af m~ r-oma I~U im I (I US 0 00 05) I03 d~L.I 0 0jJ𔃾 . 0 0 u...0u a) 04 t -C/. a)C 00w <-t o o. ~ ~ O to~t to0C) LC o 0. Do) CA x )o >o C 0 ) 4g -. u)I z3 - (0 0 -. 0 I . (0 o oo czt 0.. to ClL 0) 0 .0t ) 0 H 0

The effects of the activation of the inner-hair-cell basolateral K+ channels on auditory nerve responses.

PubMed

Altoè, Alessandro; Pulkki, Ville; Verhulst, Sarah

2018-07-01

The basolateral membrane of the mammalian inner hair cell (IHC) expresses large voltage and Ca 2+ gated outward K + currents. To quantify how the voltage-dependent activation of the K + channels affects the functionality of the auditory nerve innervating the IHC, this study adopts a model of mechanical-to-neural transduction in which the basolateral K + conductances of the IHC can be made voltage-dependent or not. The model shows that the voltage-dependent activation of the K + channels (i) enhances the phase-locking properties of the auditory fiber (AF) responses; (ii) enables the auditory nerve to encode a large dynamic range of sound levels; (iii) enables the AF responses to synchronize precisely with the envelope of amplitude modulated stimuli; and (iv), is responsible for the steep offset responses of the AFs. These results suggest that the basolateral K + channels play a major role in determining the well-known response properties of the AFs and challenge the classical view that describes the IHC membrane as an electrical low-pass filter. In contrast to previous models of the IHC-AF complex, this study ascribes many of the AF response properties to fairly basic mechanisms in the IHC membrane rather than to complex mechanisms in the synapse. Copyright © 2018 Elsevier B.V. All rights reserved.

Simulation of Spiral Waves and Point Sources in Atrial Fibrillation with Application to Rotor Localization

PubMed Central

Ganesan, Prasanth; Shillieto, Kristina E.; Ghoraani, Behnaz

2018-01-01

Cardiac simulations play an important role in studies involving understanding and investigating the mechanisms of cardiac arrhythmias. Today, studies of arrhythmogenesis and maintenance are largely being performed by creating simulations of a particular arrhythmia with high accuracy comparable to the results of clinical experiments. Atrial fibrillation (AF), the most common arrhythmia in the United States and many other parts of the world, is one of the major field where simulation and modeling is largely used. AF simulations not only assist in understanding its mechanisms but also help to develop, evaluate and improve the computer algorithms used in electrophysiology (EP) systems for ablation therapies. In this paper, we begin with a brief overeview of some common techniques used in simulations to simulate two major AF mechanisms – spiral waves (or rotors) and point (or focal) sources. We particularly focus on 2D simulations using Nygren et al.’s mathematical model of human atrial cell. Then, we elucidate an application of the developed AF simulation to an algorithm designed for localizing AF rotors for improving current AF ablation therapies. Our simulation methods and results, along with the other discussions presented in this paper is aimed to provide engineers and professionals with a working-knowledge of application-specific simulations of spirals and foci. PMID:29629398

Plasma proteins of rainbow trout (Oncorhynchus mykiss) isolated by binding to lipopolysaccharide from Aeromonas salmonicida.

PubMed

Hoover, G J; el-Mowafi, A; Simko, E; Kocal, T E; Ferguson, H W; Hayes, M A

1998-07-01

In an attempt to find plasma proteins that might be involved in the constitutive resistance of rainbow trout to furunculosis, a disease caused by Aeromonas salmonicida (AS), we purified serum and plasma proteins based on their calcium- and carbohydrate-dependent affinity for A. salmonicida lipopolysaccharide (LPS) coupled to an epoxy-activated synthetic matrix (Toyopearl AF Epoxy 650M). A multimeric family of high molecular weight (96 to 200-kDa) LPS-binding proteins exhibiting both calcium and mannose dependent binding was isolated. Upon reduction the multimers collapsed to subunits of approximately 16-kDa as estimated by 1D-PAGE and exhibited pI values of 5.30 and 5.75 as estimated from 2D-PAGE. Their N-terminal sequences were related to rainbow trout ladderlectin (RT-LL), a Sepharose-binding protein. Polyclonal antibodies to the LPS-purified 16-kDa subunits recognized both the reduced 16-kDa subunits and the non-reduced multimeric forms. A calcium- and N-acetylglucosamine (GlcNAc)-dependent LPS-binding multimeric protein (approximately 207-kDa) composed of 34.5-kDa subunits was purified and found to be identical to trout serum amyloid P (SAP) by N-terminal sequence (DLQDLSGKVFV). A protein of 24-kDa, in reduced and non-reduced conditions, was isolated and had N-terminal sequence identity with a known C-reactive protein (CRP) homologue, C-polysaccharide-binding protein 2 (TCBP2) of rainbow trout. A novel calcium-dependent LPS-binding protein was purified and termed rainbow trout lectin 37 (RT-L37). This protein, composed of dimers, tetramers and pentamers of 37 kDa subunits (pI 5.50-6.10) with N-terminal sequence (IQE(D/N)GHAEAPGATTVLNEILR) showed no close homology to proteins known or predicted from cDNA sequences. These findings demonstrate that rainbow trout have several blood proteins with lectin properties for the LPS of A. salmonicida; the biological functions of these proteins in resistance to furunculosis are still unknown.

Environmental Assessment for the Beddown and Flight Operations of Unmanned Aircraft Systems at Cape Canaveral Air Force Station, Florida

DTIC Science & Technology

2011-07-01

Banana River to the west. PURPOSE AND NEED: The purpose of this action is to . establish a U.S. CBP A&M Southeastern Region Operations Center that...barrier island bordered by the Atlantic Ocean to the east and the Banana River to the west. CCAFS is home to the 45th Space Wing (45 SW) Mission...Hangar C Cape Canaveral AFS Skid Strip Figure 3-2. Cape Canaveral AFS Land Use July 20113-5Final EA Atlantic Ocean Banana River Legend CCAFS

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

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1

PubMed Central

Davies, Christopher J.; Regouski, Misha; Hall, Justin; Olsen, Aaron L.; Meng, Qinggang; Rutigliano, Heloisa M.; Dosdall, Derek J.; Angel, Nathan A.; Sachse, Frank B.; Seidel, Thomas; Thomas, Aaron J.; Stott, Rusty; Panter, Kip E.; Lee, Pamela M.; Van Wettere, Arnaud J.; Stevens, John R.; Wang, Zhongde; MacLeod, Rob S.; Marrouche, Nassir F.; White, Kenneth L.

2016-01-01

Introduction Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Methods and Results Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12-month of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas, none of 6 controls displayed sustained AF (P<0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687±212.02 vs. 2.50±0.88 seconds, P<0.0001), but no persistent or permanent AF was observed. Conclusion A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. PMID:27447370

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1.

PubMed

Polejaeva, Irina A; Ranjan, Ravi; Davies, Christopher J; Regouski, Misha; Hall, Justin; Olsen, Aaron L; Meng, Qinggang; Rutigliano, Heloisa M; Dosdall, Derek J; Angel, Nathan A; Sachse, Frank B; Seidel, Thomas; Thomas, Aaron J; Stott, Rusty; Panter, Kip E; Lee, Pamela M; Van Wettere, Arnaud J; Stevens, John R; Wang, Zhongde; MacLeod, Rob S; Marrouche, Nassir F; White, Kenneth L

2016-10-01

Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed. A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. © 2016 Wiley Periodicals, Inc.

Installation Restoration Program. Phase 1 - Records Search, Travis AFB, California

DTIC Science & Technology

1983-08-01

Personnel Transportation Assistance Office Navy Construction Office (ROICC) Navy Quick Trans CPE Cargo OL-K AFESC/CEMRT OL OH AF Commissary/ FCS Operating Loc...du u U C AS I- z I- < L z Z ’CIA F,.- **z z - C -o -C Z. -2 X.,~a S.. ’ l - x CO I II I EAI IIV I - -. I t1 -1 z In-’S I LA- 0..u 2gU, 0 z u Fc -jIL...used at the site comprised, AFFF , protein foam and water. The site has no berms or dikes to contain the runoff. Surface runoff from the site has to

Mortality and Atrial Fibrillation in the FIACA Study: Evidence of a Differential Effect According to Admission Diagnosis.

PubMed

Clavel-Ruipérez, Francisco Guillermo; Consuegra-Sánchez, Luciano; Félix Redondo, Francisco Javier; Lozano Mera, Luis; Mellado-Delgado, Pedro; Martínez-Díaz, Juan José; López Mínguez, José Ramón; Fernández-Bergés, Daniel

2018-03-01

Atrial fibrillation (AF) is an independent risk factor for mortality in several diseases. However, data published in acute decompensated heart failure (DHF) are contradictory. Our objective was to investigate the impact of AF on mortality in patients admitted to hospital for DHF compared with those admitted for other reasons. This retrospective cohort study included all patients admitted to hospital within a 10-year period due to DHF, acute myocardial infarction (AMI), or ischemic stroke (IS), with a median follow-up of 6.2 years. We included 6613 patients (74 ± 11 years; 54.6% male); 2177 with AMI, 2208 with DHF, and 2228 with IS. Crude postdischarge mortality was higher in patients with AF hospitalized for AMI (incident rate ratio, 2.48; P < .001) and IS (incident rate ratio, 1.84; P < .001) than in those without AF. No differences were found in patients with DHF (incident rate ratio, 0.90; P = .12). In adjusted models, AF was not an independent predictor of in-hospital mortality by clinical diagnosis. However, AF emerged as an independent predictor of postdischarge mortality in patients with AMI (HR, 1.494; P = .001) and IS (HR, 1.426; P < .001), but not in patients admitted for DHF (HR, 0.964; P = .603). AF was as an independent risk factor for postdischarge mortality in patients admitted to hospital for AMI and IS but not in those admitted for DHF. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Comparison of the 1.5 Mile Run Times at 7,200 Feet and Simulated 850 Feet in a Hyperoxic Room

DTIC Science & Technology

2012-03-01

run test was developed as an easy, inexpensive, and accurate way to estimate VO2 max, in large groups of AF personnel. In 2004 the AF fitness program...The average max VO2 was 48.6 mL.kg.-1min-1. A 30.6 seconds, or 4.2%, significant difference (p<.001) was observed between the two runs. These...6 Figure 2 – Maximal Oxygen Update ( VO2 max) Test

The role of nonconserved residues of Archaeoglobus fulgidus ferritin on its unique structure and biophysical properties.

PubMed

Sana, Barindra; Johnson, Eric; Le Magueres, Pierre; Criswell, Angela; Cascio, Duilio; Lim, Sierin

2013-11-08

Archaeoglobus fulgidus ferritin (AfFtn) is the only tetracosameric ferritin known to form a tetrahedral cage, a structure that remains unique in structural biology. As a result of the tetrahedral (2-3) symmetry, four openings (∼45 Å in diameter) are formed in the cage. This open tetrahedral assembly contradicts the paradigm of a typical ferritin cage: a closed assembly having octahedral (4-3-2) symmetry. To investigate the molecular mechanism affecting this atypical assembly, amino acid residues Lys-150 and Arg-151 were replaced by alanine. The data presented here shed light on the role that these residues play in shaping the unique structural features and biophysical properties of the AfFtn. The x-ray crystal structure of the K150A/R151A mutant, solved at 2.1 Å resolution, indicates that replacement of these key residues flips a "symmetry switch." The engineered molecule no longer assembles with tetrahedral symmetry but forms a typical closed octahedral ferritin cage. Small angle x-ray scattering reveals that the overall shape and size of AfFtn and AfFtn-AA in solution are consistent with those observed in their respective crystal structures. Iron binding and release kinetics of the AfFtn and AfFtn-AA were investigated to assess the contribution of cage openings to the kinetics of iron oxidation, mineralization, or reductive iron release. Identical iron binding kinetics for AfFtn and AfFtn-AA suggest that Fe(2+) ions do not utilize the triangular pores for access to the catalytic site. In contrast, relatively slow reductive iron release was observed for the closed AfFtn-AA, demonstrating involvement of the large pores in the pathway for iron release.

AF presents fiscal year 2017 budget > U.S. Air Force > Article Display

Science.gov Websites

Speeches Archive Former AF Top 3 Viewpoints and Speeches Air Force Warrior Games 2017 Events 2018 Air Force Strategic Documents Desert Storm 25th Anniversary Observances DoD Warrior Games Portraits in Courage

The ortho:para-H_2 ratio in C- and J-type shocks

NASA Astrophysics Data System (ADS)

Wilgenbus, D.; Cabrit, S.; Pineau des Forêts, G.; Flower, D. R.

2000-04-01

We have computed extensive grids of models of both C- and J-type planar shock waves, propagating in dark, cold molecular clouds, in order to study systematically the behaviour of the ortho:para-H_2 ratio. Careful attention was paid to both macroscopic (dynamical) and microscopic (chemical reactions and collisional population transfer in H_2) aspects. We relate the predictions of the models to observational determinations of the ortho:para-H_2 ratio using both pure rotational lines and rovibrational lines. As an illustration, we consider ISO and ground-based H_2 observations of HH 54. Neither planar C-type nor planar J-type shocks appear able to account fully for these observations. Given the additional constraints provided by the observed ortho:para H_2 ratios, a C-type bowshock, or a C-type precursor followed by a J-type shock, remain as plausible models. Tables~2a-f and 4a-f are 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/Abstract.html

Multinational Operations: A Selected Bibliography

DTIC Science & Technology

2007-02-01

Backgrounder: Logistics Support for NATO Operations. Brus - sels: NATO, February 2006. 12pp. http://www.nato.int/docu/logistics/logistics-e.pdf North...racks: U.S. Army War College, Strategic Studies Institute, 2004. 112pp. (U413 .A66P64 2004) http://handle.dtic.mil/100.2/ADA429105 Pond, Elizabeth ...U.S., Britain, Europe, and the War in Iraq. New York: Public Af- fairs, 2004. 261pp. (DS79.76 .S31 2004) Sherwood-Randall, Elizabeth . Alliances and

Test Message Generator and Controller for AFSATCOM Testing.

DTIC Science & Technology

1983-03-01

RW o Sk;I Af IiAA C 1 I SYNDET -JZDf CXT2/ gzl 3M52 140A 2 P7 54 1LPro/ I, RIOa Itw I 4"A 4 RZi o I~~- Co-P a F ’~T14 1W Cf14K A460 hi ,2 L PFa/ tip II...W CZt / -o 0U(zuouC. go P U A00. OC -c )toM f w z)0 C 0 Z0w 0 C)~~~- -- 4 -0- - --- 4 4 En 04I-.4z- N N N-- 0.44- N -44 L A A AA A A A A A A A A AA A A...C3 70 02 ....... 0290=77 AF 23 77 C9 21 AC 04 CD 23 02 I1 00 00 CD E7 .. #..!...# ...... 02AO=02 FE FF CA 95 02 FE OD CA CO 02 47 OE 04 7B 17

Roles of polypyrimidine tract binding proteins in major immediate-early gene expression and viral replication of human cytomegalovirus.

PubMed

Cosme, Ruth S Cruz; Yamamura, Yasuhiro; Tang, Qiyi

2009-04-01

Human cytomegalovirus (HCMV), a member of the beta subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns.

Roles of Polypyrimidine Tract Binding Proteins in Major Immediate-Early Gene Expression and Viral Replication of Human Cytomegalovirus▿

PubMed Central

Cosme, Ruth S. Cruz; Yamamura, Yasuhiro; Tang, Qiyi

2009-01-01

Human cytomegalovirus (HCMV), a member of the β subgroup of the family Herpesviridae, causes serious health problems worldwide. HCMV gene expression in host cells is a well-defined sequential process: immediate-early (IE) gene expression, early-gene expression, DNA replication, and late-gene expression. The most abundant IE gene, major IE (MIE) gene pre-mRNA, needs to be spliced before being exported to the cytoplasm for translation. In this study, the regulation of MIE gene splicing was investigated; in so doing, we found that polypyrimidine tract binding proteins (PTBs) strongly repressed MIE gene production in cotransfection assays. In addition, we discovered that the repressive effects of PTB could be rescued by splicing factor U2AF. Taken together, the results suggest that PTBs inhibit MIE gene splicing by competing with U2AF65 for binding to the polypyrimidine tract in pre-mRNA. In intron deletion mutation assays and RNA detection experiments (reverse transcription [RT]-PCR and real-time RT-PCR), we further observed that PTBs target all the introns of the MIE gene, especially intron 2, and affect gene splicing, which was reflected in the variation in the ratio of pre-mRNA to mRNA. Using transfection assays, we demonstrated that PTB knockdown cells induce a higher degree of MIE gene splicing/expression. Consistently, HCMV can produce more viral proteins and viral particles in PTB knockdown cells after infection. We conclude that PTB inhibits HCMV replication by interfering with MIE gene splicing through competition with U2AF for binding to the polypyrimidine tract in MIE gene introns. PMID:19144709

Low-cost humic acid-bonded silica as an effective solid-phase extraction sorbent for convenient determination of aflatoxins in edible oils.

PubMed

Zhou, Neng-Zhi; Liu, Ping; Su, Xiao-Chuan; Liao, Yan-Hua; Lei, Ning-Sheng; Liang, Yong-Hong; Zhou, Shao-Huan; Lin, Wen-Si; Chen, Jie; Feng, Yu-Qi; Tang, Yang

2017-06-01

Aflatoxins (AFs) are highly toxic, mutagenic, carcinogenic, and teratogenic secondary metabolites produced by the toxigenic fungi Aspergillus flavus and Aspergillus parasiticus. AFs tend to contaminate a wide range of foods which is a serious and recurring food safety problem worldwide. Currently, immunoaffinity chromatography (IAC) has become the most conventional sample clean-up method for determining AFs in foodstuffs. However, IAC method is limited in the large-scale food analysis because it requires the use of expensive disposable cartridges and the IA procedure is time-consuming. Herein, to achieve the cost-effective determination of AFs in edible oils, we developed a promising solid-phase extraction (SPE) method based on commercially available humic acid-bonded silica (HAS) sorbent, followed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) analysis. In HAS-SPE, AFs can be captured by the HAS sorbent with both hydrophobic and hydrophilic interactions, whereas the oil matrix was captured only with the hydrophobic interactions. The oil matrix can be sufficiently washed off with isopropanol, while the AFs were still retained on the SPE packing, thus achieving selective extraction of AFs and clean-up of oil matrices. Under the optimal conditions of HAS-SPE, satisfactory recoveries ranging from 82% to 106% for four AFs (B 1 , B 2 , G 1 , and G 2 ) were achieved in various oil matrices, containing blended oil, tea oil, rapeseed oil, peanut oil, sunflower seed oil, corn oil, blended olive oil, rice oil, soybean oil, and sesame oil. Only minor matrix effects ranging from 99% to 105% for four AFs were observed. Moreover, the LODs of AFs between 0.012 and 0.035 μg/kg completely meet the regulatory levels fixed by the EU, China or other countries. The methodology was further validated for assaying the naturally contaminated peanut oils, and consistent results between the HAS-SPE and the referenced IAC were obtained. In addition, HAS-SPE can directly treat diluted oil sample without liquid-liquid extraction and is automatable, thus making it simple and convenient for the large-scale determination of AFs in edible oils. Using this method, we successfully detected four AFs in the naturally contaminated peanut oils, which is, to the best of our knowledge, the first report about the determination of AFs in edible oils using HA-based SPE. Copyright © 2017 Elsevier B.V. All rights reserved.

Grissom AFB, Indiana. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1983-07-01

8.8i 15.51 1b.3 27.1 7%39 USAFETAC 0 TOS N. OL. ), O~ Poyaw 0mo IMS rOR Omm V~ Jm- - - - - -- - - -- - - - - - - U A 2AL CLIMATOLOY B’ANCH 2 Z .Ac...2Z812.o3410.911 S. 945 ,.137 6.561 6.607 8.977 9.95612.15813.1I5 19.923 6~ 3 .46 927. 920 --U 9 R. Z 9Z5. 3 U. 9CC 93 Q 900 927. 1 C9 4. 13. 11.7 3j

Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML.

PubMed

Hirabayashi, Shinsuke; Flotho, Christian; Moetter, Jessica; Heuser, Michael; Hasle, Henrik; Gruhn, Bernd; Klingebiel, Thomas; Thol, Felicitas; Schlegelberger, Brigitte; Baumann, Irith; Strahm, Brigitte; Stary, Jan; Locatelli, Franco; Zecca, Marco; Bergstraesser, Eva; Dworzak, Michael; van den Heuvel-Eibrink, Marry M; De Moerloose, Barbara; Ogawa, Seishi; Niemeyer, Charlotte M; Wlodarski, Marcin W

2012-03-15

Somatic mutations of the spliceosomal machinery occur frequently in adult patients with myelodysplastic syndrome (MDS). We resequenced SF3B1, U2AF35, and SRSF2 in 371 children with MDS or juvenile myelomonocytic leukemia. We found missense mutations in 2 juvenile myelomonocytic leukemia cases and in 1 child with systemic mastocytosis with MDS. In 1 juvenile myelomonocytic leukemia patient, the SRSF2 mutation that initially coexisted with an oncogenic NRAS mutation was absent at relapse, whereas the NRAS mutation persisted and a second, concomitant NRAS mutation later emerged. The patient with systemic mastocytosis and MDS carried both mutated U2AF35 and KIT in a single clone as confirmed by clonal sequencing. In the adult MDS patients sequenced for control purposes, we detected previously reported mutations in 7/30 and a novel SRSF2 deletion (c.284_307del) in 3 of 30 patients. These findings implicate that spliceosome mutations are rare in pediatric MDS and juvenile myelomonocytic leukemia and are unlikely to operate as driver mutations.

Test-retest reproducibility of accommodative facility measures in primary school children.

PubMed

Adler, Paul; Scally, Andrew J; Barrett, Brendan T

2018-05-08

To determine the test-retest reproducibility of accommodative facility (AF) measures in an unselected sample of UK primary school children. Using ±2.00 DS flippers and a viewing distance of 40 cm, AF was measured in 136 children (range 4-12 years, average 8.1 ± 2.1) by five testers on three occasions (average interval between successive tests: eight days, range 1-21 days). On each occasion, AF was measured monocularly and binocularly, for two minutes. Full datasets were obtained in 111 children (81.6 per cent). Intra-individual variation in AF was large (standard deviation [SD] = 3.8 cycles per minute [cpm]) and there was variation due to the identity of the tester (SD = 1.6 cpm). On average, AF was greater: (i) in monocular compared to binocular testing (by 1.4 cpm, p < 0.001); (ii) in the second minute of testing compared to the first (by 1.3 cpm, p < 0.001); (iii) in older compared to younger children (for example, AF for 4/5-year-olds was 3.3 cpm lower than in children ≥ 10 years old, p = 0.009); and (iv) on subsequent testing occasions (for example, visit-2 AF was 2.0 cpm higher than visit-1 AF, p < 0.001). After the first minute of testing at visit-1, only 36.9 per cent of children exceeded published normative values for AF (≥ 11 cpm monocularly and ≥ 8 cpm binocularly), but this rose to 83.8 per cent after the third test. Using less stringent pass criteria (≥ 6 cpm monocularly and ≥ 3 cpm binocularly), the equivalent figures were 82.9 and 96.4 per cent, respectively. Reduced AF did not co-exist with abnormal near point of accommodation or reduced visual acuity. The results reveal considerable intra-individual variability in raw AF measures in children. When the results are considered as pass/fail, children who initially exhibit normal AF continued to do so on repeat testing. Conversely, the vast majority of children with initially reduced AF exhibit normal performance on repeat testing. Using established pass/fail criteria, the prevalence of persistently reduced AF in this sample is 3.6 per cent. © 2018 Optometry Australia.

Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin-labeled liposomes.

PubMed

Hara, T; Aramaki, Y; Takada, S; Koike, K; Tsuchiya, S

1995-12-01

Asialofetuin-labeled liposomes (AF-liposomes) were developed as a nonviral vector having high transfection activity for receptor-mediated gene transfer to hepatocytes by systemic administration. Initially, the majority of pSV2CAT, a chloramphenicol acetyltransferase (CAT) gene expression plasmid, was associated with AF-liposomes (AF-liposome-pSV2CAT), and they were injected into the portal vein of an adult mouse. Significantly high CAT activity was observed in the liver. The CAT activity in the liver was further increased two-fold by using AF-liposomes completely encapsulating pSV2CAT. Nonlabeled control liposomes, on the other hand, showed lower CAT activity in the liver than in the spleen or lung. The level of CAT mRNA reflected the CAT activity obtained by each liposome preparation in each tissue. Immunohistochemical staining showed that CAT was produced in a large number of parenchymal cells localizing in the periportal area. The plasmid encapsulated in the internal aqueous layer of the liposomes was effectively protected from environmental degradation. Thus, by administration into the blood circulation, AF-liposomes would be successfully incorporated into hepatocytes through receptor-mediated endocytosis, and the encapsulated plasmid would be transferred to the intracellular pathway.

Novel pharmacological targets for the rhythm control management of atrial fibrillation.

PubMed

Burashnikov, Alexander; Antzelevitch, Charles

2011-12-01

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Development of safe and effective pharmacological treatments for AF is one of the greatest unmet medical needs facing our society. In spite of significant progress in non-pharmacological AF treatments (largely due to the use of catheter ablation techniques), anti-arrhythmic agents (AADs) remain first line therapy for rhythm control management of AF for most AF patients. When considering efficacy, safety and tolerability, currently available AADs for rhythm control of AF are less than optimal. Ion channel inhibition remains the principal strategy for termination of AF and prevention of its recurrence. Practical clinical experience indicates that multi-ion channel blockers are generally more optimal for rhythm control of AF compared to ion channel-selective blockers. Recent studies suggest that atrial-selective sodium channel block can lead to safe and effective suppression of AF and that concurrent inhibition of potassium ion channels may potentiate this effect. An important limitation of the ion channel block approach for AF treatment is that non-electrical factors (largely structural remodeling) may importantly determine the generation of AF, so that "upstream therapy", aimed at preventing or reversing structural remodeling, may be required for effective rhythm control management. This review focuses on novel pharmacological targets for the rhythm control management of AF. Copyright © 2011 Elsevier Inc. All rights reserved.

Delimitation of Umbelopsis (Mucorales, Umbelopsidaceae fam. nov.) based on ITS sequence and RFLP data.

PubMed

Meyer, Wieland; Gams, Walter

2003-03-01

In a continuation of studies started by de Ruiter et al. (1993), all known species of the Mortierella isabellina-group (Micromucor/Umbelopsis clade of O'Donnell et al. 2001) and a few other Mucorales and species of Mortierella were investigated by RFLP (including ITS1, 5.8S, ITS2 and the 5' end of the large subunit rDNA gene) and ITS1 sequence analyses. This monophyletic group is unrelated to Mortierella and is only distantly related to the core group of the Mucoraceae. M. longicollis falls outside the Umbelopsis clade. Molecular data resolved two subclades within the M. isabellina-group; however, they are not correlated with any differences in sporangial wall and shape, spore pigmentation and shape, or sporangiophore branching. Therefore we subsume all taxa in one genus, Umbelopsis. The new family Umbelopsidaceae and the new combinations U. isabellina, U. ramanniana, and U. autotrophica are proposed.

Two Routes to Genetic Suppression of RNA Trimethylguanosine Cap Deficiency via C-Terminal Truncation of U1 snRNP Subunit Snp1 or Overexpression of RNA Polymerase Subunit Rpo26.

PubMed

Qiu, Zhicheng R; Schwer, Beate; Shuman, Stewart

2015-04-24

The trimethylguanosine (TMG) caps of small nuclear (sn) RNAs are synthesized by the enzyme Tgs1 via sequential methyl additions to the N2 atom of the m(7)G cap. Whereas TMG caps are inessential for Saccharomyces cerevisiae vegetative growth at 25° to 37°, tgs1∆ cells that lack TMG caps fail to thrive at 18°. The cold-sensitive defect correlates with ectopic stoichiometric association of nuclear cap-binding complex (CBC) with the residual m(7)G cap of the U1 snRNA and is suppressed fully by Cbc2 mutations that weaken cap binding. Here, we show that normal growth of tgs1∆ cells at 18° is also restored by a C-terminal deletion of 77 amino acids from the Snp1 subunit of yeast U1 snRNP. These results underscore the U1 snRNP as a focal point for TMG cap function in vivo. Casting a broader net, we conducted a dosage suppressor screen for genes that allowed survival of tgs1∆ cells at 18°. We thereby recovered RPO26 (encoding a shared subunit of all three nuclear RNA polymerases) and RPO31 (encoding the largest subunit of RNA polymerase III) as moderate and weak suppressors of tgs1∆ cold sensitivity, respectively. A structure-guided mutagenesis of Rpo26, using rpo26∆ complementation and tgs1∆ suppression as activity readouts, defined Rpo26-(78-155) as a minimized functional domain. Alanine scanning identified Glu89, Glu124, Arg135, and Arg136 as essential for rpo26∆ complementation. The E124A and R135A alleles retained tgs1∆ suppressor activity, thereby establishing a separation-of-function. These results illuminate the structure activity profile of an essential RNA polymerase component. Copyright © 2015 Qiu et al.

Cathode Life Test Facility Users Manual Operating and Measurement Procedures

DTIC Science & Technology

1990-12-01

towerag I how pm rsa q rkig d tknu riwwww ruv tr m suwori"m~g i ao soJas . gl - il w - rv &a g U iu -u w- -, wvj rrnwriig eificokb d irlawriow Send vrwf...OflA AfU) A .- flflf lA A AA A-s൴ m .544455554l...45455444444 54 c. " C44.5ൾ -45( 2 114.14...................4.4. . . . A .44 AA.4 A4A14 14.44.A4.A4A

The Functional Role of eL19 and eB12 Intersubunit Bridge in the Eukaryotic Ribosome.

PubMed

Kisly, Ivan; Gulay, Suna P; Mäeorg, Uno; Dinman, Jonathan D; Remme, Jaanus; Tamm, Tiina

2016-05-22

During translation, the two eukaryotic ribosomal subunits remain associated through 17 intersubunit bridges, five of which are eukaryote specific. These are mainly localized to the peripheral regions and are believed to stabilize the structure of the ribosome. The functional importance of these bridges remains largely unknown. Here, the essentiality of the eukaryote-specific bridge eB12 has been investigated. The main component of this bridge is ribosomal protein eL19 that is composed of an N-terminal globular domain, a middle region, and a long C-terminal α-helix. The analysis of deletion mutants demonstrated that the globular domain and middle region of eL19 are essential for cell viability, most likely functioning in ribosome assembly. The eB12 bridge, formed by contacts between the C-terminal α-helix of eL19 and 18S rRNA in concert with additional stabilizing interactions involving either eS7 or uS17, is dispensable for viability. Nevertheless, eL19 mutants impaired in eB12 bridge formation displayed slow growth phenotypes, altered sensitivity/resistance to translational inhibitors, and enhanced hyperosmotic stress tolerance. Biochemical analyses determined that the eB12 bridge contributes to the stability of ribosome subunit interactions in vitro. 60S subunits containing eL19 variants defective in eB12 bridge formation failed to form 80S ribosomes regardless of Mg(2+) concentration. The reassociation of 40S and mutant 60S subunits was markedly improved in the presence of deacetylated tRNA, emphasizing the importance of tRNAs during the subunit association. We propose that the eB12 bridge plays an important role in subunit joining and in optimizing ribosome functionality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial.

PubMed

Adabag, A Selcuk; Mithani, Salima; Al Aloul, Basel; Collins, Dorothea; Bertog, Stefan; Bloomfield, Hanna E

2009-05-01

Peroxisome proliferator-activated receptor alpha (PPARalpha) activators reduce inflammation and oxidative stress. Inflammation plays an important role in the initiation and maintenance of atrial fibrillation (AF). It has been suggested that PPARalpha activators may have antiarrhythmic properties, but no clinical data exist. The objective of this study was to investigate whether the PPARalpha activator gemfibrozil prevents or delays the development of AF in patients with coronary heart disease. We retrospectively analyzed the electrocardiograms (ECGs) performed in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial, a multicenter, randomized, double-blinded, secondary prevention trial of gemfibrozil and matching placebo. The ECGs were performed annually or biannually and when clinically indicated. Participants who were in AF on baseline ECG were excluded from the present analysis. Relative risk for AF was calculated from Cox regression with death as a competing risk factor. A total of 12,605 ECGs from 2,130 participants were interpreted (5.9 +/- 2.1 ECGs per participant, range 2-20). At baseline, the gemfibrozil (n = 1,070) and placebo (n = 1,060) groups were well matched. Mean age was 64.1 +/- 7.1 years. Over 4.4 +/- 1.5 years of follow-up, 123 (5.8%) participants developed new AF. There was no difference in AF incidence between the gemfibrozil and placebo groups (64/1,070 vs 59/1,060, respectively; P = .33). In Cox regression, the risk of AF was similar between the 2 study groups (hazard ratio 1.04, 95% CI 0.73-1.49, P = .82). In this post hoc analysis of a multicenter, double-blinded, randomized controlled trial, the PPARalpha activator gemfibrozil did not reduce the 4-year incidence of AF among men with coronary heart disease.

Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

PubMed

Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

2016-11-08

To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

Improved purification of brine-shrimp (Artemia saline) (Na+ + K+)-activated adenosine triphosphatase and amino-acid and carbohydrate analyses of the isolated subunits.

PubMed Central

Peterson, G L; Hokin, L E

1980-01-01

Purification of the (Na+ + K+)-activated ATPase has been improved 2-fold the respect to both purity and yield over the previous method [Peterson, Ewing, Hootman & Conte (1978) J. Biol. Chem. 253, 4762-4770] by using Lubrol WX and non-denaturing concentrations of sodium dodecyl sulphate (SDS). The enzyme was purified 200-fold over the homogenate. The preparation had a specific activity of about 600 mumol of Pi/h per mg of protein, and was about 60% pure according to quantification of Coomassie Blue-stained SDS/polyacrylamide gels. The yield of purified enzyme was about 10 mg of protein per 100g of dry brine-shrimp (Artemia salina) cysts. The method is highly suitable for purification either on a small scale (10-25g of dry cysts) or on a large scale (900g of dry cysts) and methods are described for both. The large (Na+ + K+)-activated ATPase subunit (alpha-subunit) was isolated in pure form by SDS-gel filtration on Bio-Gel A 1.5m. The small subunit (beta-subunit) was eluted with other contaminating proteins on the Bio-Gel column, but was isolated in pure form by extraction from SDS/polyacrylamide gels. The amino acid and carbohydrate compositions of both subunits are reported. The alpha-subunit contained 5.2% carbohydrate by weight, and the beta-subunit 9.2%. Sialic acid was absent from both subunits. Images Fig. 3. Fig. 4. PMID:6272692

Generation of a constitutive Na+-dependent inward-rectifier current in rat adult atrial myocytes by overexpression of Kir3.4.

PubMed

Mintert, Elisa; Bösche, Leif I; Rinne, Andreas; Timpert, Mathias; Kienitz, Marie-Cécile; Pott, Lutz; Bender, Kirsten

2007-11-15

Apart from gating by interaction with betagamma subunits from heterotrimeric G proteins upon stimulation of appropriate receptors, Kir.3 channels have been shown to be gated by intracellular Na+. However, no information is available on how Na+-dependent gating affects endogenous Kir3.1/Kir3.4 channels in mammalian atrial myocytes. We therefore studied how loading of adult atrial myocytes from rat hearts via the patch pipette filling solution with different concentrations of Na+ ([Na+]pip) affects Kir3 current. Surprisingly, in a range between 0 and 60 mm, Na+ neither had an effect on basal inward-rectifier current nor on the current activated by acetylcholine. Overexpression of Kir3.4 in adult atrial myocytes forced by adenoviral gene transfer results in formation of functional homomeric channels that interact with betagamma subunits upon activation of endogenous muscarinic receptors. These channels are activated at [Na+]pip >or= 15 mm, resulting in a receptor-independent basal inward rectifier current (I bir). I bir was neither affected by pertussis toxin nor by GDP-beta-S, suggesting G-protein-independent activation. PIP(2) depletion via endogenous PLC-coupled alpha1 adrenergic receptors causes inhibition of endogenous Kir3.1/3.4 channel currents by about 75%. In contrast, inhibition of Na+-activated I bir amounts to < 20%. The effect of the Kir3 channel blocker tertiapin-Q can be described using an IC50 of 12 nm (endogenous I K(ACh)) and 0.61 nm (I bir). These data clearly identify I bir as a homotetrameric Kir3.4 channel current with novel properties of regulation and pharmacology. Ibir shares some properties with a basal current recently described in atrial myocytes from an animal model of atrial fibrillation (AF) and AF patients.

Prevalence and predictors of low voltage zones in the left atrium in patients with atrial fibrillation.

PubMed

Huo, Yan; Gaspar, Thomas; Pohl, Matthias; Sitzy, Judith; Richter, Utz; Neudeck, Sebastian; Mayer, Julia; Kronborg, Mads Brix; Piorkowski, Christopher

2017-06-10

To describe the extent and distribution of low voltage zones (LVZ) in a large cohort of patients undergoing ablation for paroxysmal and persistent atrial fibrillation (AF), and to explore baseline predictors of LVZ in these patients. Consecutive patients who underwent a bipolar voltage map guided AF ablation, were enrolled. Voltage maps were conducted for each patient using 3-dimensional electroanatomical mapping system and LVZ were defined as areas of bipolar voltage < 0.5 mV. A total of 539 patients (309 male, age 65 ± 10 years) were included. Low voltage zones was present in 58 out of 292 patients with paroxysmal and 134 out of 247 persistent AF (P < 0.001). The area of LVZ was larger in patients with persistent as compare to paroxysmal AF, 5 cm2 (IQR 3-18.6) vs. 12.1 cm2 (IQR 3.6-28.5), P = 0.026, respectively. In the multivariate analysis age (OR 1.07, 95%CI 1.05-1.10, P < 0.001), female gender (OR 2.18, 95%CI 1.38-3.43, P = 0.001), sinoatrial node dysfunction (OR 3.90, 95%CI 1.24-12.21, P = 0.020), larger surface area of left atrium pr. cm2 (OR 1.01, 95%CI 1.00-1.02, P = 0.016), and persistent AF (OR 5.03, 95%CI 3.20-7.90, P<0.001) were associated with presence of LVZ. In a large cohort of patients undergoing ablation for AF, the prevalence of LVZ was higher and LVZ areas larger in patients with persistent as compared with paroxysmal AF. The most frequent localization of LVZ was anterior wall, septum and posterior wall. Presence of LVZ was associated with higher age, female gender, larger LA surface area, and sinoatrial node dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Regular Inversion of the Divergence Operator with Dirichlet Boundary Conditions on a Polygon,

DTIC Science & Technology

1987-04-01

E c- xC 0 Czt C- -- &C -nC CL C~ E C - U U C U C0 V C ( C CC C L 6- - C C- 1 -CLL r = .c L C A C *C CCC F 4 C CC> C C 4D C3 1 ZC -’ c OC.LL fUC I...Iil Moreover by Lemmna 2.1, there is a single cons aiit C such that IIIIIPpV Chi 1 /, p e < CII, 1 2/P p. holds for all such 9. Thus / . af l( I-,0)1

Neighborhood of 16S rRNA nucleotides U788/U789 in the 30S ribosomal subunit determined by site-directed crosslinking.

PubMed

Mundus, D; Wollenzien, P

1998-11-01

Site-specific photo crosslinking has been used to investigate the RNA neighborhood of 16S rRNA positions U788/ U789 in Escherichia coli 30S subunits. For these studies, site-specific psoralen (SSP) which contains a sulfhydryl group on a 17 A side chain was first added to nucleotides U788/U789 using a complementary guide DNA by annealing and phototransfer. Modified RNA was purified from the DNA and unmodified RNA. For some experiments, the SSP, which normally crosslinks at an 8 A distance, was derivitized with azidophenacylbromide (APAB) resulting in the photoreactive azido moiety at a maximum of 25 A from the 4' position on psoralen (SSP25APA). 16S rRNA containing SSP, SSP25APA or control 16S rRNA were reconstituted and 30S particles were isolated. The reconstituted subunits containing SSP or SSP25APA had normal protein composition, were active in tRNA binding and had the usual pattern of chemical reactivity except for increased kethoxal reactivity at G791 and modest changes in four other regions. Irradiation of the derivatized 30S subunits in activation buffer produced several intramolecular RNA crosslinks that were visualized and separated by gel electrophoresis and characterized by primer extension. Four major crosslink sites made by the SSP reagent were identified at positions U561/U562, U920/U921, C866 and U723; a fifth major crosslink at G693 was identified when the SSP25APA reagent was used. A number of additional crosslinks of lower frequency were seen, particularly with the APA reagent. These data indicate a central location close to the decoding region and central pseudoknot for nucleotides U788/U789 in the activated 30S subunit.

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

PubMed Central

Torres, Yolima P.; Granados, Sara T.; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above. PMID:25346693

Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.

PubMed

Torres, Yolima P; Granados, Sara T; Latorre, Ramón

2014-01-01

Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca(2+) concentration, the large conductance voltage- and Ca(2+)-activated K(+) channel (BK) is unique among the superfamily of K(+) channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K(+) channels) and a large C terminus composed of two regulators of K(+) conductance domains (RCK domains), where the Ca(2+)-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca(2+) sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.

144th Fighter Wing

Science.gov Websites

, the wing provides agile combat support, and intelligence, surveillance and reconnaissance to combatant the U.S. Air Force AF Week in Photos Senior leaders meet with industry to discuss utilizing artificial intelligence and quantum science throughout the Air Force AF announces 2018 Blacks in Government Meritorious

78 FR 53809 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... (Rule 1009A(f)), U.S. Dollar-Settled Foreign Currency option contracts (Rule 1057) and PHLX FOREX option... 1037, 1042(c) and (h), 1057, 1006A, 1009A(f), 1042A(b), 1101A(c), Rule 1101A, Commentary .01, 1006C(a...

Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis.

PubMed

Baykaner, Tina; Rogers, Albert J; Meckler, Gabriela L; Zaman, Junaid; Navara, Rachita; Rodrigo, Miguel; Alhusseini, Mahmood; Kowalewski, Christopher A B; Viswanathan, Mohan N; Narayan, Sanjiv M; Clopton, Paul; Wang, Paul J; Heidenreich, Paul A

2018-05-01

The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure. Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I 2 statistic. Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%-81.8%; P <0.01) and from all arrhythmias of 57.8% (CI, 47.5%-67.7%; P <0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3-7.7; P =0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2-2.7; P <0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%-50.9%) and predicted favorable outcome from ablation( P <0.05). In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI. © 2018 American Heart Association, Inc.

A protein with an inactive pterin-4a-carbinolamine dehydratase domain is required for Rubisco biogenesis in plants.

PubMed

Feiz, Leila; Williams-Carrier, Rosalind; Belcher, Susan; Montano, Monica; Barkan, Alice; Stern, David B

2014-12-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a critical role in sustaining life by catalysis of carbon fixation in the Calvin-Benson pathway. Incomplete knowledge of the assembly pathway of chloroplast Rubisco has hampered efforts to fully delineate the enzyme's properties, or seek improved catalytic characteristics via directed evolution. Here we report that a Mu transposon insertion in the Zea mays (maize) gene encoding a chloroplast dimerization co-factor of hepatocyte nuclear factor 1 (DCoH)/pterin-4α-carbinolamine dehydratases (PCD)-like protein is the causative mutation in a seedling-lethal, Rubisco-deficient mutant named Rubisco accumulation factor 2 (raf2-1). In raf2 mutants newly synthesized Rubisco large subunit accumulates in a high-molecular weight complex, the formation of which requires a specific chaperonin 60-kDa isoform. Analogous observations had been made previously with maize mutants lacking the Rubisco biogenesis proteins RAF1 and BSD2. Chemical cross-linking of maize leaves followed by immunoprecipitation with antibodies to RAF2, RAF1 or BSD2 demonstrated co-immunoprecipitation of each with Rubisco small subunit, and to a lesser extent, co-immunoprecipitation with Rubisco large subunit. We propose that RAF2, RAF1 and BSD2 form transient complexes with the Rubisco small subunit, which in turn assembles with the large subunit as it is released from chaperonins. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

REMBASS Commandability. Trade Off Analysis (TOA)/Trade Off Determination (TOD)

DTIC Science & Technology

1977-12-15

3 " 1 0 r-4 V) C-H ) 4-4 4-) 9 4 4- q)$- G C C) P U4J~4 0 4)rz Q1 ’ :;l CZt 4- -4 > E Cd P4r 4 .+ 0. 0 co a) u~f V) UA0 G + ZU) <D +J U) ’-I 4 4-4...i I- . .I I .... . ..... . . .... ... .. . . .. . .... ; = = r ; - *~rj ~*r r P55 - U i- :t4 1 SA" I I-I * I,. " aF " -- UP*5 6...to LC)LO n O L L LnLf LOCL0 3 .L) C’- LuJE4 V)I )L nLIV)tX:X af -VC / "*.-n = CO ccccccca oC . O C,-oCor-.oC CCaOC) tCM W 4WMwC o nU) MWO 4- 4. 4-) 0.-U

Crystal structure of heterotetrameric sarcosine oxidase from Corynebacterium sp. U-96

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

Ida, Koh; E-mail: idakoh@sci.kitasato-u.ac.jp; Moriguchi, Tomotaka

2005-07-29

Sarcosine oxidase from Corynebacterium sp. U-96 is a heterotetrameric enzyme. Here we report the crystal structures of the enzyme in complex with dimethylglycine and folinic acid. The {alpha} subunit is composed of two domains, contains NAD{sup +}, and binds folinic acid. The {beta} subunit contains dimethylglycine, FAD, and FMN, and these flavins are approximately 10 A apart. The {gamma} subunit is in contact with two domains of {alpha} subunit and has possibly a folate-binding structure. The {delta} subunit contains a single atom of zinc and has a Cys{sub 3}His zinc finger structure. Based on the structures determined and on themore » previous works, the structure-function relationship on the heterotetrameric sarcosine oxidase is discussed.« less

Large conductance Ca(2+)-activated K(+) channel (BKCa) activating properties of a series of novel N-arylbenzamides: Channel subunit dependent effects.

PubMed

Kirby, R W; Martelli, A; Calderone, V; McKay, N G; Lawson, K

2013-07-15

Large conductance calcium activated potassium channels (BKCa) are fundamental in the control of cellular excitability. Thus, compounds that activate BKCa channels could provide potential therapies in the treatment of pathologies of the cardiovascular and central nervous system. A series of novel N-arylbenzamide compounds, and the reference compound NS1619, were evaluated for BKCa channel opener properties in Human Embryonic Kidney (HEK293) cells expressing the human BKCa channel α-subunit alone or α+β1-subunit complex. Channel activity was determined using a non-radioactive Rb(+) efflux assay to construct concentration effect curves for each compound. All N-arylbenzamide compounds and NS1619 evoked significant (p <0.05) concentration related increases in Rb(+) efflux both in cells expressing α-subunit alone or α+β1-subunits. Co-expression of the β1-subunit modified the Rb(+) efflux responses, relative to that obtained in cells expressing the α-subunit alone, for most of the N-arylbenzamide compounds, in contrast to NS1619. The EC40 values of NS1619, BKMe1 and BKOEt1 were not significantly affected by the co-expression of the BKCa channel α+β1-subunits. In contrast, 5 other N-arylbenzamides (BKPr2, BKPr3, BKPr4, BKH1 and BKVV) showed a significant (p <0.05) 2- to 10-fold increase in EC40 values when tested on the BKCa α+β1-subunit expressing cells compared to BKCa α-subunit expressing cells. Further, the Emax values for BKPr4, BKVV and BKH1 were lower in the BKCa channel α+β1-subunit expressing cells. In conclusion, the N-arylbenzamides studied, like NS1619, were able to activate BKCa channels formed of the α-subunit only. The co-expression of the β1-subunit, however, modified the ability of certain compounds to active the channel leading to differentiated pharmacodynamic profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors.

PubMed

Has, Ahmad Tarmizi Che; Chebib, Mary

2018-05-15

GABAA receptors (GABAARs) are members of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which includes nicotinic acetylcholine, glycine, and serotonin (5HT3) receptors [1,2,3,4]. LGICs typically mediate fast synaptic transmission via the movement of ions through channels gated by neurotransmitters, such as acetylcholine for nicotinic receptors and GABA for GABAARs [5]. The term Cys-loop receptors originates from the presence of a conserved disulphide bond (or bridge) which holds together two cysteine amino acids of the loop that forms from the structure of polypeptides in the extracellular domain of the receptor's subunit [6]. GABAARs are pentameric transmembrane protein complexes consisting of five subunits from a variety of polypeptide subunits [7,8]. All of these subunits are pseudo-symmetrically organized in the plane of the membrane, with a Cl--selective channel in the middle of the complex. To date, nineteen GABAAR subunits have been identified and categorized into eight classes, α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3, but their variety is further broadened by the existence of several splice forms for certain subunits (e.g., α6, β2 and γ2) [9,10,11,12]. The subunits within each class have an amino acid sequence homology of 70% or more, whereas those with a sequence homology of 30% or less are grouped into different classes [13,14]. A subunit consists of four transmembrane domains (TM1-TM4), each forming an α-helix; a large extracellular N-terminal domain that incorporates part of the orthosteric agonist/antagonist binding site; a large intracellular loop between the TM3 and TM4; a small intracellular loop between TM1 and TM2; a small extracellular loop between TM2 and TM3; and a C-terminal extracellular domain [15,16]. Each subunit is arranged in such a way as to create principal and complementary interfaces with the other subunits, and in a position such that the TM2 of each subunit forms the wall of the channel pore [17,18,19]. The major subunit combination found in the brain comprises α1, β2 and γ2 subunits with the stoichiometry 2α1:2β2:1γ2 [18,20]. For the GABAA α1β2γ2 receptors, the subunits form a specific arrangement in which α1 and β2 subunits alternate with each other and are connected by a γ2 subunit (Figure A) [16,20,21]. For minor subtypes, different α and β subunits have been detected to co-exist as proven by the existence of GABAARs containing α1α2, α1α3, α1α5, α2α3, α3α5, α4α1, α4α2 and α4α3 in the central nervous system [22,23]. Meanwhile, the same pattern has been detected with β and γ subunits, at least the co-occurrence of β in the same GABAAR as well as γ2 with γ3, indicating that these subunits have the capacity to co-exist with each other [24,25,26]. Since different subunits can actually occur in one receptor, GABAARs are considered to exist in a multi-subunit arrangement, leading to ambiguity in the determination of a receptor's stoichiometry. In this review, we first briefly discuss the different subunit arrangements of α1 and β3 subunits in the binary α1β3 receptors. Then we review the GABAA ε-containing receptors predominantly in terms of the ability of ε subunit to present in different position in the ternary α1β3ε receptors, which introduce distinct populations of receptor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

u d b \\xAF b \\xAF tetraquark resonances with lattice QCD potentials and the Born-Oppenheimer approximation

NASA Astrophysics Data System (ADS)

Bicudo, Pedro; Cardoso, Marco; Peters, Antje; Pflaumer, Martin; Wagner, Marc

2017-09-01

We study tetraquark resonances with lattice QCD potentials computed for a static b ¯b ¯ pair in the presence of two lighter quarks u d , the Born-Oppenheimer approximation and the emergent wave method. As a proof of concept we focus on the system with isospin I =0 , but consider different relative angular momenta l of the heavy quarks b ¯b ¯. For l =0 a bound state has already been predicted with quantum numbers I (JP)=0 (1+). Exploring various angular momenta we now compute the phase shifts and search for S and T matrix poles in the second Riemann sheet. We predict a tetraquark resonance for l =1 , decaying into two B mesons, with quantum numbers I (JP)=0 (1-) , mass m =10 57 6-4+4 MeV and decay width Γ =11 2-103+90 MeV .

Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex

PubMed Central

Lyumkis, Dmitry; Oliveira dos Passos, Dario; Tahara, Erich B.; Webb, Kristofor; Bennett, Eric J.; Vinterbo, Staal; Potter, Clinton S.; Carragher, Bridget; Joazeiro, Claudio A. P.

2014-01-01

All organisms have evolved mechanisms to manage the stalling of ribosomes upon translation of aberrant mRNA. In eukaryotes, the large ribosomal subunit-associated quality control complex (RQC), composed of the listerin/Ltn1 E3 ubiquitin ligase and cofactors, mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. How RQC recognizes stalled ribosomes and performs its functions has not been understood. Using single-particle cryoelectron microscopy, we have determined the structure of the RQC complex bound to stalled 60S ribosomal subunits. The structure establishes how Ltn1 associates with the large ribosomal subunit and properly positions its E3-catalytic RING domain to mediate nascent chain ubiquitylation. The structure also reveals that a distinguishing feature of stalled 60S particles is an exposed, nascent chain-conjugated tRNA, and that the Tae2 subunit of RQC, which facilitates Ltn1 binding, is responsible for selective recognition of stalled 60S subunits. RQC components are engaged in interactions across a large span of the 60S subunit surface, connecting the tRNA in the peptidyl transferase center to the distally located nascent chain tunnel exit. This work provides insights into a mechanism linking translation and protein degradation that targets defective proteins immediately after synthesis, while ignoring nascent chains in normally translating ribosomes. PMID:25349383

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

PubMed

Bernstein, Richard A; Kamel, Hooman; Granger, Christopher B; Kowal, Robert C; Ziegler, Paul D; Schwamm, Lee H

2017-08-01

Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Amniotic fluid digestive enzyme analysis is useful for identifying CFTR gene mutations of unclear significance.

PubMed

Oca, Florine; Dreux, Sophie; Gérard, Bénédicte; Simon-Bouy, Brigitte; de Becdelièvre, Alix; Ferec, Claude; Girodon, Emmanuelle; Muller, Françoise

2009-12-01

The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations. The AF-DE pattern (gamma-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied. Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases. AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.

First Term Enlisted Attrition. Volume 2. Summary

DTIC Science & Technology

1977-08-01

Washington, DC 20370 Or. Joseph H. Kanner U.S. Army Training a Doctrine Command Dr. Robert F. Lockman Fort Monroe, VA 23651 Center for Naval Analyses...Personnel Research and Washington, DC 20590 Development Center San Diego, CA 92152Mr. James M. Wilbourn AF Human Resources Laboratory (PEM) Lackland

Moron AB, Moron, Spain. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1972-05-12

I _ o 6 > 5 -, A 3 2, 2 - , >1_ S >5 >5 16 > S2000 * ~>. 1000 7i - ’doO ’tl~l 1,+*U 3,*’’ lj i. bI8 1 .- AT-hJ---..?4 4 , 4.-&) * ;A 1o00 _) 74...4 o3 .0 .0 _ 603 603 970 1171 4:/ 47 ,6 3@2 1o1 1, ,2 90 472 472 e05 1090 46/ 45 .6 2,9 a# 94 .0 412 412 635 937 44/ 431 *6 1.7,6 ,& It3t 20 4 -28U

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

PubMed

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Test of a Supersonic Axial Compressor Stage Incorporating Splitter Vanes in the Rotor

DTIC Science & Technology

1975-06-01

fi~,l n~~.0.t *o f- -t -03 ............ 1, C(4’ . . . . . . . . ~.e .. rN.. n..s m ee, "N .NS af @.,V(p . . . .. . . A42 g -.*o flea a’ ip *. ’a...4oP= #4u’Ol4Dj. I- ft000. #W~*g~De.ftsýtl9.".1 Is no Io *1 Otis 0.ee gee.. 0000 0.. . .. 00 00 OA La ’a. af ~.4i teeA @rJ~t a4 f" *.ge g e~ee. no Iŕ...aV .4f1M f .jlu~M p ttpt t Ij I`G 4-" Lccfpf t** *S* ** **dm4( -W* A 4.162CPCC=2DOC440CCM in ~~~6- OlL tftl " J"If" ’t~f.0a4ft= OW -.. ot- af t0m.*.J

Base Structure Annex to Manpower Requirements Report for FY 1980

DTIC Science & Technology

1979-01-01

Printing and Reproduction Installation Safety Installation Engineering Service Related Investment"* Support Groups/Units assigned to these functions...c 04 o1 fn n a K~~~2 W U4u~ S -Ct ’- .dc w u .S . . . ...... - . ..l .. .AF) . ... .. . z -, IVf ’ N 1 j C0 ---- -K dl fl~ t. I . .Wz x A jt vd idz "oz...actions must beanalyzed to determine if any of the activities associated with the action will cause a significuant impact on the human environ-ment or

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

Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

PubMed Central

Choi, Eue-Keun; Chang, Po-Cheng; Lee, Young-Soo; Lin, Shien-Fong; Zhu, Wuqiang; Maruyama, Mitsunori; Fishbein, Michael C.; Chen, Zhenhui; der Lohe, Michael Rubart-von; Field, Loren J.; Chen, Peng-Sheng

2013-01-01

Background Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Cai) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1). Methods and Results MHC-TGFcys33ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Cai transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Cai transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca2+-ATPase 2a. Conclusions Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Cai transient, EAD and triggered activity. Inhibition of Ca2+ release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria. PMID:22447020

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

PubMed

Ten Cate, V; Ten Cate, H; Verheugt, F W A

2016-10-01

There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

Integrating Breeding Bird Survey and demographic data to estimate Wood Duck population size in the Atlantic Flyway

USGS Publications Warehouse

Zimmerman, Guthrie S.; Sauer, John; Boomer, G. Scott; Devers, Patrick K.; Garrettson, Pamela R.

2017-01-01

The U.S. Fish and Wildlife Service (USFWS) uses data from the North American Breeding Bird Survey (BBS) to assist in monitoring and management of some migratory birds. However, BBS analyses provide indices of population change rather than estimates of population size, precluding their use in developing abundance-based objectives and limiting applicability to harvest management. Wood Ducks (Aix sponsa) are important harvested birds in the Atlantic Flyway (AF) that are difficult to detect during aerial surveys because they prefer forested habitat. We integrated Wood Duck count data from a ground-plot survey in the northeastern U.S. with AF-wide BBS, banding, parts collection, and harvest data to derive estimates of population size for the AF. Overlapping results between the smaller-scale intensive ground-plot survey and the BBS in the northeastern U.S. provided a means for scaling BBS indices to the breeding population size estimates. We applied these scaling factors to BBS results for portions of the AF lacking intensive surveys. Banding data provided estimates of annual survival and harvest rates; the latter, when combined with parts-collection data, provided estimates of recruitment. We used the harvest data to estimate fall population size. Our estimates of breeding population size and variability from the integrated population model (N̄ = 0.99 million, SD = 0.04) were similar to estimates of breeding population size based solely on data from the AF ground-plot surveys and the BBS (N̄ = 1.01 million, SD = 0.04) from 1998 to 2015. Integrating BBS data with other data provided reliable population size estimates for Wood Ducks at a scale useful for harvest and habitat management in the AF, and allowed us to derive estimates of important demographic parameters (e.g., seasonal survival rates, sex ratio) that were not directly informed by data.

Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation.

PubMed

Magrì, Damiano; Agostoni, Piergiuseppe; Corrà, Ugo; Passino, Claudio; Scrutinio, Domenico; Perrone-Filardi, Pasquale; Correale, Michele; Cattadori, Gaia; Metra, Marco; Girola, Davide; Piepoli, Massimo F; Iorio, AnnaMaria; Emdin, Michele; Raimondo, Rosa; Re, Federica; Cicoira, Mariantonietta; Belardinelli, Romualdo; Guazzi, Marco; Limongelli, Giuseppe; Clemenza, Francesco; Parati, Gianfranco; Frigerio, Maria; Casenghi, Matteo; Scardovi, Angela B; Ferraironi, Alessandro; Di Lenarda, Andrea; Bussotti, Maurizio; Apostolo, Anna; Paolillo, Stefania; La Gioia, Rocco; Gargiulo, Paola; Palermo, Pietro; Minà, Chiara; Farina, Stefania; Battaia, Elisa; Maruotti, Antonello; Pacileo, Giuseppe; Contini, Mauro; Oliva, Fabrizio; Ricci, Roberto; Sinagra, Gianfranco

2015-08-01

Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p = 0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted. © The European Society of Cardiology 2014.

Transfusion Independency and Histological Remission in a Patient with Advanced Primary Myelofibrosis Receiving Iron-Chelation Therapy with Deferasirox.

PubMed

Groepper, Stefanie; Schlue, Jerome; Haferlach, Claudia; Giagounidis, Aristoteles

2016-01-01

Iron overload is a common problem in patients with primary myelofibrosis and anemia due to transfusion dependency. This results in organ damage and toxic effects on hematopoietic cells in the bone marrow. At present, iron chelation therapy is not recommended in patients with myeloproliferative syndromes. We describe a very interesting development in a patient with primary myelofibrosis receiving iron chelation. Transfusion independency and a nearly complete histological remission of the underlying disease occurred within a few weeks of therapy. In addition, a change in molecular genetic findings was observed. Initially a JAK2 and a U2AF1 mutation were detected in the core biopsy. During and after therapy the U2AF1 mutation progressed, whereas the JAK2 mutation could no longer be verified. The improvement in hematopoiesis might results from reduction of oxidative stress on hematopoietic progenitor cells or other unclear deferasirox-mediated effects, whereas the reason for the change in molecular genetic findings is unclear. It appears that deferasirox might have a modulating effect on JAK2-kinase mutations. However, further investigation of selective molecular suppression properties of deferasirox are warranted. © 2016 S. Karger GmbH, Freiburg.

The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

PubMed Central

Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

1996-01-01

The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

Distinct cellular distributions of Kv4 pore-forming and auxiliary subunits in rat dorsal root ganglion neurons.

PubMed

Matsuyoshi, Hiroko; Takimoto, Koichi; Yunoki, Takakazu; Erickson, Vickie L; Tyagi, Pradeep; Hirao, Yoshihiko; Wanaka, Akio; Yoshimura, Naoki

2012-09-17

Dorsal root ganglia contain heterogeneous populations of primary afferent neurons that transmit various sensory stimuli. This functional diversity may be correlated with differential expression of voltage-gated K(+) (Kv) channels. Here, we examine cellular distributions of Kv4 pore-forming and ancillary subunits that are responsible for fast-inactivating A-type K(+) current. Expression pattern of Kv α-subunit, β-subunit and auxiliary subunit was investigated using immunohistochemistry, in situ hybridization and RT-PCR technique. The two pore-forming subunits Kv4.1 and Kv4.3 show distinct cellular distributions: Kv4.3 is predominantly in small-sized C-fiber neurons, whereas Kv4.1 is seen in DRG neurons in various sizes. Furthermore, the two classes of Kv4 channel auxiliary subunits are also distributed in different-sized cells. KChIP3 is the only significantly expressed Ca(2+)-binding cytosolic ancillary subunit in DRGs and present in medium to large-sized neurons. The membrane-spanning auxiliary subunit DPP6 is seen in a large number of DRG neurons in various sizes, whereas DPP10 is restricted in small-sized neurons. Distinct combinations of Kv4 pore-forming and auxiliary subunits may constitute A-type channels in DRG neurons with different physiological roles. Kv4.1 subunit, in combination with KChIP3 and/or DPP6, form A-type K(+) channels in medium to large-sized A-fiber DRG neurons. In contrast, Kv4.3 and DPP10 may contribute to A-type K(+) current in non-peptidergic, C-fiber somatic afferent neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

Fibrin-Genipin Adhesive Hydrogel for Annulus Fibrosus Repair: Performance Evaluation with Large Animal Organ Culture, In Situ Biomechanics, and In Vivo Degradation Tests

PubMed Central

Likhitpanichkul, M.; Dreischarf, M.; Illien-Junger, S.; Walter, B. A.; Nukaga, T.; Long, R. G; Sakai, D.; Hecht, A. C.; Iatridis, J. C.

2015-01-01

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation. PMID:25036053

Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests.

PubMed

Likhitpanichkul, M; Dreischarf, M; Illien-Junger, S; Walter, B A; Nukaga, T; Long, R G; Sakai, D; Hecht, A C; Iatridis, J C

2014-07-18

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation.

Installation Restoration Program. Phase I. Records Search, Air Force Plant 44, Tucson, Arizona.

DTIC Science & Technology

1985-10-01

Biographical Data APPENDIX B List of Interviewees and Outside Agency Contacts APPENDIX C Master List of Industrial Shops * APPENDIX D References APPENDIX E AF...Collected by the Tucson Groundwater Contamination Study Task Force * Annual Generator’s Reports and Quarterly Reports from AFP 44 to ADHS. Appendix D ...cn (INcC. iU u u a L- - -2 a 0 0) CL C 1-4~~ ~ r % %- d ’ 00 A to did 1-44 L0 47% 0 z- d Ci - Z ..-i I2-8 00 -4 40 0 -0 0j c 0 Sb. 1.- 41 CL "-4 CLV

Distinctive interactions of the Arabidopsis homolog of the 30 kD subunit of the cleavage and polyadenylation specificity factor (AtCPSF30) with other polyadenylation factor subunits

USDA-ARS?s Scientific Manuscript database

Background: The Arabidopsis ortholog of the 30 kD subunit of the mammalian Cleavage and Polyadenylation Specificity Factor (AtCPSF30) is an RNA-binding endonuclease that is associated with other Arabidopsis CPSF subunits (orthologs of the 160, 100, and 73 kD subunits of CPSF). In order to better u...

The Future of the Andrew File System

ScienceCinema

Brashear, Drrick; Altman, Jeffry

2018-05-25

The talk will discuss the ten operational capabilities that have made AFS unique in the distributed file system space and how these capabilities are being expanded upon to meet the needs of the 21st century. Derrick Brashear and Jeffrey Altman will present a technical road map of new features and technical innovations that are under development by the OpenAFS community and Your File System, Inc. funded by a U.S. Department of Energy Small Business Innovative Research grant. The talk will end with a comparison of AFS to its modern days competitors.

The Future of the Andrew File System

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

Brashear, Drrick; Altman, Jeffry

2011-02-23

The talk will discuss the ten operational capabilities that have made AFS unique in the distributed file system space and how these capabilities are being expanded upon to meet the needs of the 21st century. Derrick Brashear and Jeffrey Altman will present a technical road map of new features and technical innovations that are under development by the OpenAFS community and Your File System, Inc. funded by a U.S. Department of Energy Small Business Innovative Research grant. The talk will end with a comparison of AFS to its modern days competitors.

Geranyl diphosphate synthase large subunit, and methods of use

DOEpatents

Croteau, Rodney B.; Burke, Charles C.; Wildung, Mark R.

2001-10-16

A cDNA encoding geranyl diphosphate synthase large subunit from peppermint has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Replicable recombinant cloning vehicles are provided which code for geranyl diphosphate synthase large subunit). In another aspect, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding geranyl diphosphate synthase large subunit. In yet another aspect, the present invention provides isolated, recombinant geranyl diphosphate synthase protein comprising an isolated, recombinant geranyl diphosphate synthase large subunit protein and an isolated, recombinant geranyl diphosphate synthase small subunit protein. Thus, systems and methods are provided for the recombinant expression of geranyl diphosphate synthase.

Analysis of expressed sequence tags from the Ulva prolifera (Chlorophyta)

NASA Astrophysics Data System (ADS)

Niu, Jianfeng; Hu, Haiyan; Hu, Songnian; Wang, Guangce; Peng, Guang; Sun, Song

2010-01-01

In 2008, a green tide broke out before the sailing competition of the 29th Olympic Games in Qingdao. The causative species was determined to be Enteromorpha prolifera ( Ulva prolifera O. F. Müller), a familiar green macroalga along the coastline of China. Rapid accumulation of a large biomass of floating U. prolifera prompted research on different aspects of this species. In this study, we constructed a nonnormalized cDNA library from the thalli of U. prolifera and acquired 10 072 high-quality expressed sequence tags (ESTs). These ESTs were assembled into 3 519 nonredundant gene groups, including 1 446 clusters and 2 073 singletons. After annotation with the nr database, a large number of genes were found to be related with chloroplast and ribosomal protein, GO functional classification showed 1 418 ESTs participated in photosynthesis and 1 359 ESTs were responsible for the generation of precursor metabolites and energy. In addition, rather comprehensive carbon fixation pathways were found in U. prolifera using KEGG. Some stress-related and signal transduction-related genes were also found in this study. All the evidences displayed that U. prolifera had substance and energy foundation for the intense photosynthesis and the rapid proliferation. Phylogenetic analysis of cytochrome c oxidase subunit I revealed that this green-tide causative species is most closely affiliated to Pseudendoclonium akinetum (Ulvophyceae).

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Imaging Lenticular Autofluorescence in Older Subjects.

PubMed

Charng, Jason; Tan, Rose; Luu, Chi D; Sadigh, Sam; Stambolian, Dwight; Guymer, Robyn H; Jacobson, Samuel G; Cideciyan, Artur V

2017-10-01

To evaluate whether a practical method of imaging lenticular autofluorescence (AF) can provide an individualized measure correlated with age-related lens yellowing in older subjects undergoing tests involving shorter wavelength lights. Lenticular AF was imaged with 488-nm excitation using a confocal scanning laser ophthalmoscope (cSLO) routinely used for retinal AF imaging. There were 75 older subjects (ages 47-87) at two sites; a small cohort of younger subjects served as controls. At one site, the cSLO was equipped with an internal reference to allow quantitative AF measurements; at the other site, reduced-illuminance AF imaging (RAFI) was used. In a subset of subjects, lens density index was independently estimated from dark-adapted spectral sensitivities performed psychophysically. Lenticular AF intensity was significantly higher in the older eyes than the younger cohort when measured with the internal reference (59.2 ± 15.4 vs. 134.4 ± 31.7 gray levels; P < 0.05) as well as when recorded with RAFI without the internal reference (10.9 ± 1.5 vs. 26.1 ± 5.7 gray levels; P < 0.05). Lenticular AF was positively correlated with age; however, there could also be large differences between individuals of similar age. Lenticular AF intensity correlated well with lens density indices estimated from psychophysical measures. Lenticular AF measured with a retinal cSLO can provide a practical and individualized measure of lens yellowing, and may be a good candidate to distinguish between preretinal and retinal deficits involving short-wavelength lights in older eyes.

Analysis of the Association Between Electrocardiographic P-wave Characteristics and Atrial Fibrillation in the REGICOR Study.

PubMed

Massó-van Roessel, Albert; Escobar-Robledo, Luis Alberto; Dégano, Irene R; Grau, María; Sala, Joan; Ramos, Rafel; Marrugat, Jaume; Bayés de Luna, Antoni; Elosua, Roberto

2017-10-01

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. P-wave duration and interatrial blocks (IAB) have been reported to be associated with AF. Our aim was to determine the individual and combined association of P-wave duration and advanced IAB morphology with AF. We designed an age-, sex-, and survey-matched case-control study nested in a population-based cohort (REGICOR: REgistre GIroní del COR). Two different surveys recruited a total of 9380 participants from 1999 to 2005; all participants were invited to a second examination between 2009 and 2013. For the present study, we selected participants aged 25 to 79 years with follow-up through the end of the study. All electrocardiograms were analyzed by 2 observers to determine P-wave duration and morphology (normal, partial, or advanced IAB). The median follow-up was 7.12 years. Eighty participants presented with AF, had a legible baseline electrocardiogram, and were included in the study, along with 160 controls. P-wave duration and the presence of partial or advanced IAB were associated with AF. When P-wave duration and morphology were considered together, only P-wave duration (≥ 110 milliseconds) showed an independent and strong association with AF. The odds ratio for AF of P-wave duration between 110-119, 120-129 and ≥ 130 milliseconds vs < 110 milliseconds were 5.33; 95%CI, 1.74-16.33, 5.08; 95%CI, 1.73-14.90 and 5.44; 95%CI, 1.95-15.15, respectively. A P-wave longer than 110 milliseconds increases the risk of AF. Advanced IAB morphology did not seem to provide an additional AF risk beyond that of P-wave duration. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Uncertainty in recharge estimation: impact on groundwater vulnerability assessments for the Pearl Harbor Basin, O'ahu, Hawai'i, U.S.A.

NASA Astrophysics Data System (ADS)

Giambelluca, Thomas W.; Loague, Keith; Green, Richard E.; Nullet, Michael A.

1996-06-01

In this paper, uncertainty in recharge estimates is investigated relative to its impact on assessments of groundwater contamination vulnerability using a relatively simple pesticide mobility index, attenuation factor (AF). We employ a combination of first-order uncertainty analysis (FOUA) and sensitivity analysis to investigate recharge uncertainties for agricultural land on the island of O'ahu, Hawai'i, that is currently, or has been in the past, under sugarcane or pineapple cultivation. Uncertainty in recharge due to recharge component uncertainties is 49% of the mean for sugarcane and 58% of the mean for pineapple. The components contributing the largest amounts of uncertainty to the recharge estimate are irrigation in the case of sugarcane and precipitation in the case of pineapple. For a suite of pesticides formerly or currently used in the region, the contribution to AF uncertainty of recharge uncertainty was compared with the contributions of other AF components: retardation factor (RF), a measure of the effects of sorption; soil-water content at field capacity (ΘFC); and pesticide half-life (t1/2). Depending upon the pesticide, the contribution of recharge to uncertainty ranks second or third among the four AF components tested. The natural temporal variability of recharge is another source of uncertainty in AF, because the index is calculated using the time-averaged recharge rate. Relative to the mean, recharge variability is 10%, 44%, and 176% for the annual, monthly, and daily time scales, respectively, under sugarcane, and 31%, 112%, and 344%, respectively, under pineapple. In general, uncertainty in AF associated with temporal variability in recharge at all time scales exceeds AF. For chemicals such as atrazine or diuron under sugarcane, and atrazine or bromacil under pineapple, the range of AF uncertainty due to temporal variability in recharge encompasses significantly higher levels of leaching potential at some locations than that indicated by the AF estimate.

Enhanced Oil Production by the Tropical Marine Diatom Thalassiosira Sp. Cultivated in Outdoor Photobioreactors.

PubMed

Kusumaningtyas, Pintaka; Nurbaiti, Santi; Suantika, Gede; Amran, Muhammad Bachri; Nurachman, Zeily

2017-08-01

Microalgae-derived oils have potential as a biofuel feedstock. To produce microalgal oils at a large scale, large amounts of nutrients and energy are needed to grow the algae. In this study, we evaluated three types of agricultural fertilizer (AF)-based culture media (AF1, AF2, and AF3) based on a previously published enriched seawater (ES) medium to produce biomass and oils from Thalassiosira sp. Under laboratory conditions, the highest cell productivity of Thalassiosira sp. was obtained with the AF3 medium. Thalassiosira sp. cultured in the AF3 medium produced 10.4 ± 0.9 mg L -1  day -1 oils, which is significantly higher than the 5.8 ± 0.7 mg L -1  day -1 produced in the ES medium. The higher production was due to the presence of nitrate and trace elements, both of which played roles in enhancing biomass and oil content, respectively. During cell growth, resting spores appeared inside the cells and were a marker to harvest the cells. Because of the abundant availability of sunlight in the tropics during the year, the oil production of Thalassiosira sp. in the AF3 medium was scaled up using outdoor photobioreactors under different weather conditions (rainy and dry seasons). Thalassiosira sp. produced more unsaturated fatty acids during the rainy season and produced more saturated fatty acids during the dry season. This study also demonstrated that it was possible to culture Thalassiosira sp. under outdoor conditions using a low-cost agricultural fertilizer-based culture medium (AF3 medium) to produce biodiesel feedstock with an annual production of 8.1 ± 0.4 t ha -1 during the dry season and of 23.9 ± 6.8 t ha -1 during the rainy season.

Marek’s Disease Virus Encoded Ribonucleotide Reductase Large Subunit is not Essential for In Vitro Replication

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV) infected cells express a viral ribonucleotide reductase (RR) that is distinguishable from that present in uninfected cells by monoclonal antibody T81. Open reading frames UL39 and UL40 of the MDV genome encode the large (RR1) and small (RR2) subunits of RR enzyme, respe...

Cognitive predictors of adaptive functioning in children with symptomatic epilepsy.

PubMed

Kerr, Elizabeth N; Fayed, Nora

2017-10-01

The current study sought to understand the contribution of the attention and working memory challenges experienced by children with active epilepsy without an intellectual disability to adaptive functioning (AF) while taking into account intellectual ability, co-occurring brain-based psychosocial diagnoses, and epilepsy-related variables. The relationship of attention and working memory with AF was examined in 76 children with active epilepsy with intellectual ability above the 2nd percentile recruited from a tertiary care center. AF was measured using the Scales of Independent Behavior-Revised (SIB-R) and compared with norm-referenced data. Standardized clinical assessments of attention span, sustained attention, as well as basic and more complex working memory were administered to children. Commonality analysis was used to investigate the importance of the variables with respect to the prediction of AF and to construct parsimonious models to elucidate the factors most important in explaining AF. Seventy-one percent of parents reported that their child experienced mild to severe difficulties with overall AF. Similar proportions of children displayed limitations in domain-specific areas of AF (Motor, Social/Communication, Person Living, and Community Living). The reduced models for Broad and domain-specific AF produced a maximum of seven predictor variables, with little loss in overall explained variance compared to the full models. Intellectual ability was a powerful predictor of Broad and domain-specific AF. Complex working memory was the only other cognitive predictor retained in each of the parsimonious models of AF. Sustained attention and complex working memory explained a large amount of the total variance in Motor AF. Children with a previously diagnosed comorbidity displayed lower Social/Communication, Personal Living, and Broad AF than those without a diagnosis. At least one epilepsy-related variable appeared in each of the reduced models, with age of seizure onset and seizure type (generalized or partial) being the main predictors. Intellectual ability was the most powerful predictor of AF in children with epilepsy whose intellectual functioning was above the 2nd percentile. Co-occurring brain-based cognitive and psychosocial issues experienced by children with living epilepsy, particularly complex working memory and diagnosed comorbidities, contribute to AF and may be amenable to intervention. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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

DTIC Science & Technology

2017-09-01

that the AFS seeded ANA used for nerve repair resulted in an improved functional outcome for the rats compared to ANA alone and were equivalent to...junction morphology were equivalent between the AFS seeded ANA. Additional studies investigated the use of post-partum acellular materials to...techniques for repairing large-gap (6 cm) nerve injuries in non -human primates. This pre-clinical model represents a more translational model of

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2017-09-01

AFS seeded ANA used for nerve repair resulted in an improved functional outcome for the rats compared to ANA alone and were equivalent to those...junction morphology were equivalent between the AFS seeded ANA. Additional studies investigated the use of post-partum acellular materials to promote...techniques for repairing large-gap (6 cm) nerve injuries in non -human primates. This pre-clinical model represents a more translational model of peripheral

Atrial fibrillation in patients on haemodialysis in Andalusia. Prevalence, clinical profile and therapeutic management.

PubMed

Sánchez Perales, Carmen; Vázquez Sánchez, Teresa; Salas Bravo, Daniel; Ortega Anguiano, Sonia; Vázquez Ruiz de Castroviejo, Eduardo

Atrial fibrillation (AF) represents an important social and healthcare problem. There is wide variability in the prevalence of this arrhythmia in studies analysing patients on haemodialysis (HD). To investigate the prevalence, clinical profile and therapeutic management of patients with AF on HD in Andalusia. We asked the public healthcare system of Andalusia to provide us with the number of patients who were being treated with HD. We asked attending nephrologists from all hospital and outpatient centres in 5 of the 8 Andalusian provinces to perform an electrocardiogram and to fill out a questionnaire on patients selected by simple random sampling. A total of 2,348 patients were being treated with HD in the 5provinces included in the study. The estimated sample size was 285 patients. We obtained an electrocardiogram and information from 252 patients (88.4%); mean age 65.3±16 years; 40.9% women. Sixty-three patients (25%) had AF. Of these, 36 (14.3%) had AF in the recorded ECG and in the rest it had been documented previously. In the multivariate analysis, older age (OR: 1.071; 95% CI: 1.036-1.107; P=0.000) and greater time on HD (OR: 1.009; 95% CI: 1.004-1.014; P=0.000) were independently associated with the presence of AF. Of the patients with AF, 41.3% were on anticoagulant treatment at the time of the study; and 41.2% were on antiplatelet agents. AF in dialysis units is an important finding. Establishing the risk-benefit ratio of anticoagulant treatment constitutes a real challenge. Well-designed clinical trials are pivotal in order to define the rational use of antithrombotic drugs. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

D1/D2 domain of large-subunit ribosomal DNA for differentiation of Orpinomyces spp.

PubMed

Dagar, Sumit S; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K

2011-09-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation.

A Case-by-Case Evolutionary Analysis of Four Imprinted Retrogenes

PubMed Central

McCole, Ruth B; Loughran, Noeleen B; Chahal, Mandeep; Fernandes, Luis P; Roberts, Roland G; Fraternali, Franca; O'Connell, Mary J; Oakey, Rebecca J

2011-01-01

Retroposition is a widespread phenomenon resulting in the generation of new genes that are initially related to a parent gene via very high coding sequence similarity. We examine the evolutionary fate of four retrogenes generated by such an event; mouse Inpp5f_v2, Mcts2, Nap1l5, and U2af1-rs1. These genes are all subject to the epigenetic phenomenon of parental imprinting. We first provide new data on the age of these retrogene insertions. Using codon-based models of sequence evolution, we show these retrogenes have diverse evolutionary trajectories, including divergence from the parent coding sequence under positive selection pressure, purifying selection pressure maintaining parent-retrogene similarity, and neutral evolution. Examination of the expression pattern of retrogenes shows an atypical, broad pattern across multiple tissues. Protein 3D structure modeling reveals that a positively selected residue in U2af1-rs1, not shared by its parent, may influence protein conformation. Our case-by-case analysis of the evolution of four imprinted retrogenes reveals that this interesting class of imprinted genes, while similar in regulation and sequence characteristics, follow very varied evolutionary paths. PMID:21166792

Atrial fibrillation and silent stroke: links, risks, and challenges.

PubMed

Hahne, Kathrin; Mönnig, Gerold; Samol, Alexander

2016-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a projected number of 1 million affected subjects in Germany. Changes in age structure of the Western population allow for the assumption that the number of concerned people is going to be doubled, maybe tripled, by the year 2050. Large epidemiological investigations showed that AF leads to a significant increase in mortality and morbidity. Approximately one-third of all strokes are caused by AF and, due to thromboembolic cause, these strokes are often more severe than those caused by other etiologies. Silent brain infarction is defined as the presence of cerebral infarction in the absence of corresponding clinical symptomatology. Progress in imaging technology simplifies diagnostic procedures of these lesions and leads to a large amount of diagnosed lesions, but there is still no final conclusion about frequency, risk factors, and clinical relevance of these infarctions. The prevalence of silent strokes in patients with AF is higher compared to patients without AF, and several studies reported high incidence rates of silent strokes after AF ablation procedures. While treatment strategies to prevent clinically apparent strokes in patients with AF are well investigated, the role of anticoagulatory treatment for prevention of silent infarctions is unclear. This paper summarizes developments in diagnosis of silent brain infarction and its context to AF.

Three-dimensional structure of thymidine phosphorylase from E. coli in complex with 3'-azido-2'-fluoro-2',3'-dideoxyuridine

NASA Astrophysics Data System (ADS)

Timofeev, V. I.; Abramchik, Yu. A.; Fateev, I. V.; Zhukhlistova, N. E.; Murav'eva, T. I.; Kuranova, I. P.; Esipov, R. S.

2013-11-01

The three-dimensional structures of thymidine phosphorylase from E. coli containing the bound sulfate ion in the phosphate-binding site and of the complex of thymidine phosphorylase with sulfate in the phosphate-binding site and the inhibitor 3'-azido-2'-fluoro-2',3'-dideoxyuridine (N3F-ddU) in the nucleoside-binding site were determined at 1.55 and 1.50 Å resolution, respectively. The amino-acid residues involved in the ligand binding and the hydrogen-bond network in the active site occupied by a large number of bound water molecules are described. A comparison of the structure of thymidine phosphorylase in complex with N3F-ddU with the structure of pyrimidine nucleoside phosphorylase from St. Aureus in complex with the natural substrate thymidine (PDB_ID: 3H5Q) shows that the substrate and the inhibitor in the nucleoside-binding pocket have different orientations. It is suggested that the position of N3F-ddU can be influenced by the presence of the azido group, which prefers a hydrophobic environment. In both structures, the active sites of the subunits are in the open conformation.

Variations in cause and management of atrial fibrillation in a prospective registry of 15,400 emergency department patients in 46 countries: the RE-LY Atrial Fibrillation Registry.

PubMed

Oldgren, Jonas; Healey, Jeff S; Ezekowitz, Michael; Commerford, Patrick; Avezum, Alvaro; Pais, Prem; Zhu, Jun; Jansky, Petr; Sigamani, Alben; Morillo, Carlos A; Liu, Lisheng; Damasceno, Albertino; Grinvalds, Alex; Nakamya, Juliet; Reilly, Paul A; Keltai, Katalin; Van Gelder, Isabelle C; Yusufali, Afzal Hussein; Watanabe, Eiichi; Wallentin, Lars; Connolly, Stuart J; Yusuf, Salim

2014-04-15

Atrial fibrillation (AF) is the most common sustained arrhythmia; however, little is known about patients in a primary care setting from high-, middle-, and low-income countries. This prospective registry enrolled patients presenting to an emergency department with AF at 164 sites in 46 countries representing all inhabited continents. Patient characteristics were compared among 9 major geographic regions. Between September 2008 and April 2011, 15,400 patients were enrolled. The average age was 65.9, standard deviation 14.8 years, ranging from 57.2, standard deviation 18.8 years in Africa, to 70.1, standard deviation 13.4 years in North America, P<0.001. Hypertension was globally the most common risk factor for AF, ranging in prevalence from 41.6% in India to 80.7% in Eastern Europe, P<0.001. Rheumatic heart disease was present in only 2.2% of North American patients, in comparison with 21.5% in Africa and 31.5% in India, P<0.001. The use of oral anticoagulation among patients with a CHADS2 score of ≥2 was greatest in North America (65.7%) but was only 11.2% in China, P<0.001. The mean time in the therapeutic range was 62.4% in Western Europe, 50.9% in North America, but only between 32% and 40% in India, China, Southeast Asia, and Africa, P<0.001. There is a large global variation in age, risk factors, concomitant diseases, and treatment of AF among regions. Improving outcomes globally requires an understanding of this variation and the conduct of research focused on AF associated with different underlying conditions and treatment of AF and predisposing conditions in different socioeconomic settings.

Regulatory Relief: Simplifying and Eliminating Contract Clauses. Volume 1

DTIC Science & Technology

1989-11-01

CA Mzu IG1z czt I, r= w1 2 E I cn 2 d Q A- O.jI I3 Ir c:I w0 10 00 0 14 0 0 0 rI- 0 u1 t8 0 - Iu "I IU -I U w .0I 1u I efl I ~ >I2I I ’.4 0 1~ 0"’ a)w...10 -4 ~ ~ 4I 1- I~~ ~ C) I O *r O I O 4) I C 1W-. af I24)I 0 11- I 10.1 0 10 1 .*( lwMIC . W t. 12 W - I rW I n 0 12 0 4)J~I 0" 0 C13 V0 01uO I 0 (14

Origin and ablation of the adenosine triphosphate induced atrial fibrillation after circumferential pulmonary vein isolation: effects on procedural success rate.

PubMed

Zhang, Jinlin; Tang, Cheng; Zhang, Yonghua; Su, X I

2014-04-01

Adenosine triphosphate (ATP) has been used to provoke dormant pulmonary vein (PV) conduction after circumferential PV isolation (CPVI). However, there have been no systematic studies examining the incidence and the mechanism of ATP-induced atrial fibrillation (AF) following CPVI in paroxysmal AF. In this study, we explore the mechanism of ATP-induced AF and assess the feasibility of eliminating this response by additional radiofrequency (RF) ablation. A total of 300 consecutive patients with paroxysmal AF underwent CPVI. After all PVs were isolated, intravenous ATP (40 mg) was administered during an intravenous isoproterenol (ISP) infusion (5 μg/min). AF was reproducibly induced by ATP in 39 patients. Non-PV foci were confirmed and located in 29 of these patients at the onset of AF, including 27 foci in the superior vena cava (SVC), 1 focus in the crista terminalis, and 1 focus near the antrum of the PV. In all these cases, ATP-induced AF was eliminated after the non-PV foci were successfully ablated. For the other 10 patients, the foci triggering AF could not be confirmed or located due to the transient effect of ATP, thus no further ablation was performed. After a mean follow-up period of 18.7 ± 6.4 (8-24) months, the success rate in the ATP-induced AF group was not significantly different compared with the conventional treatment group who did not exhibit ATP-induced AF (76.9% vs 67.3%; P = 0.25). But in the subgroup of which the ATP-induced AF could be eliminated by additional RF ablation, the success rate was significantly higher than the non-ATP inducible group (86.2% vs 67.3%; P = 0.04). A large proportion of the ATP-induced AF post CPVI were initiated by rapid firing in the SVC. Eliminating this response by additional ablation may have an influence on clinical results of paroxysmal AF ablation. © 2014 Wiley Periodicals, Inc.

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

DTIC Science & Technology

1983-03-01

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Reengineering ribosome export.

PubMed

Lo, Kai-Yin; Johnson, Arlen W

2009-03-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages.

Reengineering Ribosome Export

PubMed Central

Lo, Kai-Yin

2009-01-01

Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMID:19144820

Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection.

PubMed

Miura, Yuichiro; Payne, Matthew S; Keelan, Jeffrey A; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Newnham, John P; Kemp, Matthew W

2014-09-01

Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index 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) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Chang, YuChiao; Singer, Daniel E; Lokhnygina, Yuliya; Go, Alan S; Patel, Manesh R; Mahaffey, Kenneth W; Halperin, Jonathan L; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M

2013-01-15

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In 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), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes

PubMed Central

Glöckner, Gernot; Scherer, Stephen; Schattevoy, Ruben; Boright, Andrew; Weber, Jacqueline; Tsui, Lap-Chee; Rosenthal, André

1998-01-01

We have sequenced and annotated two genomic regions located in the Giemsa negative band q22 of human chromosome 7. The first region defined by the erythropoietin (EPO) locus is 228 kb in length and contains 13 genes. Whereas 3 genes (GNB2, EPO, PCOLCE) were known previously on the mRNA level, we have been able to identify 10 novel genes using a newly developed automatic annotation tool RUMMAGE-DP, which comprises >26 different programs mainly for exon prediction, homology searches, and compositional and repeat analysis. For precise annotation we have also resequenced ESTs identified to the region and assembled them to build large cDNAs. In addition, we have investigated the differential splicing of genes. Using these tools we annotated 4 of the 10 genes as a zonadhesin, a transferrin homolog, a nucleoporin-like gene, and an actin gene. Two genes showed weak similarity to an insulin-like receptor and a neuronal protein with a leucine-rich amino-terminal domain. Four predicted genes (CDS1–CDS4) CDS that have been confirmed on the mRNA level showed no similarity to known proteins and a potential function could not be assigned. The second region in 7q22 defined by the CUTL1 (CCAAT displacement protein and its splice variant) locus is 416 kb in length and contains three known genes, including PMSL12, APS, CUTL1, and a novel gene (CDS5). The CUTL1 locus, consisting of two splice variants (CDP and CASP), occupies >300 kb. Based on the G,C profile an isochore switch can be defined between the CUTL1 gene and the APS and PMSL12 genes. [Clones 37G3, 164c7, and 235f8 are deposited in GenBank under accession no. AF053356; clone 123e15, accession no. AF024533; 186d2, accession no. AF024534; 46f6, accession no. AF006752; 50h2, accession no. AF047825; and 76h2, accession no. AF030453] PMID:9799793

The AFS Volunteer Resources Study: Summary of Findings from Australia.

ERIC Educational Resources Information Center

Walsh, Desmond; And Others

The American Field Service (AFS) has 3,500 volunteers throughout Australia. Local chapters recruit potential host families and participants. Host families are recruited actively and selectively while volunteers are recruited largely through AFS presentations at schools, through friends, and by returning volunteers. Due to a high level of demand…

Simultaneous Biatrial High-Density (510-512 Electrodes) Epicardial Mapping of Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: New Insights Into the Mechanism of Its Maintenance.

PubMed

Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Cakulev, Ivan; Markowitz, Alan; Waldo, Albert L

2015-12-01

The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation. Twelve patients with persistent and LSP AF (1 month to 9 years duration) were studied at open heart surgery. During AF, electrograms were recorded from both atria simultaneously for 1 to 5 minutes from 510 to 512 epicardial electrodes with ECG lead II. Thirty-two consecutive seconds of activation sequence maps were produced per patient. During AF, multiple foci (QS unipolar atrial electrograms) of different cycle lengths (mean, 175 ± 18 ms) were present in both atria in 11 of 12 patients. Foci (2-4 per patient, duration 5-32 s) were either sustained or intermittent, were predominantly found in the lateral left atrial free wall, and likely acted as drivers. Random and nonrandom breakthrough activation sites (initial r or R in unipolar atrial electrograms) were also found. In 1 of 12 patients, only breakthrough sites were found. All wave fronts emanated from foci and breakthrough sites, and largely either collided or merged with each other at variable sites. Repetitive focal QS activation occasionally generated repetitive wannabe reentrant activation in 5 of 12 patients. No actual reentry was found. During persistent and LSP AF in 12 patients, wave fronts emanating from foci and breakthrough sites maintained AF. No reentry was demonstrated. © 2015 American Heart Association, Inc.

Haliotis tuberculata hemocyanin (HtH): analysis of oligomeric stability of HtH1 and HtH2, and comparison with keyhole limpet hemocyanin KLH1 and KLH2.

PubMed

Harris, J R; Scheffler, D; Gebauer, W; Lehnert, R; Markl, J

2000-12-01

The multimeric/higher oligomeric states of the two isoforms of Haliotis tuberculata hemocyanin (HtH1 and HtH2) have been assessed by transmission electron microscopy (TEM) of negatively stained specimens, for comparison with previously published structural data from keyhole limpet hemocyanin (KLH1 and KLH2) [see Harris, J.R., Gebauer, W., Guderian, F.U., Markl, J., 1997a. Keyhole limpet hemocyanin (KLH), I: Reassociation from Immucothel followed by separation of KLH1 and KLH2. Micron, 28, 31-41; Harris, J.R., Gebauer, W., Söhngen, S.M., Nermut, M.V., Markl, J., 1997b. Keyhole limpet hemocyanin (KLH). II: Characteristic reassociation properties of purified KLH1 and KLH2. Micron, 28, 43-56; Harris, J.R., Gebauer, W., Adrian, M., Markl, J., 1998. Keyhole limpet hemocyanin (KLH): Slow in vitro reassociation of KLH1 and KLH2 from Immucothel. Micron, 29, 329-339]. In purified samples of both HtH isoforms, the hollow cylindrical ca 8MDa didecamer predominates together with a small number of decamers, but tri- and longer multidecamers are detectable only in the HtH2. The stability of the two HtH isoforms under varying ionic conditions have been monitored, thereby enabling conditions for the production of stable decamers to be established. The ability of these decamers to reform multimers in the presence of 10 and 100mM concentrations of calcium and magnesium ions in Tris-HCl buffer (pH 7.4), and also of individual HtH1 and HtH2 subunits (produced by pH 9.6 dissociation in glycine-NaOH buffer), to reassociate in the presence of calcium and magnesium ions, has been assessed. For the HtH1 decamers, the predominant multimeric product is the didecamer at 10 and 100mM calcium and magnesium concentrations, whereas for the HtH2 decamers, large numbers of multidecamers are produced, with the reaction proceeding more completely at the higher calcium and magnesium concentration. With the HtH1 subunit, reassociation in the presence of 10 and 100mM calcium and magnesium ions yielded an almost 100% conversion into didecamers, whereas the HtH2 subunit produced a mixture containing large numbers of short multidecamers and relatively few didecamers, together with a considerable number of smaller diameter helical/tubular polymers. The association properties of the HtH1 and HtH2 decamers, and the subunit reassociation, firmly indicate the integrity and structural competency of the protein under the experimental conditions used. Data on the association of KLH2 decamers is also presented, which together with previously published data on the association KLH1 decamers and the reassociation of KLH1 and KLH2 subunits, enables a detailed comparison of the two hemocyanin isoforms from both molluscan species to be made. Biochemical manipulation of the oligomer states and the subunit reassociation of molluscan hemocyanins can usefully be assessed by the study of negatively stained TEM specimens.

[Cytokine-mediated regulation of expression of Gfi1 and U2afll4 genes activated by T-cells with different differentiation status in vitro].

PubMed

Yurova, K A; Sokhonevich, N A; Khaziakhmatova, O G; Litvinova, L S

2016-01-01

The dose-dependent effects of cytokines (IL-2, IL-7, and IL-15), which have a common g-chain, on mRNA expression of U2afll4 and GFi1 genes involved in regulation of alternative splicing of the Ptprc gene, have been investigated in vitro using T-lymphocyte cultures with different degrees of differentiation. IL-2, IL-7, and IL-15 caused a similar unidirectional inhibitory effect of various severity on restimulated CD45RO+ T-cells exposed to an antigen-independent activation; they caused a dose-dependent decrease of the U2af1l4 gene expression, and an increase of Gfi1 gene expression. This may suggest formation of active forms of the CD45 receptor, and also limitation of the formation of low-molecular short splice variants of the CD45RO receptor. Under conditions of antigen-independent stimulation of naive CD45RA+-cells rIL-7 and IL-15 exhibited opposite effects on U2af1l4 and Gfi1 gene expression. The increase of IL-7 concentrations in the incubation medium of naive cells was accompanied by a decrease in expression of both genes. IL-15 IL-7 exhibited opposite effects. Cytokines possessing a common g-chain (IL-2, IL-7, and IL-15) prevented antigen-independent differentiation of naive T-cells, by preventing the formation of polyclonal "surrogate" cells. In general, the study of the molecular mechanisms of genetic control determining homeostatic processes of T-cells in response to exposure to antigenic or non-antigenic treatments may be important for construction of a general model of self-maintenance and differentiation of immune cells.

Revisiting the phylogeny of Ocellularieae, the second largest tribe within Graphidaceae (lichenized Ascomycota: Ostropales)

Treesearch

Ekaphan Kraichak; Sittiporn Parnmen; Robert Lücking; Eimy Rivas Plata; Andre Aptroot; Marcela E.S. Caceres; Damien Ertz; Armin Mangold; Joel A. Mercado-Diaz; Khwanruan Papong; Dries Van der Broeck; Gothamie Weerakoon; H. Thorsten Lumbsch; NO-VALUE

2014-01-01

We present an updated 3-locus molecular phylogeny of tribe Ocellularieae, the second largest tribe within subfamily Graphidoideae in the Graphidaceae. Adding 165 newly generated sequences from the mitochondrial small subunit rDNA (mtSSU), the nuclear large subunit rDNA (nuLSU), and the second largest subunit of the DNA-directed RNA polymerase II (RPB2), we currently...

Marek’s disease virus encoded ribonucleotide reductase large subunit is essential for in vivo replication and plays a critical role in viral pathogenesis.

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus encodes a ribonucleotide reductase (RR) that consists of two subunits namely RR1 and RR2, both of which associate to form an active holoenzyme and both subunits are necessary for enzyme activity. It is an essential enzyme for the conversion of ribonucleotides to deoxyribonucleo...

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

PubMed

Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

2017-12-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes.

PubMed

Treuter, E; Johansson, L; Thomsen, J S; Wärnmark, A; Leers, J; Pelto-Huikko, M; Sjöberg, M; Wright, A P; Spyrou, G; Gustafsson, J A

1999-03-05

Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.

Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation.

PubMed

Masè, Michela; Grasso, Margherita; Avogaro, Laura; D'Amato, Elvira; Tessarolo, Francesco; Graffigna, Angelo; Denti, Michela Alessandra; Ravelli, Flavia

2017-01-24

MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-C q , GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions.

Is There Any Difference in Risk Factors between Male and Female Patients in New-Onset Atrial Fibrillation after Coronary Artery Bypass Grafting?

PubMed

Akça, Barış; Erdil, Nevzat; Colak, Mehmet Cengiz; Disli, Olcay Murat; Battaloglu, Bektas; Colak, Cemil

2018-03-06

 We aimed to investigate the risk factors of post-coronary artery bypass grafting (CABG) atrial fibrillation (AF) in male and female patients without any history of AF, to identify the sex-specific risk factors, and to examine the effect of sex-specific risk factors on the overall population.  This retrospective study was conducted using the hospital database with 4,758 patients who underwent CABG surgery. Among them, 2,836 patients with complete data participated in this study. The female patients were divided into two groups as patients who developed new-onset AF after CABG and those who did not. The relationship between the patients' variables and risk factors of post-CABG AF was examined.  The overall incidence of post CABG AF was 12.9% (386/2,836). Sex-specific incidence of AF was similar: 3.2% (91/690) and 12.9% (277/2146) in female and male patients, respectively ( p  = 0.849). Multiple analysis revealed the independent risk factors for male and female patients, respectively: mean age (odds ratio [OR] = 1.057, OR = 1,076), age over 65 years (OR = 2.156, OR = 2.736), the European System For Cardiac Operative Risk Evaluation Scores (EuroSCORE) (OR = 1.13, OR = 1.218), COPD (OR = 1.589, OR = 1.789), BUN level (OR = 1.026, OR = 1.019), mean cardiopulmonary bypass (CPB) time (OR = 1.007, OR = 1.010), prolonged CPB time (OR = 1.604, OR = 2.309), mean cross-clamp time (OR = 1.009, OR = 1.017), need of inotropic support (OR = 2.249, OR = 2.731), and mean mechanical ventilation time (VT) (OR = 1.026, OR = 1.027).Low left ventricular ejection fraction (LVEF) (OR = 1.419), left ventricular (LV) aneurysm repair (OR = 1.533), carotid artery disease (OR = 1.750), prolonged VT (OR = 1.729), and use of intra-aortic balloon pump (IABP) (OR = 2.436) were found to be the risk factors only for male AF patients.Unstable angina (OR = 1.969), right coronary artery (RCA) disease (OR = 2), prolonged cross-clamp time (OR = 2.152), and the number of grafts per operation (OR = 1.298) were found to be the risk factors only for female AF patients.  This study suggests that predictors of AF in the overall population may be due to isolated patient groups. Multiple regression analysis and artificial intelligence modelling should be performed on large-scale, isolated groups to make strong AF prediction. Georg Thieme Verlag KG Stuttgart · New York.

Annotated Bibliography of the Air Force Human Resources Laboratory Technical Reports - 1979.

DTIC Science & Technology

1981-05-01

Force Human Resources Laboratory, March 1980. (Covers all AFHRL projects.) NTIS. This document provides the academic and industrial R&D community with...D-AI02 04𔃾 AIR FORCE HUMAN RESOURCES LAB BROOKS AF TX F/G 5/2 ANNOTATED BIBLIOGRAPHY OF THE AIR FORCE HUMAN RESOURCES LABORAT--ETC(U) MAY 81 E M...OF THE AIR FORCE HUMAN RESOURCES LABORATORY TECHNICAL REPORTS - 1979U M By M Esther M. Barlow A N TECHNICAL SERVICES DIVISION Brooks Air Force Base

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

PubMed

Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H

2017-08-01

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Association between Air Pollution and Emergency Room Visits for Atrial Fibrillation

PubMed Central

Solimini, Angelo G.; Renzi, Matteo

2017-01-01

Despite the large prevalence in the population, possible factors responsible for the induction of atrial fibrillation (AF) events in susceptible individuals remain incompletely understood. We investigated the association between air pollution levels and emergency department admissions for AF in Rome. We conducted a 14 years’ time-series study to evaluate the association between the daily levels of air pollution (particulate matter, PM10 and PM2.5, and nitrogen dioxide, NO2) and the daily count of emergency accesses for AF (ICD-9 code: 427.31). We applied an over-dispersed conditional Poisson model to analyze the associations at different lags after controlling for time, influenza epidemics, holiday periods, temperature, and relative humidity. Additionally, we evaluated bi-pollutant models by including the other pollutant and the influence of several effect modifiers such as personal characteristics and pre-existing medical conditions. In the period of study, 79,892 individuals were admitted to the emergency departments of Rome hospitals because of AF (on average, 15.6 patients per day: min = 1, max = 36). Air pollution levels were associated with increased AF emergency visits within 24 h of exposure. Effect estimates ranged between 1.4% (0.7–2.3) for a 10 µg/m3 increase of PM10 to 3% (1.4–4.7) for a 10 µg/m3 increase of PM2.5 at lag 0–1 day. Those effects were higher in patients ≥75 years for all pollutants, male patients for PM10, and female patients for NO2. The presence of previous cardiovascular conditions, but not other effect modifiers, increase the pollution effects by 5–8% depending on the lag. This study found evidence that air pollution is associated with AF emergency visits in the short term. PMID:28632149

Effects of Newcastle Disease Virus Strains AF2240 and V4-UPM on Cytolysis and Apoptosis of Leukemia Cell Lines

PubMed Central

Alabsi, Aied M.; Bakar, Siti Aishah Abu; Ali, Rola; Omar, Abdul Rahman; Bejo, Mohd Hair; Ideris, Aini; Ali, Abdul Manaf

2011-01-01

Newcastle disease virus (NDV) is used as an antineoplastic agent in clinical tumor therapy. It has prompted much interest as an anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. This study was carried out to determine the oncolytic potential of NDV strain AF2240 and V4-UPM on WEHI-3B leukemia cell line. Results from MTT cytotoxicity assay showed that the CD50 values for both strains were 2 and 8 HAU for AF2240 and V4-UPM, respectively. In addition, bromodeoxyuridine (BrdU) and trypan blue dye exclusion assays showed inhibition in cell proliferation after different periods. Increase in the cellular level of caspase-3 and detection of DNA laddering using agarose gel electrophoresis on treated cells with NDV confirmed that the mode of cell death was apoptosis. In addition, flow-cytometry analysis of cellular DNA content showed that the virus caused an increase in the sub-G1 region (apoptosis peaks). In conclusion, NDV strains AF2240 and V4-UPM caused cytolytic effects against WEHI-3B leukemic cell line. PMID:22272097

D1/D2 Domain of Large-Subunit Ribosomal DNA for Differentiation of Orpinomyces spp.▿

PubMed Central

Dagar, Sumit S.; Kumar, Sanjay; Mudgil, Priti; Singh, Rameshwar; Puniya, Anil K.

2011-01-01

This study presents the suitability of D1/D2 domain of large-subunit (LSU) ribosomal DNA (rDNA) for differentiation of Orpinomyces joyonii and Orpinomyces intercalaris based on PCR-restriction fragment length polymorphism (RFLP). A variation of G/T in O. intercalaris created an additional restriction site for AluI, which was used as an RFLP marker. The results demonstrate adequate heterogeneity in the LSU rDNA for species-level differentiation. PMID:21784906

Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter.

PubMed

Golden, Keith; Mounsey, John Paul; Chung, Eugene; Roomiani, Pahresah; Morse, Michael Andew; Patel, Ankit; Gehi, Anil

2012-05-01

Catheter ablation is an effective therapy for symptomatic, medically refractory atrial fibrillation (AF). Open-irrigated radiofrequency (RF) ablation catheters produce transmural lesions at the cost of increased fluid delivery. In vivo models suggest closed-irrigated RF catheters create equivalent lesions, but clinical outcomes are limited. A cohort of 195 sequential patients with symptomatic AF underwent stepwise AF ablation (AFA) using a closed-irrigation ablation catheter. Recurrence of AF was monitored and outcomes were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mean age was 59.0 years, 74.9% were male, 56.4% of patients were paroxysmal and mean duration of AF was 5.4 years. Patients had multiple comorbidities including hypertension (76.4%), tobacco abuse (42.1%), diabetes (17.4%), and obesity (mean body mass index 30.8). The median follow-up was 55.8 weeks. Overall event-free survival was 73.6% with one ablation and 77.4% after reablation (reablation rate was 8.7%). Median time to recurrence was 26.9 weeks. AF was more likely to recur in patients being treated with antiarrhythmic therapy at the time of last follow-up (recurrence rate 30.3% with antiarrhythmic drugs, 13.2% without antiarrhythmic drugs; hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.1-4.4, P = 0.024) and in those with a history of AF greater than 2 years duration (HR 2.7, 95% CI 1.1-6.9, P = 0.038). Our study represents the largest cohort of patients receiving AFA with closed-irrigation ablation catheters. We demonstrate comparable outcomes to those previously reported in studies of open-irrigation ablation catheters. Given the theoretical benefits of a closed-irrigation system, a large head-to-head comparison using this catheter is warranted. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Perturbation of Chromatin Structure Globally Affects Localization and Recruitment of Splicing Factors

PubMed Central

Risso, Guillermo J.; Pawellek, Andrea; Ule, Jernej; Lamond, Angus I.; Kornblihtt, Alberto R.

2012-01-01

Chromatin structure is an important factor in the functional coupling between transcription and mRNA processing, not only by regulating alternative splicing events, but also by contributing to exon recognition during constitutive splicing. We observed that depolarization of neuroblastoma cell membrane potential, which triggers general histone acetylation and regulates alternative splicing, causes a concentration of SR proteins in nuclear speckles. This prompted us to analyze the effect of chromatin structure on splicing factor distribution and dynamics. Here, we show that induction of histone hyper-acetylation results in the accumulation in speckles of multiple splicing factors in different cell types. In addition, a similar effect is observed after depletion of the heterochromatic protein HP1α, associated with repressive chromatin. We used advanced imaging approaches to analyze in detail both the structural organization of the speckle compartment and nuclear distribution of splicing factors, as well as studying direct interactions between splicing factors and their association with chromatin in vivo. The results support a model where perturbation of normal chromatin structure decreases the recruitment efficiency of splicing factors to nascent RNAs, thus causing their accumulation in speckles, which buffer the amount of free molecules in the nucleoplasm. To test this, we analyzed the recruitment of the general splicing factor U2AF65 to nascent RNAs by iCLIP technique, as a way to monitor early spliceosome assembly. We demonstrate that indeed histone hyper-acetylation decreases recruitment of U2AF65 to bulk 3′ splice sites, coincident with the change in its localization. In addition, prior to the maximum accumulation in speckles, ∼20% of genes already show a tendency to decreased binding, while U2AF65 seems to increase its binding to the speckle-located ncRNA MALAT1. All together, the combined imaging and biochemical approaches support a model where chromatin structure is essential for efficient co-transcriptional recruitment of general and regulatory splicing factors to pre-mRNA. PMID:23152763

An Aromatic Cap Seals the Substrate Binding Site in an ECF-Type S Subunit for Riboflavin

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

Karpowich, Nathan K.; Song, Jinmei; Wang, Da-Neng

2016-06-13

ECF transporters are a family of active membrane transporters for essential micronutrients, such as vitamins and trace metals. Found exclusively in archaea and bacteria, these transporters are composed of four subunits: an integral membrane substrate-binding subunit (EcfS), a transmembrane coupling subunit (EcfT), and two ATP-binding cassette ATPases (EcfA and EcfA'). We have characterized the structural basis of substrate binding by the EcfS subunit for riboflavin from Thermotoga maritima, TmRibU. TmRibU binds riboflavin with high affinity, and the protein–substrate complex is exceptionally stable in solution. The crystal structure of riboflavin-bound TmRibU reveals an electronegative binding pocket at the extracellular surface inmore » which the substrate is completely buried. Analysis of the intermolecular contacts indicates that nearly every available substrate hydrogen bond is satisfied. A conserved aromatic residue at the extracellular end of TM5, Tyr130, caps the binding site to generate a substrate-bound, occluded state, and non-conservative mutation of Tyr130 reduces the stability of this conformation. Using a novel fluorescence binding assay, we find that an aromatic residue at this position is essential for high-affinity substrate binding. Comparison with other S subunit structures suggests that TM5 and Loop5-6 contain a dynamic, conserved motif that plays a key role in gating substrate entry and release by S subunits of ECF transporters.« less

Imaging Lenticular Autofluorescence in Older Subjects

PubMed Central

Charng, Jason; Tan, Rose; Luu, Chi D.; Sadigh, Sam; Stambolian, Dwight; Guymer, Robyn H.; Jacobson, Samuel G.; Cideciyan, Artur V.

2017-01-01

Purpose To evaluate whether a practical method of imaging lenticular autofluorescence (AF) can provide an individualized measure correlated with age-related lens yellowing in older subjects undergoing tests involving shorter wavelength lights. Methods Lenticular AF was imaged with 488-nm excitation using a confocal scanning laser ophthalmoscope (cSLO) routinely used for retinal AF imaging. There were 75 older subjects (ages 47–87) at two sites; a small cohort of younger subjects served as controls. At one site, the cSLO was equipped with an internal reference to allow quantitative AF measurements; at the other site, reduced-illuminance AF imaging (RAFI) was used. In a subset of subjects, lens density index was independently estimated from dark-adapted spectral sensitivities performed psychophysically. Results Lenticular AF intensity was significantly higher in the older eyes than the younger cohort when measured with the internal reference (59.2 ± 15.4 vs. 134.4 ± 31.7 gray levels; P < 0.05) as well as when recorded with RAFI without the internal reference (10.9 ± 1.5 vs. 26.1 ± 5.7 gray levels; P < 0.05). Lenticular AF was positively correlated with age; however, there could also be large differences between individuals of similar age. Lenticular AF intensity correlated well with lens density indices estimated from psychophysical measures. Conclusions Lenticular AF measured with a retinal cSLO can provide a practical and individualized measure of lens yellowing, and may be a good candidate to distinguish between preretinal and retinal deficits involving short-wavelength lights in older eyes. PMID:28973367

Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy.

PubMed Central

Rubin, H; Salem, J S; Li, L S; Yang, F D; Mama, S; Wang, Z M; Fisher, A; Hamann, C S; Cooperman, B S

1993-01-01

Malaria remains a leading cause of morbidity and mortality worldwide, accounting for more than one million deaths annually. We have focused on the reduction of ribonucleotides to 2'-deoxyribonucleotides, catalyzed by ribonucleotide reductase, which represents the rate-determining step in DNA replication as a target for antimalarial agents. We report the full-length DNA sequence corresponding to the large (PfR1) and small (PfR2) subunits of Plasmodium falciparum ribonucleotide reductase. The small subunit (PfR2) contains the major catalytic motif consisting of a tyrosyl radical and a dinuclear Fe site. Whereas PfR2 shares 59% amino acid identity with human R2, a striking sequence divergence between human R2 and PfR2 at the C terminus may provide a selective target for inhibition of the malarial enzyme. A synthetic oligopeptide corresponding to the C-terminal 7 residues of PfR2 inhibits mammalian ribonucleotide reductase at concentrations approximately 10-fold higher than that predicted to inhibit malarial R2. The gene encoding the large subunit (PfR1) contains a single intron. The cysteines thought to be involved in the reduction mechanism are conserved. In contrast to mammalian ribonucleotide reductase, the genes for PfR1 and PfR2 are located on the same chromosome and the accumulation of mRNAs for the two subunits follow different temporal patterns during the cell cycle. Images Fig. 2 Fig. 4 Fig. 5 PMID:8415692

AlphaScreen-based homogeneous assay using a pair of 25-residue artificial proteins for high-throughput analysis of non-native IgG.

PubMed

Senga, Yukako; Imamura, Hiroshi; Miyafusa, Takamitsu; Watanabe, Hideki; Honda, Shinya

2017-09-29

Therapeutic IgG becomes unstable under various stresses in the manufacturing process. The resulting non-native IgG molecules tend to associate with each other and form aggregates. Because such aggregates not only decrease the pharmacological effect but also become a potential risk factor for immunogenicity, rapid analysis of aggregation is required for quality control of therapeutic IgG. In this study, we developed a homogeneous assay using AlphaScreen and AF.2A1. AF.2A1 is a 25-residue artificial protein that binds specifically to non-native IgG generated under chemical and physical stresses. This assay is performed in a short period of time. Our results show that AF.2A1-AlphaScreen may be used to evaluate the various types of IgG, as AF.2A1 recognizes the non-native structure in the constant region (Fc region) of IgG. The assay was effective for detection of non-native IgG, with particle size up to ca. 500 nm, generated under acid, heat, and stirring conditions. In addition, this technique is suitable for analyzing non-native IgG in CHO cell culture supernatant and mixed with large amounts of native IgG. These results indicate the potential of AF.2A1-AlphaScreen to be used as a high-throughput evaluation method for process monitoring as well as quality testing in the manufacturing of therapeutic IgG.

Cloning and developmental expression of pea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit N-methyltransferase

DOEpatents

Houtz, Robert L.

1998-01-01

The gene sequence for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS) .epsilon.N-methyltransferase (protein methylase III or Rubisco LSMT) is disclosed. This enzyme catalyzes methylation of the .epsilon.-amine of lysine-14 in the large subunit of Rubisco. In addition, a full-length cDNA clone for Rubisco LSMT is disclosed. Transgenic plants and methods of producing same which (1) have the Rubisco LSMT gene inserted into the DNA, and (2) have the Rubisco LSMT gene product or the action of the gene product deleted from the DNA are also provided. Further, methods of using the gene to selectively deliver desired agents to a plant are also disclosed.

Cloning and developmental expression of pea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit epsilon N-methyltransferase

DOEpatents

Houtz, Robert L.

1999-01-01

The gene sequence for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS) .sup..epsilon. N-methyltransferase (protein methylase III or Rubisco LSMT) is disclosed. This enzyme catalyzes methylation of the .epsilon.-amine of lysine-14 in the large subunit of Rubisco. In addition, a full-length cDNA clone for Rubisco LSMT is disclosed. Transgenic plants and methods of producing same which (1) have the Rubisco LSMT gene inserted into the DNA, and (2) have the Rubisco LSMT gene product or the action of the gene product deleted from the DNA are also provided. Further, methods of using the gene to selectively deliver desired agents to a plant are also disclosed.

Cloning and developmental expression of pea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit N-methyltransferase

DOEpatents

Houtz, R.L.

1998-03-03

The gene sequence for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS) {epsilon}N-methyltransferase (protein methylase III or Rubisco LSMT) is disclosed. This enzyme catalyzes methylation of the {epsilon}-amine of lysine-14 in the large subunit of Rubisco. In addition, a full-length cDNA clone for Rubisco LSMT is disclosed. Transgenic plants and methods of producing same which (1) have the Rubisco LSMT gene inserted into the DNA, and (2) have the Rubisco LSMT gene product or the action of the gene product deleted from the DNA are also provided. Further, methods of using the gene to selectively deliver desired agents to a plant are also disclosed. 5 figs.

Cloning and developmental expression of pea ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit epsilon N-methyltransferase

DOEpatents

Houtz, R.L.

1999-02-02

The gene sequence for ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunit (LS){sup {epsilon}}N-methyltransferase (protein methylase III or Rubisco LSMT) is disclosed. This enzyme catalyzes methylation of the {epsilon}-amine of lysine-14 in the large subunit of Rubisco. In addition, a full-length cDNA clone for Rubisco LSMT is disclosed. Transgenic plants and methods of producing same which (1) have the Rubisco LSMT gene inserted into the DNA, and (2) have the Rubisco LSMT gene product or the action of the gene product deleted from the DNA are also provided. Further, methods of using the gene to selectively deliver desired agents to a plant are also disclosed. 8 figs.

The influence of residual apixaban on bleeding complications during and after catheter ablation of atrial fibrillation.

PubMed

Mukai, Yutaro; Wada, Kyoichi; Miyamoto, Koji; Nakagita, Kazuki; Fujimoto, Mai; Hosomi, Kouichi; Kuwahara, Takeshi; Takada, Mitsutaka; Kusano, Kengo; Oita, Akira

2017-10-01

The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications. Fifty-eight patients (Mean age of 64.7±12.5 years; 31 males, 27 females) were enrolled and administered apixaban twice daily. We analyzed trough apixaban concentration, activated clotting time (ACT), heparin dose, and bleeding complications during/after AF ablation. Apixaban concentrations were directly measured using mass spectrometry. Bleeding complications were observed in 19 patients (delayed hemostasis at the puncture site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion. The mean trough apixaban concentration was significantly lower in patients with bleeding complications than without (152.4±73.1 vs. 206.8±98.8 ng/mL respectively, P =0.037), while the heparin dose to achieve ACT>300 s was significantly higher in patients with bleeding complications (9368.4±2929.0 vs. 7987.2±2135.2 U/body respectively, P =0.046). Interestingly, a negative correlation was found between the trough apixaban concentration and the heparin dose to achieve ACT>300 s ( P =0.033, R=-0.281). Low residual plasma apixaban is associated with a higher incidence of bleeding complications during/after AF ablation, potentially because of a greater heparin requirement during AF ablation.

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

PubMed

Lanters, Eva A H; Teuwen, Christophe P; Yaksh, Ameeta; Kik, Charles; van der Does, Lisette J M E; Mouws, Elisabeth M J P; Knops, Paul; van Groningen, Nicole J; Hokken, Thijmen; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-10

Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF. Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery ( P =0.159), or between different types of surgery ( P =0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF ( P >0.05). EPoAF was not correlated with LPoAF in patients without a history of AF ( P =0.116), in contrast to patients with AF before surgery ( P <0.001). Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

PubMed Central

Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

2013-01-01

A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

Aberrant splicing in maize rough endosperm3 reveals a conserved role for U12 splicing in eukaryotic multicellular development

PubMed Central

Barbazuk, W. Brad

2017-01-01

RNA splicing of U12-type introns functions in human cell differentiation, but it is not known whether this class of introns has a similar role in plants. The maize ROUGH ENDOSPERM3 (RGH3) protein is orthologous to the human splicing factor, ZRSR2. ZRSR2 mutations are associated with myelodysplastic syndrome (MDS) and cause U12 splicing defects. Maize rgh3 mutants have aberrant endosperm cell differentiation and proliferation. We found that most U12-type introns are retained or misspliced in rgh3. Genes affected in rgh3 and ZRSR2 mutants identify cell cycle and protein glycosylation as common pathways disrupted. Transcripts with retained U12-type introns can be found in polysomes, suggesting that splicing efficiency can alter protein isoforms. The rgh3 mutant protein disrupts colocalization with a known ZRSR2-interacting protein, U2AF2. These results indicate conserved function for RGH3/ZRSR2 in U12 splicing and a deeply conserved role for the minor spliceosome to promote cell differentiation from stem cells to terminal fates. PMID:28242684

Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.

PubMed

Hussein, Ayman A; Bartz, Traci M; Gottdiener, John S; Sotoodehnia, Nona; Heckbert, Susan R; Lloyd-Jones, Donald; Kizer, Jorge R; Christenson, Robert; Wazni, Oussama; deFilippi, Christopher

2015-05-01

Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset. The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF). In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses. Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF. The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

DiBAC4(3) hits a “sweet spot” for the activation of arterial large-conductance Ca2+-activated potassium channels independently of the β1-subunit

PubMed Central

Scornik, Fabiana S.; Bucciero, Ronald S.; Wu, Yuesheng; Selga, Elisabet; Bosch Calero, Cristina; Brugada, Ramon

2013-01-01

The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)] has been reported as a novel large-conductance Ca2+-activated K+ (BK) channel activator with selectivity for its β1- or β4-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming α-subunit and a smooth muscle-abundant regulatory β1-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the β1-subunit, we explored the effects of DiBAC4(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC4(3) relies mostly on its α-subunit. We studied BK channels from wild-type and transgenic β1-knockout mice in excised patches. BK channels from brain arteries, with or without the β1-subunit, were similarly activated by DiBAC4(3). In addition, we found that saturating concentrations of DiBAC4(3) (∼30 μM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as −300 mV. This “sweet spot” for persistent activation is independent of Ca2+ and/or the β1–4-subunits and is fully achieved when DiBAC4(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC4(3) varies across species and/or vascular beds. DiBAC4(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. PMID:23542916

Marshall AAF, Manhattan, Kansas. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1980-02-25

TQACE 1.8 6.7 66-4 -5 -6 -- .0 § Td .0 .C .. 2 . -7 1.1 TRAM0 .6 TRACE .0 :0 :0’ :0 0 : TRACE- S 3. 0: 2.4! T .0 .0 .0 .0 .0 .0 TRACE 4.1 4 .1 TjWU TRCti...I’ / / // / ’ L!-OL LLitCf- ILOIY A.. CH L.t r TPSYCHROMETRIC SUMMARY A. LdA Td ~ ; tA,-VICLI/4AC 1 4 -IRSHHALL AAF KS (j-t V-7 v sTATON...82𔃻. 98z/10. 74!, 9.505 3.2bO I.959 d.2e,’,IU1921U.94411.T13?1...b 1b I ?1 00 TOTAL1OBS lUt 93 1! 112 1 99U 1014: 98W: 1U2 1: 1U11 98 8 L V 9 L 1q3 1

Diverse roles for ionotropic glutamate receptors on inhibitory interneurons in developing and adult brain.

PubMed

Akgül, Gülcan; McBain, Chris J

2016-10-01

Glutamate receptor-mediated recruitment of GABAergic inhibitory interneurons is a critical determinant of network processing. Early studies observed that many, but not all, interneuron glutamatergic synapses contain AMPA receptors that are GluA2-subunit lacking and Ca(2+) permeable, making them distinct from AMPA receptors at most principal cell synapses. Subsequent studies demonstrated considerable alignment of synaptic AMPA and NMDA receptor subunit composition within specific subtypes of interneurons, suggesting that both receptor expression profiles are developmentally and functionally linked. Indeed glutamate receptor expression profiles are largely predicted by the embryonic origins of cortical interneurons within the medial and caudal ganglionic eminences of the developing telencephalon. Distinct complements of AMPA and NMDA receptors within different interneuron subpopulations contribute to the differential recruitment of functionally divergent interneuron subtypes by common afferent inputs for appropriate feed-forward and feedback inhibitory drive and network entrainment. In contrast, the lesser-studied kainate receptors, which are often present at both pre- and postsynaptic sites, appear to follow an independent developmental expression profile. Loss of specific ionotropic glutamate receptor (iGluR) subunits during interneuron development has dramatic consequences for both cellular and network function, often precipitating circuit inhibition-excitation imbalances and in some cases lethality. Here we briefly review recent findings highlighting the roles of iGluRs in interneuron development. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Fish oil and postoperative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial.

PubMed

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G; Ferrazzi, Paolo; Gardner, Timothy J; Latini, Roberto; Libby, Peter; Lombardi, Federico; O'Gara, Patrick T; Page, Richard L; Tavazzi, Luigi; Tognoni, Gianni

2012-11-21

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results. To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF. The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first. Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events. In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00970489.

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.

Cloning, Purification, and Characterization of a Heterodimeric β-Galactosidase from Lactobacillus kefiranofaciens ZW3.

PubMed

He, Xi; Han, Ning; Wang, Yan-Ping

2016-01-01

Lactobacillus kefiranofaciens ZW3 was obtained from kefir grains, which have high lactose hydrolytic activity. In this study, a heterodimeric LacLM-type β-galactosidase gene (lacLM) from ZW3 was isolated, which was composed of two overlapping genes, lacL (1,884 bp) and lacM (960 bp) encoding large and small subunits with calculated molecular masses of 73,620 and 35,682 Da, respectively. LacLM, LacL, and LacM were expressed in Escherichia coli BL21(DE3) and these recombinant proteins were purified and characterized. The results showed that, compared with the recombinant holoenzyme, the recombinant large subunit exhibits obviously lower thermostability and hydrolytic activity. Moreover, the optimal temperature and pH of the holoenzyme and large subunit are 60°C and 7.0, and 50°C and 8.0, respectively. However, the recombinant small subunit alone has no activity. Interestingly, the activity and thermostability of the large subunit were greatly improved after mixing it with the recombinant small subunit. Therefore, the results suggest that the small subunit might play an important role in maintaining the stability of the structure of the catalytic center located in the large subunit.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

PubMed

Steinhubl, Steven R; Mehta, Rajesh R; Ebner, Gail S; Ballesteros, Marissa M; Waalen, Jill; Steinberg, Gregory; Van Crocker, Percy; Felicione, Elise; Carter, Chureen T; Edmonds, Shawn; Honcz, Joseph P; Miralles, Gines Diego; Talantov, Dimitri; Sarich, Troy C; Topol, Eric J

2016-05-01

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Fort Knox/Godman AAF, Kentucky Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1985-03-01

255-504 OVER 50 ASU’ O 1 S, .. . .- -- -2..... . 2 2 ABLE 0 S MEAN GREATEST LEAST S¢ NOWo ~l NONE TR AC E I i 2 i .4 I 2 66 2 VR10 A TS - 21C 3 4.6 7 12...ls ; P- . I - i r,--- 41a A.’g) i-u u At L 33.4 56.3 5P.9 1 L1.J1 1.11 61.161.1 61.1 61.1 61 1 I I.1f 61.11 1. 1 ! 61.11 61.1’ B )0r 347 - 6 Di 63. 65

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

PubMed

Massicotte-Azarniouch, David; Kuwornu, John Paul; Carrero, Juan-Jesus; Lam, Ngan N; Molnar, Amber O; Zimmerman, Deborah; McCallum, Megan K; Garg, Amit X; Sood, Manish M

2018-02-01

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Targeting mechanisms of high voltage-activated Ca2+ channels.

PubMed

Herlitze, Stefan; Xie, Mian; Han, Jing; Hümmer, Alexander; Melnik-Martinez, Katya V; Moreno, Rosa L; Mark, Melanie D

2003-12-01

Functional voltage-dependent Ca2+ channel complexes are assembled by three to four subunits: alpha1, beta, alpha2delta subunits (C. Leveque et al., 1994, J. Biol Chem. 269, 6306-6312; M. W. McEnery et al., 1991, Proc. Natl. Acad. Sci. U.S.A. 88, 11095-11099) and at least in muscle cells also y subunits (B. M. Curtis and W. A. Catterall, 1984, Biochemistry 23, 2113-2118). Ca2+ channels mediate the voltage-dependent Ca2+ influx in subcellular compartments, triggering such diverse processes as neurotransmitter release, dendritic action potentials, excitation-contraction, and excitation-transcription coupling. The targeting of biophysically defined Ca2+ channel complexes to the correct subcellular structures is, thus, critical to proper cell and physiological functioning. Despite their importance, surprisingly little is known about the targeting mechanisms by which Ca2+ channel complexes are transported to their site of function. Here we summarize what we know about the targeting of Ca2+ channel complexes through the cell to the plasma membrane and subcellular structures.

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

AWARD NUMBER: W81XWH-13-1-0309 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD RECIPIENT: Wake Forest University Health Sciences

Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants*

PubMed Central

Chen, Lie; Bi, Danlei; Tian, Lijun; McClafferty, Heather; Steeb, Franziska; Ruth, Peter; Knaus, Hans Guenther; Shipston, Michael J.

2013-01-01

Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels. PMID:23504458

Modulated exchange bias in NiFe/CoO/α-Fe2O3 trilayers and NiFe/CoO bilayers

NASA Astrophysics Data System (ADS)

Li, X.; Lin, K.-W.; Yeh, W.-C.; Desautels, R. D.; van Lierop, J.; Pong, Philip W. T.

2017-02-01

While the exchange bias in ferromagnetic/antiferromagnetic (FM/AF) bilayer and FM1/AF/FM2 trilayer configurations has been widely investigated, the role of an AF2 layer in FM/AF1/AF2 trilayer configurations is still not well understood. In this work, the magnetic properties of NiFe/CoO, NiFe/α-Fe2O3 bilayers, and NiFe/CoO/α-Fe2O3 trilayer were studied comparatively. The microstructure and chemical composition were characterized. Temperature dependent magnetometry reveals increased irreversibility temperature in NiFe/CoO/α-Fe2O3 trilayer compared with NiFe/CoO bilayer. The magnetic hysteresis loops show that the exchange bias (Hex) and coercivity (Hc) depend strongly on the anisotropy of AF layer (CoO, α-Fe2O3 and CoO/α-Fe2O3). Our work shows that the AF1/AF2 interfacial interactions can be used effectively for tuning the exchange bias in FM/AF1/AF2 trilayers.

Catalytic Subunit 1 of Protein Phosphatase 2A Is a Subunit of the STRIPAK Complex and Governs Fungal Sexual Development.

PubMed

Beier, Anna; Teichert, Ines; Krisp, Christoph; Wolters, Dirk A; Kück, Ulrich

2016-06-21

The generation of complex three-dimensional structures is a key developmental step for most eukaryotic organisms. The details of the molecular machinery controlling this step remain to be determined. An excellent model system to study this general process is the generation of three-dimensional fruiting bodies in filamentous fungi like Sordaria macrospora Fruiting body development is controlled by subunits of the highly conserved striatin-interacting phosphatase and kinase (STRIPAK) complex, which has been described in organisms ranging from yeasts to humans. The highly conserved heterotrimeric protein phosphatase PP2A is a subunit of STRIPAK. Here, catalytic subunit 1 of PP2A was functionally characterized. The Δpp2Ac1 strain is sterile, unable to undergo hyphal fusion, and devoid of ascogonial septation. Further, PP2Ac1, together with STRIPAK subunit PRO22, governs vegetative and stress-related growth. We revealed in vitro catalytic activity of wild-type PP2Ac1, and our in vivo analysis showed that inactive PP2Ac1 blocks the complementation of the sterile deletion strain. Tandem affinity purification, followed by mass spectrometry and yeast two-hybrid analysis, verified that PP2Ac1 is a subunit of STRIPAK. Further, these data indicate links between the STRIPAK complex and other developmental signaling pathways, implying the presence of a large interconnected signaling network that controls eukaryotic developmental processes. The insights gained in our study can be transferred to higher eukaryotes and will be important for understanding eukaryotic cellular development in general. The striatin-interacting phosphatase and kinase (STRIPAK) complex is highly conserved from yeasts to humans and is an important regulator of numerous eukaryotic developmental processes, such as cellular signaling and cell development. Although functional insights into the STRIPAK complex are accumulating, the detailed molecular mechanisms of single subunits are only partially understood. The first fungal STRIPAK was described in Sordaria macrospora, which is a well-established model organism used to study the formation of fungal fruiting bodies, three-dimensional organ-like structures. We analyzed STRIPAK subunit PP2Ac1, catalytic subunit 1 of protein phosphatase PP2A, to study the importance of the catalytic activity of this protein during sexual development. The results of our yeast two-hybrid analysis and tandem affinity purification, followed by mass spectrometry, indicate that PP2Ac1 activity connects STRIPAK with other signaling pathways and thus forms a large interconnected signaling network. Copyright © 2016 Beier et al.

Atrial Fibrillation Ablation and its Impact on Stroke.

PubMed

Graves, Kevin G; Jacobs, Victoria; May, Heidi T; Cutler, Michael J; Day, John D; Bunch, T Jared

2018-01-24

Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet fully understood. Catheter ablation has shown to be an effective strategy for rhythm management and several small or retrospective studies have shown that stroke rates are decreased in ablated AF patients compared to those medically managed. Several studies even show that ablation returns stroke risk to that of non-AF patients. Large scale, prospective trials will further illuminate this connection and provide mechanistic understanding of the role of the procedure versus the process of selection for the procedure and peri- and post-procedural therapy and management. Furthermore, modification of risk factors associated with AF show a significant increase in the sustained success of AF ablation and can also moderate the progression of AF.

Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review.

PubMed

Roman, Crina; Bruley des Varannes, Stanislas; Muresan, Lucian; Picos, Alina; Dumitrascu, Dan L

2014-07-28

To analyze the potential relationship between gastroesophageal reflux disease (GERD) and the development of atrial fibrillation (AF). Using the key words "atrial fibrillation and gastroesophageal reflux", "atrial fibrillation and esophagitis, peptic", "atrial fibrillation and hernia, hiatal" the PubMed, EMBASE, Cochrane Library, OVIDSP, WILEY databases were screened for relevant publications on GERD and AF in adults between January 1972-December 2013. Studies written in languages other than English or French, studies not performed in humans, reviews, case reports, abstracts, conference presentations, letters to the editor, editorials, comments and opinions were not taken into consideration. Articles treating the subject of radiofrequency ablation of AF and the consecutive development of GERD were also excluded. Two thousand one hundred sixty-one titles were found of which 8 articles met the inclusion criteria. The presence of AF in patients with GERD was reported to be between 0.62%-14%, higher compared to those without GERD. Epidemiological data provided by these observational studies showed that patients with GERD, especially those with more severe GERD-related symptoms, had an increased risk of developing AF compared with those without GERD, but a causal relationship between GERD and AF could not be established based on these studies. The mechanisms of AF as a consequence of GERD remain largely unknown, with inflammation and vagal stimulation playing a possible role in the development of these disorders. Treatment with proton pomp inhibitors may improve symptoms related to AF and facilitate conversion to sinus rhythm. Although links between AF and GERD exist, large randomized clinical studies are required for a better understanding of the relationship between these two entities.

Improving cost-effectiveness of and outcomes from drug therapy in patients with atrial fibrillation in managed care: role of the pharmacist.

PubMed

Johnson, Samuel G

2009-08-01

The medical care costs for procedures, medications, and testing associated with atrial fibrillation (AF) in the United States are high and projected to increase markedly in the future as the number of Americans affected grows. The burden on patient quality of life, the health care system, and society are pharmacoeconomic considerations in managing AF. To identify key pharmacoeconomic considerations in managing AF and describe ways in which managed care pharmacists can improve the cost-effectiveness of and outcomes from drug therapy for AF. The high medical care costs of AF are largely the result of the high cost of hospitalization and inpatient procedures. Recurrence of AF dramatically increases costs, especially for hospital care. Managed care pharmacists have many opportunities to provide cost-effective care to and improve outcomes in patients with AF. Policy and process review, population management, and case management are key strategies for improving outcomes in patients with AF. Pharmacist input into policy and process review, including pharmacy benefits design, formulary management, and the use of information technology, can help ensure that the use of drug therapy for AF is cost-effective. Population management strategies, such as development of clinical pathways and patient registries, seek to improve the quality, consistency, and cost-effectiveness of care and the likelihood that desired therapeutic outcomes are achieved through targeted interventions. Case management strategies focus on longitudinal care for individuals in order to improve quality. Pharmacist-managed anticoagulation services and antiarrhythmic drug monitoring are the 2 most widely known case management strategies for patients with AF. Managed care pharmacists can screen patients with AF for the use of anticoagulation, which is needed to prevent embolic stroke but is under-used, even though recommended by evidence-based guidelines. The clinical efficacy and cost-effectiveness of pharmacist-managed anticoagulation services for patients with AF are well documented. Pharmacist-managed antiarrhythmic drug monitoring is a less well-known case management strategy that facilitates early detection and intervention to minimize toxicity. Managed care pharmacists can play an instrumental role in implementing strategies to improve the cost-effectiveness of and outcomes from drug therapy for AF.

Clinical significance of nutritional status in patients with atrial fibrillation: An overview of current evidence.

PubMed

Anaszewicz, Marzena; Budzyński, Jacek

2017-05-01

Obesity is a well-known atherosclerosis risk factor; however, its role and the importance of undernutrition in atrial fibrillation (AF) pathogenesis are still not well understood. The aim of this study was to present the current state of knowledge on this issue in different groups of patients. Systematic review of papers published between 1980 and 2016. The literature shows contradicting views regarding the impact of nutritional status on the risk, course, and complications of AF. On the one hand, it has been revealed that overweight, obesity, and high birth mass increase the risk of AF, and that their reduction is linked to an improved course of AF and reduced all-cause and cardiovascular mortality. On the other hand, a so-called obesity paradox has been found, which shows lower all-cause mortality in overweight patients with AF compared to those of normal weight or who are underweight. It has also been shown, although based on a small number of studies, that the relationship between nutritional status and risk of AF and its complication may be U-shaped, which means that not only patients with obesity, but also individuals with underweight, cachexia, and low birth weight may have an increased risk and poor outcome of AF. The relationship between patients' nutritional status and the course of AF has become clearer but it requires further studies examining the importance of weight reduction on AF course. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

U.S. EPA, Pesticide Product Label, ULTRA-FRESH AF-5, 10/21/1983

EPA Pesticide Factsheets

2011-04-19

... It tlI'Gathtl''1 i. • u"tcult. 91"" • .uYlJrn. Cell. ,.hydO:'oIA. Jt .. ... tOl leal. I., in tho p' ••• nc. ~f .... t.tu.o. t

Thickness dependence of exchange anisotropy for (0 0 1) oriented Mn 89Pt 11/NiFe and Mn 80Ir 20/NiFe bilayers

NASA Astrophysics Data System (ADS)

Kume, T.; Yamato, T.; Kato, T.; Tsunashima, S.; Iwata, S.

2007-03-01

Antiferromagnetic layer thickness dependences of exchange anisotropy for (0 0 1) oriented Mn 89Pt 11 ( tAF nm)/Ni 80Fe 20 (5 nm) and Mn 80Ir 20 ( tAF nm)/Ni 80Fe 20 (5 nm) were investigated. For Mn 89Pt 11/NiFe, the exchange bias field appeared at tAF⩾5 nm. This critical thickness was found to be thicker than that of Mn 80Ir 20/NiFe ( tAF=3 nm). The thickness dependence of exchange bias field agreed well with that of 1-fold Fourier amplitude estimated from in-plane torque curves. The large coercivity of about 100 Oe was found for Mn 89Pt 11/NiFe at tAF=30 nm compared to that of Mn 80Ir 20/NiFe. The large coercivity in Mn 89Pt 11/NiFe bilayers seems to result from the large 4-fold anisotropy in their torque curve.

Proliferative Enterocolitis Associated with Dual Infection with Enteropathogenic Escherichia coli and Lawsonia intracellularis in Rabbits

PubMed Central

Schauer, David B.; McCathey, Sonya N.; Daft, Barbara M.; Jha, Sharda S.; Tatterson, Lisa E.; Taylor, Nancy S.; Fox, James G.

1998-01-01

Both enteropathogenic Escherichia coli (EPEC) and an obligate intracellular bacterium, previously referred to as an intracellular Campylobacter-like organism and now designated Lawsonia intracellularis, have been reported as causes of enterocolitis in rabbits. An outbreak of enterocolitis in a group of rabbits, characterized by an unusually high rate of mortality, was found to be associated with dual infection with EPEC and L. intracellularis. The EPEC strain was found to have eaeA gene homology but was negative for afrA homology. The absence of the afrA gene, which encodes the structural subunit for the AF/R1 pilus, indicates that this rabbit EPEC strain is distinct from the prototypic RDEC-1 strain. This finding suggests that rabbit EPEC strains widely reported in Western Europe, which lack AF/R1 pili, are also present in rabbits in the United States. Dual infection with these two pathogens in rabbits has not been previously reported and may have contributed to the unusually high mortality observed in this outbreak. PMID:9620403

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

Reducing Air Force Fighter Pilot Shortages

DTIC Science & Technology

2015-12-31

that active-component fighter pilot requirements (particularly nonflying staff requirements) exceed its capacity to train and provide initial...pilots in the reserve components. This research was sponsored by four elements of the U.S. Air Force: the Deputy Chief of Staff for Operations (AF/A3...the Deputy Chief of Staff for Manpower, Personnel and Services (AF/A1); the Commander, Air Force Reserve Command (AFRC/CC); and the Director, Air

Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation

PubMed Central

Masè, Michela; Grasso, Margherita; Avogaro, Laura; D’Amato, Elvira; Tessarolo, Francesco; Graffigna, Angelo; Denti, Michela Alessandra; Ravelli, Flavia

2017-01-01

MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-Cq, GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions. PMID:28117343

The role of modifications in codon discrimination by tRNA(Lys)UUU.

PubMed

Murphy, Frank V; Ramakrishnan, Venki; Malkiewicz, Andrzej; Agris, Paul F

2004-12-01

The natural modification of specific nucleosides in many tRNAs is essential during decoding of mRNA by the ribosome. For example, tRNA(Lys)(UUU) requires the modification N6-threonylcarbamoyladenosine at position 37 (t(6)A37), adjacent and 3' to the anticodon, to bind AAA in the A site of the ribosomal 30S subunit. Moreover, it can only bind both AAA and AAG lysine codons when doubly modified with t(6)A37 and either 5-methylaminomethyluridine or 2-thiouridine at the wobble position (mnm(5)U34 or s(2)U34). Here we report crystal structures of modified tRNA anticodon stem-loops bound to the 30S ribosomal subunit with lysine codons in the A site. These structures allow the rationalization of how modifications in the anticodon loop enable decoding of both lysine codons AAA and AAG.

PUB22 and PUB23 U-BOX E3 ligases directly ubiquitinate RPN6, a 26S proteasome lid subunit, for subsequent degradation in Arabidopsis thaliana.

PubMed

Cho, Seok Keun; Bae, Hansol; Ryu, Moon Young; Wook Yang, Seong; Kim, Woo TaeK

2015-09-04

Drought stress strongly affects plant growth and development, directly connected with crop yields, accordingly. However, related to the function of U-BOX E3 ligases, the underlying molecular mechanisms of desiccation stress response in plants are still largely unknown. Here we report that PUB22 and PUB23, two U-box E3 ligase homologs, tether ubiquitins to 19S proteasome regulatory particle (RP) subunit RPN6, leading to its degradation. RPN6 was identified as an interacting substrate of PUB22 by yeast two-hybrid screening, and in vitro pull-down assay confirmed that RPN6 interacts not only with PUB22, but also with PUB23. Both PUB22 and PUB23 were able to conjugate ubiquitins on RPN6 in vitro. Furthermore, RPN6 showed a shorter protein half-life in PUB22 overexpressing plants than in wild-type, besides RPN6 was significantly stabilized in pub22pub23 double knockout plants. Taken together, these results solidify a notion that PUB22 and PUB23 can alter the activity of 26S proteasome in response to drought stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two different complexes

PubMed Central

Soltanieh, Sahar; Lapensée, Martin; Dragon, François

2014-01-01

Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the early processing steps leading to the production of 18S ribosomal RNA. We also found that Bfr2 and Enp2 associate with the U3 small nucleolar RNA (snoRNA), the U3-specific protein Mpp10 and various pre-18S ribosomal RNA species. Thus, we propose that Bfr2, Dbp4 and Enp2 are components of the small subunit (SSU) processome, a large complex of ∼80S. Sucrose gradient sedimentation analyses indicated that Dbp4, Bfr2 and Enp2 sediment in a peak of ∼50S and in a peak of ∼80S. Bfr2, Dbp4 and Enp2 associate together in the 50S complex, which does not include the U3 snoRNA; however, they associate with U3 snoRNA in the 80S complex (SSU processome). Immunoprecipitation experiments revealed that U14 snoRNA associates with Dbp4 in the 50S complex, but not with Bfr2 or Enp2. The assembly factor Tsr1 is not part of the ‘50S’ complex, indicating this complex is not a pre-40S ribosome. A combination of experiments leads us to propose that Bfr2, Enp2 and Dbp4 are recruited at late steps during assembly of the SSU processome. PMID:24357410

Characterization and Evolution of Anthranilate 1,2-Dioxygenase from Acinetobacter sp. Strain ADP1

PubMed Central

Eby, D. Matthew; Beharry, Zanna M.; Coulter, Eric D.; Kurtz, Donald M.; Neidle, Ellen L.

2001-01-01

The two-component anthranilate 1,2-dioxygenase of the bacterium Acinetobacter sp. strain ADP1 was expressed in Escherichia coli and purified to homogeneity. This enzyme converts anthranilate (2-aminobenzoate) to catechol with insertion of both atoms of O2 and consumption of one NADH. The terminal oxygenase component formed an α3β3 hexamer of 54- and 19-kDa subunits. Biochemical analyses demonstrated one Rieske-type [2Fe-2S] center and one mononuclear nonheme iron center in each large oxygenase subunit. The reductase component, which transfers electrons from NADH to the oxygenase component, was found to contain approximately one flavin adenine dinucleotide and one ferredoxin-type [2Fe-2S] center per 39-kDa monomer. Activities of the combined components were measured as rates and quantities of NADH oxidation, substrate disappearance, product appearance, and O2 consumption. Anthranilate conversion to catechol was stoichiometrically coupled to NADH oxidation and O2 consumption. The substrate analog benzoate was converted to a nonaromatic benzoate 1,2-diol with similarly tight coupling. This latter activity is identical to that of the related benzoate 1,2-dioxygenase. A variant anthranilate 1,2-dioxygenase, previously found to convey temperature sensitivity in vivo because of a methionine-to-lysine change in the large oxygenase subunit, was purified and characterized. The purified M43K variant, however, did not hydroxylate anthranilate or benzoate at either the permissive (23°C) or nonpermissive (39°C) growth temperatures. The wild-type anthranilate 1,2-dioxygenase did not efficiently hydroxylate methylated or halogenated benzoates, despite its sequence similarity to broad-substrate specific dioxygenases that do. Phylogenetic trees of the α and β subunits of these terminal dioxygenases that act on natural and xenobiotic substrates indicated that the subunits of each terminal oxygenase evolved from a common ancestral two-subunit component. PMID:11114907

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

User Requirements Analyzer (URA) User’s Manual H6180/Multics/Version 3.3.

DTIC Science & Technology

1978-07-01

4.3 Enterinq Data Into An Input File 11 4.4 Using NAME- GEN 11 4.5 Using PUNCH Files 12 5. Receiving Output From URA Commands 12 5.1 The...CONSISTENCY RBPOPT 2fc^ KWIC INDEX 27? LIST-CHANGES Report 276 NAME- GEN 28C NAME LIST 29? PICTURE 313 PROCESS CHAIN...428 FREQUENCY U32 HELP U33 INPUT-PSL 434 INTERVAL-CONSISTENCY 435 KWIC 436 LIST-CtlANGES 437 N Af.E- GEN 4 38 NAf’B-LIST

Mather AFB, California. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-06-15

8217:A 3 513 MATHER 4FB :ALIFOPNIA REIurED UNIFORM IIMMARY ’,F TECN: AL APPLI:AT I 3KN CENTiiR CC A 15 UN37 N: :F ED U:AFC:.A: D:-37 042 F -,4/2 MI. L3A...cr : 2 a IA 4 0. 3 2 0 m W X 0 3r at 24- 4A or0 z 49 o- K6 aL 4 .l vi U, t 4 62 K KA =, -J4 eK 0.0 9k 0 0 ,4 K U, U, -r cc Li La a.. 2 64. 0 x 4 cc " A...N*. 0 0 0 0 0 a, 0 * 00 * N. * 00 * z 11 cr al z -a 0P 03 . 0 . n f-0 M * 0 via f- OM ~ -4 A . mf LA 0 1 0 6A0 *0 li "Z .0 0 0 0 L. 4L 0 .~ 0 -j U

Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?

PubMed Central

Contractor, Tahmeed; Khasnis, Atul

2011-01-01

Atrial Fibrillation (AF) is a common arrhythmia with an incidence that is as high as 10% in the elderly population. Given the large proportion of strokes caused by AF as well as the associated morbidity and mortality, reducing stroke burden is the most important part of AF management. While warfarin significantly reduces the risk of AF-related stroke, perceived bleeding risks and compliance limit its widespread use in the high-risk AF population. The left atrial appendage is believed to be the “culprit” for thrombogenesis in nonvalvular AF and is a new therapeutic target for stroke prevention. The purpose of this review is to explore the evolving field of percutaneous LAA occlusion. After briefly highlighting the risk of stroke with AF, problems with warfarin, and the role of the LAA in clot formation, this article discusses the feasibility and efficacy of various devices which have been developed for percutaneous LAA occlusion. PMID:21559225

Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study

PubMed Central

Søgaard, Mette; Skjøth, Flemming; Kjældgaard, Jette Nordstrøm; Larsen, Torben Bjerregaard; Hjortshøj, Søren Pihlkjær; Riahi, Sam

2017-01-01

Objectives Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders. Design Nationwide registry-based cohort study. Setting Denmark (population 5.6 million), 2000–2015. Participants Patients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders. Exposure Inpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease. Primary and secondary outcome measures HRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT). Results Compared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15). Conclusion Patients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders. PMID:29217725

Association between Air Pollution and Emergency Room Visits for Atrial Fibrillation.

PubMed

Solimini, Angelo G; Renzi, Matteo

2017-06-20

Despite the large prevalence in the population, possible factors responsible for the induction of atrial fibrillation (AF) events in susceptible individuals remain incompletely understood. We investigated the association between air pollution levels and emergency department admissions for AF in Rome. We conducted a 14 years' time-series study to evaluate the association between the daily levels of air pollution (particulate matter, PM 10 and PM 2.5 , and nitrogen dioxide, NO₂) and the daily count of emergency accesses for AF (ICD-9 code: 427.31). We applied an over-dispersed conditional Poisson model to analyze the associations at different lags after controlling for time, influenza epidemics, holiday periods, temperature, and relative humidity. Additionally, we evaluated bi-pollutant models by including the other pollutant and the influence of several effect modifiers such as personal characteristics and pre-existing medical conditions. In the period of study, 79,892 individuals were admitted to the emergency departments of Rome hospitals because of AF (on average, 15.6 patients per day: min = 1, max = 36). Air pollution levels were associated with increased AF emergency visits within 24 h of exposure. Effect estimates ranged between 1.4% (0.7-2.3) for a 10 µg/m³ increase of PM 10 to 3% (1.4-4.7) for a 10 µg/m³ increase of PM 2.5 at lag 0-1 day. Those effects were higher in patients ≥75 years for all pollutants, male patients for PM 10 , and female patients for NO₂. The presence of previous cardiovascular conditions, but not other effect modifiers, increase the pollution effects by 5-8% depending on the lag. This study found evidence that air pollution is associated with AF emergency visits in the short term.

How the structure of the large subunit controls function in an oxygen-tolerant [NiFe]-hydrogenase

PubMed Central

Bowman, Lisa; Flanagan, Lindsey; Fyfe, Paul K.; Parkin, Alison; Hunter, William N.; Sargent, Frank

2014-01-01

Salmonella enterica is an opportunistic pathogen that produces a [NiFe]-hydrogenase under aerobic conditions. In the present study, genetic engineering approaches were used to facilitate isolation of this enzyme, termed Hyd-5. The crystal structure was determined to a resolution of 3.2 Å and the hydro-genase was observed to comprise associated large and small subunits. The structure indicated that His229 from the large subunit was close to the proximal [4Fe–3S] cluster in the small subunit. In addition, His229 was observed to lie close to a buried glutamic acid (Glu73), which is conserved in oxygen-tolerant hydrogenases. His229 and Glu73 of the Hyd-5 large subunit were found to be important in both hydrogen oxidation activity and the oxygen-tolerance mechanism. Substitution of His229 or Glu73 with alanine led to a loss in the ability of Hyd-5 to oxidize hydrogen in air. Furthermore, the H229A variant was found to have lost the overpotential requirement for activity that is always observed with oxygen-tolerant [NiFe]-hydrogenases. It is possible that His229 has a role in stabilizing the super-oxidized form of the proximal cluster in the presence of oxygen, and it is proposed that Glu73could play a supporting role in fine-tuning the chemistry of His229 to enable this function. PMID:24428762

Kinetic properties of two Rhizopus exo-polygalacturonase enzymes hydrolyzing galacturonic acid oligomers using isothermal titration calorimetry

USDA-ARS?s Scientific Manuscript database

The kinetic characteristics of two Rhizopus oryzae exo-polygalacturonases acting on galacturonic acid oligomers (GalpA) were determined using isothermal titration calorimetry (ITC). RPG15 hydrolyzing (GalpA)2 demonstrated a Km of 55 uM and kcat of 10.3 s^-1^ while RPG16 was shown to have greater af...

Novel ECCM Techniques for Army Tactical Communications.

DTIC Science & Technology

1979-06-29

spectral density 89 AA993 83 TELECOMU4ICATIONS ASSOCIATES FAIRFAX VA F/ 17/4 NOVEL ECCN TECHIU9ES FOR ARMY TACTICAL COMMUNICATIONSd(U) JUN 79 R L...pi-g Geterator ?ijuz. A.8 -?cwer Scectra2. :ems±t 7; N 4, Af~ 7 AA093 W3 TELECOMUNICATIONS ASSOCIATES FAIRFAX VA F/6 17/4 NOVEL ECCN TECHNIQUE F R

Dobbins AFB, Georgia Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1984-04-25

Ii4 GL(,BAL CLIMATOLOGY BRANCH uSArETAC WEATHER CONDITIONS Ar7 WEATHFR SERVICE/MAC 2ATIN DORINS AFR TIONNAME I -A YEARS PE;?CENTAGE FREQUENCY OF...USAFETAC CEILING VERSUS VISIBILITY AIr WEATHER SF1VICE/MAC ?"󈧚’ " DORIN , 4FB GA _4-81 JU - PERCENTAGE FREQUENCY OF OCCURRENCE (FROM HOURLY OBSERVATIONS

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes.

PubMed

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I; Yoon, Bo Hyun; Hassan, Sonia S; Kim, Chong Jai; Yeo, Lami

2014-11-01

Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation. AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). (i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02). (i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

PubMed Central

Gu, Mingyu; Liu, Qiang; Watanabe, Shigeki; Sun, Lin; Hollopeter, Gunther; Grant, Barth D; Jorgensen, Erik M

2013-01-01

The clathrin adaptor complex AP2 is thought to be an obligate heterotetramer. We identify null mutations in the α subunit of AP2 in the nematode Caenorhabditis elegans. α-adaptin mutants are viable and the remaining μ2/β hemicomplex retains some function. Conversely, in μ2 mutants, the alpha/sigma2 hemicomplex is localized and is partially functional. α-μ2 double mutants disrupt both halves of the complex and are lethal. The lethality can be rescued by expression of AP2 components in the skin, which allowed us to evaluate the requirement for AP2 subunits at synapses. Mutations in either α or μ2 subunits alone reduce the number of synaptic vesicles by about 30%; however, simultaneous loss of both α and μ2 subunits leads to a 70% reduction in synaptic vesicles and the presence of large vacuoles. These data suggest that AP2 may function as two partially independent hemicomplexes. DOI: http://dx.doi.org/10.7554/eLife.00190.001 PMID:23482940

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Hansen, J.; Sander, M.; Horn, K.; Ogoh, S.; Smith, M. L.; Secher, N. H.; Raven, P. B.

2001-01-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

PubMed

Fadel, P J; Stromstad, M; Hansen, J; Sander, M; Horn, K; Ogoh, S; Smith, M L; Secher, N H; Raven, P B

2001-06-01

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

PubMed

Sardana, Mayank; Ogunsua, Adedotun A; Spring, Matthew; Shaikh, Amir; Asamoah, Owusu; Stokken, Glenn; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; Floyd, Kevin C; Aurigemma, Gerard P; Parikh, Nisha I; McManus, David D

2016-12-01

Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA. All AF patients undergoing index CA were enrolled in a prospective institutional AF Treatment Registry between 2011 and 2014. LAFI was measured post hoc from pre-ablation clinical echocardiographic images in 168 participants. Participants were mostly male (33% female), middle-aged (60 ± 10 years), obese and had paroxysmal AF (64%). Mean LAFI was 25.9 ± 17.6. Over 12 months of follow-up, 78 participants (46%) experienced a late AF recurrence. In logistic regression analyses adjusting for factors known to be associated with AF, lower LAFI remained associated with AF recurrence after CA [OR 0.04 (0.01-0.67), P = 0.02]. LAFI discriminated AF recurrence after CA slightly better than CHADS2 (C-statistic 0.60 LAFI, 0.57 CHADS2). For participants with persistent AF, LAFI performed significantly better than CHADS2 score (C statistic = 0.79 LAFI, 0.56 CHADS2, P = 0.02). LAFI, an echocardiographic measure of atrial function, is associated with AF recurrence after CA and has improved ability to discriminate AF recurrence as compared to the CHADS-2 score, especially among persistent AF patients. Since LAFI can be calculated using standard 2D echocardiographic images, it may be a helpful tool for predicting AF recurrence. © 2016 Wiley Periodicals, Inc.

The N-terminus of RPA large subunit and its spatial position are important for the 5'->3' resection of DNA double-strand breaks.

PubMed

Tammaro, Margaret; Liao, Shuren; McCane, Jill; Yan, Hong

2015-10-15

The first step of homology-dependent repair of DNA double-strand breaks (DSBs) is the resection of the 5' strand to generate 3' ss-DNA. Of the two major nucleases responsible for resection, EXO1 has intrinsic 5'->3' directionality, but DNA2 does not. DNA2 acts with RecQ helicases such as the Werner syndrome protein (WRN) and the heterotrimeric eukaryotic ss-DNA binding protein RPA. We have found that the N-terminus of the RPA large subunit (RPA1N) interacts with both WRN and DNA2 and is essential for stimulating WRN's 3'->5' helicase activity and DNA2's 5'->3' ss-DNA exonuclease activity. A mutant RPA complex that lacks RPA1N is unable to support resection in Xenopus egg extracts and human cells. Furthermore, relocating RPA1N to the middle subunit but not to the small subunit causes severe defects in stimulating DNA2 and WRN and in supporting resection. Together, these findings suggest that RPA1N and its spatial position are critical for restricting the directionality of the WRN-DNA2 resection pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The N-terminus of RPA large subunit and its spatial position are important for the 5′->3′ resection of DNA double-strand breaks

PubMed Central

Tammaro, Margaret; Liao, Shuren; McCane, Jill; Yan, Hong

2015-01-01

The first step of homology-dependent repair of DNA double-strand breaks (DSBs) is the resection of the 5′ strand to generate 3′ ss-DNA. Of the two major nucleases responsible for resection, EXO1 has intrinsic 5′->3′ directionality, but DNA2 does not. DNA2 acts with RecQ helicases such as the Werner syndrome protein (WRN) and the heterotrimeric eukaryotic ss-DNA binding protein RPA. We have found that the N-terminus of the RPA large subunit (RPA1N) interacts with both WRN and DNA2 and is essential for stimulating WRN's 3′->5′ helicase activity and DNA2's 5′->3′ ss-DNA exonuclease activity. A mutant RPA complex that lacks RPA1N is unable to support resection in Xenopus egg extracts and human cells. Furthermore, relocating RPA1N to the middle subunit but not to the small subunit causes severe defects in stimulating DNA2 and WRN and in supporting resection. Together, these findings suggest that RPA1N and its spatial position are critical for restricting the directionality of the WRN-DNA2 resection pathway. PMID:26227969

The role of the atrial electromechanical delay in predicting atrial fibrillation in beta-thalassemia major patients.

PubMed

Rago, Anna; Russo, Vincenzo; Papa, Andrea Antonio; Ciardiello, Carmine; Pannone, Bruno; Mayer, Maria Carolina; Cimmino, Giovanni; Nigro, Gerardo

2017-03-01

Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (β-TM) patients. The aim of the current study was to evaluate the atrial electromechanical delay (AEMD) in a large β-TM population with normal cardiac function and its relationship to atrial fibrillation (AF) onset. Eighty β-TM patients (44 men, 36 women), with a mean age of 36.2 ± 11.1 years, and 80 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of AF during a 5-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram (ECG). Compared to the healthy control group, the β-TM patients showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the β-TM group into two subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD were significantly higher in the subgroup with AF compared to the subgroup without AF. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying β-TM patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a sensitivity of 81.2% and a specificity of 98.7% in identifying this category of patients. Our results showed that the echocardiographic atrial electromechanical delay indices (intra-left and inter-AEMD) and the PD were significantly increased in β-TM subjects with normal cardiac function. PD and AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess the AF risk in β-TM patients.

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.

An all sulfur analogue of the smallest subunit of F420-non-reducing hydrogenase from Methanococcus voltae--metal binding and structure.

PubMed

Pfeiffer, M; Klein, A; Steinert, P; Schomburg, D

The 25 amino acid long subunit VhuU of the F420-non-reducing hydrogenase from Methanococcus voltae contains selenocysteine within the consensus sequence of known [NiFe] hydrogenases DP(C or U)CxxCxxH (U = selenocysteine). The sulfur-analogue VhuUc was chemically synthesized, purified and its metal binding capability, the catalytic properties, and structural features were investigated. The polypeptide was able to bind nickel, but did not catalyse the heterolytic activation of H2. 2D-NMR spectroscopy revealed an alpha-helical secondary structure for the 15 N-terminal amino acids in 50% TFE. Nickel only binds to the C-terminus, which contains the conserved amino acid motif. Structures derived from the NMR data are compatible with the participation of both sulfur atoms from the conserved cysteine residues in a metal ion binding. Structures obtained from the data sets for Ni.VhuUc as well as Zn.VhuUc showed no further ligands. The informational value for Ni.VhuUc was low due to paramagnetism.

The Purification of the Chlamydomonas reinhardtii chloroplast ClpP complex: additional subunits and structural features

PubMed Central

Derrien, Benoît; Majeran, Wojciech; Effantin, Grégory; Ebenezer, Joseph; Friso, Giulia; van Wijk, Klaas J.; Steven, Alasdair C.; Maurizi, Michael R.; Vallon, Olivier

2012-01-01

The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero-oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub-complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits PMID:22772861

Implications of High Molecular Divergence of Nuclear rRNA and Phylogenetic Structure for the Dinoflagellate Prorocentrum (Dinophyceae, Prorocentrales).

PubMed

Boopathi, Thangavelu; Faria, Daphne Georgina; Cheon, Ju-Yong; Youn, Seok Hyun; Ki, Jang-Seu

2015-01-01

The small and large nuclear subunit molecular phylogeny of the genus Prorocentrum demonstrated that the species are dichotomized into two clades. These two clades were significantly different (one-factor ANOVA, p < 0.01) with patterns compatible for both small and large subunit Bayesian phylogenetic trees, and for a larger taxon sampled dinoflagellate phylogeny. Evaluation of the molecular divergence levels showed that intraspecies genetic variations were significantly low (t-test, p < 0.05), than those for interspecies variations (> 2.9% and > 26.8% dissimilarity in the small and large subunit [D1/D2], respectively). Based on the calculated molecular divergence, the genus comprises two genetically distinct groups that should be considered as two separate genera, thereby setting the pace for major systematic changes for the genus Prorocentrum sensu Dodge. Moreover, the information presented in this study would be useful for improving species identification, detection of novel clades from environmental samples. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?

PubMed

García-Seara, Javier; Gude Sampedro, Francisco; Martínez Sande, Jose L; Fernández López, Xesus Alberte; Rodríguez Mañero, Moisés; González Melchor, Laila; Alvarez Alvarez, Belén; Iglesias Alvarez, Diego; González Juanatey, José Ramón

2016-09-01

We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)); 2) old AF (prior AF and no AF during FU); 3) prior and post AF (AF prior and post CTI ablation); and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65-1.50; p = 0.95) and 1.00 (CI 95%: 0.57-1.77; p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87-2.28; p = 0.17) and 1.79 (CI 95%: 0.96-3.35; p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35-4.40; p = 0.003), a HR of 2.88 (CI 95%: 1.36-6.10; p = 0.006) and a HR of 3.68 (CI 95%: 1.71-7.94; p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.

[Expression of proteasome subunits PSMB5 and PSMB9 mRNA in hippocampal neurons in experimental diabetes mellitus: link with apoptosis and necrosis].

PubMed

Lebid', Iu V; Dosenko, V Ie; Skybo, H H

2010-01-01

There is a huge body of evidence showing that long-termed diabetes mellitus is followed with hippocampal dysfunction. The goal of this work was to investigate the expression of proteasome subunits PSMB5 and PSMB9 mRNA in CA1, CA2 and CA3 areas of hippocampus in parallel with processes of cell death (apoptosis and necrosis) in development dynamics of streptozotocine-induced diabetes. We have studied hippocampal neurons using chromatine dye Hoechst-33342 and immunohistochemical detection of apoptotic cell death marker caspase-3. At day 3 and 7 after injection of streptozotocine we have performed visualization of caspase-3-immunopositive neurons showing signs of neurodegeneration in hippocampal sections using confocal microscope Olympus FV1000. The rate of proteasome subunits PSMB5 and PSMB9 mRNA expression was determined with RT-PCR. The results indicated elevation of PSMB9 mRNA content (from 4807 +/- 0.392 arbU up to 20,023 +/- 4949 arbU on day 3 and up to 20,253 +/- 5141 arbU on day 7). A maximal number of cells with signs of chromatin condensation was observed at day 3 and day 7 in CA2 and CA3 area (11.51% and 12.49% respectively). That indicates an intensification of proapoptotic processes. Summarizing the results presented above we can conclude that during the first week of diabetes mellitus development, hippocampal cells undergo the process of impairment and degeneration.

Atrial fibrillation in patients with gastroesophageal reflux disease: A comprehensive review

PubMed Central

Roman, Crina; Bruley des Varannes, Stanislas; Muresan, Lucian; Picos, Alina; Dumitrascu, Dan L

2014-01-01

AIM: To analyze the potential relationship between gastroesophageal reflux disease (GERD) and the development of atrial fibrillation (AF). METHODS: Using the key words “atrial fibrillation and gastroesophageal reflux”, “atrial fibrillation and esophagitis, peptic”, “atrial fibrillation and hernia, hiatal” the PubMed, EMBASE, Cochrane Library, OVIDSP, WILEY databases were screened for relevant publications on GERD and AF in adults between January 1972-December 2013. Studies written in languages other than English or French, studies not performed in humans, reviews, case reports, abstracts, conference presentations, letters to the editor, editorials, comments and opinions were not taken into consideration. Articles treating the subject of radiofrequency ablation of AF and the consecutive development of GERD were also excluded. RESULTS: Two thousand one hundred sixty-one titles were found of which 8 articles met the inclusion criteria. The presence of AF in patients with GERD was reported to be between 0.62%-14%, higher compared to those without GERD. Epidemiological data provided by these observational studies showed that patients with GERD, especially those with more severe GERD-related symptoms, had an increased risk of developing AF compared with those without GERD, but a causal relationship between GERD and AF could not be established based on these studies. The mechanisms of AF as a consequence of GERD remain largely unknown, with inflammation and vagal stimulation playing a possible role in the development of these disorders. Treatment with proton pomp inhibitors may improve symptoms related to AF and facilitate conversion to sinus rhythm. CONCLUSION: Although links between AF and GERD exist, large randomized clinical studies are required for a better understanding of the relationship between these two entities. PMID:25071357

Postdeployment Battlemind Training for the U.K. Armed Forces: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Mulligan, Kathleen; Fear, Nicola T.; Jones, Norman; Alvarez, Helen; Hull, Lisa; Naumann, Ulrike; Wessely, Simon; Greenberg, Neil

2012-01-01

Objective: Combat exposure can increase the risk of subsequent psychological ill-health in armed forces (AF) personnel. A U.S. postdeployment psycho-educational intervention, Battlemind, showed a beneficial effect on mental health in U.S. military personnel exposed to high combat levels. We evaluated the effectiveness of an anglicized version of…

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

PubMed

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient setting before admission. Our findings support the current literature, indicating that many patients with AF are not receiving appropriate thromboprophylaxis to counter their risk for stroke. Increased use of appropriate anticoagulation, particularly in high-risk patients, has the potential to reduce the incidence of stroke along with associated fatalities and morbidities.

Antiferromagnetism, charge density wave, and d-wave superconductivity in the extended t-J-U model: role of intersite Coulomb interaction and a critical overview of renormalized mean field theory.

PubMed

Abram, M; Zegrodnik, M; Spałek, J

2017-09-13

In the first part of the paper, we study the stability of antiferromagnetic (AF), charge density wave (CDW), and superconducting (SC) states within the t-J-U-V model of strongly correlated electrons by using the statistically consistent Gutzwiller approximation (SGA). We concentrate on the role of the intersite Coulomb interaction term V in stabilizing the CDW phase. In particular, we show that the charge ordering appears only above a critical value of V in a limited hole-doping range δ. The effect of the V term on SC and AF phases is that a strong interaction suppresses SC, whereas the AF order is not significantly influenced by its presence. In the second part, separate calculations for the case of a pure SC phase have been carried out within an extended approach (the diagrammatic expansion for the Gutzwiller wave function, DE-GWF) in order to analyze the influence of the intersite Coulomb repulsion on the SC phase with the higher-order corrections included beyond the SGA method. The upper concentration for the SC disappearance decreases with increasing V, bringing the results closer to experiment. In appendices A and B we discuss the ambiguity connected with the choice of the Gutzwiller renormalization factors within the renormalized mean filed theory when either AF or CDW orders are considered. At the end, we overview briefly the possible extensions of the current models to put descriptions of the SC, AF, and CDW states on equal footing.

Functional overreaching: the key to peak performance during the taper?

PubMed

Aubry, Anaël; Hausswirth, Christophe; Louis, Julien; Coutts, Aaron J; LE Meur, Yann

2014-09-01

The purpose of this study is to examine whether performance supercompensation during taper is maximized in endurance athletes after experiencing overreaching during an overload training (OT) period. Thirty-three trained male triathletes were assigned to either OT (n = 23) or normal training groups (n = 10, CTL) during 8 wk. Cycling performance and maximal oxygen uptake (V˙O2max) were measured after 1 wk of moderate training, a 3-wk period of OT, and then each week during 4-wk taper. Eleven of the 23 subjects from the OT group were diagnosed as functionally overreached (F-OR) after the overload period (decreased performance with concomitant high perceived fatigue), whereas the 12 other subjects were only acutely fatigued (AF) (no decrease in performance). According to qualitative statistical analysis, the AF group demonstrated a small to large greater peak performance supercompensation than the F-OR group (2.6% ± 1.1%) and the CTL group (2.6% ± 1.6%). V˙O2max increased significantly from baseline at peak performance only in the CTL and AF groups. Of the peak performances, 60%, 83%, and 73% occurred within the two first weeks of taper in CTL, AF, and OR, respectively. Ten cases of infection were reported during the study with higher prevalence in F-OR (70%) than that in AF (20%) and CTL (10%). This study showed that 1) greater gains in performance and V˙O2max can be achieved when higher training load is prescribed before the taper but not in the presence of F-OR; 2) peak performance is not delayed during taper when heavy training loads are completed immediately prior; and 3) F-OR provides higher risk for training maladaptation, including increased infection risks.

Pentagon spokesman: Up to 250 more U.S. forces to deploy to Syria > U.S.

Science.gov Websites

the CMSAF The Book Speeches Archive Former AF Top 3 Viewpoints and Speeches Air Force Warrior Games Games Portraits in Courage Portraits In Courage Vol. I Portraits In Courage Vol. II Portraits In Courage

Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions

PubMed Central

Wasserman, Michael R.; Pulk, Arto; Zhou, Zhou; Altman, Roger B.; Zinder, John C.; Green, Keith D.; Garneau-Tsodikova, Sylvie; Doudna Cate, Jamie H.; Blanchard, Scott C.

2015-01-01

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin—paromomycin, ribostamycin and neamine—each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6′-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6′-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin–ribosome complex, we observe specific contacts between the apical tip of H69 and the 6′-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation. PMID:26224058

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

DTIC Science & Technology

1983-08-10

around the world.This Is the provenance of the number (e.g., HSC 999999) which will appear onfuture OL-A standard products. I t . _ _. > r1 ’" . U S...16-20 9.6 .11 19.2 16.2 2.9 .4 2.81 930 21-23 6.3 .1 13.8 19.1 9.7 1.0 5.6 930 TTL .0 5.21 .11 . 7 (CUSAMETAC AAV 0-10-50L.Al. inmwm.emicinpomAn J .00

Anatomy of the dead sea transform from lithospheric to microscopic scale

USGS Publications Warehouse

Weber, M.; Abu-Ayyash, K.; Abueladas, A.; Agnon, A.; Alasonati-Tasarova, Z.; Al-Zubi, H.; Babeyko, A.; Bartov, Y.; Bauer, K.; Becken, M.; Bedrosian, P.A.; Ben-Avraham, Z.; Bock, G.; Bohnhoff, M.; Bribach, J.; Dulski, P.; Ebbing, J.; El-Kelani, R.; Forster, A.; Forster, H.-J.; Frieslander, U.; Garfunkel, Z.; Goetze, H.J.; Haak, V.; Haberland, C.; Hassouneh, M.; Helwig, S.; Hofstetter, A.; Hoffmann-Rotrie, A.; Jackel, K.H.; Janssen, C.; Jaser, D.; Kesten, D.; Khatib, M.; Kind, R.; Koch, O.; Koulakov, I.; Laske, Gabi; Maercklin, N.; Masarweh, R.; Masri, A.; Matar, A.; Mechie, J.; Meqbel, N.; Plessen, B.; Moller, P.; Mohsen, A.; Oberhansli, R.; Oreshin, S.; Petrunin, A.; Qabbani, I.; Rabba, I.; Ritter, O.; Romer, R.L.; Rumpker, G.; Rybakov, M.; Ryberg, T.; Saul, J.; Scherbaum, F.; Schmidt, S.; Schulze, A.; Sobolev, S.V.; Stiller, M.; Stromeyer, D.; Tarawneh, K.; Trela, C.; Weckmann, U.; Wetzel, U.; Wylegalla, K.

2009-01-01

Fault zones are the locations where motion of tectonic plates, often associated with earthquakes, is accommodated. Despite a rapid increase in the understanding of faults in the last decades, our knowledge of their geometry, petrophysical properties, and controlling processes remains incomplete. The central questions addressed here in our study of the Dead Sea Transform (DST) in the Middle East are as follows: (1) What are the structure and kinematics of a large fault zone? (2) What controls its structure and kinematics? (3) How does the DST compare to other plate boundary fault zones? The DST has accommodated a total of 105 km of leftlateral transform motion between the African and Arabian plates since early Miocene (???20 Ma). The DST segment between the Dead Sea and the Red Sea, called the Arava/ Araba Fault (AF), is studied here using a multidisciplinary and multiscale approach from the ??m to the plate tectonic scale. We observe that under the DST a narrow, subvertical zone cuts through crust and lithosphere. First, from west to east the crustal thickness increases smoothly from 26 to 39 km, and a subhorizontal lower crustal reflector is detected east of the AF. Second, several faults exist in the upper crust in a 40 km wide zone centered on the AF, but none have kilometer-size zones of decreased seismic velocities or zones of high electrical conductivities in the upper crust expected for large damage zones. Third, the AF is the main branch of the DST system, even though it has accommodated only a part (up to 60 km) of the overall 105 km of sinistral plate motion. Fourth, the AF acts as a barrier to fluids to a depth of 4 km, and the lithology changes abruptly across it. Fifth, in the top few hundred meters of the AF a locally transpressional regime is observed in a 100-300 m wide zone of deformed and displaced material, bordered by subparallel faults forming a positive flower structure. Other segments of the AF have a transtensional character with small pull-aparts along them. The damage zones of the individual faults are only 5-20 m wide at this depth range. Sixth, two areas on the AF show mesoscale to microscale faulting and veining in limestone sequences with faulting depths between 2 and 5 km. Seventh, fluids in the AF are carried downward into the fault zone. Only a minor fraction of fluids is derived from ascending hydrothermal fluids. However, we found that on the kilometer scale the AF does not act as an important fluid conduit. Most of these findings are corroborated using thermomechanical modeling where shear deformation in the upper crust is localized in one or two major faults; at larger depth, shear deformation occurs in a 20-40 km wide zone with a mechanically weak decoupling zone extending subvertically through the entire lithosphere. Copyright 2009 by the American Geophysical Union.

B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability

PubMed Central

Houge, Gunnar; Haesen, Dorien; Vissers, Lisenka E.L.M.; Mehta, Sarju; Parker, Michael J.; Wright, Michael; Vogt, Julie; McKee, Shane; Tolmie, John L.; Cordeiro, Nuno; Kleefstra, Tjitske; Willemsen, Marjolein H.; Reijnders, Margot R.F.; Berland, Siren; Hayman, Eli; Lahat, Eli; Brilstra, Eva H.; van Gassen, Koen L.I.; Zonneveld-Huijssoon, Evelien; de Bie, Charlotte I.; Hoischen, Alexander; Eichler, Evan E.; Holdhus, Rita; Steen, Vidar M.; Døskeland, Stein Ove; Hurles, Matthew E.; FitzPatrick, David R.; Janssens, Veerle

2015-01-01

Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function. Ten patients had mutations within a highly conserved acidic loop of the PPP2R5D-encoded B56δ regulatory subunit, with the same E198K mutation present in 6 individuals. Five patients had mutations in the PPP2R1A-encoded scaffolding Aα subunit, with the same R182W mutation in 3 individuals. Some Aα cases presented with large ventricles, causing macrocephaly and hydrocephalus suspicion, and all cases exhibited partial or complete corpus callosum agenesis. Functional evaluation revealed that mutant A and B subunits were stable and uncoupled from phosphatase activity. Mutant B56δ was A and C binding–deficient, while mutant Aα subunits bound B56δ well but were unable to bind C or bound a catalytically impaired C, suggesting a dominant-negative effect where mutant subunits hinder dephosphorylation of B56δ-anchored substrates. Moreover, mutant subunit overexpression resulted in hyperphosphorylation of GSK3β, a B56δ-regulated substrate. This effect was in line with clinical observations, supporting a correlation between the ID degree and biochemical disturbance. PMID:26168268

Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

PubMed Central

Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

2012-01-01

Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex.

PubMed

Tsai, Ming-Feng; Phillips, Charles B; Ranaghan, Matthew; Tsai, Chen-Wei; Wu, Yujiao; Willliams, Carole; Miller, Christopher

2016-04-21

Mitochondrial Ca(2+) uptake, a process crucial for bioenergetics and Ca(2+) signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca(2+)-activated Ca(2+) channel, with the Ca(2+) pore formed by the MCU protein and Ca(2+)-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca(2+) permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca(2+) landscape.

Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

PubMed

Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

2016-04-01

Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Dewland, Thomas A; Soliman, Elsayed Z; Yamal, Jose-Miguel; Davis, Barry R; Alonso, Alvaro; Albert, Christine M; Simpson, Lara M; Haywood, L Julian; Marcus, Gregory M

2017-12-01

Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P =0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P =0.16) was not associated with a significant reduction in incident AF/AFL. Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

Patient Factors Associated with Quality of Life in Atrial Fibrillation Randolph—Determinants of Quality of Life in Atrial Fibrillation

PubMed Central

Randolph, Tiffany C.; Simon, DaJuanicia N.; Thomas, Laine; Allen, Larry A.; Fonarow, Gregg C.; Gersh, Bernard J.; Kowey, Peter R.; Reiffel, James A.; Naccarelli, Gerald V.; Chan, Paul S.; Spertus, John A.; Peterson, Eric D.; Piccini, Jonathan P.

2016-01-01

Background As treatment options for atrial fibrillation (AF) increase, more attention is focused on patients’ experiences and quality of life (QoL). However, little is known about the factors associated with these outcomes. Methods The Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) is a disease-specific QoL tool for AF, with domain and summary scores ranging from 0 (the worst QoL) to 100. Using multivariable linear regression, we evaluated factors associated with baseline AFEQT Summary and Subscale Scores in ORBIT AF, a large, community-based AF registry. Independent associations were reported as coefficient estimates in scores and 95% confidence intervals (CI). Results Overall, AFEQT was assessed in 2,007 AF outpatients from 99 sites. Median age (IQR) was 76 years (67-82) and 43% were female. The median AFEQT summary score was 82 (67-94). Female sex, younger age, new onset AF, higher heart rate, obstructive sleep apnea, symptomatic heart failure (HF), chronic obstructive pulmonary disease and coronary artery disease were all independently associated with reduced QoL. Female sex [Estimate −7.03, 95% CI (−9.31, −4.75)] and new onset versus permanent AF [Estimate −7.44, 95% CI (−11.03, −3.84)] were independently associated with increased symptoms. NYHA Class III or IV HF [Estimate -14.44, 95% CI (−19.46, −8.76)] and female sex [Estimate −7.91, 95% CI (−9.95, −5.88)] were most independently associated with impaired daily activities. Conclusions QoL in patients with AF varies widely and is associated with several patient factors. Understanding patient factors independently associated with worse QoL can be a foundation for tailoring treatment. PMID:27914493

Escherichia coli gamma-glutamyltranspeptidase mutants deficient in processing to subunits.

PubMed

Hashimoto, W; Suzuki, H; Nohara, S; Kumagai, H

1992-11-30

Arginyl residues 513 and 571 of Escherichia coli K-12 gamma-glutamyl-transpeptidase (EC 2.3.2.2) were substituted with alanyl and glycyl residues, respectively, by oligonucleotide-directed in vitro mutagenesis. Both mutants were devoid of the enzymatic activity. On Western blot analysis, we found that both mutants accumulated a gamma-glutamyltranspeptidase precursor which was not processed into large and small subunits in the periplasmic space of Escherichia coli.

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Subunit interactions in horse spleen apoferritin. Dissociation by extremes of pH

PubMed Central

Crichton, Robert R.; Bryce, Charles F. A.

1973-01-01

1. The dissociation of horse spleen apoferritin as a function of pH was analysed by sedimentation-velocity techniques. The oligomer is stable in the range pH2.8–10.6. Between pH2.8 and 1.6 and 10.6 and 13.0 both oligomer and subunits can be detected. At pH values between 1.6 and 1.0 the subunit is the only species observed, although below pH1.0 aggregation of the subunits to a particle sedimenting much faster than the oligomer occurs. 2. When apoferritin is first dissociated into subunits at low pH values and then dialysed into buffers of pH1.5–5.0, the subunit reassociates to oligomer in the pH range 3.1–4.3. 3. U.v.-difference spectroscopy was used to study conformational changes occurring during the dissociation process. The difference spectrum in acid can be accounted for by the transfer of four to five tyrosine residues/subunit from the interior of the protein into the solvent. This process is reversed on reassociation, but shows the same hysteresis as found by sedimentation techniques. The difference spectrum in alkali is more complex, but is consistent with the deprotonation of tyrosine residues, which appear to have rather high pK values. 4. In addition to the involvement of tyrosine residues in the conformational change at low pH values, spectral evidence is presented that one tryptophan residue/subunit also changes its environment before dissociation and subsequent to reassociation. 5. Analysis of the dissociation and reassociation of apoferritin at low pH values suggests that this is a co-operative process involving protonation and deprotonation of at least two carboxyl functions of rather low intrinsic pK. The dissociation at alkaline pH values does not appear to be co-operative. 6. Of the five tyrosine residues/subunit only one can be nitrated with tetranitromethane. Guanidination of lysine residues results in the modification of seven out of a total of nine residues/subunit. Nine out of the ten arginine residues/subunit react with cyclohexanedione. PMID:4737425

Expression of Functional Human α6β2β3* Acetylcholine Receptors in Xenopus laevis Oocytes Achieved through Subunit Chimeras and Concatamers

PubMed Central

Kuryatov, Alexandre

2011-01-01

α6β2β3* acetylcholine receptors (AChRs) on dopaminergic neurons are important targets for drugs to treat nicotine addiction and Parkinson's disease. However, it has not been possible to efficiently express functional α6β2β3* AChRs in oocytes or transfected cells. α6/α3 subunit chimeras permit expression of functional AChRs and reveal that parts of the α6 M1 transmembrane domain and large cytoplasmic domain impair assembly. Concatameric subunits permit assembly of functional α6β2β3* AChRs with defined subunit compositions and subunit orders. Assembly of accessory subunits is limiting in formation of mature AChRs. A single linker between the β3 accessory subunit and an α4 or α6 subunit is sufficient to permit assembly of complex β3-(α4β2)(α6β2) or β3-(α6β2)(α4β2) AChRs. Concatameric pentamers such as β3-α6-β2-α4-β2 have been functionally characterized. α6β2β3* AChRs are sensitive to activation by drugs used for smoking cessation therapy (nicotine, varenicline, and cytisine) and by sazetidine. All these are partial agonists. (α6β2)(α4β2)β3 AChRs are most sensitive to agonists. (α6β2)2β3 AChRs have the greatest Ca2+ permeability. (α4β2)(α6β2)β3 AChRs are most efficiently transported to the cell surface, whereas (α6β2)2β3 AChRs are the least efficiently transported. Dopaminergic neurons may have special chaperones for assembling accessory subunits with α6 subunits and for transporting (α6β2)2β3 AChRs to the cell surface. Concatameric pentamers and pentamers formed from combinations of trimers, dimers, and monomers exhibit similar properties, indicating that the linkers between subunits do not alter their functional properties. For the first time, these concatamers allow analysis of functional properties of α6β2β3* AChRs. These concatamers should enable selection of drugs specific for α6β2β3* AChRs. PMID:20923852

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 media that was added gradually, followed by the addition of nutrients and aeration. Furthermore, in the biodegradation process of AF2B, the result of acclimatization (as a starter) was fed into the AF2B, then added to the hospital wastewater at a certain volume (as variables), and followed by aeration at a certain flow rate (as variables). Sampling was done at any time to determine the decrease of the concentration of BOD, NH3-N, and MLSS (Mixed Liqour Suspended Solid). BOD and Ammonia-free analyses were conducted using winkler bottle titration and spectrophotometry method. MLSS analysis used gravimetric methods. The results of the research shos that the volume of starter 85% (v) and air supplies of 7.5 L/min can reduce BOD and NH3-N of 92% and 76% respectively. Besides that, AF2B and bacterial consortium have a great ability and are very fast in degrading BOD and NH3-N.

Scaling Up, "Writ Small": Using an Assessment for Learning Audit Instrument to Stimulate Site-Based Professional Development, One School at a Time

ERIC Educational Resources Information Center

Lysaght, Zita; O'Leary, Michael

2017-01-01

Exploiting the potential that Assessment for Learning (AfL) offers to optimise student learning is contingent on both teachers' knowledge and use of AfL and the fidelity with which this translates into their daily classroom practices. Quantitative data derived from the use of an Assessment for Learning Audit Instrument (AfLAI) with a large sample…

Characterizing the antiferromagnetic ordering of fermions in a compensated optical lattice

NASA Astrophysics Data System (ADS)

Duarte, P. M.; Hart, R. A.; Yang, T. L.; Liu, X.; Hulet, R. G.; Paiva, T. C. L.; Huse, D.; Scalettar, R.; Trivedi, N.

2014-05-01

We realize the Fermi-Hubbard model with fermionic 6Li atoms in a three-dimensional, red-detuned optical lattice. The lattice is compensated by the addition of three blue-detuned gaussian beams which overlap each of the lattice laser beams, but are not retro-reflected. Using the compensated lattice potential, we have reached temperatures low enough to produce antiferromagnetic (AF) spin correlations, which we detect via Bragg scattering of light. The variation of the measured AF correlations as a function of the Hubbard interaction strength, U / t , provides a way to determine the temperature of the atoms in the lattice by comparison with quantum Monte Carlo calculations. This method suggests our temperature is in the range of 2-3 times the Néel ordering temperature. In this poster we present our Bragg scattering results along with our studies of the effect of the compensating potential in helping us cool the atoms in the lattice and also enlarge the size of the AF phase. Work supported by DARPA, ONR, NSF and The Welch Foundation.

Strategy-Policy Mismatch: How the U.S. Army Can Help Close Gaps in Countering Weapons of Mass Destruction

DTIC Science & Technology

2014-01-01

Niblack, and Dana J. Johnson, A League of Airmen: U.S. Air Power in the Gulf War, Santa Monica, Calif.: RAND Corporation, MR-343-AF, 1994. 8 Lolita C...Sanger, and Anne Barnard, “Off-the-Cuff Obama Line Put U.S. in Bind on Syria,” New York Times, May 4, 2013. Baldor, Lolita C., “U.S. Troops Could

The impact of smoking on thromboembolism and mortality in patients with incident atrial fibrillation: insights from the Danish Diet, Cancer, and Health study.

PubMed

Albertsen, Ida Ehlers; Rasmussen, Lars Hvilsted; Lane, Deirdre A; Overvad, Thure Filskov; Skjøth, Flemming; Overvad, Kim; Lip, Gregory Y H; Larsen, Torben Bjerregaard

2014-03-01

Smoking and atrial fibrillation (AF) are major health problems worldwide and are responsible for substantial health-care costs. Our aim was to investigate whether smoking impacts the risk of stroke and death in patients with AF. To test this hypothesis, we analyzed data from a large Danish cohort: the Diet, Cancer, and Health study. This was a cohort study of 57,053 people (27,178 men; 29,876 women) aged 50 to 64 years. The risk of thromboembolism (ischemic stroke/arterial thromboembolism) or death according to smoking habits among 3,161 patients with incident AF (mean age, 66.9 years; 2,032 men, 1,129 women) was assessed using Cox proportional hazard models after a median follow-up of 4.9 years. Of those with AF, 34% were current smokers and 37% former smokers. After adjustment for vitamin K antagonist treatment, the hazard ratios (HRs) (95% CI) of thromboembolism or death were 3.13 (1.72-6.37) and 2.73 (2.02-3.70) among women and men who currently were heavy smokers (>25 g/d), respectively. The associations remained after adjustment for well-established risk factors with HRs of 3.64 (1.88-7.07) and 2.17 (1.59-2.95) among women and men, respectively. In a sensitivity analysis, smoking was still strongly associated with thromboembolism or death after censoring people with a cancer diagnosis during follow-up. Smoking is associated with a higher risk of thromboembolism or death in patients with AF even after adjusting for well-recognized risk factors used in stroke risk stratification schemes. The associations may be modified by sex, as the associations were strongest among women.

Hyperthyroidism, but not hypertension, impairs PITX2 expression leading to Wnt-microRNA-ion channel remodeling

PubMed Central

Lozano-Velasco, Estefanía; Wangensteen, Rosemary; Quesada, Andrés; Garcia-Padilla, Carlos; Osorio, Julia A.; Ruiz-Torres, María Dolores; Aranega, Amelia

2017-01-01

PITX2 is a homeobox transcription factor involved in embryonic left/right signaling and more recently has been associated to cardiac arrhythmias. Genome wide association studies have pinpointed PITX2 as a major player underlying atrial fibrillation (AF). We have previously described that PITX2 expression is impaired in AF patients. Furthermore, distinct studies demonstrate that Pitx2 insufficiency leads to complex gene regulatory network remodeling, i.e. Wnt>microRNAs, leading to ion channel impairment and thus to arrhythmogenic events in mice. Whereas large body of evidences has been provided in recent years on PITX2 downstream signaling pathways, scarce information is available on upstream pathways influencing PITX2 in the context of AF. Multiple risk factors are associated to the onset of AF, such as e.g. hypertension (HTN), hyperthyroidism (HTD) and redox homeostasis impairment. In this study we have analyzed whether HTN, HTD and/or redox homeostasis impact on PITX2 and its downstream signaling pathways. Using rat models for spontaneous HTN (SHR) and experimentally-induced HTD we have observed that both cardiovascular risk factors lead to severe Pitx2 downregulation. Interesting HTD, but not SHR, leads to up-regulation of Wnt signaling as well as deregulation of multiple microRNAs and ion channels as previously described in Pitx2 insufficiency models. In addition, redox signaling is impaired in HTD but not SHR, in line with similar findings in atrial-specific Pitx2 deficient mice. In vitro cell culture analyses using gain- and loss-of-function strategies demonstrate that Pitx2, Zfhx3 and Wnt signaling influence redox homeostasis in cardiomyocytes. Thus, redox homeostasis seems to play a pivotal role in this setting, providing a regulatory feedback loop. Overall these data demonstrate that HTD, but not HTN, can impair Pitx2>>Wnt pathway providing thus a molecular link to AF. PMID:29194452

Identification of a Kinase in Wheat Germ that Phosphorylates the Large Subunit of Initiation Factor 4F 1

PubMed Central

Humphreys, Jean; Browning, Karen S.; Ravel, Joanne M.

1988-01-01

A kinase has been isolated from wheat (Triticum aestivum) germ that phosphorylates the 220 kilodaltons (kD) subunit of wheat germ initiation factor (eIF) 4F, the 80 kD subunit of eIF-4B (an isozyme form of eIF-4F) and eIF-4G (the functional equivalent to mammalian eIF-4B). The kinase elutes from Sephacryl S-200 slightly in front of ovalbumin. The kinase phosphorylates casein and histone IIA to a small extent, but does not phosphorylate phosvitin. Of the wheat germ initiation factors, elongation factors, and small and large ribosomal subunits, only eIF-4F, eIF-4B, and eIF-4G are phosphorylated to a significant extent. The kinase phosphorylates eIF-4F to the extent of two phosphates per mole of the 220 kD subunit and phosphorylates eIF-4B to the extent of one phosphate per mole of the 80 kD subunit. The 26 kD subunit of eIF-4F and the 28 kD subunit of eIF-4B are not phosphorylated by the kinase. The kinase phosphorylates the 59 kD component of eIF-4G to the extent of 0.25 phosphate per mole of eIF-4G. Phosphorylation of eIF-4F and eIF-4B does not affect their ability to support the binding of mRNA to small ribosomal subunits in vitro. Images Fig. 2 Fig. 3 PMID:16666331

Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

NASA Astrophysics Data System (ADS)

Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

2014-05-01

Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had a greater fraction of their DOM that was more humic-like than the paired non-AfDE samples, though differences were small. Similarly, FTICR-MS analysis of hot water extracts suggests that differences among the three sites analyzed were larger than between the paired AfDE and non-AfDE extracts. Overall, in spite of substantial differences in the composition of bulk SOM, the extractable fractions appear to be relatively similar between the AfDE and non-AfDE soils.

A Comparison of Thinking and Writing Patterns in Korea and the United States. AFS Occasional Papers in Intercultural Learning No. 12.

ERIC Educational Resources Information Center

Norton, Robert F.

Major writing style differences between Korean and U.S. essayists are examined in order to determine: (1) the types of relationships expressed in a specific essay; (2) the sequence in which related ideas are expressed; and (3) the distance between two ideas that comprise each relationship. Eighteen basic types of relationships were examined in…

Inhalation Toxicology of Fog Oil Smoke

DTIC Science & Technology

1986-12-01

PROLO) program (Russell et al., 1977). The 2.0-hr data suffered from heterogeneity of variance. The 6.0-hr data reflected too high an index of...CcwartiuLcWt fcrs, rtio lw x ur aptct Vtitv , klci utbhj" ctt. U S ft vtttltp 350 4) 3--0 Study AF J5--4 Study B 250 A-Combined Studies Aand B*. 150 1 300 -600

75 FR 54880 - Eddie Floyd, Licensee of FM Translator Station K273AF, Carson City, NV, Facility ID No. 13529...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

... relating to money laundering and his apparent failure to inform the Commission about such misconduct in the...), involving money laundering, and one count of violating 18 U.S.C. 2, aiding and abetting a felony crime, both... the company in exchange for $27,500. The court found these payments constituted money laundering by...

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place, Fiscal Year 1987. Part 9. Hawthorne Srvc. & Medical U SC-Input Output Technology.

DTIC Science & Technology

1987-01-01

0 0 m 0 V7 a Mo00tI 04 aF 04 0 U..04 0 0 4 0004 000 0004 00v4l A a 1 o < 1 - 08- 0 m 4N00ŕ-1.- 0 0o1-) 000-) CN 00- co D W -co 00- W- ca 0 0 4 004...a 00 0 ’nw 000 gr Go00 C- 4)NN 01?--(- ... J 40 CAD 00 00- -40-00 0 000 3 4 ’- m- -A4 (D a- E ’ w- Cl m- 0 0 M4 0-l (14 af ((0-C’N 0A (4 V) 0 0 0)0...4, -4-4 lin n in -4 (00(4 I -- 10-4( IC) Mum0 1 r a I0 > 0 0. ) 0 1C 04 ’ -4 = tC z -4 4 ( )- 4. J I M 04 N af .- C.-4- C14 If,4 cl UI 0, C r

Air Force Officer Specialty Structure. Reviewing the Fundamentals

DTIC Science & Technology

2009-01-01

Corporation, is the U.S. Air Force’s federally funded research and development center for studies and analyses. PAF pro - vides the Air Force with...Shirlene LeBleu for sharing their database and insights about job con - tent and specialty analyses. At the Air Force Manpower Agency, we thank Col...processes. Also, we thank Maj Ernest Wearren (AF/ A1MZ) and Gary Stockinger (AF/A1MX) for sharing their knowledge of the Manpower Pro - gramming Execution

Small Business Specialists

DTIC Science & Technology

1993-01-01

AF) Ms. Nicole A. Dillon Williams AFB AC 602/988-6618 85224-5004 Fort Huachuca HQ U.S. Army Information Systems Command (A) Mr. Michael P. Dean* ATTN...Army Medical Center (A) Maj Paul G. Michaels ATTN: HSAA-L Mr. William Brundage Presidio of San Francisco AC 415/561-5473/6289 94124-6700 SUPSHIP...Systems Division AC 408/224-7748 P. 0. Box 49028 95161-9028 San Luis Obispo National Guard (A)(AF) Col William T. Mongold USPFO for California AC 805

Niagara Falls IAP NY. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-10-01

14 Date of Report: Oct 1987 15 .tpas Comet: 312 16 Supplementary Notation: 17 COSATI Codes: Field --04, Group--02 18 Subject Term: *climatology...2.’ .3 .6 .3 .2 .0 .3 331. I ~ .3 2.0 7.! .6 .6. 04. 131 1U1 . . Z.9 2.? . .0 1.2 10.3 T(16 I !. 21.3 $S 3s3.. t. 1.2 .3 .2 100.0 . dm-C -LOsAL CLII...SIATL’Tr MILLS [9 3 GE GE GE I.E GE GE GE GE GE or G£ G GE GE 61 GE FEEI I I" b 5 4 32 lie 2 1 112 1 l I4 ! 1/4 518 1/1 ilb 114 U r.0 EIL I 22.7 75.b

Industrial Water Treatment Primer

DTIC Science & Technology

1992-03-01

calculated as follows: Sulfite, ppm = (ml solution) x (factor). EXAMPLE: 2.3 ml of Potassium Iodide - Iodate Solution were required to change the color of ...8217. 4A"O aqd. nd coffOicTAq ofd𔃾ne I" c ot(¶O f any.~.o W’dcmclojdn fb’e’ ~~t ,~~ P4 uOqj of 1’i 40flc~nof "fo~s~rmU l. If i Igo4 t fo, ’edvong IN% bw to...4sal g V IOA af e So ýn o irv , aw lo w inton ra ton 0w rtovr4 • a i I v j holq w- F _ O.f ,stwa. tjieI*.AI: 9 b. 1U 2 02. snd to thw Of ~e 0 ,*ot

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.

Large subunit of the ribonucleotide reductase gene is a virulent factor and plays a critical role in Marek's disease virus pathogenesis

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV) encodes a ribonucleotide reductase (RR) gene consisting of two subunits UL39 (RR1) and UL40 (RR2). Both RR1 and RR2 form an active holoenzyme and are necessary for enzyme activity. This gene was indentified by monoclonal antibody T81 in a gt11 MDV expression library and f...

Brunswick NAS, Maine. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1982-06-02

23.’f .a. .3 2,.- .fl .i rOTAL NUEE Of ONATIONS 913 C (- porn USAPETAC Poe" 04.5 (OLA) avo. n ,,,inm oI tis pow Am iounnln AI. 6 GLOBAL CLIMATOLOGY...N U 29-20 31 D.. Boy lb Wet i61wb POWn.S ,16/-IT9, F ( " - --21--,,10 -22/-23-- 5 -24/-25 2 r OTAL 2*lZD40*O0. T .I .3 h 01 *1 821811 821 _ 821 (j1

Transcriptional fidelities of human mitochondrial POLRMT, yeast mitochondrial Rpo41, and phage T7 single-subunit RNA polymerases.

PubMed

Sultana, Shemaila; Solotchi, Mihai; Ramachandran, Aparna; Patel, Smita S

2017-11-03

Single-subunit RNA polymerases (RNAPs) are present in phage T7 and in mitochondria of all eukaryotes. This RNAP class plays important roles in biotechnology and cellular energy production, but we know little about its fidelity and error rates. Herein, we report the error rates of three single-subunit RNAPs measured from the catalytic efficiencies of correct and all possible incorrect nucleotides. The average error rates of T7 RNAP (2 × 10 -6 ), yeast mitochondrial Rpo41 (6 × 10 -6 ), and human mitochondrial POLRMT (RNA polymerase mitochondrial) (2 × 10 -5 ) indicate high accuracy/fidelity of RNA synthesis resembling those of replicative DNA polymerases. All three RNAPs exhibit a distinctly high propensity for GTP misincorporation opposite dT, predicting frequent A→G errors in RNA with rates of ∼10 -4 The A→C, G→A, A→U, C→U, G→U, U→C, and U→G errors mostly due to pyrimidine-purine mismatches were relatively frequent (10 -5 -10 -6 ), whereas C→G, U→A, G→C, and C→A errors from purine-purine and pyrimidine-pyrimidine mismatches were rare (10 -7 -10 -10 ). POLRMT also shows a high C→A error rate on 8-oxo-dG templates (∼10 -4 ). Strikingly, POLRMT shows a high mutagenic bypass rate, which is exacerbated by TEFM (transcription elongation factor mitochondrial). The lifetime of POLRMT on terminally mismatched elongation substrate is increased in the presence of TEFM, which allows POLRMT to efficiently bypass the error and continue with transcription. This investigation of nucleotide selectivity on normal and oxidatively damaged DNA by three single-subunit RNAPs provides the basic information to understand the error rates in mitochondria and, in the case of T7 RNAP, to assess the quality of in vitro transcribed RNAs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Structure and Location of the Regulatory β Subunits in the (αβγδ)4 Phosphorylase Kinase Complex* ♦

PubMed Central

Nadeau, Owen W.; Lane, Laura A.; Xu, Dong; Sage, Jessica; Priddy, Timothy S.; Artigues, Antonio; Villar, Maria T.; Yang, Qing; Robinson, Carol V.; Zhang, Yang; Carlson, Gerald M.

2012-01-01

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)4 complex that regulates glycogenolysis in skeletal muscle. Activity of the catalytic γ subunit is regulated by allosteric activators targeting the regulatory α, β, and δ subunits. Three-dimensional EM reconstructions of PhK show it to be two large (αβγδ)2 lobes joined with D2 symmetry through interconnecting bridges. The subunit composition of these bridges was unknown, although indirect evidence suggested the β subunits may be involved in their formation. We have used biochemical, biophysical, and computational approaches to not only address the quaternary structure of the β subunits within the PhK complex, i.e. whether they compose the bridges, but also their secondary and tertiary structures. The secondary structure of β was determined to be predominantly helical by comparing the CD spectrum of an αγδ subcomplex with that of the native (αβγδ)4 complex. An atomic model displaying tertiary structure for the entire β subunit was constructed using chemical cross-linking, MS, threading, and ab initio approaches. Nearly all this model is covered by two templates corresponding to glycosyl hydrolase 15 family members and the A subunit of protein phosphatase 2A. Regarding the quaternary structure of the β subunits, they were directly determined to compose the four interconnecting bridges in the (αβγδ)4 kinase core, because a β4 subcomplex was observed through both chemical cross-linking and top-down MS of PhK. The predicted model of the β subunit was docked within the bridges of a cryoelectron microscopic density envelope of PhK utilizing known surface features of the subunit. PMID:22969083

U.S. EPA, Pesticide Product Label, SANTIMINE - 150, 01/31/1989

EPA Pesticide Factsheets

2011-04-21

... It •• ; u.1 ., l •• n •• f (h. I'",,, C •••• , 1 '" .fI' ,,, . UfO not .t' If! .,., Oil III" ., cl.'llIn~ 'h,af,1 " .... It~ .. ,of V •• , ,.t .. Of II(' ." • 14 ~n" ,"1111" Jl.", .. ...

76 FR 5680 - Small Business, Small Disadvantaged Business, HUBZone, and Service-Disabled Veteran-Owned...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

... SMALL BUSINESS ADMINISTRATION 13 CFR Parts 121, 124, 125, 126, and 134 RIN 3245-AF65 Small Business, Small Disadvantaged Business, HUBZone, and Service-Disabled Veteran-Owned Business Status Protest and Appeal Regulations. AGENCY: U.S. Small Business Administration. ACTION: Final rule. SUMMARY: The U...

Fish Oil and Post-Operative Atrial Fibrillation – Results of the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial

PubMed Central

Mozaffarian, Dariush; Marchioli, Roberto; Macchia, Alejandro; Silletta, Maria G.; Ferrazzi, Paolo; Gardner, Timothy J.; Latini, Roberto; Libby, Peter; Lombardi, Federico; O’Gara, Patrick T.; Page, Richard L.; Tavazzi, Luigi; Tognoni, Gianni

2013-01-01

Context Post-operative atrial fibrillation/flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and healthcare utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFA) reduce post-op AF, with mixed results. Objective To determine whether peri-operative n-3-PUFA supplementation reduces post-op AF. Design Randomized, double-blind, placebo-controlled, multinational, clinical trial. Patients A total of 1,516 patients scheduled for cardiac surgery across 28 centers in the US, Italy, and Argentina, enrolled between Aug 2010 and Jun 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Forty-eight percent of screened patients and 94% of eligible patients were enrolled. Intervention Patients were randomized to receive fish oil (1 g capsules containing ≥840 mg n-3-PUFA as ethyl esters) or placebo, with pre-operative loading of 10g over 3-5 days (or 8g over 2 days) followed post-operatively by 2g/d until hospital discharge or post-op day10, whichever first. Main Outcome Measures The primary endpoint was occurrence of post-op AF >30 sec. We also evaluated post-op AF lasting >1hr, resulting in symptoms, or treated with cardioversion; other secondary post-op AF endpoints; other tachyarrhythmias; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events. All endpoints and analyses plans were prespecified. Results At enrollment, mean±SD age was 64±13 years, 72.2% were male, and 51.8% had planned valvular surgery. The primary endpoint occurred in 233 (30.7%) and 227 (30.0%) patients assigned to placebo and n-3-PUFA, respectively (OR=0.96, 95%CI=0.77-1.20; P=0.74). None of the secondary endpoints were significantly different, including post-op AF that was sustained, symptomatic, or treated (n=231 [30.5%] vs. n=224 [29.6%], P=0.70) or number of post-op AF episodes per patient (1 episode: n=220 [29.0%] vs. n=217 [28.6%]; 2 episodes: n=156 [20.6%] vs. n=157 [20.7%]; 3+ episodes: n=18 [2.4%] vs. n=21 [2.8%]; P=0.73). n-3-PUFA was generally well-tolerated, with no evidence for increased risk of bleeding or serious adverse events. Conclusions In this large multinational trial among patients undergoing cardiac surgery, peri-operative supplementation with n-3-PUFA, compared to placebo, did not reduce the risk of post-operative AF. PMID:23128104

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified.

PubMed

Movérare-Skrtic, Sofia; Börjesson, Anna E; Farman, Helen H; Sjögren, Klara; Windahl, Sara H; Lagerquist, Marie K; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-21

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-2(0)) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-2(0) mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-2(0) mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.

High incidence of echocardiographic abnormalities of the interatrial septum in patients undergoing ablation for atrial fibrillation.

PubMed

Schernthaner, Christiana; Danmayr, Franz; Daburger, Apollonia; Eichinger, Jörg; Hammerer, Matthias; Strohmer, Bernhard

2013-04-01

Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters. © 2012, Wiley Periodicals, Inc.

Proceedings of the International Meeting on Advances in Learning Held in Les Arcs, France 28 July-1 August 1986,

DTIC Science & Technology

1986-08-01

Are6 IM3 On Ou n. W Param d ft 91139 Uso � 440PO mut s wae ___L - IM poaber Wsm to 9.4’ gi ~ aF a &a 3134 V77 I W% Mik AN 001 Pet 110 (13414 amn...metatheory. What if smart control isn’t enough? It may be that the object level theory is so large or badly structured that even cleverly guided object level...research was supported by the U.S. Air Force Space Division under contract F04701-85-C-0086 and by the Aerospace Sponsored Research Program. References [1

Three new anascosporic genera of the Saccharomycotina: Danielozyma gen. nov., Deakozyma gen. nov. and Middelhovenomyces gen. nov.

USDA-ARS?s Scientific Manuscript database

Three new non-ascosporic, ascomycetous yeast genera are proposed based on their isolation from currently described species and genera. Phylogenetic placement of the genera was determined from analysis of nuclear gene sequences for D1/D2 large subunit rRNA, small subunit rRNA, translation elongation...

Assembling a protein-protein interaction map of the SSU processome from existing datasets.

PubMed

Lim, Young H; Charette, J Michael; Baserga, Susan J

2011-03-10

The small subunit (SSU) processome is a large ribonucleoprotein complex involved in small ribosomal subunit assembly. It consists of the U3 snoRNA and ∼72 proteins. While most of its components have been identified, the protein-protein interactions (PPIs) among them remain largely unknown, and thus the assembly, architecture and function of the SSU processome remains unclear. We queried PPI databases for SSU processome proteins to quantify the degree to which the three genome-wide high-throughput yeast two-hybrid (HT-Y2H) studies, the genome-wide protein fragment complementation assay (PCA) and the literature-curated (LC) datasets cover the SSU processome interactome. We find that coverage of the SSU processome PPI network is remarkably sparse. Two of the three HT-Y2H studies each account for four and six PPIs between only six of the 72 proteins, while the third study accounts for as little as one PPI and two proteins. The PCA dataset has the highest coverage among the genome-wide studies with 27 PPIs between 25 proteins. The LC dataset was the most extensive, accounting for 34 proteins and 38 PPIs, many of which were validated by independent methods, thereby further increasing their reliability. When the collected data were merged, we found that at least 70% of the predicted PPIs have yet to be determined and 26 proteins (36%) have no known partners. Since the SSU processome is conserved in all Eukaryotes, we also queried HT-Y2H datasets from six additional model organisms, but only four orthologues and three previously known interologous interactions were found. This provides a starting point for further work on SSU processome assembly, and spotlights the need for a more complete genome-wide Y2H analysis.

Assembling a Protein-Protein Interaction Map of the SSU Processome from Existing Datasets

PubMed Central

Baserga, Susan J.

2011-01-01

Background The small subunit (SSU) processome is a large ribonucleoprotein complex involved in small ribosomal subunit assembly. It consists of the U3 snoRNA and ∼72 proteins. While most of its components have been identified, the protein-protein interactions (PPIs) among them remain largely unknown, and thus the assembly, architecture and function of the SSU processome remains unclear. Methodology We queried PPI databases for SSU processome proteins to quantify the degree to which the three genome-wide high-throughput yeast two-hybrid (HT-Y2H) studies, the genome-wide protein fragment complementation assay (PCA) and the literature-curated (LC) datasets cover the SSU processome interactome. Conclusions We find that coverage of the SSU processome PPI network is remarkably sparse. Two of the three HT-Y2H studies each account for four and six PPIs between only six of the 72 proteins, while the third study accounts for as little as one PPI and two proteins. The PCA dataset has the highest coverage among the genome-wide studies with 27 PPIs between 25 proteins. The LC dataset was the most extensive, accounting for 34 proteins and 38 PPIs, many of which were validated by independent methods, thereby further increasing their reliability. When the collected data were merged, we found that at least 70% of the predicted PPIs have yet to be determined and 26 proteins (36%) have no known partners. Since the SSU processome is conserved in all Eukaryotes, we also queried HT-Y2H datasets from six additional model organisms, but only four orthologues and three previously known interologous interactions were found. This provides a starting point for further work on SSU processome assembly, and spotlights the need for a more complete genome-wide Y2H analysis. PMID:21423703

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

DTIC Science & Technology

1974-08-07

8217 C IN @1 iN 2,2 71 SE 5, _ I _____. ws . 2,. A,’ , S _____ __ . _____ ____Sw . , 2, - :j ih , I. I I 12 .. SSWA NABE O2 .O 1.4 a CIO.S921 0 soi 4... SY HrsOMthTprat u MMA c Pe. H. AFD573 t ) 91660R 77 0 41 0 2-408b- 0_F_32_F_67_F73_F _8__F_ 93_ _ol I’- a ii-E 29(,06 899 3*CE/MA296.C4.19 -4- -E _1

Revised Uniform Summary of Surface Weather Observations for Vandenberg AFB, California, MSC 723930. Parts A-F

DTIC Science & Technology

1985-05-01

4 sq Al U-X z a’ M 4n al Ni Z u 0I a, -z Con % ui1 ~o* uU cc< 0u :’_ - x LZ Wa IL aw 44 _ X1 9 .j u " ift 13 4 W WIL Of 110’~ aR e Mi Ui 6 U2, D 0 4 u...ginA r ln In n n 4 .0 at ~ N t . I- -iN 0000v 0 v0 0 A0.. 00vN4 - V 0M iNinMfN N. M a 0 P. P. 0000 00000 Samoa 000memo40 gMO P: 1. 0 m9,a a .1 z *J Z...u oa . ow i ob to- fa U F a 0 a 4 0 0 00 Co Eq Eq 0 W vw Moo f - 0 *a 1040 - d - oo - -w_--_ _ 4Fe A AV 42~ PRO i it a 1 -- ’We-- _ - - - te 03 0 0

Simultaneous adsorption of Cu2+ and Acid fuchsin (AF) from aqueous solutions by CMC/bentonite composite.

PubMed

Gong, Ning; Liu, Yanping; Huang, Ruihua

2018-04-21

Carboxymethyl-chitosan (CMC)/bentonite composite was prepared by the method of membrane-forming, and characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) techniques. The simultaneous adsorption of Cu 2+ and Acid fuchsin (AF) applying CMC/bentonite composite as an adsorbent in single or binary systems was investigated. The adsorption study was conducted systematically by varying the ratio of CMC to bentonite, adsorbent dosage, initial pH value, initial Cu 2+ (or AF) concentration, contact time and the interaction of two components in binary solutions. The results showed that the presence of Cu 2+ hindered the adsorption of AF, while the presence of AF almost had no influence on the adsorption of Cu 2+ in binary systems. The adsorption data of Cu 2+ and AF were both suitable for Langmuir isotherm model, and the maximum adsorption capacities of CMC/bentonite composite, according to the Langmuir isotherm model were 81.4 mg/g for Cu 2+ and 253.2 mg/g for AF at 298 K. The pseudo-second-order model could better describe the adsorption process of Cu 2+ and AF. Thermodynamic constant values illustrated that the adsorption of Cu 2+ was endothermic, while the adsorption process of AF was exothermic. Copyright © 2018. Published by Elsevier B.V.

Coordinating Subdomains of Ferritin Protein Cages with Catalysis and Biomineralization viewed from the C4 Cage Axes

PubMed Central

Theil, Elizabeth C.; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-01-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3•H2O minerals from Fe2+, for metabolic iron concentrates and oxidant protection; biomineral order varies in different ferritin proteins. The conserved 4, 3, 2 geometric symmetry of ferritin protein cages, parallels subunit dimer, trimer and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self- assembling ferritin nanocages have functional relationships to cage symmetry such as Fe2+ transport though ion channels (3-fold symmetry), biomineral nucleation/order (4-fold symmetry) and mineral dissolution (3-fold symmetry) studied in ferritin variants. Cage subunit dimers (2-fold symmetry) influence iron oxidation and mineral dissolution, based on effects of natural or synthetic subunit dimer crosslinks. 2Fe2+/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n=3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of 3 subunits. Here, we study 2Fe2+ + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3•H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein 2-fold and 3-fold cage axes to show function at ferritin 4-fold cage axes. Here, conserved amino acids facilitate dissolution of ferritin protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage 4-fold symmetry and solid state mineral properties remain largely unexplored. PMID:24504941

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

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.

Climate-driven sediment aggradation and incision phases since the Late Pleistocene in the NW Himalaya, India

NASA Astrophysics Data System (ADS)

Dey, Saptarshi; Thiede, Rasmus C.; Schildgen, Taylor F.; Wittmann, Hella; Bookhagen, Bodo; Scherler, Dirk; Jain, Vikrant; Strecker, Manfred R.

2016-04-01

Deciphering the response of sediment routing systems to climatic forcing is fundamental for understanding the impacts of climate change on landscape evolution and depositional systems. In the Sub-Himalaya, late Pleistocene to Holocene alluvial fills and fluvial terraces record periodic fluctuations of sediment supply and transport capacity on timescale of 103 to 105 years, most likely related to past climatic fluctuations. To evaluate the climatic control on sediment supply and transport capacity, we analyze remnant alluvial fans and terraces in the Kangra Basin of the northwestern Sub-Himalaya. Based on field observations and OSL and CRN-dating, we recognized two sedimentary cycles with major sediment aggradation and subsequent re-incision phases. The large one developed over the entire last glacial period with ˜200 m high alluvial fan (AF1) and the second one during the latest Pleistocene/Holocene with ˜50 m alluvial fan (AF2) and its re-incision . Surface-exposure dating of six terrace levels with in-situ cosmogenic nuclides (10Be) indicates the onset of channel abandonment and ensuing incision phases. Two terrace surfaces from the highest level (T1) sculpted into the oldest-preserved AF1 dates back to 48.9 ± 4.1 ka and 42.1 ± 2.7 ka (2σ error). T2 surfaces sculpted into the remnants of AF1 have exposure ages of 16.8 ± 2 ka and 14.1 ± 0.9 ka, while terraces sculpted into the late Pleistocene- Holocene fan (AF2) provide ages of 8.4± 0.8 ka, 6.6± 0.7 ka, 4.9± 0.4 ka and 3.1± 0.3 ka. Together with previously-published ages on the timing of aggradation, we find a correlation between variations in sediment transport with oxygen-isotope records from regions affected by Indian Summer Monsoon. During stronger monsoon phases and post-LGM glacial retreat manifested by increased sediment delivery (moraines and hillslope-derived) to the trunk streams, causing aggradation in the basin; whereas, weakened monsoon phases characterized by reduced sediment-delivery from the hillslope or moraines resulted into incision of the transiently-stored sediments. Sediment cycles in the Kangra Basin are largely synchronous with those documented from other NW Himalayan valleys.

The Involvement of Ser1898 of the Human L-Type Calcium Channel in Evoked Secretion

PubMed Central

Bachnoff, Niv; Cohen-Kutner, Moshe; Atlas, Daphne

2011-01-01

A PKA consensus phosphorylation site S1928 at the α 11.2 subunit of the rabbit cardiac L-type channel, CaV1.2, is involved in the regulation of CaV1.2 kinetics and affects catecholamine secretion. This mutation does not alter basal CaV1.2 current properties or regulation of CaV1.2 current by PKA and the beta-adrenergic receptor, but abolishes CaV1.2 phosphorylation by PKA. Here, we test the contribution of the corresponding PKA phosphorylation site of the human α 11.2 subunit S1898, to the regulation of catecholamine secretion in bovine chromaffin cells. Chromaffin cells were infected with a Semliki-Forest viral vector containing either the human wt or a mutated S1898A α 11.2 subunit. Both subunits harbor a T1036Y mutation conferring nifedipine insensitivity. Secretion evoked by depolarization in the presence of nifedipine was monitored by amperometry. Depolarization-triggered secretion in cells infected with either the wt α 11.2 or α 11.2/S1898A mutated subunit was elevated to a similar extent by forskolin. Forskolin, known to directly activate adenylyl-cyclase, increased the rate of secretion in a manner that is largely independent of the presence of S1898. Our results are consistent with the involvement of additional PKA regulatory site(s) at the C-tail of α 11.2, the pore forming subunit of CaV1.2. PMID:22216029

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

PubMed

Graves, Kevin G; May, Heidi T; Jacobs, Victoria; Bair, Tami L; Stevens, Scott M; Woller, Scott C; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Peter Weiss, J; Jared Bunch, T

2017-06-01

Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Temporal trends of in-hospital complications associated with catheter ablation of atrial fibrillation in the United States: An update from Nationwide Inpatient Sample database (2011-2014).

PubMed

Tripathi, Byomesh; Arora, Shilpkumar; Kumar, Varun; Abdelrahman, Mohamed; Lahewala, Sopan; Dave, Mihir; Shah, Mahek; Tan, Bryan; Savani, Sejal; Badheka, Apurva; Gopalan, Radha; Shantha, Ghanshyam Palamaner Subash; Viles-Gonzalez, Juan; Deshmukh, Abhishek

2018-05-01

Catheter ablation is widely accepted intervention for atrial fibrillation (AF) refractory to antiarrhythmic drugs, but limited data are available regarding contemporary trends in major complications and in-hospital mortality due to the procedure. This study was aimed at exploring the temporal trends of in-hospital mortality, major complications, and impact of hospital volume on frequency of AF ablation-related outcomes. The Nationwide Inpatient Sample database was utilized to identify the AF patients treated with catheter ablation. In-hospital death and common complications including vascular access complications, cardiac perforation and/or tamponade, pneumothorax, stroke, and transient ischemic attack, were identified using International Classification of Disease (ICD-9-CM) codes. In-hospital mortality rate of 0.15% and overall complication rate of 5.46% were noted among AF ablation recipients (n = 50,969). Significant increase in complications during study period (relative increase 56.37%, P-trend < 0.001) was observed. Cardiac (2.65%), vascular (1.33%), and neurological (1.05%) complications were most common. On multivariate analysis (odds ratio [OR]; 95% confidence interval [95% CI]; P value), significant predictors of complications were female sex (OR = 1.40; CI = 1.17-1.68; P value < 0.001), high burden of comorbidity as indicated by Charlson Comorbidity Index ≥2 (OR = 2.84; CI = 2.29-3.52; P value < 0.001), and low hospital volume (< 50 procedures). Our study noted a decline in AF ablation-related hospitalizations and complications associated with the procedure. These findings largely reflect shifting trends of outpatient performance of the procedure and increasing safety profile due to improved institutional expertise and catheter techniques. © 2018 Wiley Periodicals, Inc.

Integrating Genetic, Transcriptional, and Functional Analyses to Identify Five Novel Genes for Atrial Fibrillation

PubMed Central

Sinner, Moritz F.; Tucker, Nathan R.; Lunetta, Kathryn L.; Ozaki, Kouichi; Smith, J. Gustav; Trompet, Stella; Bis, Joshua C.; Lin, Honghuang; Chung, Mina K.; Nielsen, Jonas B.; Lubitz, Steven A.; Krijthe, Bouwe P.; Magnani, Jared W.; Ye, Jiangchuan; Gollob, Michael H.; Tsunoda, Tatsuhiko; Müller-Nurasyid, Martina; Lichtner, Peter; Peters, Annette; Dolmatova, Elena; Kubo, Michiaki; Smith, Jonathan D.; Psaty, Bruce M.; Smith, Nicholas L.; Jukema, J. Wouter; Chasman, Daniel I.; Albert, Christine M.; Ebana, Yusuke; Furukawa, Tetsushi; MacFarlane, Peter; Harris, Tamara B.; Darbar, Dawood; Dörr, Marcus; Holst, Anders G.; Svendsen, Jesper H.; Hofman, Albert; Uitterlinden, Andre G.; Gudnason, Vilmundur; Isobe, Mitsuaki; Malik, Rainer; Dichgans, Martin; Rosand, Jonathan; Van Wagoner, David R.; Benjamin, Emelia J.; Milan, David J.; Melander, Olle; Heckbert, Susan R.; Ford, Ian; Liu, Yongmei; Barnard, John; Olesen, Morten S.; Stricker, Bruno H.C.; Tanaka, Toshihiro; Kääb, Stefan; Ellinor, Patrick T.

2014-01-01

Background Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. Methods & Results To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 – 1.23, p=6.5×10−16), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 – 1.14, p=2.2×10−8), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 – 1.16, p=5.7×10−11), and CAND2 (rs4642101, RR=1.10, 95%CI 1.06 – 1.14, p=9.8×10−9). In Japanese, novel loci were identified near NEURL (rs6584555, RR=1.32, 95%CI 1.26–1.39, p=2.0×10−25) and CUX2 (rs6490029, RR=1.12, 95%CI 1.08–1.16, p=3.9×10−9). The top SNPs or their proxies were identified as cis-eQTLs for the genes CAND2 (p=2.6×10−19), GJA1 (p=2.66×10−6), and TBX5 (p=1.36×10−05). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). Conclusions We have identified five novel loci for AF. Our results further expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation. PMID:25124494

Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Rushton-Smith, Sophie K; Goldhaber, Samuel Z; Fitzmaurice, David A; Mantovani, Lorenzo G; Goto, Shinya; Haas, Sylvia; Bassand, Jean-Pierre; Camm, Alan John; Ambrosio, Giuseppe; Janský, Petr; Al Mahmeed, Wael; Oh, Seil; van Eickels, Martin; Raatikainen, Pekka; Steffel, Jan; Oto, Ali; Kayani, Gloria; Accetta, Gabriele; Kakkar, Ajay K

2015-03-01

Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92-1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. http://www.clinicaltrials.gov. Unique identifier: NCT01090362. © 2015 American Heart Association, Inc.

Chocolate Intake and Risk of Clinically Apparent Atrial Fibrillation: the Danish Diet, Cancer, and Health Study

PubMed Central

Mostofsky, Elizabeth; Johansen, Martin Berg; Tjønneland, Anne; Chahal, Harpreet S.; Mittleman, Murray A.; Overvad, Kim

2018-01-01

Objective To evaluate the association between chocolate intake and incident clinically apparent atrial fibrillation or flutter (AF).. Methods The Danish Diet, Cancer and Health Study is a large population-based prospective cohort study. The present study is based on 55,502 participants (26,400 men and 29,102 women) aged 50–64 years who had provided information on chocolate intake at baseline. Incident cases of AF were ascertained by linkage with nationwide registries. Results During a median of 13.5 years, there were 3,346 cases of AF. Compared with chocolate intake less than once per month, the rate of AF was lower for people consuming 1–3 servings/month (Hazard Ratio [HR]= 0.90, 95% confidence interval [CI] 0.82–0.98), 1 serving/week (HR= 0.83, 95% CI 0.74–0.92), 2–6 servings/week (HR= 0.80, 95% CI 0.71–0.91) and 1 servings/day (HR= 0.84, 95 %CI 0.65–1.09; p-linear trend<0.0001), with similar results for men and women. Conclusions Accumulating evidence indicates that moderate chocolate intake may be inversely associated with AF risk, though residual confounding cannot be ruled out. PMID:28536115

Amino acid sequence of the human fibronectin receptor

PubMed Central

1987-01-01

The amino acid sequence deduced from cDNA of the human placental fibronectin receptor is reported. The receptor is composed of two subunits: an alpha subunit of 1,008 amino acids which is processed into two polypeptides disulfide bonded to one another, and a beta subunit of 778 amino acids. Each subunit has near its COOH terminus a hydrophobic segment. This and other sequence features suggest a structure for the receptor in which the hydrophobic segments serve as transmembrane domains anchoring each subunit to the membrane and dividing each into a large ectodomain and a short cytoplasmic domain. The alpha subunit ectodomain has five sequence elements homologous to consensus Ca2+- binding sites of several calcium-binding proteins, and the beta subunit contains a fourfold repeat strikingly rich in cysteine. The alpha subunit sequence is 46% homologous to the alpha subunit of the vitronectin receptor. The beta subunit is 44% homologous to the human platelet adhesion receptor subunit IIIa and 47% homologous to a leukocyte adhesion receptor beta subunit. The high degree of homology (85%) of the beta subunit with one of the polypeptides of a chicken adhesion receptor complex referred to as integrin complex strongly suggests that the latter polypeptide is the chicken homologue of the fibronectin receptor beta subunit. These receptor subunit homologies define a superfamily of adhesion receptors. The availability of the entire protein sequence for the fibronectin receptor will facilitate studies on the functions of these receptors. PMID:2958481

New antiarrhythmic agents for atrial fibrillation and atrial flutter: United States drug market response as an indicator of acceptance.

PubMed

LaPointe, Nancy M Allen; Pamer, Carol A; Kramer, Judith M

2003-10-01

To determine how well dofetilide and Betapace AF (sotalol, approved solely for atrial fibrillation and atrial flutter), with their detailed dosing and monitoring guidelines for safety, were accepted into clinical practice during the 2 calendar years after their introduction. We reviewed the number of new, refill, and total prescriptions of all antiarrhythmic agents in the United States from April 2000-December 2001 to assess use of dofetilide and Betapace AF in the drug market. Both were prescribed very infrequently throughout the study period. In addition, the infrequent reported use of these drugs for patients with atrial fibrillation and flutter indicated poor acceptance of these agents by prescribing physicians. We speculated that the restricted distribution and required educational program for dofetilide, as well as the availability of generic sotalol products, may have discouraged physicians from prescribing both dofetilide and Betapace AE CONCLUSION: A common goal for both the dofetilide risk-management program and the creation of a sotalol product indicated solely for atrial fibrillation and atrial flutter was to provide safer treatment for patients with these arrhythmias. Unfortunately, limited penetration of dofetilide and Betapace AF into the U.S. market suggests that drugs without a risk-management program or detailed dosing guidelines were more likely than dofetilide or Betapace AF to be selected for treatment of atrial fibrillation and atrial flutter.

Comparisons between vs30 and spectral response for 30 sites in Newcastle, Australia from collocated seismic cone penetrometer, active- and passive-source vs data

USGS Publications Warehouse

Volti, Theodora; Burbidge, David; Collins, Clive; Asten, Michael W.; Odum, Jackson K.; Stephenson, William J.; Pascal, Chris; Holzschuh, Josef

2016-01-01

Although the time‐averaged shear‐wave velocity down to 30 m depth (VS30) can be a proxy for estimating earthquake ground‐motion amplification, significant controversy exists about its limitations when used as a single parameter for the prediction of amplification. To examine this question in absence of relevant strong‐motion records, we use a range of different methods to measure the shear‐wave velocity profiles and the resulting theoretical site amplification factors (AFs) for 30 sites in the Newcastle area, Australia, in a series of blind comparison studies. The multimethod approach used here combines past seismic cone penetrometer and spectral analysis of surface‐wave data, with newly acquired horizontal‐to‐vertical spectral ratio, passive‐source surface‐wave spatial autocorrelation (SPAC), refraction microtremor (ReMi), and multichannel analysis of surface‐wave data. The various measurement techniques predicted a range of different AFs. The SPAC and ReMi techniques have the smallest overall deviation from the median AF for the majority of sites. We show that VS30 can be related to spectral response above a period T of 0.5 s but not necessarily with the maximum amplification according to the modeling done based on the measured shear‐wave velocity profiles. Both VS30 and AF values are influenced by the velocity ratio between bedrock and overlying sediments and the presence of surficial thin low‐velocity layers (<2  m thick and <150  m/s), but the velocity ratio is what mostly affects the AF. At 0.20.5  s do the amplification curves consistently show higher values for soft site classes and lower for hard classes.

Purification and Characterization of a Novel Thermostable α-l-Arabinofuranosidase from a Color-Variant Strain of Aureobasidium pullulans

PubMed Central

Saha, Badal C.; Bothast, Rodney J.

1998-01-01

A color-variant strain of Aureobasidium pullulans (NRRL Y-12974) produced α-l-arabinofuranosidase (α-l-AFase) when grown in liquid culture on oat spelt xylan. An extracellular α-l-AFase was purified 215-fold to homogeneity from the culture supernatant by ammonium sulfate treatment, DEAE Bio-Gel A agarose column chromatography, gel filtration on a Bio-Gel A-0.5m column, arabinan-Sepharose 6B affinity chromatography, and SP-Sephadex C-50 column chromatography. The purified enzyme had a native molecular weight of 210,000 and was composed of two equal subunits. It had a half-life of 8 h at 75°C, displayed optimal activity at 75°C and pH 4.0 to 4.5, and had a specific activity of 21.48 μmol · min−1 · mg−1 of protein against p-nitrophenyl-α-l-arabinofuranoside (pNPαAF). The purified α-l-AFase readily hydrolyzed arabinan and debranched arabinan and released arabinose from arabinoxylans but was inactive against arabinogalactan. The Km values of the enzyme for the hydrolysis of pNPαAF, arabinan, and debranched arabinan at 75°C and pH 4.5 were 0.26 mM, 2.14 mg/ml, and 3.25 mg/ml, respectively. The α-l-AFase activity was not inhibited at all by l-arabinose (1.2 M). The enzyme did not require a metal ion for activity, and its activity was not affected by p-chloromercuribenzoate (0.2 mM), EDTA (10 mM), or dithiothreitol (10 mM). PMID:9435077

Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass

PubMed Central

Lee, Young-Sam; Gregory, Mark T.; Yang, Wei

2014-01-01

DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3–Rev7–PolD2–PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3–Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3′ guanine and Pol ζ4 to extend the primers. PMID:24449906

Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.

PubMed

Lee, Young-Sam; Gregory, Mark T; Yang, Wei

2014-02-25

DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3-Rev7-PolD2-PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3-Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3' guanine and Pol ζ4 to extend the primers.

Military Service Records and Unit Histories: A Guide to Locating Sources

DTIC Science & Technology

2012-07-26

records, therefoa- e , written authorization from the veta -an or ne.’Ct of kin is not rEqUired. However, in ordet" to protect the privacy of the...line E -mail: MPR.center@nara.gov Older military personnel records (generally prior to World War I, depending on the service branch) are located at...AFB, DC 20032-5000 E -mail: afhso.research@pentagon.af.mil http://www.afhso.af.mil/ (202) 404-2264 National Museum of the U.S. Air Force 1100

Reference Book of Nuclear Testing Contractors 1945-1965. Revision 1

DTIC Science & Technology

1987-05-30

Corps of Engineers W49-129-Eng-148 Armour Research Foundation of Illinois Institute of Technology Project 3.3 AF 33(038)9761 (Air Material Command...VnVnPT^^flW1iVi’U’*J ’^." v*-" I*H*JI w VI«HIIWIWI^I ^ -i« - BUSTER JANGLE Armour Research Foundation Illinois Institute of Technology Chicago, IL...v TUMBLER SNAPPER Armour Research Foundation (ARF) AF 33(616)3218 Bendix Corp/Bendix Aviation Aviation Pacific Division Development

Project CHECO Southeast Asia Report. USAF Civic Action in Thailand

DTIC Science & Technology

1969-03-22

SECOND CLASS HEALTH CENTERS MIDWIFERY CENTER MOBILE MEDICAL TEAMS , I SPECIAL 7AF/l3AF FORCES I I I I t I i ! L------·-. 56 ACW -t I i 1 I i...direct treatment of patients by U.S. personnel and the wide variety of drugs offered by the Americans were considered to be contrary to the stated...while diminishing the sophistication 10/ of drugs .-- The variety of drugs supplied by the USAF created a dual problem: (1) Thai resources were

Coordinating subdomains of ferritin protein cages with catalysis and biomineralization viewed from the C4 cage axes.

PubMed

Theil, Elizabeth C; Turano, Paola; Ghini, Veronica; Allegrozzi, Marco; Bernacchioni, Caterina

2014-06-01

Integrated ferritin protein cage function is the reversible synthesis of protein-caged, solid Fe2O3·H2O minerals from Fe(2+) for metabolic iron concentrates and oxidant protection; biomineral order differs in different ferritin proteins. The conserved 432 geometric symmetry of ferritin protein cages parallels the subunit dimer, trimer, and tetramer interfaces, and coincides with function at several cage axes. Multiple subdomains distributed in the self-assembling ferritin nanocages have functional relationships to cage symmetry such as Fe(2+) transport though ion channels (threefold symmetry), biomineral nucleation/order (fourfold symmetry), and mineral dissolution (threefold symmetry) studied in ferritin variants. On the basis of the effects of natural or synthetic subunit dimer cross-links, cage subunit dimers (twofold symmetry) influence iron oxidation and mineral dissolution. 2Fe(2+)/O2 catalysis in ferritin occurs in single subunits, but with cooperativity (n = 3) that is possibly related to the structure/function of the ion channels, which are constructed from segments of three subunits. Here, we study 2Fe(2+) + O2 protein catalysis (diferric peroxo formation) and dissolution of ferritin Fe2O3·H2O biominerals in variants with altered subunit interfaces for trimers (ion channels), E130I, and external dimer surfaces (E88A) as controls, and altered tetramer subunit interfaces (L165I and H169F). The results extend observations on the functional importance of structure at ferritin protein twofold and threefold cage axes to show function at ferritin fourfold cage axes. Here, conserved amino acids facilitate dissolution of ferritin-protein-caged iron biominerals. Biological and nanotechnological uses of ferritin protein cage fourfold symmetry and solid-state mineral properties remain largely unexplored.

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.

Proteopedia Entry: The Large Ribosomal Subunit of "Haloarcula Marismortui"

ERIC Educational Resources Information Center

Decatur, Wayne A.

2010-01-01

This article presents a "Proteopedia" page that shows the refined version of the structure of the "Haloarcula" large ribosomal subunit as solved by the laboratories of Thomas Steitz and Peter Moore. The landmark structure is of great impact as it is the first atomic-resolution structure of the highly conserved ribosomal subunit which harbors…

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Characteristics and Prognosis of Pacemaker-Identified New-Onset Atrial Fibrillation in Japanese People.

PubMed

Ogino, Yutaka; Ishikawa, Toshiyuki; Ishigami, Tomoaki; Matsumoto, Katsumi; Hosoda, Junya; Iguchi, Kouhei; Matsushita, Hirooki; Taguchi, Yuka; Horiguchi, Yoriko; Kimura, Kazuo

2017-05-25

The characteristics and prognosis of implanted pacemaker-identified new-onset atrial fibrillation (AF) in Japanese people has not been well evaluated.Methods and Results:A total of 395 consecutive patients with newly implanted pacemakers were retrospectively analyzed between January 2010 and December 2015 at Yokohama City University Hospital. Patients with a prior history of AF, VVI mode pacemaker, congenital heart disease, severe valvular heart disease, and cardiovascular surgery before pacemaker implantation were excluded. Among the remaining patients, 44 (21.3%) developed new AF during follow-up (mean follow-up, 1,115±651 days; range, 9-2,176 days). Patients with new-onset AF had a significantly higher CHADS 2 score (2.09±1.27 vs. 1.31±1.08, P<0.001) and CHA 2 DS 2 -VASc score (3.00±1.39 vs. 2.26±1.19, P<0.001) compared with those without new-onset AF. On Cox regression analysis only age at implantation was significantly correlated with new-onset AF. Interestingly, the incidence of hospitalization due to heart failure was significantly higher in the new-onset AF than in the without new-onset AF group. A total of 21.3% of pacemaker-implanted patients with high CHADS 2 and CHA 2 DS 2 -VASc scores developed new-onset AF during a mean follow-up of 3.1 years; and pacemaker-identified AF was associated with an increased risk of worsening heart failure.

Increased expression of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in human atria during atrial fibrillation.

PubMed

De-An, Pei; Li, Li; Zhi-Yun, Xu; Jin-Yu, Huang; Zheng-Ming, Xu; Min, Wang; Qiang, Yao; Shi-Eng, Huang

2010-01-01

Atrialfibrillation (AF) is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of a mineralocorticoid receptor (MR), or 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), conferring aldosterone specificity to the MR, in patients with AF is altered. Patients with AF may be associated with increased expression of MR and 11betaHSD2 in the atria. Atrial tissue samples of 25 patients with rheumatic heart valve disease undergoing a valve replacement operation were examined. A total of 13 patients had chronic persistent AF (>6 mo) and 12 patients had no history of AF. The MR and 11betaHSD2 expression were analyzed at the mRNA and protein level. The localization of MR and 11betaHSD2 in atrial tissue was performed using specific immunohistochemistry staining. The results of real-time quantitative polymerase chain reaction (PCR) showed that AF groups, in comparison with sinus rhythm, had a higher mRNA expression level of MR or 11betaHSD2 (all P < 0.01). Both the MR and 11betaHSD2 protein expression level in atrial tissue were also significantly increased in patients with AF compared with patients with sinus rhythm (P < 0.05 or P < 0.01). The immunohistochemical staining of MR or 11betaHSD2 demonstrated that MR and 11betaHSD2 predominately located in the cytoplasm of myocardial cells in the atrium and the intensity and density of immunostaining appeared to be increased in the atria of patients with AF compared to those without AF. Increasing expression of MR and 11betaHSD2 in the atria during AF is one of the molecular mechanisms for development of atrial interstitial fibrosis in patients with AF. These findings may have an important impact on the treatment of AF with aldosterone antagonists. Copyright 2010 Wiley Periodicals, Inc.

Impaired Spermatogenesis, Muscle, and Erythrocyte Function in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.

PubMed

Horiuchi, Keiko; Perez-Cerezales, Serafín; Papasaikas, Panagiotis; Ramos-Ibeas, Priscila; López-Cardona, Angela Patricia; Laguna-Barraza, Ricardo; Fonseca Balvís, Noelia; Pericuesta, Eva; Fernández-González, Raul; Planells, Benjamín; Viera, Alberto; Suja, Jose Angel; Ross, Pablo Juan; Alén, Francisco; Orio, Laura; Rodriguez de Fonseca, Fernando; Pintado, Belén; Valcárcel, Juan; Gutiérrez-Adán, Alfonso

2018-04-03

The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility. Testis RNA sequencing (RNA-seq) analyses revealed increased intron retention of both U2- and U12-type introns, including U12-type intron events in genes with key functions in spermatogenesis and spermatid development. Affected U2 introns were commonly found flanking U12 introns, suggesting functional cross-talk between the two spliceosomes. The splicing and tissue defects observed in mutant mice attributed to ZRSR1 loss of function suggest a physiological role for this factor in U12 intron splicing. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The application of a multi-dimensional assessment approach to talent identification in Australian football.

PubMed

Woods, Carl T; Raynor, Annette J; Bruce, Lyndell; McDonald, Zane; Robertson, Sam

2016-07-01

This study investigated whether a multi-dimensional assessment could assist with talent identification in junior Australian football (AF). Participants were recruited from an elite under 18 (U18) AF competition and classified into two groups; talent identified (State U18 Academy representatives; n = 42; 17.6 ± 0.4 y) and non-talent identified (non-State U18 Academy representatives; n = 42; 17.4 ± 0.5 y). Both groups completed a multi-dimensional assessment, which consisted of physical (standing height, dynamic vertical jump height and 20 m multistage fitness test), technical (kicking and handballing tests) and perceptual-cognitive (video decision-making task) performance outcome tests. A multivariate analysis of variance tested the main effect of status on the test criterions, whilst a receiver operating characteristic curve assessed the discrimination provided from the full assessment. The talent identified players outperformed their non-talent identified peers in each test (P < 0.05). The receiver operating characteristic curve reflected near perfect discrimination (AUC = 95.4%), correctly classifying 95% and 86% of the talent identified and non-talent identified participants, respectively. When compared to single assessment approaches, this multi-dimensional assessment reflects a more comprehensive means of talent identification in AF. This study further highlights the importance of assessing multi-dimensional performance qualities when identifying talented team sports.

Atrial Fibrillation Ablation Guided by a Novel Nonfluoroscopic Navigation System.

PubMed

Ballesteros, Gabriel; Ramos, Pablo; Neglia, Renzo; Menéndez, Diego; García-Bolao, Ignacio

2017-09-01

Rhythmia is a new nonfluoroscopic navigation system that is able to create high-density electroanatomic maps. The aim of this study was to describe the acute outcomes of atrial fibrillation (AF) ablation guided by this system, to analyze the volume provided by its electroanatomic map, and to describe its ability to locate pulmonary vein (PV) reconnection gaps in redo procedures. This observational study included 62 patients who underwent AF ablation with Rhythmia compared with a retrospective cohort who underwent AF ablation with a conventional nonfluoroscopic navigation system (Ensite Velocity). The number of surface electrograms per map was significantly higher in Rhythmia procedures (12 125 ± 2826 vs 133 ± 21 with Velocity; P < .001), with no significant differences in the total procedure time. The Orion catheter was placed for mapping in 99.5% of PV (95.61% in the control group with a conventional circular mapping catheter; P = .04). There were no significant differences in the percentage of PV isolation between the 2 groups. In redo procedures, an ablation gap could be identified on the activation map in 67% of the reconnected PV (40% in the control group; P = .042). The measured left atrial volume was lower than that calculated by computed tomography (109.3 v 15.2 and 129.9 ± 13.2 mL, respectively; P < .001). There were no significant differences in the number of complications. The Rhythmia system is effective for AF ablation procedures, with procedure times and safety profiles similar to conventional nonfluoroscopic navigation systems. In redo procedures, it appears to be more effective in identifying reconnected PV conduction gaps. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

LEGO-NMR spectroscopy: a method to visualize individual subunits in large heteromeric complexes.

PubMed

Mund, Markus; Overbeck, Jan H; Ullmann, Janina; Sprangers, Remco

2013-10-18

Seeing the big picture: Asymmetric macromolecular complexes that are NMR active in only a subset of their subunits can be prepared, thus decreasing NMR spectral complexity. For the hetero heptameric LSm1-7 and LSm2-8 rings NMR spectra of the individual subunits of the complete complex are obtained, showing a conserved RNA binding site. This LEGO-NMR technique makes large asymmetric complexes accessible to detailed NMR spectroscopic studies. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons the Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

PubMed

Lip, Gregory Y H; Collet, Jean Philippe; Caterina, Raffaele de; Fauchier, Laurent; Lane, Deirdre A; Larsen, Torben B; Marin, Francisco; Morais, Joao; Narasimhan, Calambur; Olshansky, Brian; Pierard, Luc; Potpara, Tatjana; Sarrafzadegan, Nizal; Sliwa, Karen; Varela, Gonzalo; Vilahur, Gemma; Weiss, Thomas; Boriani, Giuseppe; Rocca, Bianca

2017-11-01

Atrial fibrillation (AF) is a major worldwide public health problem, and AF in association with valvular heart disease (VHD) is also common. However, management strategies for this group of patients have been less informed by randomized trials, which have largely focused on 'non-valvular AF' patients. Thrombo-embolic risk also varies according to valve lesion and may also be associated with CHA2DS2VASc score risk factor components, rather than only the valve disease being causal. Given marked heterogeneity in the definition of valvular and non-valvular AF and variable management strategies, including non-vitamin K antagonist oral anticoagulants (NOACs) in patients with VHD other than prosthetic heart valves or haemodynamically significant mitral valve disease, there is a need to provide expert recommendations for professionals participating in the care of patients presenting with AF and associated VHD. To address this topic, a Task Force was convened by the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Thrombosis, with representation from the ESC Working Group on Valvular Heart Disease, Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE) with the remit to comprehensively review the published evidence, and to publish a joint consensus document on the management of patients with AF and associated VHD, with up-to-date consensus recommendations for clinical practice for different forms of VHD. This consensus document proposes that the term 'valvular AF' is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional Evaluated Heartvalves, Rheumatic or Artificial (EHRA) categorization in relation to the type of OAC use in patients with AF, as follows: (i) EHRA Type 1 VHD, which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA); and (ii) EHRA Type 2 VHD, which refers to AF patients with 'VHD needing therapy with a VKA or a Non-VKA oral anticoagulant (NOAC)', also taking into consideration CHA2DS2VASc score risk factor components. This consensus document also summarizes current developments in the field, and provides general recommendations for the management of these patients based on the principles of evidence-based medicine. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Subclinical Hyperthyroidism and the Risk of Coronary Heart Disease and Mortality

PubMed Central

Collet, Tinh-Hai; Gussekloo, Jacobijn; Bauer, Douglas C.; den Elzen, Wendy P. J.; Cappola, Anne R.; Balmer, Philippe; Iervasi, Giorgio; Åsvold, Bjørn O.; Sgarbi, José A.; Völzke, Henry; Gencer, Bariş; Maciel, Rui M. B.; Molinaro, Sabrina; Bremner, Alexandra; Luben, Robert N.; Maisonneuve, Patrick; Cornuz, Jacques; Newman, Anne B.; Khaw, Kay-Tee; Westendorp, Rudi G. J.; Franklyn, Jayne A.; Vittinghoff, Eric; Walsh, John P.; Rodondi, Nicolas

2013-01-01

Background Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. Methods Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. Results Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age-and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06–1.46), CHD mortality (HR, 1.29; 95% CI, 1.02–1.62), CHD events (HR, 1.21; 95% CI, 0.99–1.46), and AF (HR, 1.68; 95% CI, 1.16–2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03). Conclusion Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L. PMID:22529182

Understanding the mechanisms of ATPase beta family genes for cellular thermotolerance in crossbred bulls

NASA Astrophysics Data System (ADS)

Deb, Rajib; Sajjanar, Basavaraj; Singh, Umesh; Alex, Rani; Raja, T. V.; Alyethodi, Rafeeque R.; Kumar, Sushil; Sengar, Gyanendra; Sharma, Sheetal; Singh, Rani; Prakash, B.

2015-12-01

Na+/K+-ATPase is an integral membrane protein composed of a large catalytic subunit (alpha), a smaller glycoprotein subunit (beta), and gamma subunit. The beta subunit is essential for ion recognition as well as maintenance of the membrane integrity. Present study was aimed to analyze the expression pattern of ATPase beta subunit genes (ATPase B1, ATPase B2, and ATPase B3) among the crossbred bulls under different ambient temperatures (20-44 °C). The present study was also aimed to look into the relationship of HSP70 with the ATPase beta family genes. Our results demonstrated that among beta family genes, transcript abundance of ATPase B1 and ATPase B2 is significantly ( P < 0.05) higher during the thermal stress. Pearson correlation coefficient analysis revealed that the expression of ATPase Β1, ATPase B2, and ATPase B3 is highly correlated ( P < 0.01) with HSP70, representing that the change in the expression pattern of these genes is positive and synergistic. These may provide a foundation for understanding the mechanisms of ATPase beta family genes for cellular thermotolerance in cattle.

Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

PubMed

Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2015-12-01

To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

A Novel Strategy to Control and Prevent Norovirus Gastroenteritis

DTIC Science & Technology

2006-11-01

Vibrio cholerae , Candida, etc.) have been reported to recognize the HBGAs as their receptors. NV is the first viral pathogen in the list. Human...and genogroup II: BUDS (AY660568), Grimsby (GrV; AJ004864), Hawaii (HV; U07611), Mexico (MxV; U22498), MOH (AF397156), Parris Island (PiV

U.S. Air Force > About Us > Observances

Science.gov Websites

Media Sites Site Registration Contact Us Search AF.mil: Highlights APIM-Rotator Womens History Month African American History Month posters African American History Month Asian American Pacific Islander . (U.S. Air Force photo by Staff Sgt. Will McCrary/Released). USAFE band member discovers family history

U.S. EPA, Pesticide Product Label, HENRY FIELD'S NEW IMPROVED BUG DUST, 04/17/1975

EPA Pesticide Factsheets

2011-04-14

... 'Qu.:utiy UIIJt.'f sev~re disease conditj<)II~. ... titan to for'm) V<.i\\~I!Y I.ili

75 FR 9129 - Small Business, Small Disadvantaged Business, HUBZone, and Service-Disabled Veteran-Owned Protest...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... SMALL BUSINESS ADMINISTRATION 13 CFR Parts 121, 124, 125, 126, and 134 RIN 3245-AF65 Small Business, Small Disadvantaged Business, HUBZone, and Service-Disabled Veteran-Owned Protest and Appeal Regulations AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: The U.S. Small...

Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma.

PubMed

Sorigue, Marc; Gual-Capllonch, Francisco; Garcia, Olga; Sarrate, Edurne; Franch-Sarto, Mireia; Ibarra, Gladys; Grau, Javier; Orna, Elisa; Ribera, Josep-Maria; Sancho, Juan-Manuel

2018-05-04

Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3-6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01-0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.

Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0).

PubMed

Wiesel, Joseph; Abraham, Saji; Messineo, Frank C

2013-06-01

Asymptomatic atrial fibrillation (AF) is a common cause of strokes. Physician screening for AF has been recommended. Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF. The aim of this study was to assess the feasibility and accuracy of screening for AF when taking home blood pressure (BP) measurements using an automatic AF-detecting BP monitor. Subjects aged >64 years or those with hypertension, diabetes, congestive heart failure, or previous stroke were enrolled by their primary physicians and given the AF-BP monitor and an electrocardiographic event monitor to use at home for 30 days. The AF-BP monitor reading was compared with the electrocardiographic reading to calculate the sensitivity and specificity of the device for detecting AF. A total of 160 subjects were enrolled, with 10 withdrawing, 1 excluded, and 10 with no AF-BP monitor logs or electrocardiographic recordings. Of the 139 subjects included, 14 had known AF. There was a total of 3,316 days with AF-BP monitor readings and electrocardiographic readings. On the basis of the initial daily AF-BP monitor readings, the AF-BP monitor demonstrated sensitivity of 99.2% and specificity of 92.9% for detecting AF. Two subjects with no histories of AF had AF-BP monitor readings of AF that were confirmed by the electrocardiographic monitor. One of these subjects was started on warfarin. In conclusion, home screening for asymptomatic AF while taking BP measurements can be performed accurately. This can be used to detect new AF, allowing treatment with anticoagulation to reduce the future risk for stroke. Copyright © 2013 Elsevier Inc. All rights reserved.

Pulmonary Vein Isolation Alone Versus Additional Linear Ablation in Patients With Persistent Atrial Fibrillation Converted to Paroxysmal Type With Antiarrhythmic Drug Therapy: A Multicenter, Prospective, Randomized Study.

PubMed

Yu, Hee Tae; Shim, Jaemin; Park, Junbeom; Kim, In-Soo; Kim, Tae-Hoon; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Young-Hoon; Pak, Hui-Nam

2017-06-01

Atrial fibrillation (AF) type can vary depending on condition and timing, and some patients who initially present with persistent AF may be changed to paroxysmal AF after antiarrhythmic drug medication and cardioversion. We investigated whether circumferential pulmonary vein isolation (CPVI) alone is an effective rhythm control strategy in patients with persistent AF to paroxysmal AF. We enrolled 113 patients with persistent AF to paroxysmal AF (male 75%, 60.4±10.1 years old) who underwent catheter ablation for nonvalvular AF at 3 tertiary hospitals. The participants were randomly assigned to 2 groups: CPVI alone (n=59) or CPVI plus linear ablation (CPVI+Line; posterior box+anterior line, n=54). Compared with the CPVI+Line, CPVI alone required shorter procedure (187.2±58.0 versus 211.2±63.9 min; P =0.043) and ablation times (4922.1±1110.5 versus 6205.7±1425.2 s; P <0.001) without difference in procedure-related major complication (3% versus 2%; P =0.611). Antiarrhythmic drug utility rates after ablation were not different between the 2 groups (22% versus 30%; P =0.356). Overall, AF-free survival (log-rank; P =0.206) and AF and antiarrhythmic drug-free survival (log-rank; P =0.321) were not different between groups. CPVI alone is an effective rhythm control strategy with a shorter procedure time in persistent AF patients converted to paroxysmal AF compared with CPVI with linear ablation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02176616. © 2017 American Heart Association, Inc.

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

PubMed Central

Movérare-Skrtic, Sofia; Börjesson, Anna E.; Farman, Helen H.; Sjögren, Klara; Windahl, Sara H.; Lagerquist, Marie K.; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-01

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. PMID:24395795

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta

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

He, Rui-Qing; Tang, Xiao-Feng; Zhang, Bao-Li

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-β and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediatedmore » Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes. - Highlights: • Direct activation of PAR1 and PAR2 led to adventitial fibroblast (AF) activation. • PAR1 and PAR2 antagonists attenuated Ang II-induced AF activation. • Ang II induced the upregulation and transactivation of PAR1/PAR2 in AFs.« less

Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

PubMed Central

Duke, Stephen O.; Kenyon, William H.

1986-01-01

The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

PubMed Central

So, Charlotte H.; Eckman, Mark H.

2016-01-01

Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events. PMID:27665101

Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes.

PubMed

Rebello, L C; Bouslama, M; Haussen, D C; Grossberg, J A; Dehkharghani, S; Anderson, A; Belagaje, S R; Bianchi, N A; Grigoryan, M; Frankel, M R; Nogueira, R G

2017-06-01

Chronic hypoperfusion from athero-stenotic lesions is thought to lead to better collateral recruitment compared to cardioembolic strokes. It was sought to compare collateral flow in stroke patients with atrial fibrillation (AF) versus stroke patients with cervical atherosclerotic steno-occlusive disease (CASOD). This was a retrospective review of a prospectively collected endovascular database. Patients with (i) anterior circulation large vessel occlusion stroke, (ii) pre-treatment computed tomography angiography (CTA) and (iii) intracranial embolism from AF or CASOD were included. CTA collateral patterns were evaluated and categorized into two groups: absent/poor collaterals (CTA collateral score 0-1) versus moderate/good collaterals (CTA collateral score 2-4). CT perfusion was also utilized for baseline core volume and evaluation of infarct growth. A total of 122 patients fitted the inclusion criteria, of whom 88 (72%) had AF and 34 (27%) CASOD. Patients with AF were older (P < 0.01) and less often males or smokers (P = 0.04 and P < 0.01 respectively). Baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were comparable between groups. Collateral scores were lower in the AF group (P = 0.01) with patients having poor collaterals in 28% of cases versus 9% in the CASOD group (P = 0.03). Mortality rates (20% vs. 0%; P = 0.02) were higher in the AF patients whilst rates of any parenchymal hemorrhage (6% vs. 26%; P < 0.01) were higher in the CASOD group. On multivariable analysis, CASOD was an independent predictor of moderate/good collaterals (odds ratio 4.70; 95% confidence interval 1.17-18.79; P = 0.03). Atheroembolic strokes seem to be associated with better collateral flow compared to cardioembolic strokes. This may in part explain the worse outcomes of AF-related stroke. © 2017 EAN.

A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring after Embolic Stroke of Unknown Source.

PubMed

Ricci, Brittany; Chang, Andrew D; Hemendinger, Morgan; Dakay, Katarina; Cutting, Shawna; Burton, Tina; Mac Grory, Brian; Narwal, Priya; Song, Christopher; Chu, Antony; Mehanna, Emile; McTaggart, Ryan; Jayaraman, Mahesh; Furie, Karen; Yaghi, Shadi

2018-06-01

Occult paroxysmal atrial fibrillation (AF) is detected in 16%-30% of patients with embolic stroke of unknown source (ESUS). The identification of AF predictors on outpatient cardiac monitoring can help guide clinicians decide on a duration or method of cardiac monitoring after ESUS. We included all patients with ESUS who underwent an inpatient diagnostic evaluation and outpatient cardiac monitoring between January 1, 2013, and December 31, 2016. Patients were divided into 2 groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, and cardiac biomarkers between the 2 groups. Multivariable logistic regression was used to determine predictors of AF. We identified 296 consecutive patients during the study period; 38 (12.8%) patients had AF detected on outpatient cardiac monitoring. In a multivariable regression analysis, advanced age (ages 65-74: odds ratio [OR] 2.36, 95% confidence interval [CI] .85-6.52; ages 75 or older: OR 4.08, 95% CI 1.58-10.52) and moderate-to-severe left atrial enlargement (OR 4.66, 95% CI 1.79-12.12) were predictors of AF on outpatient monitoring. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, 75 years or older: 2 points) and left atrial enlargement (moderate or severe: 2 points) with good prediction of AF (area under the curve .725) and was internally validated using bootstrapping. The percentage of patients with AF detected in each score category were as follows: 0: 4.2%; 1: 14.8%; 2: 20.8%; 3: 22.2%; 4: 55.6%. The Brown ESUS-AF score predicts AF on prolonged outpatient monitoring after ESUS. More studies are needed to externally validate our findings. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Intersection of Cardiovascular Disease and Kidney Disease: Atrial Fibrillation

PubMed Central

Bansal, Nisha; Hsu, Chi-yuan; Go, Alan S.

2014-01-01

Purpose of review Atrial fibrillation (AF) is the most common sustained arrhythmia in the patients with kidney disease. The purpose of this review is to describe the burden of AF in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), postulate possible mechanisms to explain this burden of disease, understand the clinical consequences of AF and review the treatment options for AF specific to patients with kidney disease. Recent findings Recent literature has revealed that the clinical multi-organ impact of AF in patients with CKD and ESRD is substantial. Although novel oral anticoagulants to treat AF and prevent associated complications have been tested in large trials in the general population, there is a paucity of data on the efficacy and safety of these agents in patients with advanced CKD and ESRD. Summary AF is a significant comorbidity in patients with CKD and ESRD with important prognostic implications. More research is needed to understand the mechanisms that contribute to the disproportionate burden of this arrhythmia in patients with kidney disease and treatment options specific to this population of high-risk patients. PMID:24709949

A Proteasome Cap Subunit Required for Spindle Pole Body Duplication in Yeast

PubMed Central

McDonald, Heather B.; Byers, Breck

1997-01-01

Proteasome-mediated protein degradation is a key regulatory mechanism in a diversity of complex processes, including the control of cell cycle progression. The selection of substrates for degradation clearly depends on the specificity of ubiquitination mechanisms, but further regulation may occur within the proteasomal 19S cap complexes, which attach to the ends of the 20S proteolytic core and are thought to control entry of substrates into the core. We have characterized a gene from Saccharomyces cerevisiae that displays extensive sequence similarity to members of a family of ATPases that are components of the 19S complex, including human subunit p42 and S. cerevisiae SUG1/ CIM3 and CIM5 products. This gene, termed PCS1 (for proteasomal cap subunit), is identical to the recently described SUG2 gene (Russell, S.J., U.G. Sathyanarayana, and S.A. Johnston. 1996. J. Biol. Chem. 271:32810– 32817). We have shown that PCS1 function is essential for viability. A temperature-sensitive pcs1 strain arrests principally in the second cycle after transfer to the restrictive temperature, blocking as large-budded cells with a G2 content of unsegregated DNA. EM reveals that each arrested pcs1 cell has failed to duplicate its spindle pole body (SPB), which becomes enlarged as in other monopolar mutants. Additionally, we have shown localization of a functional Pcs1–green fluorescent protein fusion to the nucleus throughout the cell cycle. We hypothesize that Pcs1p plays a role in the degradation of certain potentially nuclear component(s) in a manner that specifically is required for SPB duplication. PMID:9151663

The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1

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

Mattiroli, Francesca; Gu, Yajie; Balsbaugh, Jeremy L.

Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is mediated by a compositemore » interface, shaped by Cac1-bound Cac2 and the Cac1 acidic region. Cac2 is indispensable for productive histone binding, while deletion of Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These results define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical function of the middle subunit in CAF-1.« less

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

Screening of advanced cladding materials and UN-U3Si5 fuel

NASA Astrophysics Data System (ADS)

Brown, Nicholas R.; Todosow, Michael; Cuadra, Arantxa

2015-07-01

In the aftermath of Fukushima, a focus of the DOE-NE Advanced Fuels Campaign has been the development of advanced nuclear fuel and cladding options with the potential for improved performance in an accident. Uranium dioxide (UO2) fuels with various advanced cladding materials were analyzed to provide a reference for cladding performance impacts. For advanced cladding options with UO2 fuel, most of the cladding materials have some reactivity and discharge burn-up penalty (in GWd/t). Silicon carbide is one exception in that the reactor physics performance is predicted to be very similar to zirconium alloy cladding. Most candidate claddings performed similar to UO2-Zr fuel-cladding in terms of safety coefficients. The clear exception is that Mo-based materials were identified as potentially challenging from a reactor physics perspective due to high resonance absorption. This paper also includes evaluation of UN-U3Si5 fuels with Kanthal AF or APMT cladding. The objective of the U3Si5 phase in the UN-U3Si5 fuel concept is to shield the nitride phase from water. It was shown that UN-U3Si5 fuels with Kanthal AF or APMT cladding have similar reactor physics and fuel management performance over a wide parameter space of phase fractions when compared to UO2-Zr fuel-cladding. There will be a marginal penalty in discharge burn-up (in GWd/t) and the sensitivity to 14N content in UN ceramic composites is high. Analysis of the rim effect due to self-shielding in the fuel shows that the UN-based ceramic fuels are not expected to have significantly different relative burn-up distributions at discharge relative to the UO2 reference fuel. However, the overall harder spectrum in the UN ceramic composite fuels increases transuranic build-up, which will increase long-term activity in a once-thru fuel cycle but is expected to be a significant advantage in a fuel cycle with continuous recycling of transuranic material. It is recognized that the fuel and cladding properties assumed in these assessments are preliminary, and that additional data are necessary for these materials, most significantly under irradiation.

[Validation of taking arterial pulse in Primary Care for the detection of atrial fibrillation and other cardiac rhythm disorders in patients over 65 years old].

PubMed

Pérula-de Torres, L A; González-Blanco V, V; Luque-Montilla, R; Martín-Rioboó, E; Martínez-Adell, M A; Ruiz-de Castroviejo, J

2017-09-01

Atrial fibrillation (AF) is the most frequent arrhythmia in clinical practice and has important prognostic implications. The objective of this study was to demonstrate the validity and the reliability of taking the arterial pulse (TAP) in patients over 65 years for detecting in AF and other rhythm disorders. A descriptive, observational, multicentre study to validate a diagnostic test within in a controlled clinical trial. 39 Primary Care Centres in the Spanish National Health Service. A total of 318 physicians and nurses took part in the analysis of validity, and 166 of them took part in the analysis of reliability. The professionals were previously called to a meeting in which they took the arterial pulses, and were given 4 ECGs to interpret. The participants TAP of 864 patients followed by an ECG to confirm the cardiac rhythm. Sensitivity, specificity and predictive values were estimated to assess the criterial validity and the simple concordance index to check reproducibility. The sensitivity of pulse measurement for detecting AF detection was 99.4% (95% CI: 97.9-100.0), with a specificity of 30.7% (95% CI: 26.1-35.3), a positive predictive value of 36.6% (95% CI 32.0-41.2), and negative predictive value of 99.2% (97.3-100.0). The simple concordance between the researchers and the cardiologist for the ECG diagnosis of AF ranged between 84.9% and 91.6%. The TAP has a high sensitivity but a low specificity to detect AF. It is a reliable test for the opportunistic screening of arrhythmias in patients aged over 65 years. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Fail-safe mechanism of GCN4 translational control—uORF2 promotes reinitiation by analogous mechanism to uORF1 and thus secures its key role in GCN4 expression

PubMed Central

Gunišová, Stanislava; Valášek, Leoš Shivaya

2014-01-01

One of the extensively studied mechanisms of gene-specific translational regulation is reinitiation. It takes place on messenger RNAs (mRNAs) where main ORF is preceded by upstream ORF (uORF). Even though uORFs generally down-regulate main ORF expression, specific uORFs exist that allow high level of downstream ORF expression. The key is their ability to retain 40S subunits on mRNA upon termination of their translation to resume scanning for the next AUG. Here, we took advantage of the exemplary model system of reinitiation, the mRNA of yeast transcriptional activator GCN4 containing four short uORFs, and show that contrary to previous reports, not only the first but the first two of its uORFs allow efficient reinitiation. Strikingly, we demonstrate that they utilize a similar molecular mechanism relying on several cis-acting 5′ reinitiation-promoting elements, one of which they share, and the interaction with the a/TIF32 subunit of translation initiation factor eIF3. Since a similar mechanism operates also on YAP1 uORF, our findings strongly suggest that basic principles of reinitiation are conserved. Furthermore, presence of two consecutive reinitiation-permissive uORFs followed by two reinitiation-non-permissive uORFs suggests that tightness of GCN4 translational control is ensured by a fail-safe mechanism that effectively prevents or triggers GCN4 expression under nutrient replete or deplete conditions, respectively. PMID:24623812

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

DTIC Science & Technology

1987-10-01

A USAFETAC Air Weather Service (MAC) 3SSTAe’ REVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS BLYTHEVILLE AFB AR MSC 1723408 IC N 35 58 W...I IE C It I 1-3 4-b I-Il It 1 7-2 1 2 - 4- UC 4 1-4 7 4F - U S5 1(IA " SAN I9 I 1. . 217 2.0 .i D I .lF I .2 1.? .7 1 .1 1 .2 .2- 0.1I 7 I AIR4 3tf...o o o , . . .. . . .o ..oo.o.. 17-, -7 5C.-. 1-7 ’-, F t tt 71*1. Li I I L C1.2 4 t 7 1L 1 4 uC I* I. A .o o.....oo. oo ~ oo o ooo ...... ...... .o. o

Adenovirus E1A functions as a cofactor for retinoic acid receptor beta (RAR beta) through direct interaction with RAR beta.

PubMed

Folkers, G E; van der Saag, P T

1995-11-01

Transcription regulation by DNA-bound activators is thought to be mediated by a direct interaction between these proteins and TATA-binding protein (TBP), TFIIB, or TBP-associated factors, although occasionally cofactors or adapters are required. For ligand-induced activation by the retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer, the RAR beta 2 promoter is dependent on the presence of E1A or E1A-like activity, since this promoter is activated by retinoic acid only in cells expressing such proteins. The mechanism underlying this E1A requirement is largely unknown. We now show that direct interaction between RAR and E1A is a requirement for retinoic acid-induced RAR beta 2 activation. The activity of the hormone-dependent activation function 2 (AF-2) of RAR beta is upregulated by E1A, and an interaction between this region and E1A was observed, but not with AF-1 or AF-2 of RXR alpha. This interaction is dependent on conserved region III (CRIII), the 13S mRNA-specific region of E1A. Deletion analysis within this region indicated that the complete CRIII is needed for activation. The putative zinc finger region is crucial, probably as a consequence of interaction with TBP. Furthermore, the region surrounding amino acid 178, partially overlapping with the TBP binding region, is involved in both binding to and activation by AF-2. We propose that E1A functions as a cofactor by interacting with both TBP and RAR, thereby stabilizing the preinitiation complex.

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Subunit interface dynamics in hexadecameric rubisco.

PubMed

van Lun, Michiel; van der Spoel, David; Andersson, Inger

2011-09-02

Ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) plays an important role in the global carbon cycle as a hub for biomass. Rubisco catalyzes not only the carboxylation of RuBP with carbon dioxide but also a competing oxygenation reaction of RuBP with a negative impact on photosynthetic yield. The functional active site is built from two large (L) subunits that form a dimer. The octameric core of four L(2) dimers is held at each end by a cluster of four small (S) subunits, forming a hexadecamer. Each large subunit contacts more than one S subunit. These interactions exploit the dynamic flexibility of Rubisco, which we address in this study. Here, we describe seven different types of interfaces of hexadecameric Rubisco. We have analyzed these interfaces with respect to the size of the interface area and the number of polar interactions, including salt bridges and hydrogen bonds in a variety of Rubisco enzymes from different organisms and different kingdoms of life, including the Rubisco-like proteins. We have also performed molecular dynamics simulations of Rubisco from Chlamydomonas reinhardtii and mutants thereof. From our computational analyses, we propose structural checkpoints of the S subunit to ensure the functionality and/or assembly of the Rubisco holoenzyme. These checkpoints appear to fine-tune the dynamics of the enzyme in a way that could influence enzyme performance. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical predictors of risk for atrial fibrillation: implications for diagnosis and monitoring.

PubMed

Brunner, Kyle J; Bunch, T Jared; Mullin, Christopher M; May, Heidi T; Bair, Tami L; Elliot, David W; Anderson, Jeffrey L; Mahapatra, Srijoy

2014-11-01

To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Differential Phosphorylation of Plant Translation Initiation Factors by Arabidopsis thaliana CK2 Holoenzymes*

PubMed Central

Dennis, Michael D.; Browning, Karen S.

2009-01-01

A previously described wheat germ protein kinase (Yan, T. F., and Tao, M. (1982) J. Biol. Chem. 257, 7037–7043) was identified unambiguously as CK2 using mass spectrometry. CK2 is a ubiquitous eukaryotic protein kinase that phosphorylates a wide range of substrates. In previous studies, this wheat germ kinase was shown to phosphorylate eIF2α, eIF3c, and three large subunit (60 S) ribosomal proteins (Browning, K. S., Yan, T. F., Lauer, S. J., Aquino, L. A., Tao, M., and Ravel, J. M. (1985) Plant Physiol. 77, 370–373). To further characterize the role of CK2 in the regulation of translation initiation, Arabidopsis thaliana catalytic (α1 and α2) and regulatory (β1, β2, β3, and β4) subunits of CK2 were cloned and expressed in Escherichia coli. Recombinant A. thaliana CK2β subunits spontaneously dimerize and assemble into holoenzymes in the presence of either CK2α1 or CK2α2 and exhibit autophosphorylation. The purified CK2 subunits were used to characterize the properties of the individual subunits and their ability to phosphorylate various plant protein substrates. CK2 was shown to phosphorylate eIF2α, eIF2β, eIF3c, eIF4B, eIF5, and histone deacetylase 2B but did not phosphorylate eIF1, eIF1A, eIF4A, eIF4E, eIF4G, eIFiso4E, or eIFiso4G. Differential phosphorylation was exhibited by CK2 in the presence of various regulatory β-subunits. Analysis of A. thaliana mutants either lacking or overexpressing CK2 subunits showed that the amount of eIF2β protein present in extracts was affected, which suggests that CK2 phosphorylation may play a role in eIF2β stability. These results provide evidence for a potential mechanism through which the expression and/or subcellular distribution of CK2 β-subunits could participate in the regulation of the initiation of translation and other physiological processes in plants. PMID:19509278

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.

Remote magnetic navigation in atrial fibrillation.

PubMed

Szili-Torok, Tamas; Akca, Ferdi

2012-05-01

Atrial fibrillation (AF) is of profound public health importance and is largely a disease of aging and is responsible for increased morbidity- and mortality-related healthcare expenditures. Catheter ablation to isolate the pulmonary veins has become the therapy of choice for treatment of drug-refractory AF. Procedures can be very challenging and multiple difficulties must be overcome in order to achieve a successful outcome. The magnetic navigation system (MNS) has advantages in catheter maneuverability, stability and reproducibility. Due to the catheter design safety and efficacy of AF, ablation has increased. New developments are being made to allow fully remote ablation procedures in combination with the MNS. However, new technologies are still necessary to improve MNS ablation for AF.

Aspergillus sensitization or carriage in cystic fibrosis patients.

PubMed

Fillaux, Judith; Brémont, François; Murris, Marlène; Cassaing, Sophie; Tétu, Laurent; Segonds, Christine; Pipy, Bernard; Magnaval, Jean-François

2014-07-01

Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

[The effect of instrumentation on original apical foramen shape using steel vs niti rotatory: computerized analysis].

PubMed

Gallina, G; Cumbo, E; Gallo, P; Pizzo, G; D'Angelo, M

2002-01-01

A fundamental requirement to obtain a correct endodontic preparation depends on the respect, during cleaning and shaping, of the original morphology of the apical foramen, (AF), so that the filling material will form a complete seal. In our previous studies, in order to verify if this presumption was respected using rotary NiTi instruments with cutting tip, we instrumented extracted teeth characterised by a different degree of root curvatures. Using a standardized system to replace the sample, the original shape of the apical foramen of each tooth was recorded using a computerised technique and then compared to the shape after instrumentation. The data showed differences on AF shapes depending on the degree of root canal curvatures. In fact, the teeth with straight canals showed the least alterations on the original AF shape; on the contrary, the teeth with curved canals showed apical foramen enlargement or transportation. Therefore, in the current study we aimed to compare the in vitro effects of stainless steel, (Flexofile, Dentsply Maillefer, Baillaigues, Switzerland), vs NiTi safe cutting tip (Quantec SC, (Tycom Dental, Irvine CA, U:S.A.), vs NiTi non cutting tip, (Quantec LX, Tycom Dental, Irvine CA, U:S.A.), instrumentation on original apical foramen shape. We used NiTi instruments according to standard technique suggested by Tycom, and hand steel files, to instrument the apical third, according to the Crown-Down technique. Working length was fixed at -0.5 from AF. Our results suggested that in the presence of accentuated canal curves rotary Niti, with cutting tip, cause significantly more enlargement of the AF area. At the same time, we also observed that NiTi rotary files, with both cutting and non-cutting tip, cause eccentric enlargement of AF in curved canals. Therefore, NiTi engine-driven instruments should be used carefully in the presence of accentuated canal curves to avoid enlargement or transportation of AF, probably because rotary NiTi files may slip out of operative control, leaving a mark on the foramen shape. In the presence of severe curves, we suggest modifying the operative sequences by alternating rotary NiTi with hand NiTi or stainless steel instruments, especially in the preparation of apical third.

United States Air Force Research Initiation Program. 1985 Technical Report. Volume 2.

DTIC Science & Technology

1987-04-01

RESEARCH INITIATIO PORN 1985 TECHNICAL REPORT VOLUME 2(U) UNIVERSAL ENERGY SYSTEMS INC DAYTON OH R C DRRRAH APR 87 UNCLASSIFIED AFOSR-TR-87-1718 F492e-85-C...wi ves) may have to assume full responsibility for household chores and ’V child care during extended TVYs., and relinquish jobs to move with their...2 ’ Grjduate Degree 10% 5% At _east One Child iiiq ~Ho~.~ 9% 31% ,.IIlJ Livng at Hoyne 37% 56% Eployed Wives of Unemployed Wives of AF Oft icers (N=37

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.

Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda.

PubMed

Chen, Chen-Huan; Chen, Mien-Cheng; Gibbs, Harry; Kwon, Sun U; Lo, Sidney; On, Young Keun; Rosman, Azhari; Suwanwela, Nijasri C; Tan, Ru San; Tirador, Louie S; Zirlik, Andreas

2015-07-15

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reversible inhibition of spermatogenesis in rats using a new male contraceptive, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide.

PubMed

Grima, J; Silvestrini, B; Cheng, C Y

2001-05-01

The oral male contraceptive agent 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF2364) is a new analogue of indazole-carboxylic acid. AF2364 was orally administered to rats at 50 mg/kg body weight once weekly for five consecutive weeks. The effects on fertility efficacy, hormonal profile, organ weights, tissue morphology, and serum microchemistry were examined. Complete infertility was noted in rats 29 days after the initial dose of AF2364 and continued until 90 days. Fertility resumed in 25% of the group after 104 days and had resumed in 75% of the rats by the last mating at 197 days. Morphological examination of the testis showed rapid exfoliation of elongated spermatids and the generation of large multinucleated cells 6 days after the first treatment, with depletion of most germ cells after 40 days. Normal spermatogenesis was noted in 95% of the tubules in the animals that were fertile at 210 days. Morphological analysis of the epididymal compartments revealed reduced lumen size, whereas the prostate exhibited an increase in the glandular lumen with a reduction in epithelium height. No morphological changes were detected in the kidney, liver, and cerebrum by light microscopy. Kidney and liver function, as evaluated by serum chemistry, were not affected by the drug treatment. AF2364 did not alter the levels of FSH, and only minimal changes were noted for LH and testosterone, suggesting that the hypothalamic-pituitary-testicular axis was not affected. These results illustrate the potential of AF2364 as a male contraceptive.

Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Milionis, Haralambos; Makaritsis, Konstantinos; Manios, Efstathios; Spengos, Konstantinos; Michel, Patrik; Vemmos, Konstantinos

2015-01-01

A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS. © 2014 American Heart Association, Inc.

A First-Order Methodology for Calculating Probability of Mission Success

DTIC Science & Technology

1979-01-31

Af(A)/2 + T- fA1 A2 1/8 R(T) (A) -T Af(A)4,(A) + T Af(A)[Af(A) + 4)(A)1$3 A 11/4. 61~ a 2 T R T 2f2 ()+T4f2 ()7A2 -4-A2]/ R 2 f(A) T 2(1 + T 2(3A 2/2...Library ATTN: W. Wright, Jr. ATTN: P. Haas Management Science Associates ATTN: K. Kaplan Rand Corp. ATTN: A. Laupa Martin Marietta Corp, ATTN: C. Mow ATTN

Characterization of a Novel Rieske-Type Alkane Monooxygenase System in Pusillimonas sp. Strain T7-7

PubMed Central

Li, Ping; Wang, Lei

2013-01-01

The cold-tolerant bacterium Pusillimonas sp. strain T7-7 is able to utilize diesel oils (C5 to C30 alkanes) as a sole carbon and energy source. In the present study, bioinformatics, proteomics, and real-time reverse transcriptase PCR approaches were used to identify the alkane hydroxylation system present in this bacterium. This system is composed of a Rieske-type monooxygenase, a ferredoxin, and an NADH-dependent reductase. The function of the monooxygenase, which consists of one large (46.711 kDa) and one small (15.355 kDa) subunit, was further studied using in vitro biochemical analysis and in vivo heterologous functional complementation tests. The purified large subunit of the monooxygenase was able to oxidize alkanes ranging from pentane (C5) to tetracosane (C24) using NADH as a cofactor, with greatest activity on the C15 substrate. The large subunit also showed activity on several alkane derivatives, including nitromethane and methane sulfonic acid, but it did not act on any aromatic hydrocarbons. The optimal reaction condition of the large subunit is pH 7.5 at 30°C. Fe2+ can enhance the activity of the enzyme evidently. This is the first time that an alkane monooxygenase system belonging to the Rieske non-heme iron oxygenase family has been identified in a bacterium. PMID:23417490

Analysis of gene expression provides insights into the mechanism of cadmium tolerance in Acidithiobacillus ferrooxidans.

PubMed

Chen, Minjie; Li, Yanjun; Zhang, Li; Wang, Jianying; Zheng, Chunli; Zhang, Xuefeng

2015-02-01

Acidithiobacillus ferrooxidans plays a critical role in metal solubilization in the biomining industry, and occupies an ecological niche characterized by high acidity and high concentrations of toxic heavy metal ions. In order to investigate the possible metal resistance mechanism, the cellular distribution of cadmium was tested. The result indicated that Cd(2+) entered the cells upon initial exposure resulting in increased intracellular concentrations, followed by its excretion from the cells during subsequent growth and adaptation. Sequence homology analyses were used to identify 10 genes predicted to participate in heavy metal homeostasis, and the expression of these genes was investigated in cells cultured in the presence of increasing concentrations of toxic divalent cadmium (Cd(2+)). The results suggested that one gene (cmtR A.f ) encoded a putative Cd(2+)/Pb(2+)-responsive transcriptional regulator; four genes (czcA1 A.f , czcA2 A.f , czcB1 A.f ; and czcC1 A.f ) encoded heavy metal efflux proteins for Cd(2+); two genes (cadA1 A.f and cadB1 A.f ) encoded putative cation channel proteins related to the transport of Cd(2+). No significant enhancement of gene expression was observed at low concentrations of Cd(2+) (5 mM) and most of the putative metal resistance genes were up-regulated except cmtR A.f , cadB3 A.f ; and czcB1 A.f at higher concentrations (15 and 30 mM) according to real-time polymerase chain reaction. A model was developed for the mechanism of resistance to cadmium ions based on homology analyses of the predicted genes, the transcription of putative Cd(2+) resistance genes, and previous work.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction

PubMed Central

Operario, Darwin J; Platts-Mills, James A; Nadan, Sandrama; Page, Nicola; Seheri, Mapaseka; Mphahlele, Jeffrey; Praharaj, Ira; Kang, Gagandeep; Araujo, Irene T; Leite, Jose Paulo G; Cowley, Daniel; Thomas, Sarah; Kirkwood, Carl D; Dennis, Francis; Armah, George; Mwenda, Jason M; Wijesinghe, Pushpa Ranjan; Rey, Gloria; Grabovac, Varja; Berejena, Chipo; Simwaka, Chibumbya J; Uwimana, Jeannine; Sherchand, Jeevan B; Thu, Hlaing Myat; Galagoda, Geethani; Bonkoungou, Isidore J O; Jagne, Sheriffo; Tsolenyanu, Enyonam; Diop, Amadou; Enweronu-Laryea, Christabel; Borbor, Sam-Aliyah; Liu, Jie; McMurry, Timothy; Lopman, Benjamin; Parashar, Umesh; Gentsch, John; Steele, A Duncan; Cohen, Adam; Serhan, Fatima; Houpt, Eric R

2017-01-01

Abstract Background The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013–2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%–44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9–15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8–9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0–7.6]), Shigella (AF, 4.7 [95% CI, 2.8–6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0–6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9–5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%–61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%–30.4%) in age-eligible children. Conclusions Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea. PMID:28838152

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

Monoclonal antibodies against the native urease of Helicobacter pylori: synergistic inhibition of urease activity by monoclonal antibody combinations.

PubMed Central

Nagata, K; Mizuta, T; Tonokatu, Y; Fukuda, Y; Okamura, H; Hayashi, T; Shimoyama, T; Tamura, T

1992-01-01

Monoclonal antibodies (MAbs) against the native urease of Helicobacter pylori NCTC 11637 were found to clearly inhibit the urease activity. Interestingly, synergistic inhibition by two MAbs recognizing different subunits was also observed. Ten MAbs were produced and classified as two isotypes of the immunoglobulin G (IgG) subclass, IgG1, and IgG2a. Western blot (immunoblot) analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that five MAbs recognized the large subunit and the other five recognized the small subunit of the urease. Among the MAbs, L2 and S2, which recognized the large and the small subunits, respectively, were also able to inhibit the urease activity of clinical isolates from H. pylori-infected patients. The combination of L2 and S2 led to augmented synergistic inhibition. L2, but not S2, could also inhibit the urease activity from Helicobacter mustelae; enzyme-linked immunosorbent assay and Western blot analysis showed that L2 cross-reacted with this urease. These results suggested that the epitope recognized by L2 had a structure common to both Helicobacter species and may be involved in the active site of the urease. In contrast to the MAbs, a polyclonal antibody in sera from mice immunized with H. pylori urease did not have the ability to inhibit H. pylori urease activity. However, the polyclonal antibody retained the ability to abolish the inhibitory action of these MAbs. Moreover, other MAbs which could not inhibit H. pylori urease activity also abolished the inhibitory action. Images PMID:1383158

Assessing the Benefits and Costs of Motion for C-17 Flight Simulators: Technical Appendixes.

DTIC Science & Technology

1986-06-01

Conference, NAECON, 1983. 4’ U-. - 182 - Instructional System Development, AF Manual 50-2, USAF, May 25, 1979. Irish , P.A., and G.H. Buckland, "Effects of...control augmentation system ; (4) the fidelity of different siirulator motion cueing alternatives; (5) a suggested methodology for assessinq the...evaluating the benefits and costs of incorporating motion systems in C-17 transport aircraft flight simulators and in developing a general framework

Duration of Residence in the United States and the Fertility of U.S. Immigrants.

ERIC Educational Resources Information Center

Ford, Kathleen

1990-01-01

Examines census data on the fertility of U.S. immigrants to study trends in fertility after migration. Results show that immigrant fertility may rise after arrival in the new country, perhaps because immigrants are making up for births or marriages postponed because of the move, but that, with assimilation, fertility declines. (AF)

12 CFR 34.4 - Applicability of state law.

Code of Federal Regulations, 2013 CFR

2013-01-01

... circumstances under which a loan may be called due and payable upon the passage of time or a specified event... of Marion County, N.A. v. Nelson, Florida Insurance Commissioner, et al., 517 U.S. 25 (1996): (1...) Homestead laws specified in 12 U.S.C. 1462a(f); (5) Rights to collect debts; (6) Acquisition and transfer of...

12 CFR 34.4 - Applicability of state law.

Code of Federal Regulations, 2014 CFR

2014-01-01

... circumstances under which a loan may be called due and payable upon the passage of time or a specified event... of Marion County, N.A. v. Nelson, Florida Insurance Commissioner, et al., 517 U.S. 25 (1996): (1...) Homestead laws specified in 12 U.S.C. 1462a(f); (5) Rights to collect debts; (6) Acquisition and transfer of...

12 CFR 34.4 - Applicability of state law.

Code of Federal Regulations, 2012 CFR

2012-01-01

... circumstances under which a loan may be called due and payable upon the passage of time or a specified event... of Marion County, N.A. v. Nelson, Florida Insurance Commissioner, et al., 517 U.S. 25 (1996): (1...) Homestead laws specified in 12 U.S.C. 1462a(f); (5) Rights to collect debts; (6) Acquisition and transfer of...

Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular nucleus of GABAA receptor alpha3 subunit-null mice.

PubMed

Studer, Remo; von Boehmer, Lotta; Haenggi, Tatjana; Schweizer, Claude; Benke, Dietmar; Rudolph, Uwe; Fritschy, Jean-Marc

2006-09-01

Multiple GABAA-receptor subtypes are assembled from alpha, beta and gamma subunit variants. GABAA receptors containing the alpha3 subunit represent a minor population with a restricted distribution in the CNS. In addition, they predominate in monoaminergic neurons and in the nucleus reticularis thalami (nRT), suggesting a role in the regulation of cortical function and sleep. Mice with a targeted deletion of the alpha3 subunit gene (alpha3(0/0)) are viable and exhibit a subtle behavioural phenotype possibly related to dopaminergic hyperfunction. Here, we investigated immunohistochemically the consequences of the loss of alpha3 subunit for maturation of GABAA receptors and formation of GABAergic synapses in the nRT. Throughout postnatal development, the regional distribution of the alpha1, alpha2, or alpha5 subunit was unaltered in alpha3(0/0) mice and the prominent alpha3 subunit staining of nRT neurons in wildtype mice was not replaced. Subcellularly, as seen by double immunofluorescence, the alpha3 and gamma2 subunit were clustered at postsynaptic sites in the nRT of adult wildtype mice along with the scaffolding protein gephyrin. In alpha3(0/0) mice, gamma2 subunit clustering was disrupted and gephyrin formed large aggregates localized at the cell surface, but unrelated to postsynaptic sites, indicating that nRT neurons lack postsynaptic GABAA receptors in mutant mice. Furthermore, GABAergic terminals were enlarged and reduced in number, suggesting a partial deficit of GABAergic synapses. Therefore, GABAA receptors are required for gephyrin clustering and long-term synapse maintenance. The absence of GABAA-mediated transmission in the nRT may have a significant impact on the function of the thalamo-cortical loop of alpha3(0/0) mice.

A QoS scheme for a congestion core network based on dissimilar QoS structures in smart-phone environments.

PubMed

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones.

A QoS Scheme for a Congestion Core Network Based on Dissimilar QoS Structures in Smart-Phone Environments

PubMed Central

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones. PMID:22163453

Niagara Falls IAP, New York. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-09-30

TOTLS 1 21 . 32." 3 1. q 7 1 h .2 DO . 00 9.1 ..... .. . 30181 r, UPl’ OP O:’.rvI49A10.S: 33991? - A pPPPP,P~ppl A:. A RRRRR TY TIIII1 T0DD000D0...94.6 99.1 99.3 99.6 9’.q 99.9 530.0 10.0 130.0 100 .0 TO IAL hM "E" CF UnS[VATIONS: 9uU" .L K GLrObAL CLIPAIOLUGY BpAnFC P[.C[NfArE FkFELENCY OF

Chocolate intake and risk of clinically apparent atrial fibrillation: the Danish Diet, Cancer, and Health Study.

PubMed

Mostofsky, Elizabeth; Berg Johansen, Martin; Tjønneland, Anne; Chahal, Harpreet S; Mittleman, Murray A; Overvad, Kim

2017-08-01

To evaluate the association between chocolate intake and incident clinically apparent atrial fibrillation or flutter (AF). The Danish Diet, Cancer, and Health Study is a large population-based prospective cohort study. The present study is based on 55 502 participants (26 400 men and 29 102 women) aged 50-64 years who had provided information on chocolate intake at baseline. Incident cases of AF were ascertained by linkage with nationwide registries. During a median of 13.5 years there were 3346 cases of AF. Compared with chocolate intake less than once per month, the rate of AF was lower for people consuming 1-3 servings/month (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.82 to 0.98), 1 serving/week (HR 0.83, 95% CI 0.74 to 0.92), 2-6 servings/week (HR 0.80, 95% CI 0.71 to 0.91) and ≥1 servings/day (HR 0.84, 95% CI 0.65 to 1.09; p-linear trend <0.0001), with similar results for men and women. Accumulating evidence indicates that moderate chocolate intake may be inversely associated with AF risk, although residual confounding cannot be ruled out. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Panoramic Electrophysiological Mapping but not Electrogram Morphology Identifies Stable Sources for Human Atrial Fibrillation

PubMed Central

Narayan, Sanjiv M.; Shivkumar, Kalyanam; Krummen, David E.; Miller, John M.; Rappel, Wouter-Jan

2013-01-01

Background The foundation for successful arrhythmia ablation is the mapping of electric propagation to identify underlying mechanisms. In atrial fibrillation (AF), however, mapping is difficult so that ablation has often targeted electrogram features, with mixed results. We hypothesized that wide field-of-view (panoramic) mapping of both atria would identify causal mechanisms for AF and allow interpretation of local electrogram features, including complex fractionated atrial electrograms (CFAE). Methods and Results Contact mapping was performed using biatrial multipolar catheters in 36 AF subjects (29 persistent). Stable AF rotors (spiral waves) or focal sources were seen in 35 of 36 cases and targeted for ablation (focal impulse and rotor modulation) before pulmonary vein isolation. In 31 of 36 subjects (86.1%), AF acutely terminated (n=20; 16 to sinus rhythm) or organized (n=11; 19±8% slowing) with 2.5 minutes focal impulse and rotor modulation (interquartile range, 1.0–3.1) at one source, defined as the primary source. Subjects exhibited 2.1±1.0 concurrent AF sources of which the primary, by phase mapping, precessed in limited areas (persistent 2.5±1.7 versus paroxysmal 1.7±0.5 cm2; P=0.30). Notably, source regions showed mixed electrogram amplitudes and CFAE grades that did not differ from surrounding atrium (P=NS). AF sources were not consistently surrounded by CFAE (P=0.67). Conclusions Stable rotors and focal sources for human AF were revealed by contact panoramic mapping (focal impulse and rotor modulation mapping), but not by electrogram footprints. AF sources precessed within areas of ≈2 cm2, with diverse voltage characteristics poorly correlated with CFAE. Most CFAE sites lie remote from AF sources and are not suitable targets for catheter ablation of AF. PMID:23392583

Identification of epitopes of the β subunit of soybean β-conglycinin that are antigenic in pigs, dogs, rabbits and fish.

PubMed

Taliercio, Earl; Loveless, Telisa M; Turano, Marc J; Kim, Sung Woo

2014-08-01

β-Conglycinin (conglycinin) is one of the major seed storage proteins of soybean. Conglycinin is a 7S trimer composed of different combinations of β, α and α' subunits. All subunits of conglycinin have been reported to be allergenic in humans. The goal of this research is to identify epitopes of the β subunit of conglycinin that are antigenic in multiple animal species. Sera from pigs, dogs, rabbits and hybrid striped bass that had antibodies against soybean conglycinin were identified by ELISA. Most of these sera recognized peptides that represent the β subunit of conglycinin. One antigenic region of the β subunit of conglycinin had considerable overlap among all species tested. One region that was similar to a peanut allergenic epitope in humans overlapped with a region that binds IgE from dogs. One region was antigenic in multiple rabbits and pigs, suggesting it may play a role in the response of pigs to soybean in the diet. One region of the β subunit of conglycinin is an important antigen across species and abuts a region similar to the peanut allergen ARA h 1. A second region is particularly antigenic in pigs and rabbits. Variants of these antigenic regions of the β subunit of conglycinin may be useful in determining the role these regions play in the health of animals fed soybean. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Blood transfusion and risk of atrial fibrillation after coronary artery bypass graft surgery

PubMed Central

Liu, Shengqun; Li, Zhanwen; Liu, Zhe; Hu, Zhenhua; Zheng, Gaifang

2018-01-01

Abstract The aim of this study was to systematically evaluate the effect of blood transfusion (BT) on postoperative atrial fibrillation (AF) in adult patients who had undergone coronary artery bypass grafting (CABG) surgery. PubMed, Embase, and Cochrane Library databases from inception to January 2017 were searched. Cohort studies were searched that evaluated the association between BT and the risk of postoperative AF in adult patients who had undergone CABG surgery. Study quality was assessed by using the Newcastle–Ottawa scale (NOS). A meta-analysis was performed with the random-effect model. Eight cohort studies involving 7401 AF cases and 31,069 participants were identified and included in our data analysis. The pooled odds ratio of postoperative AF in patients with BT was 1.45 (95% confidence interval, 1.26–1.67), with significant heterogeneity (P < .0001, I2 = 79%). Excluding one study that had an off-pump CABG did not significantly impact this result (odds ratio, 1.36; 95% confidence interval, 1.23–1.50; n = 7). To examine the stability of the primary results, we performed subgroup analyses. The association between BT and the risk of postoperative AF was similar, as determined in the stratified analyses conducted according to study design, type of surgery, and country. The findings of the present meta-analysis demonstrated a statistically significant increase in postoperative AF risk among adult patients with BT. Further prospective large-scale studies are needed to establish causality and to elucidate the underlying mechanisms. PMID:29517692

Global Behavior in Large Scale Systems

DTIC Science & Technology

2013-12-05

release. AIR FORCE RESEARCH LABORATORY AF OFFICE OF SCIENTIFIC RESEARCH (AFOSR)/RSL ARLINGTON, VIRGINIA 22203 AIR FORCE MATERIEL COMMAND AFRL-OSR-VA...and Research 875 Randolph Street, Suite 325 Room 3112, Arlington, VA 22203 December 3, 2013 1 Abstract This research attained two main achievements: 1...microscopic random interactions among the agents. 2 1 Introduction In this research we considered two main problems: 1) large deviation error performance in

Topography of succinate dehydrogenase in the mitochondrial inner membrane. A study using limited proteolysis and immunoblotting.

PubMed Central

Clarkson, G H; Neagle, J; Lindsay, J G

1991-01-01

The arrangement of the large (70,000-Mr) and small (30,000-Mr) subunits of succinate dehydrogenase in the mitochondrial inner membrane was investigated by immunoblot analysis of bovine heart mitochondria (right-side-out, outer membrane disrupted) or submitochondrial particles (inside-out) that had been subjected to surface-specific proteolysis. Both subunits were resistant to proteinase treatment provided that the integrity of the inner membrane was preserved, suggesting that neither subunit is exposed at the cytoplasmic surface of the membrane. The bulk of the small subunit appears to protrude into the matrix compartment, since the 30,000-Mr polypeptide is degraded extensively during limited proteolysis of submitochondrial particles without the appearance of an immunologically reactive membrane-associated fragment: moreover, a soluble 27,000-Mr peptide derived from this subunit is observed transiently on incubation with trypsin. Similar data obtained from the large subunit suggest that this polypeptide interacts with the matrix side of the inner membrane via two distinct domains; these are detected as stable membrane-associated fragments of 32,000 Mr and 27,000 Mr after treatment of submitochondrial particles with papain or proteinase K, although the 27,000-Mr fragment can be degraded further to low-Mr peptides with trypsin or alpha-chymotrypsin. A stable 32,000-34,000-Mr fragment is generated by a variety of specific and non-specific proteinases, indicating that it may be embedded largely within the lipid bilayer, or is inaccessible to proteolytic attack owing to its proximity to the surface of the intact membrane, possibly interacting with the hydrophobic membrane anchoring polypeptides of the succinate: ubiquinone reductase complex. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:1996968

[Improvement of acetic acid tolerance and fermentation performance of industrial Saccharomyces cerevisiae by overexpression of flocculent gene FLO1 and FLO1c].

PubMed

Du, Zhaoli; Cheng, Yanfei; Zhu, Hui; He, Xiuping; Zhang, Borun

2015-02-01

Flocculent gene FLO1 and its truncated form FLO1c with complete deletion of repeat unit C were expressed in a non-flocculent industrial strain Saccharomyces cerevisiae CE6 to generate recombinant flocculent strains 6-AF1 and 6-AF1c respectively. Both strains of 6-AF1 and 6-AF1c displayed strong flocculation and better cell growth than the control strain CE6-V carrying the empty vector under acetic acid stress. Moreover, the flocculent strains converted glucose to ethanol at much higher rates than the control strain CE6-V under acetic acid stress. In the presence of 0.6% (V/V) acetic acid, the average ethanol production rates of 6-AF1 and 6-AF1c were 1.56 and 1.62 times of that of strain CE6-V, while the ethanol production rates of 6-AF1 and 6-AF1c were 1.21 and 1.78 times of that of strain CE6-V under 1.0% acetic acid stress. Results in this study indicate that acetic acid tolerance and fermentation performance of industrial S. cerevisiae under acetic acid stress can be improved largely by flocculation endowed by expression of flocculent genes, especially FLO1c.

Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes.

PubMed

Matern, Andreas; Pedrolli, Danielle; Großhennig, Stephanie; Johansson, Jörgen; Mack, Matthias

2016-12-01

The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B 2 ), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen Listeria monocytogenes We found that the L. monocytogenes protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Functional base-pairing interaction between highly conserved elements of U3 small nucleolar RNA and the small ribosomal subunit RNA.

PubMed

Hughes, J M

1996-06-21

The U3 nucleolar RNA has a remarkably wide phyletic distribution extending from the Eukarya to the Archaea. It functions in maturation of the small subunit (SSU) rRNA through a mechanism which is as yet unknown but which involves base-pairing with pre-rRNA. The most conserved part of U3 is within 30 nucleotides of the 5' end, but as yet no function for this domain has been proposed. Elements within this domain are complementary to highly conserved sequences in the SSU rRNA which, in the mature form, fold into a universally conserved pseudoknot. The nature of the complementarity suggests a novel mechanism for U3 function whereby U3 facilitates correct folding of the pseudoknot. Wide phylogenetic comparison provides compelling evidence in support of the interaction in that significant complementary changes have taken place, particularly in the archaeon Sulfolobus, which maintain the base-pairing. Base-substitution mutations in yeast U3 designed to disrupt the base-pairing indicate that the interaction is probably essential. These include cold-sensitivity mutations which exhibit phenotypes similar to U3-depletion, but without impairment of the AO processing step, which occurs within the 5' ETS. These phenotypes are consistent with the destabilization of SSU precursors and partial impairment of the processing steps A1, at the 5' ETS/18 S boundary, and A2, within the ITS1.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

PubMed

Oba, Kageyuki; Maeda, Minetaka; Maimaituxun, Gulinu; Yamaguchi, Satoshi; Arasaki, Osamu; Fukuda, Daiju; Yagi, Shusuke; Hirata, Yukina; Nishio, Susumu; Iwase, Takashi; Takao, Shoichiro; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Harada, Masafumi; Masuzaki, Hiroaki; Sata, Masataka; Shimabukuro, Michio

2018-05-25

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

PubMed

Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

2017-09-29

Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non-healthcare-specific disciplines in a way that yields testable hypotheses for healthcare A&F interventions. These results will serve as the foundation for further work seeking to set research priorities among the A&F research community.

[The clinical analysis of atrial fibrillation of 1 310 in patients in Urumqi of China].

PubMed

Guo, Xiaohua; Zhang, Yu; Xu, Guojun; Zhou, Xianhui; Li, Lei; Tang, Baopeng

2014-05-01

To investigate the clinical features and current therapy of atrial fibrillation (AF) of inpatients in Urumqi, China. The clinical data of inpatients diagnosed with AF from January, 2008 to December, 2012, in 12 hospitals in Urumqi were retrospectively analyzed. Totally 1 310 AF inpatients were enrolled in this study with the age of (64.8 ± 3.3) years old and a men to women ratio of 1.39. Most patients were in age groups of 61-70 years (26.5%) and 71-80 years (27.6%). More patients with paroxysmal AF were at cardiac function class I-II (75.2%), while more patients with persistent AF were at cardiac function class III-IV (31.0%) (both P values < 0.05). The most common co-morbidities of AF were hypertension (49.2%), coronary heart disease (38.5%), diabetes mellitus (20.1%). Compared with patients of chronic AF, the patients of paroxysmal AF had higher success rates in amiodarone conversation and sinus rhythm maintenance after ablation (44.8% vs 29.9%, 87.5% vs 68.9%, P values < 0.05). Among the 1 310 inpatients, 992 patients (75.7%) received antithrombotic therapy. There were statistically significant differences in CHA2DS2 score and incidence rate of cerebral infarction among patients receiving aspirin, warfarin or rivaroxaban/other anticoagulation drugs [2(1, 3) vs 3(2, 4) vs 3(2, 5) and 6.3% vs 23.8% vs 30.2%, both P values < 0.05]. Our results of AF inpatients' age, gender, related disease distribution, AF types, incidence of stoke, therapeutic and epidemiological features are in accordance with the domestic and abroad reports.

Atrial Fibrillation Patients Treated With Long-Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long-Term Warfarin for Other Indications.

PubMed

Bunch, T Jared; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Jacobs, Victoria; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C

2016-07-11

The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure. A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40-2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (≤25% versus >75%: HR=3.92, P<0.0001). The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

PubMed

Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

2018-01-01

An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

Treatment of Atrial Fibrillation By The Ablation Of Localized Sources

PubMed Central

Narayan, Sanjiv M.; Krummen, David E.; Shivkumar, Kalyanam; Clopton, Paul; Rappel, Wouter-Jan; Miller, John M.

2012-01-01

Objectives We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (Focal Impulse and Rotor Modulation, FIRM) may improve outcome from AF ablation. Background Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome. Methods We recruited 92 individuals during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-Guided) followed by conventional ablation (n=36), or conventional ablation alone (n=71; FIRM-Blinded). Results Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1±1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided versus 20% of FIRM-Blinded cases (p<0.001). FIRM ablation alone at the primary source terminated AF in 2.5 minutes (median; IQR 1.0–3.1). Total ablation time did not differ between groups (57.8±22.8 versus 52.1±17.8 minutes, p=0.16). During 273 days (median; IQR 132–681 days) after a single procedure, FIRM-Guided cases had higher freedom from AF (82.4% versus 44.9%; p<0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, ECG monitoring. Adverse events did not differ between groups. CONCLUSIONS Localized electrical rotors and focal impulse sources are prevalent sustaining-mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (ClinicalTrials.gov number, NCT01008722) PMID:22818076

Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities Study

PubMed Central

Bengtson, Lindsay G. S.; Lutsey, Pamela L.; Loehr, Laura R.; Kucharska‐Newton, Anna; Chen, Lin Y.; Chamberlain, Alanna M.; Wruck, Lisa M.; Duval, Sue; Stearns, Sally C.; Alonso, Alvaro

2014-01-01

Background Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non‐AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease–related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities. PMID:25359400

Identification of catalytic residues of a very large NAD-glutamate dehydrogenase from Janthinobacterium lividum by site-directed mutagenesis.

PubMed

Kawakami, Ryushi; Sakuraba, Haruhiko; Ohshima, Toshihisa

2014-01-01

We previously found a very large NAD-dependent glutamate dehydrogenase with approximately 170 kDa subunit from Janthinobacterium lividum (Jl-GDH) and predicted that GDH reaction occurred in the central domain of the subunit. To gain further insights into the role of the central domain, several single point mutations were introduced. The enzyme activity was completely lost in all single mutants of R784A, K810A, K820A, D885A, and S1142A. Because, in sequence alignment analysis, these residues corresponded to the residues responsible for glutamate binding in well-known small GDH with approximately 50 kDa subunit, very large GDH and well-known small GDH may share the same catalytic mechanism. In addition, we demonstrated that C1141, one of the three cysteine residues in the central domain, was responsible for the inhibition of enzyme activity by HgCl2, and HgCl2 functioned as an activating compound for a C1141T mutant. At low concentrations, moreover, HgCl2 was found to function as an activating compound for a wild-type Jl-GDH. This suggests that the mechanism for the activation is entirely different from that for the inhibition.

Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

Druck, T.; Gu, Y.; Prabhala, G.

1995-11-01

Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

The role of rotors in atrial fibrillation

PubMed Central

Swarup, Vijay; Narayan, Sanjiv M.

2015-01-01

Despite significant advances in our understanding of atrial fibrillation (AF) mechanisms in the last 15 years, ablation outcomes remain suboptimal. A potential reason is that many ablation techniques focus on anatomic, rather than patient-specific functional targets for ablation. Panoramic contact mapping, incorporating phase analysis, repolarization and conduction dynamics, and oscillations in AF rate, overcomes many prior difficulties with mapping AF. This approach provides evidence that the mechanisms sustaining human AF are deterministic, largely due to stable electrical rotors and focal sources in either atrium. Ablation of such sources (Focal Impulse and Rotor Modulation: FIRM ablation) has been shown to improve ablation outcome compared with conventional ablation alone; independent laboratories directly targeting stable rotors have shown similar results. Clinical trials examining the role of stand-alone FIRM ablation are in progress. Looking forward, translating insights from patient-specific mapping to evidence-based guidelines and clinical practice is the next challenge in improving patient outcomes in AF management. PMID:25713729

Rubisco oligomers composed of linked small and large subunits assemble in tobacco plastids and have higher affinities for CO2 and O2.

PubMed

Whitney, Spencer Michael; Kane, Heather Jean; Houtz, Robert L; Sharwood, Robert Edward

2009-04-01

Manipulation of Rubisco within higher plants is complicated by the different genomic locations of the large (L; rbcL) and small (S; RbcS) subunit genes. Although rbcL can be accurately modified by plastome transformation, directed genetic manipulation of the multiple nuclear-encoded RbcS genes is more challenging. Here we demonstrate the viability of linking the S and L subunits of tobacco (Nicotiana tabacum) Rubisco using a flexible 40-amino acid tether. By replacing the rbcL in tobacco plastids with an artificial gene coding for a S40L fusion peptide, we found that the fusions readily assemble into catalytic (S40L)8 and (S40L)16 oligomers that are devoid of unlinked S subunits. While there was little or no change in CO2/O2 specificity or carboxylation rate of the Rubisco oligomers, their Kms for CO2 and O2 were reduced 10% to 20% and 45%, respectively. In young maturing leaves of the plastome transformants (called ANtS40L), the S40L-Rubisco levels were approximately 20% that of wild-type controls despite turnover of the S40L-Rubisco oligomers being only slightly enhanced relative to wild type. The reduced Rubisco content in ANtS40L leaves is partly attributed to problems with folding and assembly of the S40L peptides in tobacco plastids that relegate approximately 30% to 50% of the S40L pool to the insoluble protein fraction. Leaf CO2-assimilation rates in ANtS40L at varying pCO2 corresponded with the kinetics and reduced content of the Rubisco oligomers. This fusion strategy provides a novel platform to begin simultaneously engineering Rubisco L and S subunits in tobacco plastids.

A large and aggressive fibromatosis in the axilla: a rare case report and review of the literature.

PubMed

Duan, Mingyue; Xing, Hua; Wang, Keren; Niu, Chunbo; Jiang, Chengwei; Zhang, Lijuan; Ezzat, Shereen; Zhang, Le

2018-01-01

Aggressive fibromatosis (AF) is a rare benign tumor, which occurs in the deep part of bone and muscle fibrous tissue. Clinical and pathological features can be challenging for definitive diagnosis. Here, we report a rare case of a large AF in the axilla. Interestingly, 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography showed significant increase in standard uptake value. Surgical resection yielded a spindle cell tumor likely of fibromatosis origin which was positive for β-catenin expression.

Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010

PubMed Central

Aschmann, André; Knechtle, Beat; Cribari, Marco; Rüst, Christoph Alexander; Onywera, Vincent; Rosemann, Thomas; Lepers, Romuald

2013-01-01

Background Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes. Methods Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses. Results For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05). Conclusion In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series. PMID:24379724

Screening for Atrial Fibrillation in Patients ≥65 Years Using an Automatic Blood Pressure Monitor in a Skilled Nursing Facility.

PubMed

Wiesel, Joseph; Salomone, Thomas J

2017-10-15

Early detection of asymptomatic atrial fibrillation (AF) provides an opportunity to treat patients to reduce their risk of stroke. Long-term residents of skilled nursing facilities frequently have multiple risk factors for strokes due to AF and may benefit from screening for AF. Patients in a skilled nursing facility 65 years and older, without a history of AF and without a pacemaker or defibrillator, were evaluated using a Microlife WatchBP Home A automatic blood pressure monitor that can detect AF when set to a triple reading mode. Those with readings positive for AF were evaluated with a standard 12-lead electrocardiogram (ECG) or a 30-second single-channel ECG to confirm the presence of AF. A total of 101 patients were screened with an average age of 78 years, and 48 (48%) were female. Nine automatic blood pressure monitor readings were positive for possible AF. Of those, 7 (6.9%, 95% confidence intervals 3.0% to 14.2%) had AF confirmed with ECG. Only 2 (2%, 95% confidence interval 0.3% to 7.7%) were false-positive readings. One-time screening for AF using an automatic blood pressure monitor in a skilled nursing facility resulted in a high number of patients with newly diagnosed AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Intradermal immunisation using the TLR3-ligand Poly (I:C) as adjuvant induces mucosal antibody responses and protects against genital HSV-2 infection

PubMed Central

Bardel, Emilie; Doucet-Ladeveze, Remi; Mathieu, Cyrille; Harandi, Ali M; Dubois, Bertrand; Kaiserlian, Dominique

2016-01-01

Development of vaccines able to induce mucosal immunity in the genital and gastrointestinal tracts is a major challenge to counter sexually transmitted pathogens such as HIV-1 and HSV-2. Herein, we showed that intradermal (ID) immunisation with sub-unit vaccine antigens (i.e., HIV-1 gp140 and HSV-2 gD) delivered with Poly(I:C) or CpG1668 as adjuvant induces long-lasting virus-specific immunoglobulin (Ig)-G and IgA antibodies in the vagina and feces. Poly(I:C)-supplemented sub-unit viral vaccines caused minimal skin reactogenicity at variance to those containing CpG1668, promoted a delayed-type hypersensitivity (DTH) to the vaccine and protected mice from genital and neurological symptoms after a lethal vaginal HSV-2 challenge. Interestingly, Poly(I:C12U) (Ampligen), a Poly(I:C) structural analogue that binds to TLR3 but not MDA-5, promoted robust mucosal and systemic IgG antibodies, a weak skin DTH to the vaccine but not IgA responses and failed to confer protection against HSV-2 infection. Moreover, Poly(I:C) was far superior to Poly(I:C12U) at inducing prompt and robust upregulation of IFNß transcripts in lymph nodes draining the injection site. These data illustrate that ID vaccination with glycoproteins and Poly(I:C) as adjuvant promotes long-lasting mucosal immunity and protection from genital HSV-2 infection, with an acceptable skin reactogenicity profile. The ID route thus appears to be an unexpected inductive site for mucosal immunity and anti-viral protection suitable for sub-unit vaccines. This works further highlights that TLR3/MDA5 agonists such as Poly(I:C) may be valuable adjuvants for ID vaccination against sexually transmitted diseases. PMID:29263853