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  1. Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A.

    PubMed

    Pons-Espinal, Meritxell; Martinez de Lagran, Maria; Dierssen, Mara

    2013-12-01

    Hippocampal adult neurogenesis disruptions have been suggested as one of the neuronal plasticity mechanisms underlying learning and memory impairment in Down syndrome (DS). However, it remains unknown whether specific candidate genes are implicated in these phenotypes in the multifactorial context of DS. Here we report that transgenic mice (TgDyrk1A) with overdosage of Dyrk1A, a DS candidate gene, show important alterations in adult neurogenesis including reduced cell proliferation rate, altered cell cycle progression and reduced cell cycle exit leading to premature migration, differentiation and reduced survival of newly born cells. In addition, less proportion of newborn hippocampal TgDyrk1A neurons are activated upon learning, suggesting reduced integration in learning circuits. Some of these alterations were DYRK1A kinase-dependent since we could rescue those using a DYRK1A inhibitor, epigallocatechin-3-gallate. Environmental enrichment also normalized DYRK1A kinase overdosage in the hippocampus, and rescued adult neurogenesis alterations in TgDyrk1A mice. We conclude that Dyrk1A is a good candidate to explain neuronal plasticity deficits in DS and that normalizing the excess of DYRK1A kinase activity either pharmacologically or using environmental stimulation can correct adult neurogenesis defects in DS. PMID:23969234

  2. Mechanism of dual specificity kinase activity of DYRK1A.

    PubMed

    Walte, Agnes; Rüben, Katharina; Birner-Gruenberger, Ruth; Preisinger, Christian; Bamberg-Lemper, Simone; Hilz, Nikolaus; Bracher, Franz; Becker, Walter

    2013-09-01

    The function of many protein kinases is controlled by the phosphorylation of a critical tyrosine residue in the activation loop. Dual specificity tyrosine-phosphorylation-regulated kinases (DYRKs) autophosphorylate on this tyrosine residue but phosphorylate substrates on aliphatic amino acids. This study addresses the mechanism of dual specificity kinase activity in DYRK1A and related kinases. Tyrosine autophosphorylation of DYRK1A occurred rapidly during in vitro translation and did not depend on the non-catalytic domains or other proteins. Expression in bacteria as well as in mammalian cells revealed that tyrosine kinase activity of DYRK1A is not restricted to the co-translational autophosphorylation in the activation loop. Moreover, mature DYRK1A was still capable of tyrosine autophosphorylation. Point mutants of DYRK1A and DYRK2 lacking the activation loop tyrosine showed enhanced tyrosine kinase activity. A series of structurally diverse DYRK1A inhibitors was used to pharmacologically distinguish different conformational states of the catalytic domain that are hypothesized to account for the dual specificity kinase activity. All tested compounds inhibited substrate phosphorylation with higher potency than autophosphorylation but none of the tested inhibitors differentially inhibited threonine and tyrosine kinase activity. Finally, the related cyclin-dependent kinase-like kinases (CLKs), which lack the activation loop tyrosine, autophosphorylated on tyrosine both in vitro and in living cells. We propose a model of DYRK autoactivation in which tyrosine autophosphorylation in the activation loop stabilizes a conformation of the catalytic domain with enhanced serine/threonine kinase activity without disabling tyrosine phosphorylation. The mechanism of dual specificity kinase activity probably applies to related serine/threonine kinases that depend on tyrosine autophosphorylation for maturation. PMID:23809146

  3. Impact of Dyrk1A level on alcohol metabolism.

    PubMed

    Renon, Marjorie; Legrand, Béatrice; Blanc, Etienne; Daubigney, Fabrice; Bokobza, Cindy; Mortreux, Marie; Paul, Jean-Louis; Delabar, Jean-Maurice; Rouach, Hélène; Andreau, Karine; Janel, Nathalie

    2016-09-01

    Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic mice. Here, we hypothesized that Dyrk1A contributes to alcohol-induced hepatic impairment in mice. Control, hyperhomocysteinemic and mice overexpressing Dyrk1A were fed using a Lieber-DeCarli liquid diet with or without ethanol (5% v/v ethanol) for one month, and liver histological examination and liver biochemical function tests were performed. Plasma alanine aminotransferase and homocysteine levels were significantly decreased in mice overexpressing Dyrk1A compared to control mice with or without alcohol administration. On the contrary, the mean plasma alanine aminotransferase and homocysteine levels were significantly higher in hyperhomocysteinemic mice than that of control mice after alcohol administration. Paraoxonase 1 and CYP2E1, two phase I xenobiotic metabolizing enzymes, were found increased in the three groups of mice after alcohol administration. However, NQO1, a phase II enzyme, was only found increased in hyperhomocysteinemic mice after alcohol exposure, suggesting a greater effect of alcohol in liver of hyperhomocysteinemic mice. We observed positive correlations between hepatic alcohol dehydrogenase activity, Dyrk1A and ADH4 protein levels. Importantly, a deleterious effect of alcohol consumption on hepatic Dyrk1A protein level was found. Our study reveals on the one hand a role of Dyrk1A in ethanol metabolism and on the other hand a deleterious effect of alcohol administration on hepatic Dyrk1A level. PMID:27216978

  4. Excitation/inhibition balance and learning are modified by Dyrk1a gene dosage.

    PubMed

    Souchet, Benoit; Guedj, Fayçal; Sahún, Ignasi; Duchon, Arnaud; Daubigney, Fabrice; Badel, Anne; Yanagawa, Yuchio; Barallobre, Maria Jose; Dierssen, Mara; Yu, Eugene; Herault, Yann; Arbones, Mariona; Janel, Nathalie; Créau, Nicole; Delabar, Jean Maurice

    2014-09-01

    Cognitive deficits in Down syndrome (DS) have been linked to increased synaptic inhibition, leading to an imbalance of excitation/inhibition (E/I). Various mouse models and studies from human brains have implicated an HSA21 gene, the serine/threonine kinase DYRK1A, as a candidate for inducing cognitive dysfunction. Here, consequences of alterations in Dyrk1a dosage were assessed in mouse models with varying copy numbers of Dyrk1a: mBACtgDyrk1a, Ts65Dn and Dp(16)1Yey (with 3 gene copies) and Dyrk1a(+/-) (one functional copy). Molecular (i.e. immunoblotting/immunohistochemistry) and behavioral analyses (e.g., rotarod, Morris water maze, Y-maze) were performed in mBACtgDyrk1a mice. Increased expression of DYRK1A in mBACtgDyrk1a induced molecular alterations in synaptic plasticity pathways, particularly expression changes in GABAergic and glutaminergic related proteins. Similar alterations were observed in models with partial trisomy of MMU16, Ts65Dn and Dp(16)1Yey, and were reversed in the Dyrk1a(+/-) model. Dyrk1a overexpression produced an increased number and signal intensity of GAD67 positive neurons, indicating enhanced inhibition pathways in three different models: mBACtgDyrk1a, hYACtgDyrk1a and Dp(16)1Yey. Functionally, Dyrk1a overexpression protected mice from PTZ-induced seizures related to GABAergic neuron plasticity. Our study shows that DYRK1A overexpression affects pathways involved in synaptogenesis and synaptic plasticity and influences E/I balance toward inhibition. Inhibition of DYRK1A activity offers a therapeutic target for DS, but its inhibition/activation may also be relevant for other psychiatric diseases with E/I balance alterations. PMID:24801365

  5. Plasma DYRK1A as a novel risk factor for Alzheimer's disease.

    PubMed

    Janel, N; Sarazin, M; Corlier, F; Corne, H; de Souza, L C; Hamelin, L; Aka, A; Lagarde, J; Blehaut, H; Hindié, V; Rain, J-C; Arbones, M L; Dubois, B; Potier, M C; Bottlaender, M; Delabar, J M

    2014-01-01

    To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-β42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD. PMID:25116835

  6. Understanding the Multifaceted Role of Human Down Syndrome Kinase DYRK1A.

    PubMed

    Kay, L J; Smulders-Srinivasan, T K; Soundararajan, M

    2016-01-01

    The dual-specificity tyrosine (Y) phosphorylation-regulated kinase DYRK1A, also known as Down syndrome (DS) kinase, is a dosage-dependent signaling kinase that was originally shown to be highly expressed in DS patients as a consequence of trisomy 21. Although this was evident some time ago, it is only in recent investigations that the molecular roles of DYRK1A in a wide range of cellular processes are becoming increasingly apparent. Since initial knowledge on DYRK1A became evident through minibrain mnb, the Drosophila homolog of DYRK1A, this review will first summarize the scientific reports on minibrain and further expand on the well-established neuronal functions of mammalian and human DYRK1A. Recent investigations across the current decade have provided rather interesting and compelling evidence in establishing nonneuronal functions for DYRK1A, including its role in infection, immunity, cardiomyocyte biology, cancer, and cell cycle control. The latter part of this review will therefore focus in detail on the emerging nonneuronal functions of DYRK1A and summarize the regulatory role of DYRK1A in controlling Tau and α-synuclein. Finally, the emerging role of DYRK1A in Parkinson's disease will be outlined. PMID:27567487

  7. Dyrk1A induces pancreatic β cell mass expansion and improves glucose tolerance

    PubMed Central

    Rachdi, Latif; Kariyawasam, Dulanjalee; Aïello, Virginie; Herault, Yann; Janel, Nathalie; Delabar, Jean-Maurice; Polak, Michel; Scharfmann, Raphaël

    2014-01-01

    Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic β cells to increase their mass and function in response to insulin resistance. The signaling pathways that positively regulate functional β cell mass have not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A significant amount of data implicates DYRK1A in brain growth and Down syndrome, and recent data indicate that Dyrk1A haploinsufficient mice have a low functional β cell mass. Here we ask whether Dyrk1A upregulation could be a way to increase functional β cell mass.     We used mice overexpressing Dyrk1A under the control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit decreased glucose levels and hyperinsulinemia in the fasting state. Improved glucose tolerance is observed in these mice as early as 4 weeks of age. Upregulation of Dyrk1A in β cells induces expansion of β cell mass through increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are protected against high-fat-diet-induced β cell failure through increase in β cell mass and insulin sensitivity. These studies show the crucial role of the DYRK1A pathway in the regulation of β cell mass and carbohydrate metabolism in vivo. Activating the DYRK1A pathway could thus represent an innovative way to increase functional β cell mass. PMID:24870561

  8. The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells

    PubMed Central

    Khor, Bernard; Gagnon, John D; Goel, Gautam; Roche, Marly I; Conway, Kara L; Tran, Khoa; Aldrich, Leslie N; Sundberg, Thomas B; Paterson, Alison M; Mordecai, Scott; Dombkowski, David; Schirmer, Melanie; Tan, Pauline H; Bhan, Atul K; Roychoudhuri, Rahul; Restifo, Nicholas P; O'Shea, John J; Medoff, Benjamin D; Shamji, Alykhan F; Schreiber, Stuart L; Sharpe, Arlene H; Shaw, Stanley Y; Xavier, Ramnik J

    2015-01-01

    The balance between Th17 and T regulatory (Treg) cells critically modulates immune homeostasis, with an inadequate Treg response contributing to inflammatory disease. Using an unbiased chemical biology approach, we identified a novel role for the dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A in regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and impairs Th17 differentiation without affecting known pathways of Treg/Th17 differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch point between commitment to either Treg or Th17 lineages. Importantly, both Treg cells generated using the DYRK1A inhibitor harmine and direct administration of harmine itself potently attenuate inflammation in multiple experimental models of systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a physiologically relevant regulator of Treg cell differentiation and suggest a broader role for other DYRK family members in immune homeostasis. These results are discussed in the context of human diseases associated with dysregulated DYRK activity. DOI: http://dx.doi.org/10.7554/eLife.05920.001 PMID:25998054

  9. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer.

    PubMed

    Yan, Haiyan; Hu, Kaishun; Wu, Wenjing; Li, Yu; Tian, Huan; Chu, Zhonghua; Koeffler, H Phillip; Yin, Dong

    2016-01-01

    Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer. PMID:27532268

  10. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2) Correlates with Poor Prognosis in Colorectal Cancer

    PubMed Central

    Wu, Wenjing; Li, Yu; Tian, Huan; Chu, Zhonghua; Koeffler, H. Phillip; Yin, Dong

    2016-01-01

    Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC) has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023), advanced clinical stages (P = 0.006) and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001). Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer. PMID:27532268

  11. Identification of DYRK1B as a substrate of ERK1/2 and characterisation of the kinase activity of DYRK1B mutants from cancer and metabolic syndrome.

    PubMed

    Ashford, Anne L; Dunkley, Tom P J; Cockerill, Mark; Rowlinson, Rachel A; Baak, Lisa M; Gallo, Raffaella; Balmanno, Kathryn; Goodwin, Louise M; Ward, Richard A; Lochhead, Pamela A; Guichard, Sylvie; Hudson, Kevin; Cook, Simon J

    2016-02-01

    The dual-specificity tyrosine-phosphorylation-regulated kinase, DYRK1B, is expressed de novo during myogenesis, amplified or mutated in certain cancers and mutated in familial cases of metabolic syndrome. DYRK1B is activated by cis auto-phosphorylation on tyrosine-273 (Y273) within the activation loop during translation but few other DYRK1B phosphorylation sites have been characterised to date. Here, we demonstrate that DYRK1B also undergoes trans-autophosphorylation on serine-421 (S421) in vitro and in cells and that this site contributes to DYRK1B kinase activity. Whilst a DYRK1B(S421A) mutant was completely defective for p-S421 in cells, DYRK1B inhibitors caused only a partial loss of p-S421 suggesting the existence of an additional kinase that could also phosphorylate DYRK1B S421. Indeed, a catalytically inactive DYRK1B(D239A) mutant exhibited very low levels of p-S421 in cells but this was increased by KRAS(G12V). In addition, selective activation of the RAF-MEK1/2-ERK1/2 signalling pathway rapidly increased p-S421 in cells whereas activation of the stress kinases JNK or p38 could not. S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro. Our results show that DYRK1B is a novel ERK2 substrate, uncovering new links between two kinases involved in cell fate decisions. Finally, we show that DYRK1B mutants that have recently been described in cancer and metabolic syndrome exhibit normal or reduced intrinsic kinase activity. PMID:26346493

  12. Characterization of DYRK2 ( dual-specificity tyrosine-phosphorylation-regulated kinase 2) from Zebrafish ( Dario rerio)

    NASA Astrophysics Data System (ADS)

    Sun, Wei; Tan, Xungang; Zhang, Peijun; Zhang, Yuqing; Xu, Yongli

    2010-07-01

    Proteins of the DYRK (dual-specificity tyrosine-phosphorylation-regulated kinase) family are characterized by the presence of a conserved kinase domain and N-terminal DH box. DYRK2 is involved in regulating key developmental and cellular processes, such as neurogenesis, cell proliferation, cytokinesis, and cellular differentiation. Herein, we report that the ortholog of DYRK2 found in zebrafish shares about 70% identity with that of human, mouse, and chick. RT-PCR showed that DYRK2 is expressed maternally and zygotically. In-situ hybridization results show that DYRK2 is expressed in somite cells that will develop into muscles. Our results provide preliminary evidence for investigating the in-vivo function of DYRK2 in zebrafish muscle development.

  13. Selective inhibition of the kinase DYRK1A by targeting its folding process.

    PubMed

    Kii, Isao; Sumida, Yuto; Goto, Toshiyasu; Sonamoto, Rie; Okuno, Yukiko; Yoshida, Suguru; Kato-Sumida, Tomoe; Koike, Yuka; Abe, Minako; Nonaka, Yosuke; Ikura, Teikichi; Ito, Nobutoshi; Shibuya, Hiroshi; Hosoya, Takamitsu; Hagiwara, Masatoshi

    2016-01-01

    Autophosphorylation of amino-acid residues is part of the folding process of various protein kinases. Conventional chemical screening of mature kinases has missed inhibitors that selectively interfere with the folding process. Here we report a cell-based assay that evaluates inhibition of a kinase at a transitional state during the folding process and identify a folding intermediate-selective inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), which we refer to as FINDY. FINDY suppresses intramolecular autophosphorylation of Ser97 in DYRK1A in cultured cells, leading to its degradation, but does not inhibit substrate phosphorylation catalysed by the mature kinase. FINDY also suppresses Ser97 autophosphorylation of recombinant DYRK1A, suggesting direct inhibition, and shows high selectivity for DYRK1A over other DYRK family members. In addition, FINDY rescues DYRK1A-induced developmental malformations in Xenopus laevis embryos. Our study demonstrates that transitional folding intermediates of protein kinases can be targeted by small molecules, and paves the way for developing novel types of kinase inhibitors. PMID:27102360

  14. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.

    PubMed

    Guedj, Fayçal; Sébrié, Catherine; Rivals, Isabelle; Ledru, Aurelie; Paly, Evelyne; Bizot, Jean C; Smith, Desmond; Rubin, Edward; Gillet, Brigitte; Arbones, Mariona; Delabar, Jean M

    2009-01-01

    Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) - a member of a natural polyphenols family, found in great amount in green tea leaves - is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice. PMID:19242551

  15. Selective inhibition of the kinase DYRK1A by targeting its folding process

    PubMed Central

    Kii, Isao; Sumida, Yuto; Goto, Toshiyasu; Sonamoto, Rie; Okuno, Yukiko; Yoshida, Suguru; Kato-Sumida, Tomoe; Koike, Yuka; Abe, Minako; Nonaka, Yosuke; Ikura, Teikichi; Ito, Nobutoshi; Shibuya, Hiroshi; Hosoya, Takamitsu; Hagiwara, Masatoshi

    2016-01-01

    Autophosphorylation of amino-acid residues is part of the folding process of various protein kinases. Conventional chemical screening of mature kinases has missed inhibitors that selectively interfere with the folding process. Here we report a cell-based assay that evaluates inhibition of a kinase at a transitional state during the folding process and identify a folding intermediate-selective inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), which we refer to as FINDY. FINDY suppresses intramolecular autophosphorylation of Ser97 in DYRK1A in cultured cells, leading to its degradation, but does not inhibit substrate phosphorylation catalysed by the mature kinase. FINDY also suppresses Ser97 autophosphorylation of recombinant DYRK1A, suggesting direct inhibition, and shows high selectivity for DYRK1A over other DYRK family members. In addition, FINDY rescues DYRK1A-induced developmental malformations in Xenopus laevis embryos. Our study demonstrates that transitional folding intermediates of protein kinases can be targeted by small molecules, and paves the way for developing novel types of kinase inhibitors. PMID:27102360

  16. Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A

    PubMed Central

    Guedj, Fayçal; Sébrié, Catherine; Rivals, Isabelle; Ledru, Aurelie; Paly, Evelyne; Bizot, Jean C.; Smith, Desmond; Rubin, Edward; Gillet, Brigitte; Arbones, Mariona; Delabar, Jean M.

    2009-01-01

    Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) — a member of a natural polyphenols family, found in great amount in green tea leaves — is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice. PMID:19242551

  17. DYRK1A: the double-edged kinase as a protagonist in cell growth and tumorigenesis

    PubMed Central

    Fernández-Martínez, P; Zahonero, C; Sánchez-Gómez, P

    2015-01-01

    DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is a kinase with multiple implications for embryonic development, especially in the nervous system where it regulates the balance between proliferation and differentiation of neural progenitors. The DYRK1A gene is located in the Down syndrome critical region and may play a significant role in the developmental brain defects, early neurodegeneration, and cancer susceptibility of individuals with this syndrome. DYRK1A is also expressed in adults, where it might participate in the regulation of cell cycle, survival, and tumorigenesis, thus representing a potential therapeutic target for certain types of cancer. However, the final readout of DYRK1A overexpression or inhibition depends strongly on the cellular context, as it has both tumor suppressor and oncogenic activities. Here, we will discuss the functions and substrates of DYRK1A associated with the control of cell growth and tumorigenesis with a focus on the potential use of DYRK1A inhibitors in cancer therapy. PMID:27308401

  18. A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition.

    PubMed

    Kim, Hyeongki; Lee, Kyu-Sun; Kim, Ae-Kyeong; Choi, Miri; Choi, Kwangman; Kang, Mingu; Chi, Seung-Wook; Lee, Min-Sung; Lee, Jeong-Soo; Lee, So-Young; Song, Woo-Joo; Yu, Kweon; Cho, Sungchan

    2016-08-01

    DYRK1A is important in neuronal development and function, and its excessive activity is considered a significant pathogenic factor in Down syndrome and Alzheimer's disease. Thus, inhibition of DYRK1A has been suggested to be a new strategy to modify the disease. Very few compounds, however, have been reported to act as inhibitors, and their potential clinical uses require further evaluation. Here, we newly identify CX-4945, the safety of which has been already proven in the clinical setting, as a potent inhibitor of DYRK1A that acts in an ATP-competitive manner. The inhibitory potency of CX-4945 on DYRK1A (IC50=6.8 nM) in vitro was higher than that of harmine, INDY or proINDY, which are well-known potent inhibitors of DYRK1A. CX-4945 effectively reverses the aberrant phosphorylation of Tau, amyloid precursor protein (APP) and presenilin 1 (PS1) in mammalian cells. To our surprise, feeding with CX-4945 significantly restored the neurological and phenotypic defects induced by the overexpression of minibrain, an ortholog of human DYRK1A, in the Drosophila model. Moreover, oral administration of CX-4945 acutely suppressed Tau hyperphosphorylation in the hippocampus of DYRK1A-overexpressing mice. Our research results demonstrate that CX-4945 is a potent DYRK1A inhibitor and also suggest that it has therapeutic potential for DYRK1A-associated diseases. PMID:27483355

  19. A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

    PubMed Central

    Kim, Hyeongki; Lee, Kyu-Sun; Kim, Ae-Kyeong; Choi, Miri; Choi, Kwangman; Kang, Mingu; Chi, Seung-Wook; Lee, Min-Sung; Lee, Jeong-Soo; Lee, So-Young; Song, Woo-Joo; Yu, Kweon

    2016-01-01

    ABSTRACT DYRK1A is important in neuronal development and function, and its excessive activity is considered a significant pathogenic factor in Down syndrome and Alzheimer's disease. Thus, inhibition of DYRK1A has been suggested to be a new strategy to modify the disease. Very few compounds, however, have been reported to act as inhibitors, and their potential clinical uses require further evaluation. Here, we newly identify CX-4945, the safety of which has been already proven in the clinical setting, as a potent inhibitor of DYRK1A that acts in an ATP-competitive manner. The inhibitory potency of CX-4945 on DYRK1A (IC50=6.8 nM) in vitro was higher than that of harmine, INDY or proINDY, which are well-known potent inhibitors of DYRK1A. CX-4945 effectively reverses the aberrant phosphorylation of Tau, amyloid precursor protein (APP) and presenilin 1 (PS1) in mammalian cells. To our surprise, feeding with CX-4945 significantly restored the neurological and phenotypic defects induced by the overexpression of minibrain, an ortholog of human DYRK1A, in the Drosophila model. Moreover, oral administration of CX-4945 acutely suppressed Tau hyperphosphorylation in the hippocampus of DYRK1A-overexpressing mice. Our research results demonstrate that CX-4945 is a potent DYRK1A inhibitor and also suggest that it has therapeutic potential for DYRK1A-associated diseases. PMID:27483355

  20. Splice Variants of the Dual Specificity Tyrosine Phosphorylation-regulated Kinase 4 (DYRK4) Differ in Their Subcellular Localization and Catalytic Activity*

    PubMed Central

    Papadopoulos, Chrisovalantis; Arato, Krisztina; Lilienthal, Eva; Zerweck, Johannes; Schutkowski, Mike; Chatain, Nicolas; Müller-Newen, Gerhard; Becker, Walter; de la Luna, Susana

    2011-01-01

    Dual specificity tyrosine phosphorylation-regulated kinases, DYRKs, are a family of conserved protein kinases that play key roles in the regulation of cell differentiation, proliferation, and survival. Of the five mammalian DYRKs, DYRK4 is the least studied family member. Here, we show that several splice variants of DYRK4 are expressed in tissue-specific patterns and that these variants have distinct functional capacities. One of these variants contains a nuclear localization signal in its extended N terminus that mediates its interaction with importin α3 and α5 and that is capable of targeting a heterologous protein to the nucleus. Consequently, the nucleocytoplasmic mobility of this variant differs from that of a shorter isoform in live cell imaging experiments. Other splicing events affect the catalytic domain, including a three-amino acid deletion within subdomain XI that markedly reduces the enzymatic activity of DYRK4. We also show that autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity, a defining feature of the DYRK family. Finally, by comparing the phosphorylation of an array of 720 peptides, we show that DYRK1A, DYRK2, and DYRK4 differ in their target recognition sequence and that preference for an arginine residue at position P −3 is a feature of DYRK1A but not of DYRK2 and DYRK4. Therefore, we highlight the use of subcellular localization as an important regulatory mechanism for DYRK proteins, and we propose that substrate specificity could be a source of functional diversity among DYRKs. PMID:21127067

  1. Inhibition of DYRK1A destabilizes EGFR and reduces EGFR-dependent glioblastoma growth

    PubMed Central

    Pozo, Natividad; Zahonero, Cristina; Fernández, Paloma; Liñares, Jose M.; Ayuso, Angel; Hagiwara, Masatoshi; Pérez, Angel; Ricoy, Jose R.; Hernández-Laín, Aurelio; Sepúlveda, Juan M.; Sánchez-Gómez, Pilar

    2013-01-01

    Glioblastomas (GBMs) are very aggressive tumors that are resistant to conventional chemo- and radiotherapy. New molecular therapeutic strategies are required to effectively eliminate the subpopulation of GBM tumor–initiating cells that are responsible for relapse. Since EGFR is altered in 50% of GBMs, it represents one of the most promising targets; however, EGFR kinase inhibitors have produced poor results in clinical assays, with no clear explanation for the observed resistance. We uncovered a fundamental role for the dual-specificity tyrosine phosphorylation–regulated kinase, DYRK1A, in regulating EGFR in GBMs. We found that DYRK1A was highly expressed in these tumors and that its expression was correlated with that of EGFR. Moreover, DYRK1A inhibition promoted EGFR degradation in primary GBM cell lines and neural progenitor cells, sharply reducing the self-renewal capacity of normal and tumorigenic cells. Most importantly, our data suggest that a subset of GBMs depends on high surface EGFR levels, as DYRK1A inhibition compromised their survival and produced a profound decrease in tumor burden. We propose that the recovery of EGFR stability is a key oncogenic event in a large proportion of gliomas and that pharmacological inhibition of DYRK1A could represent a promising therapeutic intervention for EGFR-dependent GBMs. PMID:23635774

  2. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors

    PubMed Central

    Rüben, Katharina; Wurzlbauer, Anne; Walte, Agnes; Sippl, Wolfgang; Bracher, Franz; Becker, Walter

    2015-01-01

    DYRK1A is a pleiotropic protein kinase with diverse functions in cellular regulation, including cell cycle control, neuronal differentiation, and synaptic transmission. Enhanced activity and overexpression of DYRK1A have been linked to altered brain development and function in Down syndrome and neurodegenerative diseases such as Alzheimer’s disease. The β-carboline alkaloid harmine is a high affinity inhibitor of DYRK1A but suffers from the drawback of inhibiting monoamine oxidase A (MAO-A) with even higher potency. Here we characterized a series of novel harmine analogs with minimal or absent MAO-A inhibitory activity. We identified several inhibitors with submicromolar potencies for DYRK1A and selectivity for DYRK1A and DYRK1B over the related kinases DYRK2 and HIPK2. An optimized inhibitor, AnnH75, inhibited CLK1, CLK4, and haspin/GSG2 as the only off-targets in a panel of 300 protein kinases. In cellular assays, AnnH75 dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4, and tau) without negative effects on cell viability. AnnH75 inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency. In conclusion, we have characterized an optimized β-carboline inhibitor as a highly selective chemical probe that complies with desirable properties of drug-like molecules and is suitable to interrogate the function of DYRK1A in biological studies. PMID:26192590

  3. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.

    PubMed

    Rüben, Katharina; Wurzlbauer, Anne; Walte, Agnes; Sippl, Wolfgang; Bracher, Franz; Becker, Walter

    2015-01-01

    DYRK1A is a pleiotropic protein kinase with diverse functions in cellular regulation, including cell cycle control, neuronal differentiation, and synaptic transmission. Enhanced activity and overexpression of DYRK1A have been linked to altered brain development and function in Down syndrome and neurodegenerative diseases such as Alzheimer's disease. The β-carboline alkaloid harmine is a high affinity inhibitor of DYRK1A but suffers from the drawback of inhibiting monoamine oxidase A (MAO-A) with even higher potency. Here we characterized a series of novel harmine analogs with minimal or absent MAO-A inhibitory activity. We identified several inhibitors with submicromolar potencies for DYRK1A and selectivity for DYRK1A and DYRK1B over the related kinases DYRK2 and HIPK2. An optimized inhibitor, AnnH75, inhibited CLK1, CLK4, and haspin/GSG2 as the only off-targets in a panel of 300 protein kinases. In cellular assays, AnnH75 dose-dependently reduced the phosphorylation of three known DYRK1A substrates (SF3B1, SEPT4, and tau) without negative effects on cell viability. AnnH75 inhibited the cotranslational tyrosine autophosphorylation of DYRK1A and threonine phosphorylation of an exogenous substrate protein with similar potency. In conclusion, we have characterized an optimized β-carboline inhibitor as a highly selective chemical probe that complies with desirable properties of drug-like molecules and is suitable to interrogate the function of DYRK1A in biological studies. PMID:26192590

  4. Design and Synthesis of a Library of Lead-Like 2,4-Bisheterocyclic Substituted Thiophenes as Selective Dyrk/Clk Inhibitors

    PubMed Central

    Schmitt, Christian; Kail, Dagmar; Mariano, Marica; Empting, Martin; Weber, Nadja; Paul, Tamara; Hartmann, Rolf W.; Engel, Matthias

    2014-01-01

    The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacological inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as additional targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochemical properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacological tool to dissect Dyrk2 isoform–mediated functions. PMID:24676346

  5. DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease

    PubMed Central

    Barallobre, M J; Perier, C; Bové, J; Laguna, A; Delabar, J M; Vila, M; Arbonés, M L

    2014-01-01

    In the brain, programmed cell death (PCD) serves to adjust the numbers of the different types of neurons during development, and its pathological reactivation in the adult leads to neurodegeneration. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) is a pleiotropic kinase involved in neural proliferation and cell death, and its role during brain growth is evolutionarily conserved. Human DYRK1A lies in the Down syndrome critical region on chromosome 21, and heterozygous mutations in the gene cause microcephaly and neurological dysfunction. The mouse model for DYRK1A haploinsufficiency (the Dyrk1a+/− mouse) presents neuronal deficits in specific regions of the adult brain, including the substantia nigra (SN), although the mechanisms underlying these pathogenic effects remain unclear. Here we study the effect of DYRK1A copy number variation on dopaminergic cell homeostasis. We show that mesencephalic DA (mDA) neurons are generated in the embryo at normal rates in the Dyrk1a haploinsufficient model and in a model (the mBACtgDyrk1a mouse) that carries three copies of Dyrk1a. We also show that the number of mDA cells diminishes in postnatal Dyrk1a+/− mice and increases in mBACtgDyrk1a mice due to an abnormal activity of the mitochondrial caspase9 (Casp9)-dependent apoptotic pathway during the main wave of PCD that affects these neurons. In addition, we show that the cell death induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), a toxin that activates Casp9-dependent apoptosis in mDA neurons, is attenuated in adult mBACtgDyrk1a mice, leading to an increased survival of SN DA neurons 21 days after MPTP intoxication. Finally, we present data indicating that Dyrk1a phosphorylation of Casp9 at the Thr125 residue is the mechanism by which this kinase hinders both physiological and pathological PCD in mDA neurons. These data provide new insight into the mechanisms that control cell death in brain DA neurons and they show that

  6. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.

    PubMed

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-11-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  7. [Effect of Danshen-containing serum on expression of SuFu and DYRK2 in HSCs].

    PubMed

    Han, Shi-qing; Wang, Hai-lan; Feng, Li-li; Cao, Wen-fu

    2015-11-01

    To observe the effects of Danshen-containing serum on SuFu and DYRK2 expression in the HSCs stimulated by leptin. SD rats (n = 60) were used to make danshen-containing serum by gastric perfusion for ten days with Danshen water decoction, normal saline and colchicine. The HSCs that were cultured in vitro would be stimulated for 24 hours by leptin (100 μg x L(-1)) except blank control group, after being intervened, the drug serum in each group would be cultured at 37 degrees C in 5% incubator. The cells would be collected after 24 hours, then the effects of danshen-containing serum on the proliferation of HSCs were detected by MTT, the expression of SuFu mRNA and DYRK2 mRNA were detected by RT-PCR, the expression of SuFu and DYRK2 proteins were tested by Western blot. Compared with blank control group, the expression of DYRK2 mRNA and DYRK2 proteins were enhanced obviously after stimulated the HSCs of rats by leptin (P < 0.01), but the expression of SuFu mRNA and SuFu proteins were decreased significantly (P < 0.01). Compared with the model group, after cyclopamine group (Hh pathway inhibitor), Danshen-containing serum and colchicine were interfered, the expression of DYRK2 mRNA and DYRK2 proteins were decreased clearly (P < 0.01), but the expression of SuFu mRNA and SuFu proteins were increased significantly (P < 0.01 or P < 0.05). Compared with model group, adding purmorphamine (Hh pathway agonist) to model group and making it activate could increase the expression of DYRK2 mRNA and DYRK2 proteins, but the expression of SuFu mRNA and SuFu proteins were decreased significantly (P < 0.01). Compared with the model group, using the Danshen-containing serum to interfere the purmorphamine group could make the expression of DYRK2 mRNA and DYRK2 proteins decrease and the expression of SuFu mRNA and SuFu proteins increase significantly (P < 0.01). Danshen-containing serum would inhibition the activation and increment of HSCs by interfering the expression of SuFu and DYRK2

  8. Overexpression of Dyrk1A regulates cardiac troponin T splicing in cells and mice.

    PubMed

    Lu, Shu; Yin, Xiaomin

    2016-05-13

    The human heart expresses four isoforms of cardiac troponin T (cTnT) through alternative splicing of exons 4 and 5 of the cTnT gene. Alternative splicing of cTnT exon 5 is developmentally regulated. cTnT isoforms containing exon 5 are expressed in the fetal and neonatal heart but not in the mature heart. SRp55 is an essential splicing factor involved in cTnT exon 5 splicing and it is phosphorylated by Dyrk1A (dual specificity tyrosine phosphorylation regulated kinase 1A). In the present study, we found Dyrk1A interacted with SRp55 and enhanced its promotion of cTnT exon 5 inclusion. The shift from cTnT exon 5 inclusion to exclusion during development was delayed in the heart of Ts65Dn mice due to Dyrk1A overexpression. These results provide new insight into the role of Dyrk1A in the neonatal cardiac development. PMID:27049307

  9. A Form of the Metabolic Syndrome Associated with Mutations in DYRK1B

    PubMed Central

    Choi, Murim; Faramarzi, Saeed; Mane, Shrikant; Kasaei, Mohammad; Sarajzadeh-Fard, Kazem; Hwa, John; Kidd, Kenneth K.; Babaee Bigi, Mohammad A.; Malekzadeh, Reza; Hosseinian, Adallat; Babaei, Masoud; Lifton, Richard P.; Mani, Arya

    2014-01-01

    BACKGROUND Genetic analysis has been successful in identifying causative mutations for individual cardiovascular risk factors. Success has been more limited in mapping susceptibility genes for clusters of cardiovascular risk traits, such as those in the metabolic syndrome. METHODS We identified three large families with coinheritance of early-onset coronary artery disease, central obesity, hypertension, and diabetes. We used linkage analysis and whole-exome sequencing to identify the disease-causing gene. RESULTS A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in the highly conserved kinase-like domain. The mutation precisely cosegregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Functional characterization of the disease gene revealed that nonmutant protein encoded by DYRK1B inhibits the SHH (sonic hedgehog) and Wnt signaling pathways and consequently enhances adipogenesis. Furthermore, DYRK1B promoted the expression of the key gluconeogenic enzyme glucose-6-phosphatase. The R102C allele showed gain-offunction activities by potentiating these effects. A second mutation, substituting proline for histidine 90, was found to cosegregate with a similar clinical syndrome in an ethnically distinct family. CONCLUSIONS These findings indicate a role for DYRK1B in adipogenesis and glucose homeostasis and associate its altered function with an inherited form of the metabolic syndrome. (Funded by the National Institutes of Health.) PMID:24827035

  10. Kinetic properties of a MNB/DYRK1A mutant suitable for the elucidation of biochemical pathways.

    PubMed

    Adayev, Tatyana; Chen-Hwang, Mo-Chou; Murakami, Noriko; Wegiel, Jerzy; Hwang, Yu-Wen

    2006-10-01

    Minibrain kinase/dual-specificity tyrosine phosphorylation regulated kinase 1A (MNB/DYRK1A) is a proline/arginine-directed serine/threonine kinase implicated in the learning deficits of Down syndrome. Epigallocatechin-3-gallate (EGCG), the major tea polyphenolic compound, is a potent MNB/DYRK1A inhibitor. In this study, we investigated the mechanism of EGCG inhibition of MNB/DYRK1A using a combination of genetic and biochemical approaches. In the testing system using MNB/DYRK1A-promoted Gli 1-dependent transcription as the readout, NIH3T3 cells expressing EGCG resistant MNB/DYRK1A mutant R21 were found to acquire EGCG resistance for a wide range of drug concentrations. Mutant R21 harbors a single K465R substitution, which produces a 3-fold gain in the EGCG resistance in vitro. However, the gain in the EGCG resistance alone cannot fully interpret the effectiveness of mutant R21 in suppressing EGCG in cultured cells. Kinetic analysis suggests that EGCG functions as a noncompetitive inhibitor against ATP. Interestingly, the K465R mutation changes the mode of EGCG inhibition on MNB/DYRK1A so that it becomes a competitive inhibitor against ATP. This competitive mode of EGCG inhibition coupled with high intracellular ATP concentrations and an elevated EGCG resistance are likely to be the basis for the resistant property of mutant R21 in cultured cells. The K465R mutation apparently transforms the intramolecular interactions required for MNB/DYRK1A catalysis. This mutant would also be valuable for the elucidation of the mechanisms of MNB/DYRK1A-catalyzed reaction. PMID:17002300

  11. The Down syndrome-related protein kinase DYRK1A phosphorylates p27Kip1 and Cyclin D1 and induces cell cycle exit and neuronal differentiation

    PubMed Central

    Soppa, Ulf; Schumacher, Julian; Florencio Ortiz, Victoria; Pasqualon, Tobias; Tejedor, Francisco J; Becker, Walter

    2014-01-01

    A fundamental question in neurobiology is how the balance between proliferation and differentiation of neuronal precursors is maintained to ensure that the proper number of brain neurons is generated. Substantial evidence implicates DYRK1A (dual specificity tyrosine-phosphorylation-regulated kinase 1A) as a candidate gene responsible for altered neuronal development and brain abnormalities in Down syndrome. Recent findings support the hypothesis that DYRK1A is involved in cell cycle control. Nonetheless, how DYRK1A contributes to neuronal cell cycle regulation and thereby affects neurogenesis remains poorly understood. In the present study we have investigated the mechanisms by which DYRK1A affects cell cycle regulation and neuronal differentiation in a human cell model, mouse neurons, and mouse brain. Dependent on its kinase activity and correlated with the dosage of overexpression, DYRK1A blocked proliferation of SH-SY5Y neuroblastoma cells within 24 h and arrested the cells in G1 phase. Sustained overexpression of DYRK1A induced G0 cell cycle exit and neuronal differentiation. Furthermore, we provide evidence that DYRK1A modulated protein stability of cell cycle-regulatory proteins. DYRK1A reduced cellular Cyclin D1 levels by phosphorylation on Thr286, which is known to induce proteasomal degradation. In addition, DYRK1A phosphorylated p27Kip1 on Ser10, resulting in protein stabilization. Inhibition of DYRK1A kinase activity reduced p27Kip1 Ser10 phosphorylation in cultured hippocampal neurons and in embryonic mouse brain. In aggregate, these results suggest a novel mechanism by which overexpression of DYRK1A may promote premature neuronal differentiation and contribute to altered brain development in Down syndrome. PMID:24806449

  12. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation

    PubMed Central

    Shen, Weijun; Taylor, Brandon; Jin, Qihui; Nguyen-Tran, Van; Meeusen, Shelly; Zhang, You-Qing; Kamireddy, Anwesh; Swafford, Austin; Powers, Andrew F.; Walker, John; Lamb, John; Bursalaya, Badry; DiDonato, Michael; Harb, George; Qiu, Minhua; Filippi, Christophe M.; Deaton, Lisa; Turk, Carolina N.; Suarez-Pinzon, Wilma L.; Liu, Yahu; Hao, Xueshi; Mo, Tingting; Yan, Shanshan; Li, Jing; Herman, Ann E.; Hering, Bernhard J.; Wu, Tom; Martin Seidel, H.; McNamara, Peter; Glynne, Richard; Laffitte, Bryan

    2015-01-01

    Insufficient pancreatic β-cell mass or function results in diabetes mellitus. While significant progress has been made in regulating insulin secretion from β-cells in diabetic patients, no pharmacological agents have been described that increase β-cell replication in humans. Here we report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B. Aminopyrazine-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of these compounds in diabetic mice induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Biochemical, genetic and cell biology data point to Dyrk1a as the key molecular target. This study supports the feasibility of treating diabetes with an oral therapy to restore β-cell mass, and highlights a tractable pathway for future drug discovery efforts. PMID:26496802

  13. Inhibition of DYRK1A and GSK3B induces human β-cell proliferation.

    PubMed

    Shen, Weijun; Taylor, Brandon; Jin, Qihui; Nguyen-Tran, Van; Meeusen, Shelly; Zhang, You-Qing; Kamireddy, Anwesh; Swafford, Austin; Powers, Andrew F; Walker, John; Lamb, John; Bursalaya, Badry; DiDonato, Michael; Harb, George; Qiu, Minhua; Filippi, Christophe M; Deaton, Lisa; Turk, Carolina N; Suarez-Pinzon, Wilma L; Liu, Yahu; Hao, Xueshi; Mo, Tingting; Yan, Shanshan; Li, Jing; Herman, Ann E; Hering, Bernhard J; Wu, Tom; Martin Seidel, H; McNamara, Peter; Glynne, Richard; Laffitte, Bryan

    2015-01-01

    Insufficient pancreatic β-cell mass or function results in diabetes mellitus. While significant progress has been made in regulating insulin secretion from β-cells in diabetic patients, no pharmacological agents have been described that increase β-cell replication in humans. Here we report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B. Aminopyrazine-treated human islets retain functionality in vitro and after transplantation into diabetic mice. Oral dosing of these compounds in diabetic mice induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control. Biochemical, genetic and cell biology data point to Dyrk1a as the key molecular target. This study supports the feasibility of treating diabetes with an oral therapy to restore β-cell mass, and highlights a tractable pathway for future drug discovery efforts. PMID:26496802

  14. Inhibition of DYRK1A Stimulates Human β-Cell Proliferation.

    PubMed

    Dirice, Ercument; Walpita, Deepika; Vetere, Amedeo; Meier, Bennett C; Kahraman, Sevim; Hu, Jiang; Dančík, Vlado; Burns, Sean M; Gilbert, Tamara J; Olson, David E; Clemons, Paul A; Kulkarni, Rohit N; Wagner, Bridget K

    2016-06-01

    Restoring functional β-cell mass is an important therapeutic goal for both type 1 and type 2 diabetes (1). While proliferation of existing β-cells is the primary means of β-cell replacement in rodents (2), it is unclear whether a similar principle applies to humans, as human β-cells are remarkably resistant to stimulation of division (3,4). Here, we show that 5-iodotubercidin (5-IT), an annotated adenosine kinase inhibitor previously reported to increase proliferation in rodent and porcine islets (5), strongly and selectively increases human β-cell proliferation in vitro and in vivo. Remarkably, 5-IT also increased glucose-dependent insulin secretion after prolonged treatment. Kinome profiling revealed 5-IT to be a potent and selective inhibitor of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) and cell division cycle-like kinase families. Induction of β-cell proliferation by either 5-IT or harmine, another natural product DYRK1A inhibitor, was suppressed by coincubation with the calcineurin inhibitor FK506, suggesting involvement of DYRK1A and nuclear factor of activated T cells signaling. Gene expression profiling in whole islets treated with 5-IT revealed induction of proliferation- and cell cycle-related genes, suggesting that true proliferation is induced by 5-IT. Furthermore, 5-IT promotes β-cell proliferation in human islets grafted under the kidney capsule of NOD-scid IL2Rg(null) mice. These results point to inhibition of DYRK1A as a therapeutic strategy to increase human β-cell proliferation. PMID:26953159

  15. DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly

    PubMed Central

    Litovchick, Larisa; Florens, Laurence A.; Swanson, Selene K.; Washburn, Michael P.; DeCaprio, James A.

    2011-01-01

    In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREAM (DP, RB [retinoblastoma], E2F, and MuvB) complex represses cell cycle-dependent genes during quiescence. DREAM contains p130, E2F4, DP1, and a stable core complex of five MuvB-like proteins: LIN9, LIN37, LIN52, LIN54, and RBBP4. In mammalian cells, the MuvB core dissociates from p130 upon entry into the cell cycle and binds to BMYB during S phase to activate the transcription of genes expressed late in the cell cycle. We used mass spectroscopic analysis to identify phosphorylation sites that regulate the switch of the MuvB core from BMYB to DREAM. Here we report that DYRK1A can specifically phosphorylate LIN52 on serine residue 28, and that this phosphorylation is required for DREAM assembly. Inhibiting DYRK1A activity or point mutation of LIN52 disrupts DREAM assembly and reduces the ability of cells to enter quiescence or undergo Ras-induced senescence. These data reveal an important role for DYRK1A in the regulation of DREAM activity and entry into quiescence. PMID:21498570

  16. DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly.

    PubMed

    Litovchick, Larisa; Florens, Laurence A; Swanson, Selene K; Washburn, Michael P; DeCaprio, James A

    2011-04-15

    In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREAM (DP, RB [retinoblastoma], E2F, and MuvB) complex represses cell cycle-dependent genes during quiescence. DREAM contains p130, E2F4, DP1, and a stable core complex of five MuvB-like proteins: LIN9, LIN37, LIN52, LIN54, and RBBP4. In mammalian cells, the MuvB core dissociates from p130 upon entry into the cell cycle and binds to BMYB during S phase to activate the transcription of genes expressed late in the cell cycle. We used mass spectroscopic analysis to identify phosphorylation sites that regulate the switch of the MuvB core from BMYB to DREAM. Here we report that DYRK1A can specifically phosphorylate LIN52 on serine residue 28, and that this phosphorylation is required for DREAM assembly. Inhibiting DYRK1A activity or point mutation of LIN52 disrupts DREAM assembly and reduces the ability of cells to enter quiescence or undergo Ras-induced senescence. These data reveal an important role for DYRK1A in the regulation of DREAM activity and entry into quiescence. PMID:21498570

  17. 10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic Acids Are Selective Inhibitors of DYRK1A

    PubMed Central

    2015-01-01

    The protein kinase DYRK1A has been suggested to act as one of the intracellular regulators contributing to neurological alterations found in individuals with Down syndrome. For an assessment of the role of DYRK1A, selective synthetic inhibitors are valuable pharmacological tools. However, the DYRK1A inhibitors described in the literature so far either are not sufficiently selective or have not been tested against closely related kinases from the DYRK and the CLK protein kinase families. The aim of this study was the identification of DYRK1A inhibitors exhibiting selectivity versus the structurally and functionally closely related DYRK and CLK isoforms. Structure modification of the screening hit 11H-indolo[3,2-c]quinoline-6-carboxylic acid revealed structure–activity relationships for kinase inhibition and enabled the design of 10-iodo-substituted derivatives as very potent DYRK1A inhibitors with considerable selectivity against CLKs. X-ray structure determination of three 11H-indolo[3,2-c]quinoline-6-carboxylic acids cocrystallized with DYRK1A confirmed the predicted binding mode within the ATP binding site. PMID:25730262

  18. The adaptor protein DCAF7 mediates the interaction of the adenovirus E1A oncoprotein with the protein kinases DYRK1A and HIPK2

    PubMed Central

    Glenewinkel, Florian; Cohen, Michael J.; King, Cason R.; Kaspar, Sophie; Bamberg-Lemper, Simone; Mymryk, Joe S.; Becker, Walter

    2016-01-01

    DYRK1A is a constitutively active protein kinase that has a critical role in growth and development which functions by regulating cell proliferation, differentiation and survival. DCAF7 (also termed WDR68 or HAN11) is a cellular binding partner of DYRK1A and also regulates signalling by the protein kinase HIPK2. DCAF7 is an evolutionarily conserved protein with a single WD40 repeat domain and has no catalytic activity. We have defined a DCAF7 binding motif of 12 amino acids in the N-terminal domain of class 1 DYRKs that is functionally conserved in DYRK1 orthologs from Xenopus, Danio rerio and the slime mold Dictyostelium discoideum. A similar sequence was essential for DCAF7 binding to HIPK2, whereas the closely related HIPK1 family member did not bind DCAF7. Immunoprecipitation and pulldown experiments identified DCAF7 as an adaptor for the association of the adenovirus E1A protein with DYRK1A and HIPK2. Furthermore, DCAF7 was required for the hyperphosphorylation of E1A in DYRK1A or HIPK2 overexpressing cells. Our results characterize DCAF7 as a substrate recruiting subunit of DYRK1A and HIPK2 and suggest that it is required for the negative effect of DYRK1A on E1A-induced oncogenic transformation. PMID:27307198

  19. The adaptor protein DCAF7 mediates the interaction of the adenovirus E1A oncoprotein with the protein kinases DYRK1A and HIPK2.

    PubMed

    Glenewinkel, Florian; Cohen, Michael J; King, Cason R; Kaspar, Sophie; Bamberg-Lemper, Simone; Mymryk, Joe S; Becker, Walter

    2016-01-01

    DYRK1A is a constitutively active protein kinase that has a critical role in growth and development which functions by regulating cell proliferation, differentiation and survival. DCAF7 (also termed WDR68 or HAN11) is a cellular binding partner of DYRK1A and also regulates signalling by the protein kinase HIPK2. DCAF7 is an evolutionarily conserved protein with a single WD40 repeat domain and has no catalytic activity. We have defined a DCAF7 binding motif of 12 amino acids in the N-terminal domain of class 1 DYRKs that is functionally conserved in DYRK1 orthologs from Xenopus, Danio rerio and the slime mold Dictyostelium discoideum. A similar sequence was essential for DCAF7 binding to HIPK2, whereas the closely related HIPK1 family member did not bind DCAF7. Immunoprecipitation and pulldown experiments identified DCAF7 as an adaptor for the association of the adenovirus E1A protein with DYRK1A and HIPK2. Furthermore, DCAF7 was required for the hyperphosphorylation of E1A in DYRK1A or HIPK2 overexpressing cells. Our results characterize DCAF7 as a substrate recruiting subunit of DYRK1A and HIPK2 and suggest that it is required for the negative effect of DYRK1A on E1A-induced oncogenic transformation. PMID:27307198

  20. Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID

    PubMed Central

    van Bon, Bregje W.M.; Coe, Bradley P.; Bernier, Raphael; Green, Cherie; Gerdts, Jennifer; Witherspoon, Kali; Kleefstra, Tjitske; Willemsen, Marjolein H.; Kumar, Raman; Bosco, Paolo; Fichera, Marco; Li, Deana; Amaral, David; Cristofoli, Francesca; Peeters, Hilde; Haan, Eric; Romano, Corrado; Mefford, Heather C.; Scheffer, Ingrid; Gecz, Jozef; de Vries, Bert B.A.; Eichler, Evan E.

    2015-01-01

    Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene are thought to play a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7,162 ASD/DD patients (2,446 previously reported) and 2,169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8,696 controls identified a significant enrichment of DYRK1A truncating mutations (p = 0.00851) and an excess of de novo mutations (p = 2.53×10−10) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n = 5) and recontacted (n = 3) cases to previous case reports, including larger CNV and translocation events (n = 7), identifies a syndromal disorder among the 15 patients. It is characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia, and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models. PMID:25707398

  1. Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.

    PubMed

    van Bon, B W M; Coe, B P; Bernier, R; Green, C; Gerdts, J; Witherspoon, K; Kleefstra, T; Willemsen, M H; Kumar, R; Bosco, P; Fichera, M; Li, D; Amaral, D; Cristofoli, F; Peeters, H; Haan, E; Romano, C; Mefford, H C; Scheffer, I; Gecz, J; de Vries, B B A; Eichler, E E

    2016-01-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models. PMID:25707398

  2. DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance

    PubMed Central

    Gruber, Wolfgang; Hutzinger, Martin; Elmer, Dominik Patrick; Parigger, Thomas; Sternberg, Christina; Cegielkowski, Lukasz; Zaja, Mirko; Leban, Johann; Michel, Susanne; Hamm, Svetlana; Vitt, Daniel; Aberger, Fritz

    2016-01-01

    A wide range of human malignancies displays aberrant activation of Hedgehog (HH)/GLI signaling, including cancers of the skin, brain, gastrointestinal tract and hematopoietic system. Targeting oncogenic HH/GLI signaling with small molecule inhibitors of the essential pathway effector Smoothened (SMO) has shown remarkable therapeutic effects in patients with advanced and metastatic basal cell carcinoma. However, acquired and de novo resistance to SMO inhibitors poses severe limitations to the use of SMO antagonists and urgently calls for the identification of novel targets and compounds. Here we report on the identification of the Dual-Specificity-Tyrosine-Phosphorylation-Regulated Kinase 1B (DYRK1B) as critical positive regulator of HH/GLI signaling downstream of SMO. Genetic and chemical inhibition of DYRK1B in human and mouse cancer cells resulted in marked repression of HH signaling and GLI1 expression, respectively. Importantly, DYRK1B inhibition profoundly impaired GLI1 expression in both SMO-inhibitor sensitive and resistant settings. We further introduce a novel small molecule DYRK1B inhibitor, DYRKi, with suitable pharmacologic properties to impair SMO-dependent and SMO-independent oncogenic GLI activity. The results support the use of DYRK1B antagonists for the treatment of HH/GLI-associated cancers where SMO inhibitors fail to demonstrate therapeutic efficacy. PMID:26784250

  3. DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort

    PubMed Central

    2009-01-01

    Background As dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD. Methods We examined genetic variations of DYRK1A by genotyping haplotype tagging SNPs (htSNPs) (rs11701483, rs2835740, rs1137600, rs2835761, rs2835762, rs2154545 and rs8132976) in a group of 634 Spanish AD cases and 733 controls. Results There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele. Conclusion Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between DYRK1A gene and AD risk in the Japanese population exists. PMID:19995442

  4. Exploiting the repertoire of CK2 inhibitors to target DYRK and PIM kinases.

    PubMed

    Cozza, Giorgio; Sarno, Stefania; Ruzzene, Maria; Girardi, Cristina; Orzeszko, Andrzej; Kazimierczuk, Zygmunt; Zagotto, Giuseppe; Bonaiuto, Emanuela; Di Paolo, Maria Luisa; Pinna, Lorenzo A

    2013-07-01

    Advantage has been taken of the relative promiscuity of commonly used inhibitors of protein kinase CK2 to develop compounds that can be exploited for the selective inhibition of druggable kinases other than CK2 itself. Here we summarize data obtained by altering the scaffold of CK2 inhibitors to give rise to novel selective inhibitors of DYRK1A and to a powerful cell permeable dual inhibitor of PIM1 and CK2. In the former case one of the new compounds, C624 (naphto [1,2-b]benzofuran-5,9-diol) displays a potency comparable to that of the first-in-class DYRK1A inhibitor, harmine, lacking however the drawback of drastically inhibiting monoamine oxidase-A (MAO-A) as harmine does. On the other hand the promiscuous CK2 inhibitor 4,5,6,7-tetrabromo-1H-benzimidazole (TBI,TBBz) has been derivatized with a sugar moiety to generate a 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (TDB) compound which inhibits PIM1 and CK2 with comparably high efficacy (IC50 values<100nM) and remarkable selectivity. TDB, unlike other dual PIM1/CK2 inhibitors described in the literature is readily cell permeable and displays a cytotoxic effect on cancer cells consistent with concomitant inhibition of both its onco-kinase targets. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). PMID:23360763

  5. A novel DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro.

    PubMed

    Coutadeur, Séverine; Benyamine, Hélène; Delalonde, Laurence; de Oliveira, Catherine; Leblond, Bertrand; Foucourt, Alicia; Besson, Thierry; Casagrande, Anne-Sophie; Taverne, Thierry; Girard, Angélique; Pando, Matthew P; Désiré, Laurent

    2015-05-01

    The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene is located within the Down Syndrome (DS) critical region on chromosome 21 and is implicated in the generation of Tau and amyloid pathologies that are associated with the early onset Alzheimer's Disease (AD) observed in DS. DYRK1A is also found associated with neurofibrillary tangles in sporadic AD and phosphorylates key AD players (Tau, amyloid precursor, protein, etc). Thus, DYRK1A may be an important therapeutic target to modify the course of Tau and amyloid beta (Aβ) pathologies. Here, we describe EHT 5372 (methyl 9-(2,4-dichlorophenylamino) thiazolo[5,4-f]quinazoline-2-carbimidate), a novel, highly potent (IC50 = 0.22 nM) DYRK1A inhibitor with a high degree of selectivity over 339 kinases. Models in which inhibition of DYRK1A by siRNA reduced and DYRK1A over-expression induced Tau phosphorylation or Aβ production were used. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation at multiple AD-relevant sites in biochemical and cellular assays. EHT 5372 also normalizes both Aβ-induced Tau phosphorylation and DYRK1A-stimulated Aβ production. DYRK1A is thus as a key element of Aβ-mediated Tau hyperphosphorylation, which links Tau and amyloid pathologies. EHT 5372 and other compounds in its class warrant in vivo investigation as a novel, high-potential therapy for AD and other Tau opathies. Inhibition of the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is a new high-potential therapeutic approach for Alzheimer disease. Here we describe EHT 5372, a novel potent and selective DYRK1A inhibitor. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation, Aβ production and Aβ effects on phospho-Tau, including Tau aggregation. PMID:25556849

  6. Role of dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B) in S-phase entry of HPV E7 expressing cells from quiescence

    PubMed Central

    Zhou, Na; Yuan, Shoudao; Wang, Rongchun; Zhang, Weifang; Chen, Jason J.

    2015-01-01

    The high-risk human papillomavirus (HPV) is the causative agent for cervical cancer. The HPV E7 oncogene promotes S-phase entry from quiescent state in the presence of elevated cell cycle inhibitor p27Kip1, a function that may contribute to carcinogenesis. However, the mechanism by which HPV E7 induces quiescent cells to entry into S-phase is not fully understood. Interestingly, we found that Dyrk1B, a dual-specificity kinase and negative regulator of cell proliferation in quiescent cells, was upregulated in E7 expressing cells. Surprisingly and in contrast to what was previously reported, Dyrk1B played a positive role in S-phase entry of quiescent HPV E7 expressing cells. Mechanistically, Dyrk1B contributed to p27 phosphorylation (at serine 10 and threonine 198), which was important for the proliferation of HPV E7 expressing cells. Moreover, Dyrk1B up-regulated HPV E7. Taken together, our studies uncovered a novel function of Dyrk1B in high-risk HPV E7-mediated cell proliferation. Dyrk1B may serve as a target for therapy in HPV-associated cancers. PMID:26307683

  7. Insights into mechanism of pyrido[2,3-d]pyrimidines as DYRK1A inhibitors based on molecular dynamic simulations.

    PubMed

    Li, Jiao Jiao; Tian, Yue Li; Zhai, Hong Lin; Lv, Min; Zhang, Xiao Yun

    2016-08-01

    DYRK1A is characterized by the early development and regulation of neuronal proliferation, and its over expression gives rise to neurological abnormalities. As the promising DYRK1A inhibitors, the binding mechanism between DYRK1A and pyrido[2,3-d]pyrimidines derivatives at molecular level are still veiled. In this article, it was achieved to get the structural insights into pyrido[2,3-d]pyrimidines derivatives as DYRK1A inhibitors by means of comprehensive computational approaches involving molecular docking, molecular dynamics simulation, free energy calculation, and energy decomposition analysis. The calculated energy values were highly consistent with the experimental activities. Based on the individual energy terms analysis, the van der Waals interaction was the major leading force in the DYRK1A-ligand interaction. Lys188 was the important residue that formed the hydrogen bond, which improved the inhibitory activity. Furthermore, four novel inhibitors with higher predicted activity were designed based on the obtained findings and confirmed by molecular simulations. Our study is expected to provide significant drug design strategy for the development of more promising DYRK1A inhibitors. Proteins 2016; 84:1108-1123. © 2016 Wiley Periodicals, Inc. PMID:27119584

  8. DYRK1A in Down syndrome: an oncogene or tumor suppressor?

    PubMed

    Birger, Yehudit; Izraeli, Shai

    2012-03-01

    Children with Down syndrome (DS) have a markedly increased risk of developing acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia compared with that of children without DS. Despite recent breakthroughs, it is not clear which genes on chromosome 21, the chromosome that is trisomic in individuals with DS, cause this predisposition. In this issue of the JCI, Malinge et al. report their loss- and gain-of-function experiments in mouse and human cells that show that increased expression of the kinase encoded by the chromosome 21 gene DYRK1A suppresses the nuclear factor of activated T cells pathway and promotes AMKL. Interestingly, the same protein has been suggested to contribute to the reduced risk of epithelial cancers in adults with DS, leading to the possibility that it could be proleukemic in children and antitumorigenic in adults. PMID:22354166

  9. Overexpression of Dyrk1A Is Implicated in Several Cognitive, Electrophysiological and Neuromorphological Alterations Found in a Mouse Model of Down Syndrome

    PubMed Central

    García-Cerro, Susana; Martínez, Paula; Vidal, Verónica; Corrales, Andrea; Flórez, Jesús; Vidal, Rebeca; Rueda, Noemí; Arbonés, María L.; Martínez-Cué, Carmen

    2014-01-01

    Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/−) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene

  10. Overexpression of Dyrk1A is implicated in several cognitive, electrophysiological and neuromorphological alterations found in a mouse model of Down syndrome.

    PubMed

    García-Cerro, Susana; Martínez, Paula; Vidal, Verónica; Corrales, Andrea; Flórez, Jesús; Vidal, Rebeca; Rueda, Noemí; Arbonés, María L; Martínez-Cué, Carmen

    2014-01-01

    Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/-) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene may

  11. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome.

    PubMed

    Shi, Jianhua; Zhang, Tianyi; Zhou, Chunlei; Chohan, Muhammad Omar; Gu, Xiaosong; Wegiel, Jerzy; Zhou, Jianhua; Hwang, Yu-Wen; Iqbal, Khalid; Grundke-Iqbal, Inge; Gong, Cheng-Xin; Liu, Fei

    2008-10-17

    Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS. PMID:18658135

  12. Recent Advances in the Design, Synthesis, and Biological Evaluation of Selective DYRK1A Inhibitors: A New Avenue for a Disease Modifying Treatment of Alzheimer’s?

    PubMed Central

    2012-01-01

    With 24.3 million people affected in 2005 and an estimated rise to 42.3 million in 2020, dementia is currently a leading unmet medical need and costly burden on public health. Seventy percent of these cases have been attributed to Alzheimer’s disease (AD), a neurodegenerative pathology whose most evident symptom is a progressive decline in cognitive functions. Dual specificity tyrosine phosphorylation regulated kinase-1A (DYRK1A) is important in neuronal development and plays a variety of functional roles within the adult central nervous system. The DYRK1A gene is located within the Down syndrome critical region (DSCR) on human chromosome 21 and current research suggests that overexpression of DYRK1A may be a significant factor leading to cognitive deficits in people with Alzheimer’s disease (AD) and Down syndrome (DS). Currently, treatment options for cognitive deficiencies associated with Down syndrome, as well as Alzheimer’s disease, are extremely limited and represent a major unmet therapeutic need. Small molecule inhibition of DYRK1A activity in the brain may provide an avenue for pharmaceutical intervention of mental impairment associated with AD and other neurodegenerative diseases. We herein review the current state of the art in the development of DYRK1A inhibitors. PMID:23173067

  13. Identification of a DYRK1A Inhibitor that Induces Degradation of the Target Kinase using Co-chaperone CDC37 fused with Luciferase nanoKAZ.

    PubMed

    Sonamoto, Rie; Kii, Isao; Koike, Yuka; Sumida, Yuto; Kato-Sumida, Tomoe; Okuno, Yukiko; Hosoya, Takamitsu; Hagiwara, Masatoshi

    2015-01-01

    The protein kinase family includes attractive targets for drug development. Methods for screening of kinase inhibitors remain largely limited to in vitro catalytic assays. It has been shown that ATP-competitive inhibitors antagonize interaction between the target kinase and kinase-specific co-chaperone CDC37 in living cells. Here we show a cell-based method to screen kinase inhibitors using fusion protein of CDC37 with a mutated catalytic 19-kDa component of Oplophorus luciferase, nanoKAZ (CDC37-nanoKAZ). A dual-specificity kinase DYRK1A, an importance of which has been highlighted in Alzheimer's disease, was targeted in this study. We established 293T cells stably expressing CDC37-nanoKAZ, and analyzed interaction between CDC37-nanoKAZ and DYRK1A. We revealed that DYRK1A interacted with CDC37-nanoKAZ. Importantly, point mutations that affect autophosphorylation strengthened the interaction, thus improving signal/noise ratio of the interaction relative to non-specific binding of CDC37-nanoKAZ. This high signal/noise ratio enabled screening of chemical library that resulted in identification of a potent inhibitor of DYRK1A, named CaNDY. CaNDY induced selective degradation of DYRK1A, and inhibited catalytic activity of recombinant DYRK1A with IC50 value of 7.9 nM by competing with ATP. This method based on a mutant target kinase and a bioluminescence-eliciting co-chaperone CDC37 could be applicable to evaluation and development of inhibitors targeting other kinases. PMID:26234946

  14. Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors.

    PubMed

    Bruel, Amélie; Bénéteau, Romain; Chabanne, Mylène; Lozach, Olivier; Le Guevel, Rémy; Ravache, Myriam; Bénédetti, Hélène; Meijer, Laurent; Logé, Cédric; Robert, Jean-Michel

    2014-11-01

    New pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs were synthesized and their inhibitory activities against DYRK1A, CDK5/p25, GSK3α/β and p110-α isoform of PI3K evaluated using harmine as reference. Both furan-2-yl 10 and pyridin-4-yl 19 from the two different series, exhibited submicromolar IC50 against DYRK1A with no activities against the three other kinases. In addition, compound 10 exhibited antiproliferative activities in the Huh-7, Caco2 and MDA-MB-231 cell lines. PMID:25248682

  15. Wnt Signaling Orchestration with a Small Molecule DYRK Inhibitor Provides Long-Term Xeno-Free Human Pluripotent Cell Expansion

    PubMed Central

    Hasegawa, Kouichi; Yasuda, Shin-ya; Teo, Jia-Ling; Nguyen, Cu; McMillan, Michael; Hsieh, Chih-Lin; Suemori, Hirofumi; Nakatsuji, Norio; Yamamoto, Masashi; Miyabayashi, Tomoyuki; Lutzko, Carolyn; Pera, Martin F.

    2012-01-01

    An optimal culture system for human pluripotent stem cells should be fully defined and free of animal components. To date, most xeno-free culture systems require human feeder cells and/or highly complicated culture media that contain activators of the fibroblast growth factor (FGF) and transforming growth factor-β (TGFβ) signaling pathways, and none provide for replacement of FGF/TGFβ ligands with chemical compounds. The Wnt/β-catenin signaling pathway plays an important role in mouse embryonic stem cells in leukemia inhibitory factor-independent culture; however, the role of Wnt/β-catenin signaling in human pluripotent stem cell is still poorly understood and controversial because of the dual role of Wnts in proliferation and differentiation. Building on our previous investigations of small molecules modulating Wnt/β-catenin signaling in mouse embryonic stem cells, we identified a compound, ID-8, that could support Wnt-induced human embryonic stem cell proliferation and survival without differentiation. Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) is the target of the small molecule ID-8. Its role in human pluripotent cell renewal was confirmed by DYRK knockdown in human embryonic stem cells. Using Wnt and the DYRK inhibitor ID-8, we have developed a novel and simple chemically defined xeno-free culture system that allows for long-term expansion of human pluripotent stem cells without FGF or TGFβ activation. These culture conditions do not include xenobiotic supplements, serum, serum replacement, or albumin. Using this culture system, we have shown that several human pluripotent cell lines maintained pluripotency (>20 passages) and a normal karyotype and still retained the ability to differentiate into derivatives of all three germ layers. This Wnt-dependent culture system should provide a platform for complete replacement of growth factors with chemical compounds. PMID:23197636

  16. DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome

    PubMed Central

    Duchon, Arnaud; Herault, Yann

    2016-01-01

    Down syndrome (DS) is one of the leading causes of intellectual disability, and patients with DS face various health issues, including learning and memory deficits, congenital heart disease, Alzheimer’s disease (AD), leukemia, and cancer, leading to huge medical and social costs. Remarkable advances on DS research have been made in improving cognitive function in mouse models for future therapeutic approaches in patients. Among the different approaches, DYRK1A inhibitors have emerged as promising therapeutics to reduce DS cognitive deficits. DYRK1A is a dual-specificity kinase that is overexpressed in DS and plays a key role in neurogenesis, outgrowth of axons and dendrites, neuronal trafficking and aging. Its pivotal role in the DS phenotype makes it a prime target for the development of therapeutics. Recently, disruption of DYRK1A has been found in Autosomal Dominant Mental Retardation 7 (MRD7), resulting in severe mental deficiency. Recent advances in the development of kinase inhibitors are expected, in the near future, to remove DS from the list of incurable diseases, providing certain conditions such as drug dosage and correct timing for the optimum long-term treatment. In addition the exact molecular and cellular mechanisms that are targeted by the inhibition of DYRK1A are still to be discovered. PMID:27375444

  17. Biomolecular visualization using AVS.

    PubMed

    Duncan, B S; Macke, T J; Olson, A J

    1995-10-01

    Dataflow systems for scientific visualization are becoming increasingly sophisticated in their architecture and functionality. AVS, from Advanced Visual Systems Inc., is a powerful dataflow environment that has been applied to many computation and visualization tasks. An important, yet complex, application area is molecular modeling and biomolecular visualization. Problems in biomolecular visualization tax the capability of dataflow systems because of the diversity of operations that are required and because many operations do not fit neatly into the dataflow paradigm. Here we describe visualization strategies and auxiliary programs developed to enhance the applicability of AVS for molecular modelling. Our visualization strategy is to use general-purpose AVS modules and a small number of chemistry-specific modules. We have developed methods to control AVS using AVS-tool, a programmable interface to the AVS Command Line Interpreter (CLI), and have also developed NAB, a C-like language for writing AVS modules that has extensions for operating on proteins and nucleic acids. This strategy provides a flexible and extensible framework for a wide variety of molecular modeling tasks. PMID:8603055

  18. DYRK1A-mediated phosphorylation of GluN2A at Ser1048 regulates the surface expression and channel activity of GluN1/GluN2A receptors

    PubMed Central

    Grau, Cristina; Arató, Krisztina; Fernández-Fernández, José M.; Valderrama, Aitana; Sindreu, Carlos; Fillat, Cristina; Ferrer, Isidre; de la Luna, Susana; Altafaj, Xavier

    2014-01-01

    N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural development and synaptic plasticity, as well as in neurological disease. Since NMDARs exert their function at the cell surface, their density in the plasma membrane is finely tuned by a plethora of molecules that regulate their production, trafficking, docking and internalization in response to external stimuli. In addition to transcriptional regulation, the density of NMDARs is also influenced by post-translational mechanisms like phosphorylation, a modification that also affects their biophysical properties. We previously described the increased surface expression of GluN1/GluN2A receptors in transgenic mice overexpressing the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), suggesting that DYRK1A regulates NMDARs. Here we have further investigated whether the density and activity of NMDARs were modulated by DYRK1A phosphorylation. Accordingly, we show that endogenous DYRK1A is recruited to GluN2A-containing NMDARs in the adult mouse brain, and we identify a DYRK1A phosphorylation site at Ser1048 of GluN2A, within its intracellular C-terminal domain. Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. Furthermore, GluN2A phosphorylation at Ser1048 increases the current density and potentiates the gating of GluN1/GluN2A receptors. We conclude that DYRK1A is a direct regulator of NMDA receptors and we propose a novel mechanism for the control of NMDAR activity in neurons. PMID:25368549

  19. Functional Interactions between BM88/Cend1, Ran-Binding Protein M and Dyrk1B Kinase Affect Cyclin D1 Levels and Cell Cycle Progression/Exit in Mouse Neuroblastoma Cells

    PubMed Central

    Tsioras, Konstantinos; Papastefanaki, Florentia; Politis, Panagiotis K.; Matsas, Rebecca; Gaitanou, Maria

    2013-01-01

    BM88/Cend1 is a neuronal-lineage specific modulator with a pivotal role in coordination of cell cycle exit and differentiation of neuronal precursors. In the current study we identified the signal transduction scaffolding protein Ran-binding protein M (RanBPM) as a BM88/Cend1 binding partner and showed that BM88/Cend1, RanBPM and the dual specificity tyrosine-phosphorylation regulated kinase 1B (Dyrk1B) are expressed in mouse brain as well as in cultured embryonic cortical neurons while RanBPM can form complexes with either of the two other proteins. To elucidate a potential mechanism involving BM88/Cend1, RanBPM and Dyrk1B in cell cycle progression/exit, we transiently co-expressed these proteins in mouse neuroblastoma Neuro 2a cells. We found that the BM88/Cend1-dependent or Dyrk1B-dependent down-regulation of cyclin D1 is reversed following their functional interaction with RanBPM. More specifically, functional interaction of RanBPM with either BM88/Cend1 or Dyrk1B stabilizes cyclin D1 in the nucleus and promotes 5-bromo-2'-deoxyuridine (BrdU) incorporation as a measure of enhanced cell proliferation. However, the RanBPM-dependent Dyrk1B cytosolic retention and degradation is reverted in the presence of Cend1 resulting in cyclin D1 destabilization. Co-expression of RanBPM with either BM88/Cend1 or Dyrk1B also had a negative effect on Neuro 2a cell differentiation. Our results suggest that functional interactions between BM88/Cend1, RanBPM and Dyrk1B affect the balance between cellular proliferation and differentiation in Neuro 2a cells and indicate that a potentially similar mechanism may influence cell cycle progression/exit and differentiation of neuronal precursors. PMID:24312406

  20. Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis.

    PubMed

    Ori-McKenney, Kassandra M; McKenney, Richard J; Huang, Hector H; Li, Tun; Meltzer, Shan; Jan, Lily Yeh; Vale, Ronald D; Wiita, Arun P; Jan, Yuh Nung

    2016-05-01

    Dendritic arborization patterns are consistent anatomical correlates of genetic disorders such as Down syndrome (DS) and autism spectrum disorders (ASDs). In a screen for abnormal dendrite development, we identified Minibrain (MNB)/DYRK1a, a kinase implicated in DS and ASDs, as a regulator of the microtubule cytoskeleton. We show that MNB is necessary to establish the length and cytoskeletal composition of terminal dendrites by controlling microtubule growth. Altering MNB levels disrupts dendrite morphology and perturbs neuronal electrophysiological activity, resulting in larval mechanosensation defects. Using in vivo and in vitro approaches, we uncover a molecular pathway whereby direct phosphorylation of β-tubulin by MNB inhibits tubulin polymerization, a function that is conserved for mammalian DYRK1a. Our results demonstrate that phosphoregulation of microtubule dynamics by MNB/DYRK1a is critical for dendritic patterning and neuronal function, revealing a previously unidentified mode of posttranslational microtubule regulation in neurons and uncovering a conserved pathway for a DS- and ASD-associated kinase. PMID:27112495

  1. Structural features underlying the selectivity of the kinase inhibitors NBC and dNBC: role of a nitro group that discriminates between CK2 and DYRK1A.

    PubMed

    Sarno, Stefania; Mazzorana, Marco; Traynor, Ryan; Ruzzene, Maria; Cozza, Giorgio; Pagano, Mario A; Meggio, Flavio; Zagotto, Giuseppe; Battistutta, Roberto; Pinna, Lorenzo A

    2012-02-01

    8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as "denitro NBC", dNBC), the inhibitory power toward CK2 is almost entirely lost (IC(50) > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC(50) values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68 and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A by dNBC. PMID:21720886

  2. The GBA, DYRK1A and MS4A6A polymorphisms influence the age at onset of Chinese Parkinson patients.

    PubMed

    Fan, Kuan; Tang, Bei-Sha; Wang, Ya-Qin; Kang, Ji-Feng; Li, Kai; Liu, Zhen-Hua; Sun, Qi-Ying; Xu, Qian; Yan, Xin-Xiang; Guo, Ji-Feng

    2016-05-16

    Parkinson's disease (PD) is known as the most common neurodegenerative disease after Alzheimer's disease (AD). The precise pathogenic mechanism of PD remains unclear, but genetic and environmental factors are widely recognized to be associated with it. Although many associated genes have been discovered, they account for only a few PD patients. Recently, there are growing evidences indicating that patients with PD and AD share similarities in clinical features, pathology and genetic risks. However, no study has been conducted on the relations between AD associated genes and age at onset (AAO) of PD. In this study, we have detected 14 single nucleotide polymorphisms (SNPs) in 9 AD genome wide association studies top hit genes and 4 SNPs in 4 PD-cognitive impairment related genes among 297 Chinese PD patients. Through the linear regression analysis, we identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier AAO in PD patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. This is the first report of significant associations of DYRK1A and MS4A6A SNPs and the AAO of PD. On account of their effects both in AD and PD, it is indicated that AD and PD possibly share some common pathways. PMID:27085534

  3. Arctic Visiting Speakers Series (AVS)

    NASA Astrophysics Data System (ADS)

    Fox, S. E.; Griswold, J.

    2011-12-01

    The Arctic Visiting Speakers (AVS) Series funds researchers and other arctic experts to travel and share their knowledge in communities where they might not otherwise connect. Speakers cover a wide range of arctic research topics and can address a variety of audiences including K-12 students, graduate and undergraduate students, and the general public. Host applications are accepted on an on-going basis, depending on funding availability. Applications need to be submitted at least 1 month prior to the expected tour dates. Interested hosts can choose speakers from an online Speakers Bureau or invite a speaker of their choice. Preference is given to individuals and organizations to host speakers that reach a broad audience and the general public. AVS tours are encouraged to span several days, allowing ample time for interactions with faculty, students, local media, and community members. Applications for both domestic and international visits will be considered. Applications for international visits should involve participation of more than one host organization and must include either a US-based speaker or a US-based organization. This is a small but important program that educates the public about Arctic issues. There have been 27 tours since 2007 that have impacted communities across the globe including: Gatineau, Quebec Canada; St. Petersburg, Russia; Piscataway, New Jersey; Cordova, Alaska; Nuuk, Greenland; Elizabethtown, Pennsylvania; Oslo, Norway; Inari, Finland; Borgarnes, Iceland; San Francisco, California and Wolcott, Vermont to name a few. Tours have included lectures to K-12 schools, college and university students, tribal organizations, Boy Scout troops, science center and museum patrons, and the general public. There are approximately 300 attendees enjoying each AVS tour, roughly 4100 people have been reached since 2007. The expectations for each tour are extremely manageable. Hosts must submit a schedule of events and a tour summary to be posted online

  4. NGF Upregulates the Plasminogen Activation Inhibitor-1 in Neurons via the Calcineurin/NFAT Pathway and the Down Syndrome-Related Proteins DYRK1A and RCAN1 Attenuate This Effect

    PubMed Central

    Stefos, Georgios C.; Soppa, Ulf; Dierssen, Mara; Becker, Walter

    2013-01-01

    Background Plasminogen activator inhibitor 1 (PAI-1) is a key regulator of the plasminogen activation system. Although several lines of evidence support a significant role of PAI-1 in the brain, the regulation of its expression in neurons is poorly understood. In the present study we tested the hypothesis that NGF induces the upregulation of PAI-1 via the calcineurin/nuclear factor of activated T cells (NFAT) pathway and analysed whether the overexpression of the Down syndrome-related proteins DYRK1A and RCAN1 modulated the effect of NGF on PAI-1 expression. Results NGF upregulated PAI-1 mRNA levels in primary mouse hippocampal neurons cultured for 3 days in vitro and in the rat pheochromocytoma cell line PC12. Reporter gene assays revealed that NGF activated the calcineurin/NFAT pathway in PC12 cells. Induction of PAI-1 by NGF was sensitive to the calcineurin inhibitor FK506 and the specific inhibition of NFAT activation by the cell permeable VIVIT peptide. Activation of calcineurin/NFAT signalling through other stimuli resulted in a much weaker induction of PAI-1 expression, suggesting that other NGF-induced pathways are involved in PAI-1 upregulation. Overexpression of either DYRK1A or RCAN1 negatively regulated NFAT-dependent transcriptional activity and reduced the upregulation of PAI-1 levels by NGF. Conclusion The present results show that the calcineurin/NFAT pathway mediates the upregulation of PAI-1 by NGF. The negative effect of DYRK1A and RCAN1 overexpression on NGF signal transduction in neural cells may contribute to the altered neurodevelopment and brain function in Down syndrome. PMID:23825664

  5. Pharmacokinetics of avenanthramides (AV) from AV-enriched malted oats in healthy older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avenanthramides (AV) are a unique group of phytochemicals found in oat bran. In vitro studies show both purified AV and concentrated oat AV mixtures have anti-atherogenic and anti-inflammatory activity, suggesting they may have similar effects in vivo if they are sufficiently bioavailable. The bioav...

  6. Outcomes of AV Fistulas and AV Grafts after Interventional Stent-Graft Deployment in Haemodialysis Patients

    SciTech Connect

    Schmelter, Christopher Raab, Udo; Lazarus, Friedrich; Ruppert, Volker; Vorwerk, Dierk

    2015-08-15

    PurposeThe study was designed to assess outcomes of arteriovenous (AV) accesses after interventional stent-graft deployment in haemodialysis patients.Materials and Methods63 haemodialysis patients with 66 AV fistulas and AV grafts were treated by interventional stent-graft deployment from 2006 to 2012 at our hospital. Data of these patients were retrospectively analysed for location of deployed stent-grafts, occurrence and location of (re-)stenosis and (re-)thrombosis. Complex stenosis was the most frequent indication for stent-graft deployment (45.5 %), followed by complications of angioplasty with vessel rupture or dissection (31.8 %).ResultsA high rate of procedural success was achieved (98.5 %). The most frequent location of the deployed stent-graft was the draining vein (66.7 %). Stent-graft deployment was more frequent in AV grafts than in AV fistulas. Primary patency was 45.5 % at 6 month, 31.3 % at 12 month and 19.2 % at 24 month. Primary patency was significantly better for AV fistulas than for AV grafts with deployed stent-grafts. Patency of the deployed stent-graft was much better than overall AV access primary patency with deployed stent-graft. Re-stenosis with thrombosis was the most frequent indication for re-intervention. Most frequent location of re-stenosis was the draining vein (37.1 %), followed by stenosis at the AV access (29.5 %) and the deployed stent-graft (23.5 %).ConclusionRe-stenosis and re-thrombosis remain frequent in AV fistulas and AV grafts in haemodialysis patients despite stent-graft deployment. Re-stenosis of the deployed stent-graft is, only in the minority of the cases, responsible for AV access dysfunction.

  7. Overview of AVS-video: tools, performance and complexity

    NASA Astrophysics Data System (ADS)

    Yu, Lu; Yi, Feng; Dong, Jie; Zhang, Cixun

    2005-07-01

    Audio Video coding Standard (AVS) is established by the Working Group of China in the same name. AVS-video is an application driven coding standard. AVS Part 2 targets to high-definition digital video broadcasting and high-density storage media and AVS Part 7 targets to low complexity, low picture resolution mobility applications. Integer transform, intra and inter-picture prediction, in-loop deblocking filter and context-based two dimensional variable length coding are the major compression tools in AVS-video, which are well-tuned for target applications. It achieves similar performance to H.264/AVC with lower cost.

  8. Visualization on massively parallel computers using CM/AVS

    SciTech Connect

    Krogh, M.F.; Hansen, C.D.

    1993-09-01

    CM/AVS is a visualization environment for the massively parallel CM-5 from Thinking Machines. It provides a backend to the standard commercially available AVS visualization product. At the Advanced Computing Laboratory at Los Alamos National Laboratory, we have been experimenting and utilizing this software within our visualization environment. This paper describes our experiences with CM/AVS. The conclusions reached are applicable to any implimentation of visualization software within a massively parallel computing environment.

  9. Pollen transmission of asparagus virus 2 (AV-2) may facilitate mixed infection by two AV-2 isolates in asparagus plants.

    PubMed

    Kawamura, Ryusuke; Shimura, Hanako; Mochizuki, Tomofumi; Ohki, Satoshi T; Masuta, Chikara

    2014-09-01

    Asparagus virus 2 (AV-2) is a member of the genus Ilarvirus and thought to induce the asparagus decline syndrome. AV-2 is known to be transmitted by seed, and the possibility of pollen transmission was proposed 25 years ago but not verified. In AV-2 sequence analyses, we have unexpectedly found mixed infection by two distinct AV-2 isolates in two asparagus plants. Because mixed infections by two related viruses are normally prevented by cross protection, we suspected that pollen transmission of AV-2 is involved in mixed infection. Immunohistochemical analyses and in situ hybridization using AV-2-infected tobacco plants revealed that AV-2 was localized in the meristem and associated with pollen grains. To experimentally produce a mixed infection via pollen transmission, two Nicotiana benthamiana plants that were infected with each of two AV-2 isolates were crossed. Derived cleaved-amplified polymorphic sequence analysis identified each AV-2 isolate in the progeny seedlings, suggesting that pollen transmission could indeed result in a mixed infection, at least in N. benthamiana. PMID:25116643

  10. AV Rising: Demand, Budgets, and Circulation Are All Up.

    ERIC Educational Resources Information Center

    Oder, Norman

    1998-01-01

    A survey of 486 public libraries found that audiovisual (AV) budgets have increased 53% in the last five years. Provides data on average size of AV collections; budget break downs; circulation; audiobook, video, and music CD purchases; popular authors and titles in abridged and unabridged audiobooks; and problems with audiobook, video, and music…

  11. AV-95 Sun Devil: High-Speed Military Rotorcraft

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The AV-95 Sun Devil must combine helicopter capabilities, such as vertical takeoff and landings (VTOL) and rotor-powered flight, along with long-duration cruise and high-speed dash capabilities unobtainable by conventional helicopters. To be able to perform both tasks, and perform them well, the AV-95 Sun Devil design incorporates several unconventional devices; the AV-95 uses two convertible turbofan engines, able to provide both shaft power for the main rotor and tall fan as well as jet thrust either separately or simultaneously. Other devices used for the AV-95 include a variable diameter main rotor and a blown flap. In helicopter mode, the AV-95 Sun Devil performs like a winged helicopter. The addition of wings to an attack helicopter results in two significant advantages. First, the addition of wings makes a helicopter more maneuverable than a wingless, but otherwise similar helicopter. Second, since the wings produce lift, rotor stall and compressibility effects can be significantly delayed at high tip velocities. In fixed-wing mode, the main rotor is completely off-loaded but slightly powered, and the rotor diameter has been minimized. The AV-95 Sun Devil has many advantages over other VTOL aircraft. The conversion process is simple and fast; conversion does not make the AV-95 vulnerable to enemy attack during conversion such as a tilt-wing or a tilt-rotor. Stop-rotor aircraft and a stowed rotor aircraft require heavy breaking of the rotor for conversion; this adds time for conversion and weight to the aircraft. Because the AV-95 never stops the rotor in flight, much weight is spared, and conversion is much simpler and faster.

  12. Overdrive suppression of implanted pacemakers in patients with AV block.

    PubMed Central

    Grendahl, H; Miller, M; Kjekshus, J

    1978-01-01

    Patients being permanently paced for symptomatic AV block were studied by overdrive suppression of the QRS-inhibited pacemaker, in order to observe the underlying heart rhythm. The chest wall stimulation method was used. In complete AV block the escape rhythm recovery time proved highly reproducible on repeated testing on the same day, and in many patients remained so over months or years. Occasionally, a doubling of the escape rhythm recovery time was seen, suggesting initial exit block of the escape focus. Resetting of the escape rhythm usually followed an exponential curve until stabilisation after about 3 minutes. An early escape rhythm with a recovery time of less than 4 seconds was found on every occasion in 21 of 58 patients with complete AV block, and inconstantly in 23 more; in 14 it was never observed. Accidental pacing failure was seen in 15 patients. The overdrive suppression test was helpful in selecting pacemaker dependent patients. PMID:637960

  13. Molecular cloning, characterization and tissue distribution of two ostrich β-defensins: AvBD2 and AvBD7.

    PubMed

    Lu, Shun; Peng, Kemei; Gao, Qishuang; Xiang, Min; Liu, Huazhen; Song, Hui; Yang, Keli; Huang, Haibo; Xiao, Ke

    2014-11-15

    Avian β-defensins (AvBDs) are a family of small antimicrobial peptides that play important roles in the innate immunity of birds. Herein, we report on two new ostrich AvBD genes, AvBD2 and AvBD7, which were isolated from the bone marrow of ostriches (Struthio camelus). The coding regions of ostrich AvBD2 and AvBD7 comprised 195 bp and 201bp, which encoded 64 and 66 amino acids, respectively. Homology analysis showed that ostrich AvBD2 had the highest similarity (up to 86%) with the swan goose (Anser cygnoides) AvBD2, while ostrich AvBD7 shared the highest similarity (up to 81%) with chicken AvBD7. Analysis of the codon-usage bias showed that the two ostrich AvBDs had different codon-usage patterns from other AvBDs. The two synthetic AvBD peptides exhibited antibacterial activities against both Gram-positive and Gram-negative bacteria, and these activities decreased significantly in the presence of 100mM NaCl (P<0.01). Real-time reverse transcription-polymerase chain reaction analysis showed that AvBD2 and AvBD7 were widely expressed at different levels in 17 different tissues. This is the first report of the nucleotide sequences of ostrich AvBDs. Further investigations of these two AvBDs may help us to gain new insights into the immune defense system of the ostrich and to make subsequent therapeutic use of ostrich defensins. PMID:25127671

  14. Genomic Analysis of Broad-Host-Range Enterobacteriophage Av-05

    PubMed Central

    Amarillas, Luis; López-Cuevas, Osvaldo; León-Félix, Josefina; Castro-del Campo, Nohelia; Gerba, Charles P.

    2015-01-01

    Lytic bacteriophages have reemerged as an alternative for the control of pathogenic bacteria. However, the effective use of phage relies on appropriate genomic characterization. In this study, we report the genome of bacteriophage Av-05 and its sequence analysis, which has strong lytic activity against Escherichia coli O157:H7 strains and several Salmonella serotypes. The analysis revealed that the phage Av-05 genome consists of 120,938 bp, containing 209 putative open reading frames (ORFs) and 9 tRNAs. PMID:26067947

  15. Assessment of the NASA AvSTAR Project Plan

    NASA Technical Reports Server (NTRS)

    Ulrey, Michael L.; Haraldsdottir, Aslaug; Berge, Matthew E.; Hopperstad, Craig A.; Schwab, Robert W.

    2004-01-01

    This report is a preliminary evaluation of NASA's proposed Aviation System Technology Advanced Research (AvSTAR) Program during the early stages of its definition, in the first half of the year 2001. This evaluation focuses on how well the program goals address the needs of the U.S. National Airspace System, the technical feasibility of the program goals, and the logistical feasibility of the program plan. This report also provides recommendations on how the AvSTAR program could be strengthened and improved. This document has two appendices.

  16. 45 CFR 156.135 - AV calculation for determining level of coverage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... calculate the AV of a health plan, the issuer must use the AV Calculator developed and made available by HHS for the given benefit year. (b) Exception to the use of the AV Calculator. If a health plan's design is not compatible with the AV Calculator, the issuer must meet the following: (1) Submit...

  17. IG/OG program for generating and displaying NASTRAN input and output data

    NASA Technical Reports Server (NTRS)

    Mishima, R.; Myojin, A.

    1978-01-01

    A software system was provided for structural analysis fields using NASTRAN. The HITAC users in Japan can use IG/OG (input generator/output generator) program for NASTRAN. The IG/OG saves time required to make a structure analysis for interpreting NASTRAN results.

  18. 2008 OG19: a highly elongated Trans-Neptunian object

    NASA Astrophysics Data System (ADS)

    Fernández-Valenzuela, E.; Ortiz, J. L.; Duffard, R.; Santos-Sanz, P.; Morales, N.

    2016-03-01

    From two observing runs during the 2014 summer at the Calar Alto Observatory in Almería (Spain) and at the Sierra Nevada Observatory in Granada (Spain), we were able to derive CCD photometry of the Trans-Neptunian object 2008 OG19. We analysed the time series and obtained a double-peaked light curve with a peak-to-valley amplitude of 0.437 ± 0.011 mag and a rotational period of 8.727 ± 0.003 h. This implies that this object is very elongated, closely resembling the case of Varuna. The photometry also allowed us to obtain an absolute magnitude in the R band of 4.39 ± 0.07 mag. From this result, we estimated an equivalent diameter of 2008 OG19 of 619^{+56}_{-113} km using an average albedo for scattered disc objects. Finally, we interpreted the results under the assumption of hydrostatic equilibrium and found a lower limit for the density of 544^{+42}_{-4} kg m-3. However, a more likely density is 609 ± 4 kg m-3 using an aspect angle of 60°, which corresponds to the most likely configuration for the spin axis with respect to the observer assuming random orientations.

  19. A new video surveillance system based on AVS

    NASA Astrophysics Data System (ADS)

    Wu, Tingwan; Chen, Chaofeng

    2010-08-01

    In this paper, we analyzed the key technology of current video surveillance systems, compared the performances, prices, and the prospects between the H.264 and AVS codec technologies, studied the advantages and disadvantages of different designs, particularly the data transmission, terminal reception facilities, decoding and demonstration of the video surveillance systems. We have optimized the core algorithms such as intra prediction, inter prediction and fast motion estimation, and performed some relevant simulations for these algorithms. Experimental results show that these new algorithms simplified the design and speeded up the compression rate. From the simulation results, we proposed a new video surveillance system based on AVS. The program reached low price, high efficiency, fast, high image quality, convenient application and operation, greatly improved the current video surveillance systems.

  20. Toward robust AV conferencing on next-generation networks

    NASA Astrophysics Data System (ADS)

    Liu, Haining; Cheng, Liang; El Zarki, Magda

    2005-01-01

    In order to enable a truly pervasive computing environment, next generation networks (including B3G and 4G) will merge the broadband wireless and wireline networking infrastructure. However, due to the tremendous complexity in administration and the unreliability of the wireless channel, provision of hard-guarantees for services on such networks will not happen in the foreseeable future. This consequently makes it particularly challenging to offer viable AV conferencing services due to their stringent synchronization, delay and data fidelity requirements. We propose in this paper a robust application-level solution for wireless mobile AV conferencing on B3G/4G networks. Expecting no special treatment from the network, we apply a novel adaptive delay and synchronization control mechanism to maintain the synchronization and reduce the latency as much as possible. We also employ a robust video coding technique that has better error-resilience capability. We investigate the performance of the proposed solution through simulations using a three-state hidden Markov chain as the generic end-to-end transport channel model. The results show that our scheme yields tight synchronization performance, relatively low end-to-end latency and satisfactory presentation quality. The scheme successfully provides a fairly robust AV conferencing service.

  1. Toward robust AV conferencing on next-generation networks

    NASA Astrophysics Data System (ADS)

    Liu, Haining; Cheng, Liang; El Zarki, Magda

    2004-12-01

    In order to enable a truly pervasive computing environment, next generation networks (including B3G and 4G) will merge the broadband wireless and wireline networking infrastructure. However, due to the tremendous complexity in administration and the unreliability of the wireless channel, provision of hard-guarantees for services on such networks will not happen in the foreseeable future. This consequently makes it particularly challenging to offer viable AV conferencing services due to their stringent synchronization, delay and data fidelity requirements. We propose in this paper a robust application-level solution for wireless mobile AV conferencing on B3G/4G networks. Expecting no special treatment from the network, we apply a novel adaptive delay and synchronization control mechanism to maintain the synchronization and reduce the latency as much as possible. We also employ a robust video coding technique that has better error-resilience capability. We investigate the performance of the proposed solution through simulations using a three-state hidden Markov chain as the generic end-to-end transport channel model. The results show that our scheme yields tight synchronization performance, relatively low end-to-end latency and satisfactory presentation quality. The scheme successfully provides a fairly robust AV conferencing service.

  2. Differential expression of MYB gene (OgMYB1) determines color patterning in floral tissue of Oncidium Gower Ramsey.

    PubMed

    Chiou, Chung-Yi; Yeh, Kai-Wun

    2008-03-01

    The yellow coloration pattern in Oncidium floral lip associated with red sepal and petal tissues is an ideal model to study coordinate regulation of anthocyanin synthesis. In this study, chromatography analysis revealed that the red coloration in floral tissues was composed of malvidin-3-O-galactoside, peonidin-3-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3-O-glucoside compounds. By contrary, these pigments were not detected in yellow lip tissue. Four key genes involved in anthocyanin biosynthetic pathway, i.e. chalcone synthase (OgCHS), chalcone isomerase (OgCHI), dihydroflavonol 4-reductase (OgDFR) and anthocyanidin synthase (OgANS) were isolated and their expression patterns were characterized. Northern blot analysis confirmed that although they are active during floral development, OgCHI and OgDFR genes are specifically down-regulated in yellow lip tissue. Bombardment with OgCHI and OgDFR genes into lip tissue driven by a flower-specific promoter, Pchrc (chromoplast-specific carotenoid-associated gene), demonstrated that transient expression of these two genes resulted in anthocyanin production in yellow lip. Further analysis of a R2R3 MYB transcription factor, OgMYB1, revealed that although it is actively expressed during floral development, it is not expressed in yellow lip tissue. Transient expression of OgMYB1 in lip tissues by bombardment can also induce formation of red pigments through the activation of OgCHI and OgDFR transcription. These results demonstrate that differential expression of OgMYB1 is critical to determine the color pattern of floral organ in Oncidium Gower Ramsey. PMID:18161007

  3. A case of reversible third-degree AV block due to Lyme carditis.

    PubMed

    Timmer, Stefan A J; Boswijk, Dirk J; Kimman, Geert P; Germans, Tjeerd

    2016-01-01

    The most common manifestation of Lyme carditis is a varying degree of atrioventricular (AV) conduction block. This case describes a 45-year-old male with third-degree AV block due to Lyme carditis. Treatment with intravenous antibiotics resulted in complete normalization of AV conduction, thereby averting permanent pacemaker implantation. PMID:27215649

  4. Artificial vision support system (AVS(2)) for improved prosthetic vision.

    PubMed

    Fink, Wolfgang; Tarbell, Mark A

    2014-11-01

    State-of-the-art and upcoming camera-driven, implanted artificial vision systems provide only tens to hundreds of electrodes, affording only limited visual perception for blind subjects. Therefore, real time image processing is crucial to enhance and optimize this limited perception. Since tens or hundreds of pixels/electrodes allow only for a very crude approximation of the typically megapixel optical resolution of the external camera image feed, the preservation and enhancement of contrast differences and transitions, such as edges, are especially important compared to picture details such as object texture. An Artificial Vision Support System (AVS(2)) is devised that displays the captured video stream in a pixelation conforming to the dimension of the epi-retinal implant electrode array. AVS(2), using efficient image processing modules, modifies the captured video stream in real time, enhancing 'present but hidden' objects to overcome inadequacies or extremes in the camera imagery. As a result, visual prosthesis carriers may now be able to discern such objects in their 'field-of-view', thus enabling mobility in environments that would otherwise be too hazardous to navigate. The image processing modules can be engaged repeatedly in a user-defined order, which is a unique capability. AVS(2) is directly applicable to any artificial vision system that is based on an imaging modality (video, infrared, sound, ultrasound, microwave, radar, etc.) as the first step in the stimulation/processing cascade, such as: retinal implants (i.e. epi-retinal, sub-retinal, suprachoroidal), optic nerve implants, cortical implants, electric tongue stimulators, or tactile stimulators. PMID:25286349

  5. First Aviation System Technology Advanced Research (AvSTAR) Workshop

    NASA Technical Reports Server (NTRS)

    Denery, Dallas G. (Editor); Weathers, Del W. (Editor); Rosen, Robert (Technical Monitor); Edwards, Tom (Technical Monitor)

    2001-01-01

    This Conference Proceedings documents the results of a two-day NASA/FAA/Industry workshop that was held at the NASA Ames Research Center, located at Moffett Field, CA, on September 21-22, 2000. The purpose of the workshop was to bring together a representative cross section of leaders in air traffic management, from industry. FAA, and academia, to assist in defining the requirements for a new research effort, referred to as AvSTAR Aviation Systems Technology Advanced Research). The Conference Proceedings includes the individual presentation, and summarizes the workshop discussions and recommendations.

  6. Harrier III-AV8B with a modern engine

    NASA Technical Reports Server (NTRS)

    Wilson, S. B., III; Wurts, J. M.

    1985-01-01

    The paper examines the application of a 26, 156-lb thrust engine (which is 30 percent more thrust than the short-lift dry rating on the F402-RR-406 Pegasus engine) to an AV-8B aircraft. This modern engine has 30 percent more thrust than the F402-RR-406 Pegasus engine with no increase in engine weight; the weight is assumed to be constant for both engines. The paper focuses on the benefit to the AV-8B in increasing short takeoff gross weight and vertical landing weight. A second comparison is made between the bigger engine with the existing thrust-versus-SFC curve, and a 10 percent lower SFC curve. The notion of a modern engine with 10 percent lower SFC and 30 percent more thrust for the same size and weight is presented as a hypothesis, and is not supported by discussing engine technology. There are no engine data or technical discussion as to how the modern engine is constructed or which manufacturer could build it. The performance estimates are generated by ACSYNT, a NASA developed computer code that is available to U.S. industry and has been reported on in a number of other publications.

  7. UNIPASS for AvSP? A Broader View

    NASA Technical Reports Server (NTRS)

    Wu, N. Eva

    2001-01-01

    UNIPASS is a general-purpose probabilistic computer program consisting of three major modules, including preprocessor, solver and postprocessor. UNIPASS contains a user-friendly Graphical User Interface (GUI), numerous state-of-the-art probabilistic analysis techniques, a large library of statistical distributions and a function module with a large library of support functions that can easily define any complex limit-state function in a scripting FORTRAN-like syntax format. Its inverse probability analysis and sensitivities analysis capabilities make it a powerful design aid in any product cycle. Its precise numerical analysis engine is accurate enough to push the failure probabilities of a design to well below 10 (exp -50). UNIPASS is equipped with advanced artificial intelligence that is designed to handle systems with an essentially unlimited number of random variables with ease and efficiency. Its modular arrangement allows you to tailor an analysis to the desired level of accuracy and efficiency. The depth and comprehensiveness of UNIPASS are built upon the decades of experience and expertise of industry leaders including Boeing Aircraft, NASA and the DoD. Its rich content also makes UNIPASS a valuable instructional tool for random processes and probabilistic mechanics. The topics include: 1) Reliability in AvSP; 2) Role of UNIPASS in AvSP; and 3) Examples. This paper is in viewgraph form.

  8. AV control system which makes use of environment stabilizations

    NASA Astrophysics Data System (ADS)

    Stojanov, Georgi; Bozinovski, Stevo; Bozinovska, Liljana

    1997-01-01

    In the present paper we propose a new, biologically inspired conceptual scheme for introducing parallelism, redundancy and learning in control systems for autonomous vehicles (AV). AV are regarded as a special class of autonomous agents (AA). Most generally stated, an AA is defined with the set of its percepts (S), the set of its elementary actions (A), and its internal structure. Within our scheme expectation is the key concept, and an agent is said to be aware of its environment if it can anticipate the effects of the actions (A) it applies in particular situations (S). If the environment stabilizes for awhile, the effects of application of a particular action will remain same for particular situation. We can take advantage of this fact and avoid recomputation of the optical action in that situation by applying instead, the action generated by the stored anticipations for that situation. In the introduction we give a brief overview of the present AA architectures in the domain of autonomous vehicles and outline the basics of our architecture. In the next section the expecting agent is described in more details. The last section is devoted to an example of implementation of this scheme within the domain of obstacle avoiding path finding autonomous vehicles control. The implementation details and the simulation results of three experiments are discussed.

  9. Spinal dural AV fistula: an unusual cause of chest pain

    PubMed Central

    Bioh, Gabriel; Bogle, Richard

    2014-01-01

    A 22 -year-old man presented with 6 months of sudden onset, incapacitating, left-sided chest pain occurring 1–2 times a week. The severity of the pain caused loss of consciousness several times leading to multiple fractures. Investigation with echocardiogram, exercise tolerance test, Holter monitor, chest X-ray and V/Q scan revealed no abnormality as did EEG and 48 h video telemetry. MRI of the thoracic and lumbar spine showed a spinal dural arteriovenous fistula (SDAVF) at the level of T6, confirmed on angiogram. The patient underwent division of the left T6 AV fistula. Following the operation, the patient has been completely pain free. Our patient, presenting in his early 20s does not fit the usual age demographic for SDAVF. A second atypical feature is his presentation with chest pain alone and no neurological symptoms. This case represents a rare presentation of SDAVF. PMID:24532234

  10. A novel influenza virus neuraminidase inhibitor AV5027.

    PubMed

    Ivachtchenko, Alexandre V; Ivanenkov, Yan A; Mitkin, Oleg D; Yamanushkin, Pavel M; Bichko, Vadim V; Leneva, Irina A; Borisova, Olga V

    2013-10-24

    A medium-sized focused library of novel Oseltamivir structural analogues with promising antiviral activity was successfully synthesized using a combinatorial approach. The synthesized compounds were then thoroughly evaluated in neuraminidase- and cell-based assays. As a result, (3R,4R,5S)-4-(2,2-difluoroacetylamino)-5-amino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid (AV5027) was identified as novel Hit-compound with picomolar potency. QSAR analysis was carried out based on the obtained biological data. Computational modeling was performed using a 3D-molecular docking approach and classical regression analysis. The developed integral model demonstrated a sufficient prediction accuracy and tolerance to evaluate compounds based on their potential activity against neuraminidase (NA) at least within the scaffold. Several compounds from the series can be reasonably regarded as promising anti-influenza drug-candidates. PMID:24513312

  11. Developing a computational model of human hand kinetics using AVS

    SciTech Connect

    Abramowitz, Mark S.

    1996-05-01

    As part of an ongoing effort to develop a finite element model of the human hand at the Institute for Scientific Computing Research (ISCR), this project extended existing computational tools for analyzing and visualizing hand kinetics. These tools employ a commercial, scientific visualization package called AVS. FORTRAN and C code, originally written by David Giurintano of the Gillis W. Long Hansen`s Disease Center, was ported to a different computing platform, debugged, and documented. Usability features were added and the code was made more modular and readable. When the code is used to visualize bone movement and tendon paths for the thumb, graphical output is consistent with expected results. However, numerical values for forces and moments at the thumb joints do not yet appear to be accurate enough to be included in ISCR`s finite element model. Future work includes debugging the parts of the code that calculate forces and moments and verifying the correctness of these values.

  12. TIME VARIATION OF AV AND RV FOR TYPE Ia SUPERNOVAE BEHIND INTERSTELLAR DUST

    NASA Astrophysics Data System (ADS)

    Huang, Xiaosheng; Biederman, M.; Herger, B.; Aldering, G. S.

    2014-01-01

    TIME VARIATION OF AV AND RV FOR TYPE Ia SUPERNOVAE BEHIND NON-UNIFORM INTERSTELLAR DUST ABSTRACT We investigate the time variation of the visual extinction, AV, and the total-to-selective extinction ratio, RV, resulting from interstellar dust in front of an expanding photospheric disk of a type Ia supernova (SN Ia). We simulate interstellar dust clouds according to a power law power spectrum and produce extinction maps that either follow a pseudo-Gaussian distribution or a lognormal distribution. The RV maps are produced through a correlation between AV and RV. With maps of AV and RV generated in each case (pseudo-Gaussian and lognormal), we then compute the effective AV and RV for a SN as its photospheric disk expands behind the dust screen. We find for a small percentage of SNe the AV and RV values can vary by a large factor from day to day in the first 40 days after explosion.

  13. An uncommon case of spontaneous conversion from AV re-entry tachycardia to AV nodal re-entry tachycardia in a patient with dual tachycardia

    PubMed Central

    Zeljković, Ivan; Benko, Ivica; Manola, Šime; Radeljić, Vjekoslav; Pavlović, Nikola

    2016-01-01

    We report the case of a 46-year old patient in whom an electrophysiology study (EP) was performed due to paroxysmal supraventricular tachycardia documented in 12-lead ECG. During the EP study, supraventricular tachycardia was induced easily and it corresponded to orthodromic AV reentry tachycardia (AVRT) using a concealed left free wall accessory pathway. However, during the study AVRT spontaneously and repeatedly converted to the typical slow-fast AV node reentry tachycardia (AVNRT). Both accessory and AV nodal slow pathways were ablated, due to the finding that both AVRT and AVNRT were independently inducible during the EP study. PMID:27134441

  14. What Engages Students in MetaL-FrOG? A Triarchy Perspective on Meta-Cognitive Learning

    ERIC Educational Resources Information Center

    Fa, Ng Sen; Hussin, Firuz Hussin

    2008-01-01

    This paper presents the central ideas of a grounded theory research by the name of Triarchy Perspective on Metacognitive Learning in Free Online Groups, or "TriP on MetaL-FrOG" in short. The research setting was online learning community on the platform of Free Online Group web (FrOG) intended for post-graduate students. The research…

  15. Nisin-Triggered Activity of Lys44, the Secreted Endolysin from Oenococcus oeni Phage fOg44▿

    PubMed Central

    Nascimento, João Gil; Guerreiro-Pereira, Maria Carolina; Costa, Sérgio Fernandes; São-José, Carlos; Santos, Mário Almeida

    2008-01-01

    The intrinsic resistance of Oenococcus oeni cells to the secreted endolysin from oenophage fOg44 (Lys44) was investigated. Experiments with several antimicrobials support the hypothesis that the full activity of Lys44 requires sudden ion-nonspecific dissipation of the proton motive force, an event undertaken by the fOg44 holin in the phage infection context. PMID:17981964

  16. Development of a Serological Assay for the Sea Lion (Zalophus californianus) Anellovirus, ZcAV.

    PubMed

    Fahsbender, Elizabeth; Rosario, Karyna; Cannon, John P; Gulland, Frances; Dishaw, Larry J; Breitbart, Mya

    2015-01-01

    New diseases in marine animals are emerging at an increasing rate, yet methodological limitations hinder characterization of viral infections. Viral metagenomics is an effective method for identifying novel viruses in diseased animals; however, determining virus pathogenesis remains a challenge. A novel anellovirus (Zalophus californianus anellovirus, ZcAV) was recently reported in the lungs of captive California sea lions involved in a mortality event. ZcAV was not detected by PCR in the blood of these animals, creating the inability to assess the prevalence of ZcAV in live sea lions. This study developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to ZcAV in sea lion serum. To assess ZcAV prevalence, paired serum and lung samples (n = 96) from wild sea lions that stranded along the California coast were tested through ELISA and PCR, respectively. Over 50% of the samples tested positive for ZcAV by ELISA (34%), PCR (29%), or both (11%) assays. ZcAV is prevalent in stranded wild sea lion populations and results suggest that PCR assays alone may grossly underestimate ZcAV exposure. This ELISA provides a tool for testing live sea lions for ZcAV exposure and is valuable for subsequent studies evaluating the potential pathogenicity of this anellovirus. PMID:25965294

  17. Development of a Serological Assay for the Sea Lion (Zalophus californianus) Anellovirus, ZcAV

    PubMed Central

    Fahsbender, Elizabeth; Rosario, Karyna; Cannon, John P.; Gulland, Frances; Dishaw, Larry J.; Breitbart, Mya

    2015-01-01

    New diseases in marine animals are emerging at an increasing rate, yet methodological limitations hinder characterization of viral infections. Viral metagenomics is an effective method for identifying novel viruses in diseased animals; however, determining virus pathogenesis remains a challenge. A novel anellovirus (Zalophus californianus anellovirus, ZcAV) was recently reported in the lungs of captive California sea lions involved in a mortality event. ZcAV was not detected by PCR in the blood of these animals, creating the inability to assess the prevalence of ZcAV in live sea lions. This study developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to ZcAV in sea lion serum. To assess ZcAV prevalence, paired serum and lung samples (n = 96) from wild sea lions that stranded along the California coast were tested through ELISA and PCR, respectively. Over 50% of the samples tested positive for ZcAV by ELISA (34%), PCR (29%), or both (11%) assays. ZcAV is prevalent in stranded wild sea lion populations and results suggest that PCR assays alone may grossly underestimate ZcAV exposure. This ELISA provides a tool for testing live sea lions for ZcAV exposure and is valuable for subsequent studies evaluating the potential pathogenicity of this anellovirus. PMID:25965294

  18. Open-Loop Audio-Visual Stimulation (AVS): A Useful Tool for Management of Insomnia?

    PubMed

    Tang, Hsin-Yi Jean; Riegel, Barbara; McCurry, Susan M; Vitiello, Michael V

    2016-03-01

    Audio Visual Stimulation (AVS), a form of neurofeedback, is a non-pharmacological intervention that has been used for both performance enhancement and symptom management. We review the history of AVS, its two sub-types (close- and open-loop), and discuss its clinical implications. We also describe a promising new application of AVS to improve sleep, and potentially decrease pain. AVS research can be traced back to the late 1800s. AVS's efficacy has been demonstrated for both performance enhancement and symptom management. Although AVS is commonly used in clinical settings, there is limited literature evaluating clinical outcomes and mechanisms of action. One of the challenges to AVS research is the lack of standardized terms, which makes systematic review and literature consolidation difficult. Future studies using AVS as an intervention should; (1) use operational definitions that are consistent with the existing literature, such as AVS, Audio-visual Entrainment, or Light and Sound Stimulation, (2) provide a clear rationale for the chosen training frequency modality, (3) use a randomized controlled design, and (4) follow the Consolidated Standards of Reporting Trials and/or related guidelines when disseminating results. PMID:26294268

  19. Location Capability and Site Characterization Installing a Borehole VBB Seismometer: the OGS Experience in Ferrara (Italy)

    NASA Astrophysics Data System (ADS)

    Pesaresi, D.; Barnaba, C.

    2014-12-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Centre) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 19 very sensitive broad band and 17 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS CRS data centre in Udine. The southwestern edge of the OGS seismic network stands on the Po alluvial basin: earthquake localization and characterization in this area is affected by the presence of soft alluvial deposits. Following the ML=5.9 earthquake that struck the Emilia region around Ferrara in Northern Italy on May 20, 2012, a cooperation of Istituto Nazionale di Geofisica e Vulcanologia, OGS, the Comune di Ferrara and the University of Ferrara lead to the reinstallation of a previously existing very broad band (VBB) borehole seismic station in Ferrara and to the deployment of a temporary seismographic network consisting of eight portable seismological stations, to record the local earthquakes that occurred during the seismic sequence. The aim of the OGS intervention was on one hand to extend its real time seismic monitoring capabilities toward South-West, including Ferrara and its surroundings, and on the other hand to evaluate seismic site responses in the area. We will introduce details of the Ferrara VBB borehole station and the OGS temporary seismographic network configuration and installation. We will then illustrate the location capability performances, and finally we will shortly describe seismic site characterization with surface/borehole comparisons in terms of seismic noise, site amplification and resonance frequencies.

  20. OGS improvements in the year 2011 in running the Northeastern Italy Seismic Network

    NASA Astrophysics Data System (ADS)

    Bragato, P. L.; Pesaresi, D.; Saraò, A.; Di Bartolomeo, P.; Durì, G.

    2013-04-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Center) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale - OGS (Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude Mw = 6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 12 very sensitive broad band and 21 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data centre in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of 93 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of Northeastern Italy, as shown in Fig. 1 (Bragato et al., 2011; Saraò et al., 2010). Since 2002 OGS-CRS is using the Antelope software suite as the main tool for collecting, analyzing, archiving and exchanging seismic data, initially in the framework of the EU Interreg IIIA project "Trans-national seismological networks in the South-Eastern Alps" (Bragato et al., 2010; Pesaresi et al., 2008). SeisComP is also used as a real time data exchange server tool. In order to improve the seismological monitoring of the Northeastern Italy area, at OGS-CRS we tuned existing programs and created ad hoc ones like: a customized web server named PickServer to manually relocate earthquakes, a script for automatic moment tensor determination, scripts for web publishing of earthquake parametric data, waveforms, state of health parameters and shaking maps, noise characterization by means of automatic spectra analysis, and last but not least scripts for email/SMS/fax alerting. A new OGS-CRS real time seismological website (http://rts.crs.inogs.it/) has also been operative since several years.

  1. ADVANCED VITRIFICATION SYSTEM (RIC AVS) RESEARCH AND DEVELOPMENT PROJECT

    SciTech Connect

    J.R. Powell; M. Reich

    2003-06-30

    The objective of this AVS testing program is to use bench-scale test equipment to produce a vitrified product at maximum waste loading from the specified AZ-101 waste simulant and conduct a TTT analysis using laboratory scale melts to show compliance with the DOE Waste Acceptance Product Specifications for Vitrified High-Level Waste Forms (WAPS). The vitrified product complies with the following WAPS. A borosilicate glass with a waste loading of 60.9-wt% was produced from a slurry feed of AZ101 simulant. Glass durability testing, glass characterization testing, and testing methodology were performed in accordance with the Department of Energy approved Test Plan. The glass has two crystalline phases and good uniformity of composition. The Product Consistency Test on the 6 location-specific samples are at least 1 to 2 orders of magnitude below the mean PCT results for the EA glass. Standard deviations were less than 10% of measured values. The glass transition temperature averaged 658 {+-} 9 C. A TTT diagram was produced. There was measured cesium loss of about 2%, and compliance with the Universal Treatment Standards.

  2. Pilot Implementation and Preliminary Evaluation of START:AV Assessments in Secure Juvenile Correctional Facilities.

    PubMed

    Desmarais, Sarah L; Sellers, Brian G; Viljoen, Jodi L; Cruise, Keith R; Nicholls, Tonia L; Dvoskin, Joel A

    2012-01-01

    The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV) is a new structured professional judgment guide for assessing short-term risks in adolescents. The scheme may be distinguished from other youth risk assessment and treatment planning instruments by its inclusion of 23 dynamic factors that are each rated for both vulnerability and strength. In addition, START:AV is also unique in that it focuses on multiple adverse outcomes-namely, violence, self-harm, suicide, unauthorized leave, substance abuse, self-neglect, victimization, and general offending-over the short-term (i.e., weeks to months) rather than long-term (i.e., years). This paper describes a pilot implementation and preliminary evaluation of START:AV in three secure juvenile correctional facilities in the southern United States. Specifically, we examined the descriptive characteristics and psychometric properties of START:AV assessments completed by 21 case managers on 291 adolescent offenders (250 boys and 41 girls) at the time of admission. Results provide preliminary support for the feasibility of completing START:AV assessments as part of routine practice. Findings also highlight differences in the characteristics of START:AV assessments for boys and girls and differential associations between the eight START:AV risk domains. Though results are promising, further research is needed to establish the reliability and validity of START:AV assessments completed in the field. PMID:23316116

  3. Vesta Compositional Diversity in Quadrangle Av-13 Tuccia

    NASA Astrophysics Data System (ADS)

    Pieters, C.; De Sanctis, M. C.; Ammanito, E.; Li, J. Y.; Nathues, A.; Kneissl, T.; Jaumann, R.; Reddy, V.; Le Corre, L.; Stephan, K.; Prusker, F.; Capaccioni, F.; Palomba, E.; Tosi, F.; Zambon, F.; Palmer, E.,; Raymond, C. A.; Russell, C. T.

    2012-04-01

    The Dawn spacecraft is currently orbiting the main belt asteroid 4 Vesta to evaluate the character of this small protoplanet and its role in early solar system evolution. Compositional data from the Gamma Ray and Neutron Detector (GRaND) are being acquired and will be available soon. Spectral data acquired with the Visible and Infrared Mapping Spectrometer (VIR) and the Framing Camera (FC) instruments provide compositional information in a spatial context. Available VIR data provide the high spectral resolution necessary for mineral identification and characterization while FC data provide selected spectral channels, but at a higher spatial resolution that enable geologic relations to be better discerned. As these different data are integrated and analyzed, broad compositional variations are observed in the mineralogy across Vesta. The diversity seen on a global scale and direct associations with HED mineralogy is discussed in DeSanctis et al. and Ammannito et al. [this meeting]. Geologic mapping of Vesta has been initiated for 15 well-defined quadrangles and coordinated mineralogical mapping has commenced at that higher scale. We discuss the mineralogical diversity observed in quadrangle Av-13 Tuccia, which spans a region between 21° -66°S latitude and 180° -270° E longitude on Vesta. The Av-13 Tuccia quadrangle includes three major geologic terrains [see Kneissl et al., this meeting]: Vestalia Terra located in the north of the quadrangle, the Equatorial Cratered Terrain, and the Ridge-and-Groove Terrain which is part of the Rheasilvia Formation. As such, the Tuccia quadrangle includes regions which transition from the equatorial terrain to the giant impact basin of Rheasilvia. Prominent spectral variations are mapped across the surface by FC and VIR, largely associated with relatively fresh impact craters. Diagnostic absorption bands of pyroxene are readily detected. The relative strength of these absorptions is seen to vary in a regular spatial context

  4. Decouple a coupled KdV system of Nutku and Og˜uz

    NASA Astrophysics Data System (ADS)

    Hu, Heng Chun; Liu, Q. P.

    2002-02-01

    A coupled KdV system with a free parameter proposed by Nutku and Og˜uz is considered. It is shown that the system passes the WTC's Painlevé test for arbitrary value of the parameter. A further analysis yields that the parameter can be removed and the system can be decoupled.

  5. From Black Power to Hip-Hop: Jeffrey O.G. Ogbar

    ERIC Educational Resources Information Center

    Smiles, Robin V.

    2005-01-01

    While history for most conjures up images of places and experiences far removed, for Dr. Jeffrey O.G. Ogbar, the field provides a "wonderful medium" to illuminate contemporary issues as well. Much of Ogbar's current research centers on events occurring in the latter half of the 20th century, such as the civil rights and Black power movements as…

  6. OGS improvements in the year 2011 in running the Northeastern Italy Seismic Network

    NASA Astrophysics Data System (ADS)

    Bragato, P. L.; Pesaresi, D.; Saraò, A.; Di Bartolomeo, P.; Durı, G.

    2012-04-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Center) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake of magnitude M=6.4 occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the Northeastern Italy Seismic Network: it currently consists of 15 very sensitive broad band and 21 simpler short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data center in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of about 100 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of Northeastern Italy. Since 2002 OGS-CRS is using the Antelope software suite on several workstations plus a SUN Cluster as the main tool for collecting, analyzing, archiving and exchanging seismic data, initially in the framework of the EU Interreg IIIA project "Trans-national seismological networks in the South-Eastern Alps". SeisComP is also used as a real time data exchange server tool. In order to improve the seismological monitoring of the Northeastern Italy area, at OGS-CRS we tuned existing programs and created ad hoc ones like: a customized web server named PickServer to manually relocate earthquakes, a script for automatic moment tensor determination, scripts for web publishing of earthquake parametric data, waveforms, state of health parameters and shaking maps, noise characterization by means of automatic spectra analysis, and last but not least scripts for email/SMS/fax alerting. The OGS-CRS Real Time Seismological website (RTS, http://rts.crs.inogs.it/) operative since several years was initially developed in the framework of the Italian DPC-INGV S3 Project: the RTS website shows classic earthquake locations

  7. ogs6 - a new concept for porous-fractured media simulations

    NASA Astrophysics Data System (ADS)

    Naumov, Dmitri; Bilke, Lars; Fischer, Thomas; Rink, Karsten; Wang, Wenqing; Watanabe, Norihiro; Kolditz, Olaf

    2015-04-01

    OpenGeoSys (OGS) is a scientific open-source initiative for numerical simulation of thermo-hydro-mechanical/chemical (THMC) processes in porous and fractured media, continuously developed since the mid-eighties. The basic concept is to provide a flexible numerical framework for solving coupled multi-field problems. OGS is targeting mainly on applications in environmental geoscience, e.g. in the fields of contaminant hydrology, water resources management, waste deposits, or geothermal energy systems, but it has also been successfully applied to new topics in energy storage recently. OGS is actively participating several international benchmarking initiatives, e.g. DECOVALEX (waste management), CO2BENCH (CO2 storage and sequestration), SeSBENCH (reactive transport processes) and HM-Intercomp (coupled hydrosystems). Despite the broad applicability of OGS in geo-, hydro- and energy-sciences, several shortcomings became obvious concerning the computational efficiency as well as the code structure became too sophisticated for further efficient development. OGS-5 was designed for object-oriented FEM applications. However, in many multi-field problems a certain flexibility of tailored numerical schemes is essential. Therefore, a new concept was designed to overcome existing bottlenecks. The paradigms for ogs6 are: - Flexibility of numerical schemes (FEM#FVM#FDM), - Computational efficiency (PetaScale ready), - Developer- and user-friendly. ogs6 has a module-oriented architecture based on thematic libraries (e.g. MeshLib, NumLib) on the large scale and uses object-oriented approach for the small scale interfaces. Usage of a linear algebra library (Eigen3) for the mathematical operations together with the ISO C++11 standard increases the expressiveness of the code and makes it more developer-friendly. The new C++ standard also makes the template meta-programming technique code used for compile-time optimizations more compact. We have transitioned the main code development to

  8. Mineralogic mapping of the Av-9 Numisia quadrangle of Vesta

    NASA Astrophysics Data System (ADS)

    Frigeri, A.; De Sanctis, M. C.; Ammannito, E.; Buczkowski, D.; Combe, J. P.; Tosi, F.; Zambon, F.; Rocchini, D.; Jaumann, R.; Raymond, C. A.; Russell, C. T.

    2015-10-01

    In this manuscript we present the mineralogic mapping of the Av-9 Numisia quadrangle of Vesta using the most up-to-date data from the NASA-Dawn mission. This quadrangle is located in Vesta's equatorial zone (22° south to 22° north, 218° to 288° east, in Claudia coordinate system) and takes its name from the impact crater Numisia. The main feature, which dominates the quadrangle, is the Vestalia Terra plateau, a topographic high about 10 km above the surrounding areas. To the south, this region fades into the Rheasilvia basin, while to the north it is bounded by the steep scarp of Postumia basin. The Visible and Infrared mapping spectrometer (VIR) onboard NASA/Dawn provided the main data source for this work, at an unprecedented level of spatial and spectral resolution. In particular we are using spectral parameters to synthesize characteristics of the whole spectra into a single value. Pyroxene-related spectral parameters allow for the detection of lower crust or mantle material (diogenites) and upper crust material (eucrites) in the study area. The combined analysis of albedo from the Framing Camera, the geologic map and the spectroscopic data offer an interesting opportunity to understand better the surface features of this region of Vesta, and their evolution. Numisia, Cornelia, Fabia, Teia and Drusilla are the main craters in the study area, rich in bright and dark material outcrops, pitted terrains and OH-rich materials. Using the spectral parameters we demonstrate that the internal composition of Vestalia Terra is mainly diogenite-rich howardite, as shown by materials excavated by Cornelia and Fabia, and the composition of the slope north of Vestalia Terra. This agrees with the strong positive Bouguer Anomaly observed in the area, indicating a higher density of these features in relation to the surrounding areas. Besides the recently published works based on gravimetric modeling and geologic interpretation, the mineralogic mapping presented herein gives

  9. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family.

    PubMed

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A; Gliemann, Jørgen; Ryan, Robert O; Olivecrona, Gunilla

    2007-03-27

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by the receptor associated protein, a known ligand for members of the low density lipoprotein receptor family. Preincubation with heparin decreased the receptor binding of apolipoprotein A-V, indicating that overlap exists between the recognition sites for these receptors and for heparin. A double mutant, apolipoprotein A-V (Arg210Glu/Lys211Gln), showed decreased binding to heparin and decreased ability to bind the low density lipoprotein receptor-related protein. Association of apolipoprotein A-V with the low density lipoprotein receptor-related protein or SorLA resulted in enhanced binding of human chylomicrons to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins. PMID:17326667

  10. Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS)

    PubMed Central

    Radhakrishna, Uppala; Albayrak, Samet; Alpay-Savasan, Zeynep; Zeb, Amna; Turkoglu, Onur; Sobolewski, Paul; Bahado-Singh, Ray O.

    2016-01-01

    Congenital heart defect (CHD) is the most common cause of death from congenital anomaly. Among several candidate epigenetic mechanisms, DNA methylation may play an important role in the etiology of CHDs. We conducted a genome-wide DNA methylation analysis using an Illumina Infinium 450k human methylation assay in a cohort of 24 newborns who had aortic valve stenosis (AVS), with gestational-age matched controls. The study identified significantly-altered CpG methylation at 59 sites in 52 genes in AVS subjects as compared to controls (either hypermethylated or demethylated). Gene Ontology analysis identified biological processes and functions for these genes including positive regulation of receptor-mediated endocytosis. Consistent with prior clinical data, the molecular function categories as determined using DAVID identified low-density lipoprotein receptor binding, lipoprotein receptor binding and identical protein binding to be over-represented in the AVS group. A significant epigenetic change in the APOA5 and PCSK9 genes known to be involved in AVS was also observed. A large number CpG methylation sites individually demonstrated good to excellent diagnostic accuracy for the prediction of AVS status, thus raising possibility of molecular screening markers for this disorder. Using epigenetic analysis we were able to identify genes significantly involved in the pathogenesis of AVS. PMID:27152866

  11. Genome-Wide DNA Methylation Analysis and Epigenetic Variations Associated with Congenital Aortic Valve Stenosis (AVS).

    PubMed

    Radhakrishna, Uppala; Albayrak, Samet; Alpay-Savasan, Zeynep; Zeb, Amna; Turkoglu, Onur; Sobolewski, Paul; Bahado-Singh, Ray O

    2016-01-01

    Congenital heart defect (CHD) is the most common cause of death from congenital anomaly. Among several candidate epigenetic mechanisms, DNA methylation may play an important role in the etiology of CHDs. We conducted a genome-wide DNA methylation analysis using an Illumina Infinium 450k human methylation assay in a cohort of 24 newborns who had aortic valve stenosis (AVS), with gestational-age matched controls. The study identified significantly-altered CpG methylation at 59 sites in 52 genes in AVS subjects as compared to controls (either hypermethylated or demethylated). Gene Ontology analysis identified biological processes and functions for these genes including positive regulation of receptor-mediated endocytosis. Consistent with prior clinical data, the molecular function categories as determined using DAVID identified low-density lipoprotein receptor binding, lipoprotein receptor binding and identical protein binding to be over-represented in the AVS group. A significant epigenetic change in the APOA5 and PCSK9 genes known to be involved in AVS was also observed. A large number CpG methylation sites individually demonstrated good to excellent diagnostic accuracy for the prediction of AVS status, thus raising possibility of molecular screening markers for this disorder. Using epigenetic analysis we were able to identify genes significantly involved in the pathogenesis of AVS. PMID:27152866

  12. The Vibrio harveyi GTPase CgtAV Is Essential and Is Associated with the 50S Ribosomal Subunit

    PubMed Central

    Sikora, A. E.; Zielke, R.; Datta, K.; Maddock, J. R.

    2006-01-01

    It was previously reported that unlike the other obg/cgtA GTPases, the Vibrio harveyi cgtAV is not essential. Here we show that cgtAV was not disrupted in these studies and is, in fact, essential for viability. Depletion of CgtAV did not result in cell elongation. CgtAV is associated with the large ribosomal particle. In light of our results, we predict that the V. harveyi CgtAV protein plays a similar essential role to that seen for Obg/CgtA proteins in other bacteria. PMID:16428430

  13. Activation of defense response pathways by OGs and Flg22 elicitors in Arabidopsis seedlings

    PubMed Central

    Denoux, Carine; Galletti, Roberta; Mammarella, Nicole; Gopalan, Suresh; Werck, Danièle; De Lorenzo, Giulia; Ferrari, Simone; Ausubel, Frederick M.; Dewdney, Julia

    2010-01-01

    We carried out transcriptional profiling analysis in 10 day-old Arabidopsis thaliana seedlings treated with oligogalacturonides (OGs), oligosaccharides derived from the plant cell wall, or the bacterial flagellin peptide Flg22, general elicitors of the basal defense response in plants. Although detected by different receptors, both OGs and Flg22 trigger a fast and transient response that is both similar and comprehensive, and characterized by activation of early stages of multiple defense signaling pathways, particularly JA-associated processes. However, the response to Flg22 is stronger in both the number of genes differentially expressed and the amplitude of change. The magnitude of induction of individual genes is in both cases dose dependent, but even at very high concentrations, OGs do not induce a response that is as comprehensive as that seen with Flg22. While high doses of either microbe-associated molecular pattern (MAMP) elicit a late response that includes activation of senescence processes, SA-dependent secretory pathway genes and PR1 expression are substantially induced only by Flg22. These results suggest a lower threshold for activation of early responses than for sustained or SA-mediated late defenses. Expression patterns of aminocyclopropane-carboxylate synthase genes also implicate ethylene biosynthesis in regulation of the late innate immune response. PMID:19825551

  14. Ectopic expression of ubiquitin-conjugating enzyme gene from wild rice, OgUBC1, confers resistance against UV-B radiation and Botrytis infection in Arabidopsis thaliana

    SciTech Connect

    Jeon, En Hee; Pak, Jung Hun; Kim, Mi Jin; Kim, Hye Jeong; Shin, Sang Hyun; Lee, Jai Heon; Kim, Doh Hoon; Oh, Ju Sung; Oh, Boung-Jun; Jung, Ho Won; Chung, Young Soo

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer We isolated a novel E2 ubiquitin-conjugating enzyme from leaves of wild rice plants. Black-Right-Pointing-Pointer The OgUBC1 was highly expressed in leaves treated with SA and UV-B radiation. Black-Right-Pointing-Pointer The recombinant OgUBC1 has an enzymatic activity of E2 in vitro. Black-Right-Pointing-Pointer The OgUBC1 could protect disruption of plant cells by UV-B radiation. Black-Right-Pointing-Pointer OgUBC1 confers disease resistance and UV-B tolerance in transgenic Arabidopsis plants. -- Abstract: A previously unidentified gene encoding ubiquitin-conjugating enzyme was isolated from leaves of wild rice plant treated with wounding and microbe-associated molecular patterns. The OgUBC1 gene was composed of 148 amino acids and contained a typical active site and 21 ubiquitin thioester intermediate interaction residues and 4 E3 interaction residues. Both exogenous application of salicylic acid and UV-B irradiation triggered expression of OgUBC1 in leaves of wild rice. Recombinant OgUBC1 proteins bound to ubiquitins in vitro, proposing that the protein might act as E2 enzyme in planta. Heterologous expression of the OgUBC1 in Arabidopsis thaliana protected plants from cellular damage caused by an excess of UV-B radiation. A stable expression of chalcone synthase gene was detected in leaves of OgUBC1-expressing Arabidopsis, resulting in producing higher amounts of anthocyanin than those in wild-type Col-0 plants. Additionally, both pathogenesis-related gene1 and 5 were transcribed in the transgenic Arabidopsis in the absence of pathogen infection. The OgUBC1-expressing plants were resistant to the infection of Botrytis cinerea. Taken together, we suggested that the OgUBC1 is involved in ubiquitination process important for cellular response against biotic and abiotic stresses in plants.

  15. Heart Rate and AV delay modify left ventricular filling vortex properties

    NASA Astrophysics Data System (ADS)

    Del Alamo, Juan C.; Benito, Yolanda; Bermejo, Javier; Alhama, Marta; Yotti, Raquel; Perez Del Villar, Candelas; Martinez-Legazpi, Pablo; Gonzalez Mansilla, Ana; Fernandez-Aviles, Francisco

    2012-11-01

    Intraventricular flow generates a vortex ring during rapid filling that optimizes filling, couples inflow kinetic energy to ejection, improves blood mixing and avoids stasis. LV vorticity has been related to chamber geometrical properties, but the effects of electrical events have never been characterized, partly due to the difficulty of performing MRI in patients with implanted devices. We have recently developed a new method that allows measuring vortex properties by processing conventional transthoracic color-Doppler sequences. Using this modality, 27 patients carrying an implantable cardiac resynchronization device were studied after AV optimization at 100 beats per minute. Our results reveal that, compared to optimal AV, the main vortex component remained closer to the base during 100BPM (difference = -20% of Lax length, p <.05) and closer to the apex when AV is minimized (diff= +11% of Lax, p <.05). Radius, circulation and energy of the vortices were larger when AV is maximized (p <.05). In conclusion, the duration of diastole, as modulated by heart rate and AV-delay, significantly modifies intraventricular vortex dynamics. Funded by NIH Grant R21HL108268.

  16. AV-8B ETARS demo proves AN/ASQ-197 versatility

    NASA Astrophysics Data System (ADS)

    Fishell, Wallace G.

    1990-11-01

    Demonstrations during the summer of 1988 culminated in a quick-turn Naval Air Development Center (NADC) engineering effort which demonstrated the feasibility of flying an Expeditionary Tactical Air Reconnaissance Pod System (ETARS) Pod on an AV-8B Night Attack aircraft. Fairchild's AN/ASQ-197 Sensor Control-Data Display Set (SC-DDS), which had recently completed Full Scale Development (FSD) Testing for the Film version of F/A-18, was modified to control the Pod, its sensors, the video tape recorder and other communication equipment from a single rotary switch, four caution indicators and the standard AV-8B multiplex bus. This paper describes the functions performed by the AN/ASQ-197 Modified during the successful AV-8B ETARS feasibility flight demonstration program.

  17. Determinants of Plasma Apolipoprotein A-V and APOA5 Gene Transcripts in Humans

    PubMed Central

    Hahne, P.; Krempler, F.; Schaap, F.G.; Soyal, S.M.; Höffinger, H.; Miller, K.; Oberkofler, H.; Strobl, W.; Patsch, W.

    2012-01-01

    Objective Apolipoprotein A-V (apoAV) contributes to the regulation of triglyceride metabolism, which plays a role in the pathogenesis of atherosclerotic diseases. We therefore ascertained determinants of hepatic APOA5 transcript and apoAV plasma levels in humans. Design We determined influences of anthropometric variables, biochemical factors related to lipid and glucose metabolism, hepatic mRNA levels transcribed from the APOA1/C3/A4/A5 cluster and transcription factor genes implicated in the regulation of APOA5 as well as common SNPs at the APOA5 locus on APOA5 expression in 89 obese patients and 22 non-obese controls. Results Mean, age and sex adjusted, hepatic APOA5 mRNA or apoAV plasma levels did not differ by obesity status, HOMA-IR or inflammatory markers. In multivariate regression models, the c56C>G SNP, plasma apoCIII, plasma non-esterified fatty acids, hepatic APOA5 transcripts, sex and a weak association with obesity status explained 61% of the variance in apoAV plasma levels. Hepatic transcript levels of CPT1A1 and PPARA, plasma non-esterified fatty acids and the c56C>G SNP explained 48% of the variance in hepatic APOA5 transcript levels. Conclusion ApoAV plasma levels are independently associated with plasma free fatty acid and hepatic APOA5 mRNA levels. Associations of APOA5 transcripts with PPARA and CPT1A1 transcripts suggest that APOA5 expression is intimately linked to hepatic lipid metabolism. PMID:18537870

  18. Comparative assessment of an Og4C3 ELISA and an ICT filariasis test: a study of Myanmar migrants in Thailand.

    PubMed

    Nuchprayoon, Surang; Porksakorn, Chantima; Junpee, Alisa; Sanprasert, Vivornpun; Poovorawan, Yong

    2003-12-01

    Detection of circulating filarial antigen has now emerged as an alternative method for the diagnosis of bancroftian filariasis. We compared two antigen detection assays, an Og4C3 ELISA and an ICT (immunochromatography) Filariasis test, for the diagnosis of Wuchereria bancrofti infections in migrant Myanmar workers in Tak province, Western Thailand. A total of 337 Myanmars participated in this study. The microfilarial rate was 3.3%. The Og4C3 ELISA could detect 19.1% of bancroftian filariasis while the ICT test detected 12.7%. Both antigen assays could detect all microfilaremics. The Og4C3 ELISA detected 14.8% of amicrofilaremics while the ICT test identified 8.1%. Those who were positive for the ICT test were also positive by the Og4C3 ELISA. Those Og4C3 positive cases, that were ICT negative (ICT-ve/Og4C3+ve) had statistically significant (p < 0.05, unpaired t-test) lower Og4C3 antigen levels (409.5 units, range 117-2,389) than those that were ICT positive (ICT+ve/Og4C3+ve) (5,252.0 units, range 130-28,062). Our results emphasize the problem of bancroftian filariasis in Myanmar migrants working in Thailand. Close monitoring and control of this disease in Myanmar migrants are of public health importance. Antigen detection systems are promising tools for the surveillance of bancroftian filariasis. PMID:15198343

  19. In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET.

    PubMed

    Hansen, Allan K; Knudsen, Karoline; Lillethorup, Thea P; Landau, Anne M; Parbo, Peter; Fedorova, Tatyana; Audrain, Hélène; Bender, Dirk; Østergaard, Karen; Brooks, David J; Borghammer, Per

    2016-07-01

    The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after

  20. Acquiring, archiving, analyzing and exchanging seismic data in real time at the Seismological Research Center of the OGS in Italy

    NASA Astrophysics Data System (ADS)

    Saraò, Angela; Pesaresi, Damiano; Bragato, Pier Luigi; di Bartolomeo, Paolo; Percy Plasencia Linares, Milton

    2010-05-01

    The Centro di Ricerche Sismologiche (CRS, Seismological Research Center) of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS, Italian National Institute for Oceanography and Experimental Geophysics) in Udine (Italy) after the strong earthquake (magnitude M=6.4) occurred in 1976 in the Italian Friuli-Venezia Giulia region, started to operate the North-east Italy (NI) seismic network: it currently consists of 11 very sensitive broad band and 23 more simple short period seismic stations, all telemetered to and acquired in real time at the OGS-CRS data center in Udine. Real time data exchange agreements in place with other Italian, Slovenian, Austrian and Swiss seismological institutes lead to a total number of 89 seismic stations acquired in real time, which makes the OGS the reference institute for seismic monitoring of Northeastern Italy. Since 2002 OGS-CRS is using the Antelope software suite as the main tool for collecting, analyzing, archiving and exchanging seismic data in the framework of the EU Interreg IIIA project "Trans-national seismological networks in the South-Eastern Alps". SeisComP is also used as a real time data exchange server tool. At OGS-CRS we then adapted existing programs and created new ones like: a customized web-accessible server to manually relocate earthquakes, a script for automatic moment tensor determination, scripts for web publishing of earthquake parametric data, waveforms, state of health parameters and shaking maps, noise characterization by means of automatic spectra analysis, plus scripts for email/SMS/fax alerting. A new OGS-CRS real time web site has also been recently designed and made operative in the framework of the DPC-INGV S3 Project.

  1. Identification of the human ApoAV gene as a novel ROR{alpha} target gene

    SciTech Connect

    Lind, Ulrika; Nilsson, Tina; McPheat, Jane; Stroemstedt, Per-Erik; Bamberg, Krister; Balendran, Clare; Kang, Daiwu . E-mail: Daiwu.Kang@astrazeneca.com

    2005-04-29

    Retinoic acid receptor-related orphan receptor-{alpha} (ROR{alpha}) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism. Previous studies have shown that ROR{alpha} regulates transcription of the murine Apolipoprotein AI gene and human Apolipoprotein CIII genes. In the present study, we present evidence that ROR{alpha} also induces transcription of the human Apolipoprotein AV gene, a recently identified apolipoprotein associated with triglyceride levels. Adenovirus-mediated overexpression of ROR{alpha} increased the endogenous expression of ApoAV in HepG2 cells and ROR{alpha} also enhanced the activity of an ApoAV promoter construct in transiently transfected HepG2 cells. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate ROR{alpha} transactivation, one of which overlaps with a previously identified binding site for PPAR{alpha}. Together, these results suggest a novel mechanism whereby ROR{alpha} modulates lipid metabolism and implies ROR{alpha} as a potential target for the treatment of dyslipidemia and atherosclerosis.

  2. Impact of e-AV Biology Website for Learning about Renewable Energy

    ERIC Educational Resources Information Center

    Nugraini, Siti Hadiati; Choo, Koo Ah; Hin, Hew Soon; Hoon, Teoh Sian

    2013-01-01

    This paper considers the design and development of a Website for Biology in senior high schools in Indonesia. The teaching media, namely e-AV Biology, was developed with the main features of video lessons and other features in supporting the students' learning process. Some video lessons describe the production process of Biofuel or Renewable…

  3. PHOTOMETRIC PROPERTIES FOR SELECTED ALGOL-TYPE BINARIES. IV. AV HYDRAE AND DZ CASSIOPEIAE

    SciTech Connect

    Yang, Y.-G.; Dai, H.-F.; Li, L.-H.

    2012-08-15

    We present BVR photometric observations and several eclipsing times for AV Hya and DZ Cas from 2004 to 2011. Using the Wilson-Devinney method, the photometric solutions with hot spots were deduced from their asymmetric light curves. The results indicate that both stars are Algol-type binaries, whose mass ratio, q{sub ph}, and fill-out factor of the primary, f{sub 1}, are q{sub ph} = 0.255({+-} 0.002) and f{sub 1} = 81.2({+-} 0.2)% for AV Hya, and q{sub ph} = 0.093({+-} 0.003) and f{sub 1} = 98.7({+-} 0.3)% for DZ Cas. Based on all available light minimum times, it is discovered that the O - C curve of each star could be described by a light-time orbit overlying on a downward parabola. Their periods and amplitudes are P{sub 3} = 37.2({+-} 0.7) yr and A = 0fd0095({+-}0fd0006) for AV Hya, and P{sub 3} = 62.5({+-} 1.0) yr and A = 0fd0183({+-}0fd0007) for DZ Cas. Cyclic variations may result from the light-time effect due to the third body. The secular period decrease rates are dP/dt = -1.47({+-} 0.04) Multiplication-Sign 10{sup -7} days yr{sup -1} for AV Hya and dP/dt = -0.92({+-} 0.04) Multiplication-Sign 10{sup -7} days yr{sup -1} for DZ Cas. This may be interpreted using mass and angular momentum loss from the system. With decreasing period, the fill-out factor of the primary increases and it may finally fill its inner Roche lobe. Therefore, AV Hya and DZ Cas with a secular period decrease will evolve from semi-detached configurations into contact ones.

  4. A Heart too Drunk to Drive; AV Block following Acute Alcohol Intoxication.

    PubMed

    van Stigt, Arthur H; Overduin, Ruben J; Staats, Liza C; Loen, Vera; van der Heyden, Marcel A G

    2016-02-29

    Acute excessive alcohol consumption is associated with heart rhythm disorders like atrial fibrillation but also premature ventricular contractions, collectively known as the "holiday heart syndrome". More rarely but clinically significant are reports of atrioventricular (AV) conduction disturbances in binge drinkers with no underlying heart disease or chronic alcohol consumption. To obtain better insights into common denominators and the potential underlying mechanisms we collected and compared individual case reports of AV block following acute alcohol intoxication in otherwise healthy people. By screening PubMed, Google Scholar, Scopus and JSTOR, fifteen cases were found of which eight were sufficiently documented for full analysis. Blood alcohol levels ranged from 90 to 958 mg/dl (19 to 205 mM). Second and third degree AV block was observed most (6/8) albeit that in two of these patients a vagal stimulus led to deterioration from first into higher order AV block. In all cases, patients reverted to normal sinus rhythm upon becoming sober again. Mildly lowered body temperature (35.9 ± 0.5°C) was observed but can be excluded as a major cause of conduction blockade. We hypothesize that ethanol induced partial inhibition of calcium and potentially also sodium currents in conductive tissue structures may be one of the mechanisms of conduction slowing and block that may become exaggerated upon increased vagal tone. An impairment of gap junction function cannot be excluded as a contributing factor. In conclusion, cases of documented alcohol induced AV block are very rare but events can occur at relatively low serum alcohol levels which should prompt to awareness of this phenomenon in alcohol intoxicated patients. PMID:26875557

  5. Geologic Mapping of the Av-11 Pinaria Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Schenk, P.; Hoogenboom, T.; Williams, D.; Yingst, R. A.; Jaumann, R.; Gaskell, R.; Preusker, F.; Nathues, A.; Roatsch, T.

    2012-04-01

    As part of the Dawn's orbital mapping investigation of Vesta, the Science Team is conducting geologic mapping of the surface in the form of 15 quadrangle maps, including quadrangle Av-11 (Pinaria). The base map is a monochrome Framing Camera (FC) mosaic at ~70 m/pixel, supplemented by Digital Terrain Models (DTM) and FC color ratio images, both at ~250 m/pixel, slope and contour maps, and Visible and Infrared (VIR) hyperspectral images. Av-11 straddles the 45-degree longitude in the South Polar Region, and is dominated by the rim of the ~505 km south polar topographic feature, Rheasilvia. Sparsely cratered (relatively), Av-11 is dominated by a 20 km high rim scarp (Matronalia Rupes) and by arcuate ridges and troughs forming a radial to spiral pattern across the basin floor. Primary geologic features of Av-11 include the following. Ridge-and-groove terrain radiating arcuately from the central mound unit, interpreted to be structural disruption of the basin floor associated with basin formation. The largest crater in Av-11 is Pinaria (37 km). Mass wasting deposits are observed on its floor. Secondary crater chains and fields are also evident. Mass wasting observed along Rheasilvia rim scarp and in the largest craters indicates scarp failure is a significant process. Parallel fault scarps mark this deposit of slumped debris at the base of 20 km high Matronalia Rupes, which may have formed during or shortly after basin excavation. We interpret most of these deposits as slump material emplaced as a result of the effects of basin formation and collapse. Lobate materials are characterized by lineations and lobate scarps and interpreted as Rheasilvia ejecta deposit outside Rheasilvia rim (the smoothest terrain on Vesta), and are consistent with formation by ejecta. Partial burial of older craters near the edge of these deposits are also observed.

  6. The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity.

    PubMed

    Bailleul, Geoffrey; Kravtzoff, Amanda; Joulin-Giet, Alix; Lecaille, Fabien; Labas, Valérie; Meudal, Hervé; Loth, Karine; Teixeira-Gomes, Ana-Paula; Gilbert, Florence B; Coquet, Laurent; Jouenne, Thierry; Brömme, Dieter; Schouler, Catherine; Landon, Céline; Lalmanach, Gilles; Lalmanach, Anne-Christine

    2016-01-01

    Defensins are frontline peptides of mucosal immunity in the animal kingdom, including birds. Their resistance to proteolysis and their ensuing ability to maintain antimicrobial potential remains questionable and was therefore investigated. We have shown by bottom-up mass spectrometry analysis of protein extracts that both avian beta-defensins AvBD2 and AvBD7 were ubiquitously distributed along the chicken gut. Cathepsin B was found by immunoblotting in jejunum, ileum, caecum, and caecal tonsils, while cathepsins K, L, and S were merely identified in caecal tonsils. Hydrolysis product of AvBD2 and AvBD7 incubated with a panel of proteases was analysed by RP-HPLC, mass spectrometry and antimicrobial assays. AvBD2 and AvBD7 were resistant to serine proteases and to cathepsins D and H. Conversely cysteine cathepsins B, K, L, and S degraded AvBD2 and abolished its antibacterial activity. Only cathepsin K cleaved AvBD7 and released Ile4-AvBD7, a N-terminal truncated natural peptidoform of AvBD7 that displayed antibacterial activity. Besides the 3-stranded antiparallel beta-sheet typical of beta-defensins, structural analysis of AvBD7 by two-dimensional NMR spectroscopy highlighted the restricted accessibility of the C-terminus embedded by the N-terminal region and gave a formal evidence of a salt bridge (Asp9-Arg12) that could account for proteolysis resistance. The differential susceptibility of avian defensins to proteolysis opens intriguing questions about a distinctive role in the mucosal immunity against pathogen invasion. PMID:27561012

  7. The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity

    PubMed Central

    Bailleul, Geoffrey; Kravtzoff, Amanda; Joulin-Giet, Alix; Lecaille, Fabien; Labas, Valérie; Meudal, Hervé; Loth, Karine; Teixeira-Gomes, Ana-Paula; Gilbert, Florence B.; Coquet, Laurent; Jouenne, Thierry; Brömme, Dieter; Schouler, Catherine; Landon, Céline; Lalmanach, Gilles; Lalmanach, Anne-Christine

    2016-01-01

    Defensins are frontline peptides of mucosal immunity in the animal kingdom, including birds. Their resistance to proteolysis and their ensuing ability to maintain antimicrobial potential remains questionable and was therefore investigated. We have shown by bottom-up mass spectrometry analysis of protein extracts that both avian beta-defensins AvBD2 and AvBD7 were ubiquitously distributed along the chicken gut. Cathepsin B was found by immunoblotting in jejunum, ileum, caecum, and caecal tonsils, while cathepsins K, L, and S were merely identified in caecal tonsils. Hydrolysis product of AvBD2 and AvBD7 incubated with a panel of proteases was analysed by RP-HPLC, mass spectrometry and antimicrobial assays. AvBD2 and AvBD7 were resistant to serine proteases and to cathepsins D and H. Conversely cysteine cathepsins B, K, L, and S degraded AvBD2 and abolished its antibacterial activity. Only cathepsin K cleaved AvBD7 and released Ile4-AvBD7, a N-terminal truncated natural peptidoform of AvBD7 that displayed antibacterial activity. Besides the 3-stranded antiparallel beta-sheet typical of beta-defensins, structural analysis of AvBD7 by two-dimensional NMR spectroscopy highlighted the restricted accessibility of the C-terminus embedded by the N-terminal region and gave a formal evidence of a salt bridge (Asp9-Arg12) that could account for proteolysis resistance. The differential susceptibility of avian defensins to proteolysis opens intriguing questions about a distinctive role in the mucosal immunity against pathogen invasion. PMID:27561012

  8. AV Reviews.

    ERIC Educational Resources Information Center

    Hays, Rachel, Ed.

    1990-01-01

    Reviewed are four videotapes for use in biology classrooms. Included are "The Biochemical Basis of Biology. Part 2--DNA and Protein Synthesis,""The Rocky Shores,""A Visit to the Rocky Shores," and "Our Immune System." Described are the content, cost, and availability of each video. (CW)

  9. AV Corner.

    ERIC Educational Resources Information Center

    Berry, Donna A., Ed.

    1990-01-01

    Reviews three videotapes for physics teachers: (1) "Determination of the Newtonian Constant of Gravitation" showing the Cavendish experiment; (2) "Preview Film for RAM-Tutor Media" introducing a series of seven videocassettes covering physics; and (3) "Determination of the Velocity of Light" using a rotating mirror. (YP)

  10. AV Corner.

    ERIC Educational Resources Information Center

    Berry, Donna A., Ed.

    1990-01-01

    Reviewed are two 35MM slide sets "Halley's Comet Revealed" and "Supernova 1987A"; and a videotape entitled "Experiments; Physics Level 1. Magnetic Fields." Features, availability, strengths and weaknesses are discussed. (CW)

  11. AV Reviews.

    ERIC Educational Resources Information Center

    Hays, Rachel, Ed.

    1989-01-01

    Presents teacher comments on audiovisual materials dealing with: biotechnology applications in immunology, agriculture, and cancer research; efforts to halt the eutrophication of Lake Tahoe; and banana slugs. Availability and costs of materials are included. (RT)

  12. AV Review.

    ERIC Educational Resources Information Center

    Friedstein, Harriet, Ed.

    1981-01-01

    Presents a list of the producer, catalog number, format, and price of audiovisual aids for: acids, bases, and salts; atomic structure and atoms; biochemistry; bonds; water chemistry (solutions); changes of state; and electrochemistry. Includes a separate list of names and addresses of randomly selected producers of audiovisual materials. (SK)

  13. COORDINATED AV.

    ERIC Educational Resources Information Center

    CLEAVES, PAUL C.; AND OTHERS

    THE INSTRUCTIONAL MATERIALS CENTER IS LOCATED IN THE LOCAL HIGH SCHOOL AND SUPPLIES ALL SCHOOLS IN THE AREA. AUDIOVISUAL EQUIPMENT ORDERS, AFTER SELECTIONS ARE MADE BY THE CLASSROOM TEACHER, ARE PROCESSED BY THE CENTER, CONFIRMED AND DELIVERED BY TRUCK THREE TIMES EACH WEEK. EACH SCHOOL HAS A BUILDING COORDINATOR WHO CHECKS THE ORDERS INTO THE…

  14. Incidence of A-V Fistulas after Renal Biopsy of Native and Transplanted Kidney - Two Centers Experience

    PubMed Central

    Lubomirova, Mila; Krasteva, Rumiana; Bogov, Boris; Paskalev, Emil

    2015-01-01

    AIM: The aim of the study is to make a retrospective analysis of the incidence of AV fistulas after renal biopsy (RB) of native and transplanted kidney. MATERIALS AND METHODS: Five hundred and sixteen (516) RB were analyzed. One hundred twenty nine (129) were native kidneys RB performed in Clinic of Nephrology (CN), 190 were performed in Clinic of Nephrology and transplantation (CNT) and 197 were transplanted kidney biopsies from the same clinic. Biopsy technique type Gun with needle 14G, 16 and 18 G was used in CN, CNT used the same technique with needles 16G. Doppler ultrasound was made for A-V fistulas diagnosis. RESULTS: The A-V fistulas incidence was 0.8%. The frequency of A-V fistulas registered in CN was significantly higher than that registered in CNT (2.3% vs. 0.5%, p < 0.01). Biopsies performed by 14 G needles provide a higher percentage of A-V fistulas compared to those done by 16 G. (3.3% vs. 2.4%, p < 0.5). The frequency of the A-V fistulas in native and transplanted kidneys in CNT was similar (0.5% vs. 0.5%, p > 0.05). CONCLUSION: The A-V fistulas incidence is very low. The needle thickness is an important factor relevant to the risk of occurrence of A-V fistulas.

  15. 77 FR 41400 - AV Solar Ranch 1, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission AV Solar Ranch 1, LLC; Supplemental Notice That Initial Market- Based Rate...-referenced proceeding of AV Solar Ranch 1, LLC's application for market-based rate authority, with...

  16. The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells

    PubMed Central

    Schuijs, Martijn J.; Hartmann, Susanne; Selkirk, Murray E.; Roberts, Luke B.

    2016-01-01

    Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease. PMID:27560829

  17. Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2.

    PubMed

    Tambunan, Usman Sf; Zahroh, Hilyatuz; Parikesit, Arli A; Idrus, Syarifuddin; Kerami, Djati

    2015-01-01

    Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide. PMID:26617459

  18. Screening Analogs of β-OG Pocket Binder as Fusion Inhibitor of Dengue Virus 2

    PubMed Central

    Tambunan, Usman SF; Zahroh, Hilyatuz; Parikesit, Arli A; Idrus, Syarifuddin; Kerami, Djati

    2015-01-01

    Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide. PMID:26617459

  19. SalB inactivation modulates culture supernatant exoproteins and affects autolysis and viability in Enterococcus faecalis OG1RF.

    PubMed

    Shankar, Jayendra; Walker, Rachel G; Wilkinson, Mark C; Ward, Deborah; Horsburgh, Malcolm J

    2012-07-01

    The culture supernatant fraction of an Enterococcus faecalis gelE mutant of strain OG1RF contained elevated levels of the secreted antigen SalB. Using differential fluorescence gel electrophoresis (DIGE) the salB mutant was shown to possess a unique complement of exoproteins. Differentially abundant exoproteins were identified using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Stress-related proteins including DnaK, Dps family protein, SOD, and NADH peroxidase were present in greater quantity in the OG1RF salB mutant culture supernatant. Moreover, several proteins involved in cell wall synthesis and cell division, including d-Ala-d-Lac ligase and EzrA, were present in reduced quantity in OG1RF salB relative to the parent strain. The salB mutant displayed reduced viability and anomalous cell division, and these phenotypes were exacerbated in a gelE salB double mutant. An epistatic relationship between gelE and salB was not identified with respect to increased autolysis and cell morphological changes observed in the salB mutant. SalB was purified as a six-histidine-tagged protein to investigate peptidoglycan hydrolytic activity; however, activity was not evident. High-pressure liquid chromatography (HPLC) analysis of reduced muropeptides from peptidoglycan digested with mutanolysin revealed that the salB mutant and OG1RF were indistinguishable. PMID:22563054

  20. Students' Decision Steps in Meta-Cognitive Learning in Free Online Groups (MetaL-FrOG): A Case Study

    ERIC Educational Resources Information Center

    Sen Fa, Kinsley Ng; Hussin, Firuz Hussin

    2011-01-01

    What prompts the students to respond in online dialogic discussion? Why some students chose to fall out? This case study through the lens of phenomenography observation attempts to explain the five decision steps of students to respond in Meta-cognitive Learning in Free Online Groups (MetaL-FrOG) discussion. It presents a part of a research…

  1. A Method for Simultaneous Determination of AV and R and Applications

    NASA Astrophysics Data System (ADS)

    Ducati, Jorge R.; Ribeiro, Daiana; Rembold, Sandro B.

    2003-05-01

    A method for the simultaneous determination of the interstellar extinction (AV) and of the ratio of total to selective extinction (R), derived from the 1989 Cardelli, Clayton, & Mathis fitting of the interstellar extinction law, is presented and applied to a set of 1900 color excesses derived from observations of stars in UBVRIJHKL. The method is used to study the stability of AV and R within selected regions in Perseus, Scorpius, Monoceros, Orion, Sagittarius, Ophiuchus, Carina, and Serpens. Analysis shows that R is approximately constant and peculiar to each sector, with mean values that vary from 3.2 in Perseus to 5.6 in Ophiuchus. These results are similar to published values by Aiello et al., He et al., Vrba & Rydgren, O'Donnell, and Cardelli, Clayton, & Mathis.

  2. Sudden death following AV node ablation in a man with Fabry disease mimicking hypertrophic cardiomyopathy.

    PubMed

    Rodda, Odette A; Lynch, Matthew; Parsons, Sarah

    2016-08-01

    We present a case of Fabry disease with an uncommon pattern of asymmetrical hypertrophy with septal prominence resulting in an erroneous diagnosis of hypertrophic cardilmyopathy clinically. The deceased presented for a medicolegal autopsy following his sudden death after an AV node ablation. Fabry disease continues to be an important misdiagnosis of hypertrophic cardiomyopathy in a clinical setting. Early diagnosis of Fabry disease is essential so that early treatment can be instituted. PMID:27213840

  3. A.V. Usova's Contribution to the Field of Concept Learning in Physics Classroom

    ERIC Educational Resources Information Center

    Yavoruk, Oleg

    2015-01-01

    A.V. Usova (1921-2014) has always been one of the leading figures in Russian physics education. Her theory of physics concept formation was formulated during the 1970s and the 1980s and directly influenced the process of physics education in the 20th and the 21st century. Over the years there have been a lot of theories of concept formation. Her…

  4. Boron and Iron in AV 304: A B-dwarf in the SMC

    NASA Astrophysics Data System (ADS)

    Brooks, A. M.; Venn, K. A.; Lambert, D. L.; Lemke, M.

    2001-11-01

    An upper limit in the boron abundance in AV 304 is determined as a test of cosmic ray spallation as the production of boron. Boron is determined from the B III resonance line at 2066 A from HST STIS data. AV 304 does not show signs of mixing or mass loss, which can destroy the fragile boron atom. The abundance othe boron seed nucleus, oxygen, is also well known in this star, and O is approximately the same from location to location in the SMC. Thus, the boron abundance from AV 304 should be representative of the abundance in ththe entire galaxy. We find an upper limit of 12+log(B/H)=1.7. This boron upper limit is lower than the oxygen depletion relative to the solar neighborhood by 0.3 dex. This is unlike the Galactic studies that suggest that boron scales linearly with oxygen. Additionally, the numerous Fe-group elements in the UV spectrum allows for a detailed Fe-group abundance determination. We find 12+log(Fe/H)=0.7+/-0.1, primarily from Fe III lines. The abundance is in excellent agreement with determinations from Fe I and Fe II lines in A-K supergiants in the SMC, and supports that O and Fe have the same underabundance in the SMC. We appreciate support for this project from NASA GO-08661, and Clare Boothe Luce research funds.

  5. Coding efficiency of AVS 2.0 for CBAC and CABAC engines

    NASA Astrophysics Data System (ADS)

    Cui, Jing; Choi, Youngkyu; Chae, Soo-Ik

    2015-12-01

    In this paper we compare the coding efficiency of AVS 2.0[1] for engines of the Context-based Binary Arithmetic Coding (CBAC)[2] in the AVS 2.0 and the Context-Adaptive Binary Arithmetic Coder (CABAC)[3] in the HEVC[4]. For fair comparison, the CABAC is embedded in the reference code RD10.1 because the CBAC is in the HEVC in our previous work[5]. The rate estimation table is employed only for RDOQ in the RD code. To reduce the computation complexity of the video encoder, therefore we modified the RD code so that the rate estimation table is employed for all RDO decision. Furthermore, we also simplify the complexity of rate estimation table by reducing the bit depth of its fractional part to 2 from 8. The simulation result shows that the CABAC has the BD-rate loss of about 0.7% compared to the CBAC. It seems that the CBAC is a little more efficient than that the CABAC in the AVS 2.0.

  6. Role of a geminivirus AV2 protein putative protein kinase C motif on subcellular localization and pathogenicity.

    PubMed

    Chowda-Reddy, R V; Achenjang, Fidelis; Felton, Christian; Etarock, Marie T; Anangfac, Marie-Therese; Nugent, Patricia; Fondong, Vincent N

    2008-07-01

    Virus-derived genes or genome fragments are increasingly being used to generate transgenic plants with resistance to plant viruses. There is need to rapidly investigate these genes in plants using transient expression prior to using them as transgenes since they may be pathogenic to plants. In this study, we investigated the AV2 protein encoded by East African cassava mosaic Cameroon virus, a virus associated with a cassava disease epidemic in western Africa. For subcellular localization, AV2 was fused to the yellow fluorescent protein (YFP) and expressed in Nicotiana benthamiana. Confocal analyses showed that AV2-YFP localizes mainly in the cytoplasm. Because it overlaps with the coat protein gene and therefore could be used to generate transgenic plants for resistance to geminiviruses, we investigated its pathogenesis in N. benthamiana by using the Potato virus X (PVX) vector. The chimeric virus PVX-AV2 induced a mild mottling in infected plants and was shown to suppress virus-induced gene silencing (VIGS). Using point mutations, we show here that AV2 pathogenicity is dependent on a conserved putative protein kinase C (PKC) phosphorylation motif. Because of its pathogenicity and ability to suppress RNA silencing, AV2 transgenic plants will less likely provide a control to geminiviruses, indeed it may weaken the resistance of the plant. We therefore suggest the use of the AV2 putative PKC mutants to generate transgenic plants. PMID:18405995

  7. Reactive transport modeling in the subsurface environment with OGS-IPhreeqc

    NASA Astrophysics Data System (ADS)

    He, Wenkui; Beyer, Christof; Fleckenstein, Jan; Jang, Eunseon; Kalbacher, Thomas; Naumov, Dimitri; Shao, Haibing; Wang, Wenqing; Kolditz, Olaf

    2015-04-01

    Worldwide, sustainable water resource management becomes an increasingly challenging task due to the growth of population and extensive applications of fertilizer in agriculture. Moreover, climate change causes further stresses to both water quantity and quality. Reactive transport modeling in the coupled soil-aquifer system is a viable approach to assess the impacts of different land use and groundwater exploitation scenarios on the water resources. However, the application of this approach is usually limited in spatial scale and to simplified geochemical systems due to the huge computational expense involved. Such computational expense is not only caused by solving the high non-linearity of the initial boundary value problems of water flow in the unsaturated zone numerically with rather fine spatial and temporal discretization for the correct mass balance and numerical stability, but also by the intensive computational task of quantifying geochemical reactions. In the present study, a flexible and efficient tool for large scale reactive transport modeling in variably saturated porous media and its applications are presented. The open source scientific software OpenGeoSys (OGS) is coupled with the IPhreeqc module of the geochemical solver PHREEQC. The new coupling approach makes full use of advantages from both codes: OGS provides a flexible choice of different numerical approaches for simulation of water flow in the vadose zone such as the pressure-based or mixed forms of Richards equation; whereas the IPhreeqc module leads to a simplification of data storage and its communication with OGS, which greatly facilitates the coupling and code updating. Moreover, a parallelization scheme with MPI (Message Passing Interface) is applied, in which the computational task of water flow and mass transport is partitioned through domain decomposition, whereas the efficient parallelization of geochemical reactions is achieved by smart allocation of computational workload over

  8. Reactive transport modeling in variably saturated porous media with OGS-IPhreeqc

    NASA Astrophysics Data System (ADS)

    He, W.; Beyer, C.; Fleckenstein, J. H.; Jang, E.; Kalbacher, T.; Shao, H.; Wang, W.; Kolditz, O.

    2014-12-01

    Worldwide, sustainable water resource management becomes an increasingly challenging task due to the growth of population and extensive applications of fertilizer in agriculture. Moreover, climate change causes further stresses to both water quantity and quality. Reactive transport modeling in the coupled soil-aquifer system is a viable approach to assess the impacts of different land use and groundwater exploitation scenarios on the water resources. However, the application of this approach is usually limited in spatial scale and to simplified geochemical systems due to the huge computational expense involved. Such computational expense is not only caused by solving the high non-linearity of the initial boundary value problems of water flow in the unsaturated zone numerically with rather fine spatial and temporal discretization for the correct mass balance and numerical stability, but also by the intensive computational task of quantifying geochemical reactions. In the present study, a flexible and efficient tool for large scale reactive transport modeling in variably saturated porous media and its applications are presented. The open source scientific software OpenGeoSys (OGS) is coupled with the IPhreeqc module of the geochemical solver PHREEQC. The new coupling approach makes full use of advantages from both codes: OGS provides a flexible choice of different numerical approaches for simulation of water flow in the vadose zone such as the pressure-based or mixed forms of Richards equation; whereas the IPhreeqc module leads to a simplification of data storage and its communication with OGS, which greatly facilitates the coupling and code updating. Moreover, a parallelization scheme with MPI (Message Passing Interface) is applied, in which the computational task of water flow and mass transport is partitioned through domain decomposition, whereas the efficient parallelization of geochemical reactions is achieved by smart allocation of computational workload over

  9. Validation of AV-8B V/STOL characteristics by full scale static and wind tunnel tests

    NASA Technical Reports Server (NTRS)

    Hollingsworth, E. G.; Aiken, T. N.; Raggets, J.

    1977-01-01

    The background which led to the requirement for the full scale powered wind tunnel tests of an AV-8B model, and the formulation of specific objectives for the test, are outlined. The detailed planning, analysis, and coordination with NASA, NAVAIR, and other industry participants is described. The modification of an AV-8A Harrier into an AV-8B configuration suitable for full scale testing at Ames is described. In addition, instrumentation and data systems are explained. Operations during the 40 ft x 80 ft wind tunnel testing and the resulting propulsion, aerodynamic, performance, stability and control data are presented and suggestions offered for future V/STOL testing.

  10. Performance evaluation and optimization of BM4D-AV denoising algorithm for cone-beam CT images

    NASA Astrophysics Data System (ADS)

    Huang, Kuidong; Tian, Xiaofei; Zhang, Dinghua; Zhang, Hua

    2015-12-01

    The broadening application of cone-beam Computed Tomography (CBCT) in medical diagnostics and nondestructive testing, necessitates advanced denoising algorithms for its 3D images. The block-matching and four dimensional filtering algorithm with adaptive variance (BM4D-AV) is applied to the 3D image denoising in this research. To optimize it, the key filtering parameters of the BM4D-AV algorithm are assessed firstly based on the simulated CBCT images and a table of optimized filtering parameters is obtained. Then, considering the complexity of the noise in realistic CBCT images, possible noise standard deviations in BM4D-AV are evaluated to attain the chosen principle for the realistic denoising. The results of corresponding experiments demonstrate that the BM4D-AV algorithm with optimized parameters presents excellent denosing effect on the realistic 3D CBCT images.

  11. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    SciTech Connect

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  12. AV3V lesions attenuate the cardiovascular responses produced by blood-borne excitatory amino acid analogs

    NASA Technical Reports Server (NTRS)

    Whalen, E. J.; Beltz, T. G.; Lewis, S. J.; Johnson, A. K.

    1999-01-01

    Systemic injections of the excitatory amino acid (EAA) analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), produce a pressor response in conscious rats that is caused by a centrally mediated activation of sympathetic drive and the release of arginine vasopressin (AVP). This study tested the hypothesis that the tissue surrounding the anteroventral part of the third ventricle (AV3V) plays a role in the expression of the pressor responses produced by systemically injected EAA analogs. Specifically, we examined whether prior electrolytic ablation of the AV3V region would affect the pressor responses to KA and NMDA (1 mg/kg iv) in conscious rats. The KA-induced pressor response was smaller in AV3V-lesioned than in sham-lesioned rats (11 +/- 2 vs. 29 +/- 2 mmHg; P < 0.05). After ganglion blockade, KA produced a pressor response in sham-lesioned but not AV3V-lesioned rats (+27 +/- 3 vs. +1 +/- 2 mmHg; P < 0.05). The KA-induced pressor response in ganglion-blocked sham-lesioned rats was abolished by a vasopressin V1-receptor antagonist. Similar results were obtained with NMDA. The pressor response to AVP (10 ng/kg iv) was slightly smaller in AV3V-lesioned than in sham-lesioned ganglion-blocked rats (45 +/- 3 vs. 57 +/- 4 mmHg; P < 0.05). This study demonstrates that the pressor responses to systemically injected EAA analogs are smaller in AV3V-lesioned rats. The EAA analogs may produce pressor responses by stimulation of EAA receptors in the AV3V region, or the AV3V region may play an important role in the expression of these responses.

  13. Atmospheric Turbulence Measurements With the Automatic Mini UAV 'M2AV Carolo'

    NASA Astrophysics Data System (ADS)

    Bange, J.; van den Kroonenberg, A. C.; Spieß, T.; Buschmann, M.; Krüger, L.; Heindorf, A.; Vörsmann, P.

    2007-05-01

    The limitations of manned airborne meteorological measurements led to the development of an autonomously operating mini aircraft, the Meteorological Mini-UAV (M2AV), at the Institute of Aerospace Systems, Technical University of Braunschweig, Germany. The task was to develop, test and verify a meteorological sensor package as payload for an already available automatic carrier aircraft, the UAV 'Carolo T200', which operates autonomously i.e. without remote control. The M2AV is a self constructed model aircraft with two electrically powered engines and a wingspan of two meters. The maximum take-off weight is 4.5~kg (the M2AV is therefore classified as an model plane which simplifies authority issues), including 1.5~kg of payload. It is hand-launched which makes operation of the aircraft easy. With an endurance of approximately 50 minutes, the range accounts for 60 km at a cruising speed of 20~m/s. The M2AV is capable of performing turbulence measurements (wind vector, temperature and humidity) within the troposphere and offers an economic component during meteorological campaigns. The meteorological sensors are mounted on a noseboom to minimise the aircraft's influence on the measurements and to position the sensors closely to each other. Wind is measured via a small five-hole probe, an inertia measurement unit and GPS. The flight mission (waypoints, altitudes, airspeed) is planned and assigned to the aircraft before the semi- automatic launch. The flight is only controlled by the on-board autopilot system which only communicates with a ground station (laptop PC) for the exchange of measured data and command updates like new waypoints etc. The talk gives details on the technical items, calibration and first missions. Results from first field experiments like the LAUNCH-2005 campaign near Berlin are used for data quality assessment by comparison with simultaneous lidar and sodar measurements. An in situ comparison with the highly accurate helicopter-borne turbulence

  14. Tissue and cell tropism of Indian cassava mosaic virus (ICMV) and its AV2 (precoat) gene product

    SciTech Connect

    Rothenstein, Dirk; Krenz, Bjoern; Selchow, Olaf; Jeske, Holger . E-mail: holger.jeske@bio.uni-stuttgart.de

    2007-03-01

    In order to establish defined viruses for challenging plants in resistance breeding programmes, Indian cassava mosaic virus (ICMV; family Geminiviridae) DNA clones were modified to monitor viral spread in plants by replacing the coat protein gene with the green fluorescent protein (GFP) reporter gene. Comparative in situ hybridization experiments showed that ICMV was restricted to the phloem in cassava and tobacco. GFP-tagged virus spread similarly, resulting in homogeneous fluorescence within nuclei and cytoplasm of infected cells. To analyze viral intercellular transport in further detail, GFP was fused to AV2, a protein that has been implicated in viral movement. Expressed from replicating viruses or from plasmids, AV2:GFP became associated with the cell periphery in punctate spots, formed cytoplasmic as well as nuclear inclusion bodies, the latter as conspicuous paired globules. Upon particle bombardment of expression plasmids, AV2:GFP was transported into neighboring cells of epidermal tissues showing that the intercellular transport of the AV2 protein is not restricted to the phloem. The results are consistent with a redundant function of ICMV AV2 acting as a movement protein, presumably as an evolutionary relic of a monopartite geminivirus that may still increase virus fitness but is no longer necessary in a bipartite genome. The fusion of ICMV ORF AV2 to the GFP gene is the first example of a reporter construct that follows the whole track of viral DNA from inside the nucleus to the cell periphery and to the next cell.

  15. Og4C3 circulating antigen: a marker of infection and adult worm burden in Wuchereria bancrofti filariasis.

    PubMed

    Chanteau, S; Moulia-Pelat, J P; Glaziou, P; Nguyen, N L; Luquiaud, P; Plichart, C; Martin, P M; Cartel, J L

    1994-07-01

    Og4C3 circulating filarial antigen was detected in the sera of 94.5% (259/274) of microfilaremic patients, 32% (239/751) of persons with presumption of filariasis, and 23% (11/48) of chronic filariasis patients. The antigen level was correlated with the microfilariae (Mf) density and patient age (P < .01). It remained stable in patients treated with microfilaricidal drugs. Og4C3 antigen, undetectable in Mf culture media, was demonstrated to be a rare somatic Mf antigen. It appears to be an excreted or secreted antigen from adult filaria. It could be used as a marker of infection and an indicator of adult worm burden. PMID:8014511

  16. PET2OGS: Algorithms to link the static model of Petrel with the dynamic model of OpenGeoSys

    NASA Astrophysics Data System (ADS)

    Park, C.-H.; Shinn, Y. J.; Park, Y.-C.; Huh, D.-G.; Lee, S. K.

    2014-01-01

    A set of three algorithms named PET2OGS is developed to integrate the static model (Petrel) with the dynamic model (OpenGeoSys). PET2OGS consists of three sub-algorithms that convert finite difference methods (FDMs) grids to finite element methods (FEMs) grids. The algorithms and the workflow of the integration procedures are described in detail. After the proposed algorithms are tested on a variety of grids both in homogeneous and heterogeneous media, the integrated platform of the static and dynamic models is applied to model CO2 storage in a saline aquifer. A successful demonstration of the proposed algorithms proved a robust integration of the platform. With some minor modifications of the algorithms in the part of input and output, the proposed algorithms can be extended to integrate different combinations of FDM-based static models and FEM-based dynamic models beyond the example combination in the paper.

  17. Meteorological profiling of the lower troposphere using the research UAV "M2AV Carolo"

    NASA Astrophysics Data System (ADS)

    Martin, S.; Bange, J.; Beyrich, F.

    2011-04-01

    Vertical profiles of temperature, humidity and wind up to a height of 1500 m a.g.l. (above ground level) were measured with the automatically operating small unmanned research aircraft M2AV (Meteorological Mini Aerial Vehicle) during the LITFASS-2009 LIndenberg-To-Falkenberg: Aircraft, Scintillometer and large-eddy Simulation) experiment. The campaign took place in July 2009 over the heterogeneous landscape around the Meteorological Observatory Lindenberg - Richard-Aßmann-Observatory in the eastern part of Germany. Due to a high vertical resolution of about 10 cm the M2AV data show details of the turbulent structure of the atmospheric boundary layer (ABL). One profile took about 10-15 min allowing for a continuous monitoring of certain phases of ABL development by successive ascents and descents during one flight (50-60 min duration). Two case studies of measurements performed during the morning and evening ABL transition periods are discussed in detail. Comparison of the aircraft-based temperature, humidity and wind profiles with tower, sodar/RASS, wind profiler/RASS, radiosoundings and microwave radiometer profiler measurements show good agreement taking into account the different sampling strategies of these measurement systems.

  18. Meteorological profiling of the lower troposphere using the research UAV "M2AV Carolo"

    NASA Astrophysics Data System (ADS)

    Martin, S.; Bange, J.; Beyrich, F.

    2010-11-01

    Vertical profiles of temperature, humidity and wind up to a height of 1500 m a.g.l. (above ground level) were measured with the automatically operating small unmanned research aircraft M2AV (Meteorological Mini Aerial Vehicle) during the LITFASS-2009 (LIndenberg-To-Falkenberg: Aircraft, Scintillometer and large-eddy Simulation) experiment. The campaign took place in July 2009 over the heterogeneous landscape around the Meteorologcial Observatory Lindenberg - Richard-Aßmann-Observatory in the eastern part of Germany. Due to a high vertical resolution of about 10 cm the M2AV data show details of the turbulent structure of the atmospheric boundary layer (ABL). One profile takes about 10-15 min allowing for a continuous monitoring of certain phases of ABL development by successive ascents and descents during one flight (50-60 min duration). Two case studies of measurements performed during the morning and evening ABL transition periods are discussed in detail. Comparison of the aircraft-based temperature, humidity and wind profiles with tower, sodar/RASS, wind profiler/RASS, radiosoundings and microwave radiometer profiler measurements show good agreement taking into account the different sampling strategies of these measurement systems.

  19. Development of cereal-based functional food using cereal-mix substrate fermented with probiotic strain - Pichia kudriavzevii OG32.

    PubMed

    Ogunremi, Omotade R; Agrawal, Renu; Sanni, Abiodun I

    2015-11-01

    Probiotic strains contribute to the functionality of foods during fermentation. In this present work, cereal-mix was fermented with probiotic Pichia kudriavzevii OG32. Selected fermentation parameters and functional properties of the product were determined. The growth of Pichia kudriavzevii OG32 was supported by the cereal-mix containing 1% salt and 0.2% red chili powder to counts of between 7.46 and 8.22 Log10 cfu/mL within 24 h. Pichia kudriavzevii OG32 increased the viscosity of cereal-mix with the highest inoculum size (1.84x105cfu/ml) giving the highest viscosity of 1793.6 mPa.S. An inoculum size of 1.98 × 10(4) cfu/mL gave the most acceptable product based on the sensory evaluation by the panelist. Forty volatile compounds were identified in the fermented product, while acids (32.21%) and esters (32.37%) accounted for the largest proportions. The cereal-based fermented product scavenged DPPH from 200 μmol/L methanolic solution by 55.71%. Probiotic yeast improved the sensory and some functional properties of cereal-based substrate during fermentation. This is one of the first reports on the volatile composition of cereal-based functional food produced with probiotic yeast. PMID:26788290

  20. Construction of Recombinant Pichia pastoris Carrying a Constitutive AvBD9 Gene and Analysis of Its Activity.

    PubMed

    Tu, Jian; Qi, Kezong; Xue, Ting; Wei, Haiting; Zhang, Yongzheng; Wu, Yanli; Zhou, Xiuhong; Lv, Xiaolong

    2015-12-28

    Avian beta-defensin 9 (AvBD9) is a small cationic peptide consisting of 41 amino acids that plays a crucial rule in innate immunity and acquired immunity in chickens. Owing to its wide antibacterial spectrum, lack of a residue, and failure to induce bacterial drug resistance, AvBD9 is expected to become a substitute for conventional antibiotics in the livestock and poultry industries. Using the preferred codon of Pichia pastoris, the mature AvBD9 peptide was designed and synthesized, based on the sequence from GenBank. The P. pastoris constitutive expression vector pGHKα was used to construct a pGHKα-AvBD9 recombinant plasmid. Restriction enzyme digestion was performed using SacI and BglII to remove the ampicillin resistance gene, and the plasmid was electrotransformed into P. pastoris GS115. High-expression strains with G418 resistance were screened, and the culture supernatant was analyzed by Tricine-SDS-PAGE and western blot assay to identify target bands of about 6 kDa. A concentrate of the supernatant containing AvBD9 was used for determination of antimicrobial activity. The supernatant concentrate was effective against Escherichia coli, Salmonella paratyphi, Salmonella pullorum, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterobacter cloacae. The fermentation product of P. pastoris carrying the recombinant AvBD9 plasmid was adjusted to 1.0 × 10(8) CFU/ml and added to the drinking water of white feather broilers at different concentrations. The daily average weight gain and immune organ indices in broilers older than 7 days were significantly improved by the AvBD9 treatment. PMID:26370794

  1. Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

    PubMed Central

    Choi, Seok Rye; Golding, Geoff; Zhuang, Zhiping; Zhang, Wei; Lim, Nathaniel; Hefti, Franz; Benedum, Tyler E.; Kilbourn, Michael R.; Skovronsky, Daniel; Kung, Hank F.

    2011-01-01

    β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain. PMID:19837759

  2. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally☆

    PubMed Central

    Kyriacou, Andreas; Pabari, Punam A.; Mayet, Jamil; Peters, Nicholas S.; Davies, D. Wyn; Lim, P. Boon; Lefroy, David; Hughes, Alun D.; Kanagaratnam, Prapa; Francis, Darrel P.; I.Whinnett, Zachary

    2014-01-01

    Background The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown. Methods Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). Results AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02). Conclusions Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”. PMID:24332598

  3. Optimization of Automated Radiosynthesis of [18F]AV-45: A New PET Imaging Agent for Alzheimer’s Disease

    PubMed Central

    Liu, Yajing; Zhu, Lin; Plössl, Karl; Choi, Seok Rye; Qiao, Hongwen; Sun, Xiaotao; Li, Song; Zha, Zhihao; Kung, Hank F

    2010-01-01

    Introduction Accumulation of β-amyloid (Aβ) aggregates in the brain is linked to the pathogenesis of Alzheimer’s disease (AD). Imaging probes targeting these Aβ aggregates in the brain may provide a useful tool to facilitate the diagnosis of AD. Recently, [18F]AV-45 ([18F]5) demonstrated high binding to the Aβ aggregates in AD patients. To improve the availability of this agent for widespread clinical application, a rapid, fully automated high yield, cGMP-compliant radiosynthesis was necessary for production of this probe. We report herein an optimal [18F]fluorination, de-protection condition and fully automated radiosynthsis of [18F]AV-45 ([18F]5) on a radiosynthesis module (BNU F-A2). Methods The preparation of [18F]AV-45 ([18F]5) was evaluated under different conditions, specifically by employing different precursors (-OTs and -Br as the leaving group), reagents (K222/K2CO3 vs. tributylammonium bicarbonate) and de-protection in different acids. With optimized conditions from these experiments, the automated synthesis of [18F]AV-45 ([18F]5) was accomplished by using a computer-programmed, standard operating procedure, and was purified on an on-line solid-phase cartridge (Oasis HLB). Results The optimized reaction conditions were successfully implemented to an automated nucleophilic fluorination module. The radiochemical purity of [18F]AV-45 ([18F]5) was > 95%, and the automated synthesis yield was 33.6 ± 5.2% (no decay corrected, n = 4), 50.1 ± 7.9% (decay corrected) in 50 min at a quantity level of 10~100 mCi (370~3700 MBq). Autoradiography studies of [18F]AV-45 ([18F]5) using postmortem AD brain and Tg mouse brain sections in the presence of different concentration of “cold” AV-136 showed a relatively low inhibition of in vitro binding of [18F]AV-45 ([18F]5) to the Aβ plaques (IC50 = 1-4 μM, a concentration several order of magnitude higher than the expected pseudo carrier concentration in the brain). Conclusions Solid phase extraction (SPE

  4. Inherently mass-conservative version of the semi-Lagrangian Absolute Vorticity (SL-AV) atmospheric model dynamical core

    NASA Astrophysics Data System (ADS)

    Shashkin, V. V.; Tolstykh, M. A.

    2013-09-01

    The semi-Lagrangian Absolute Vorticity (SL-AV) atmospheric model is the global semi-Lagrangian hydrostatic model used for operational medium-range and seasonal forecasts at Hydrometeorological centre of Russia. The distinct feature of SL-AV dynamical core is the semi-implicit semi-Lagrangian vorticity-divergence formulation on the unstaggered grid. Semi-implicit semi-Lagrangian approach allows for long time steps while violates the global and local mass-conservation. In particular, the total mass in simulations with semi-Lagrangian models can drift significantly if no aposteriori mass-fixing algorithms are applied. However, the global mass-fixing algorithms degrade the local mass conservation. The inherently mass-conservative version of SL-AV model dynamical core presented in the article ensures global and local mass conservation without mass-fixing algorithms. The mass conservation is achieved with the introduction of the finite-volume semi-Lagrangian discretization for continuity equation based on the 3-D extension of the conservative cascade semi-Lagrangian transport scheme (CCS). The numerical experiments show that the presented new version of SL-AV dynamical core combines the accuracy and stability of the standard SL-AV dynamical core with the mass-conservation properties. The results of the mountain induced Rossby wave test and baroclinic instability test for mass-conservative dynamical core are found to be in agreement with the results available in literature.

  5. Inherently mass-conservative version of the semi-Lagrangian absolute vorticity (SL-AV) atmospheric model dynamical core

    NASA Astrophysics Data System (ADS)

    Shashkin, V. V.; Tolstykh, M. A.

    2014-02-01

    The semi-Lagrangian absolute vorticity (SL-AV) atmospheric model is the global semi-Lagrangian hydrostatic model used for operational medium-range and seasonal forecasts at the Hydrometeorological Centre of Russia. The distinct feature of the SL-AV dynamical core is the semi-implicit, semi-Lagrangian vorticity-divergence formulation on the unstaggered grid. A semi-implicit, semi-Lagrangian approach allows for long time steps but violates the global and local mass conservation. In particular, the total mass in simulations with semi-Lagrangian models can drift significantly if no a posteriori mass-fixing algorithm is applied. However, the global mass-fixing algorithms degrade the local mass conservation. The new inherently mass-conservative version of the SL-AV model dynamical core presented here ensures global and local mass conservation without mass-fixing algorithms. The mass conservation is achieved with the introduction of the finite-volume, semi-Lagrangian discretization for a continuity equation based on the 3-D extension of the conservative cascade semi-Lagrangian transport scheme (CCS). Numerical experiments show that the new version of the SL-AV dynamical core presented combines the accuracy and stability of the standard SL-AV dynamical core with the mass-conservation properties. The results of the mountain-induced Rossby-wave test and baroclinic instability test for the mass-conservative dynamical core are found to be in agreement with the results available in the literature.

  6. [WPW syndrome combined with AV block 2 in an adult with glycogenosis (Type II)].

    PubMed

    Francesconi, M; Auff, E; Ursin, C; Sluga, E

    1982-08-01

    A 31 year-old female with a five year history of muscle weakness, cardiac palpitations and elevation of activity of some serum enzymes of muscular origin, showed signs of the WPW syndrome on ECG, often in combination with grade 2 A-V block. Type II glycogenosis (Pompe's disease) was diagnosed on the basis of the results of physical examination, laboratory findings--especially subtotal deficiency of acid maltase (a-1,4 glucosidase) activity-and morphological aspects of light and electron microscopy of a quadriceps muscle biopsy specimen. To our knowledge the coincidence of such a rarely encountered arrhythmia with glycogenosis type II in an adult has never been reported so far. PMID:6959422

  7. Introduction to COFFE: The Next-Generation HPCMP CREATE-AV CFD Solver

    NASA Technical Reports Server (NTRS)

    Glasby, Ryan S.; Erwin, J. Taylor; Stefanski, Douglas L.; Allmaras, Steven R.; Galbraith, Marshall C.; Anderson, W. Kyle; Nichols, Robert H.

    2016-01-01

    HPCMP CREATE-AV Conservative Field Finite Element (COFFE) is a modular, extensible, robust numerical solver for the Navier-Stokes equations that invokes modularity and extensibility from its first principles. COFFE implores a flexible, class-based hierarchy that provides a modular approach consisting of discretization, physics, parallelization, and linear algebra components. These components are developed with modern software engineering principles to ensure ease of uptake from a user's or developer's perspective. The Streamwise Upwind/Petrov-Galerkin (SU/PG) method is utilized to discretize the compressible Reynolds-Averaged Navier-Stokes (RANS) equations tightly coupled with a variety of turbulence models. The mathematics and the philosophy of the methodology that makes up COFFE are presented.

  8. An area-efficient VLSI architecture for AVS intra frame encoder

    NASA Astrophysics Data System (ADS)

    Zhang, Ke; Yu, Lu

    2007-01-01

    In this paper, we propose a VLSI architecture for AVS intra frame encoder. Reconstruction loop hinders the parallelism exploration and becomes the critical path in an intra frame encoder. A First Selection Then Prediction (FSTP) method is proposed to break the loop and enable the parallel process of intra mode selection and reconstruction on neighboring blocks. In addition, area-efficient modules were developed. Configurable intra predictor can support all the intra prediction modes. A CA-2D-VLC engine with an area-efficient Exp-Golomb encoder was developed to meet the encoding speed demand with comparably low hardware cost. Synthesized with 0.18 m CMOS standard-cell library, the overall hardware cost of the proposed intra frame encoder is 89k logic gates at the clock frequency constraint of 125MHz. Proposed encoder can satisfy real time encoding of 720x576 4:2:0 25fps video at the working frequency of 54MHz.

  9. Radiolysis of the AV-17×8 ČS anion-exchange resin

    NASA Astrophysics Data System (ADS)

    Bartoníček, B.; Habersbergerová, A.; Janovský, I.; Kysela, J.; Pejša, R.

    The mixture of the anion exchange resin AV-17×8 čs in borate form and of a deaerated aqueous solution containing H 3BO 3 and NH 3 ( pH = 7) was irradiated with gamma rays in both static and dynamic conditions. A loss of strong-base exchange capacity and an increase of weak-base capacity was observed. In the solution, (CH 3) 3N, (CH 3) 2NH and CH 3NH 2 were found as the radiolytic products, their relative ratio being 15.7 : 3.7 : 1. Further, NH 3 is formed with the concentration of the same order as that of CH 3NH 2. Beside hydrogen, which is the prevailing gaseous product of the radiolysis of the mixture, methane and ethane arise, their ratio in the dynamic irradiation being 2.8 to 6.0. The main features of the radiolysis are outlined.

  10. Transient AV Block as a Hemodynamic Complication of the Influenza A Virus: A Case Report.

    PubMed

    Rivera-Guzmán, Norwin; Del Olmo-Arroyo, Francisco; Robles-Arías, Carlos M; Rodríguez-Cintrón, William

    2016-09-01

    Influenza virus causes annual epidemics of respiratory illness characterized by sudden onset of fever, malaise, myalgias, headache, cough, and other respiratory complains. Each year in the United States, it is estimated that this debilitating respiratory illness accounts for 294,000 excess hospitalizations and 36,000 attributable deaths. Epidemiological studies describe increased cardiovascular mortality during influenza seasons. Cardiovascular involvement in acute influenza infection can occur through direct effects of the virus on the myocardium or through exacerbation of existing cardiovascular disease. The purpose of this report is to document a transient atrioventricular (AV) block with hemodynamic compromise after infection with the influenza virus in a patient with underlying cardiac disease without myocarditis. PMID:27623145

  11. Geologic Mapping of the Av-14 Urbinia Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Mest, S. C.; Yingst, R. A.; Williams, D. A.; Garry, W. B.; Pieters, C. M.; Jaumann, R.; Buczkowski, D. L.; Sykes, M. V.; Wyrick, D. Y.; Schenk, P. M.; Russell, C. T.; Raymond, C. A.; Neukum, G.; Schmedemann, N.; Roatsch, T.; Preusker, F.; Ammannito, E.

    2012-04-01

    NASA's Dawn spacecraft is providing unprecedented views of the surface of 4 Vesta since it went into orbit in July 2011. Dawn is actively gathering an abundance of image, spectral and topographic data to characterize the geology, composition, shape and internal structure of the ~560-km-diameter asteroid. Geologic mapping of Vesta's surface is being undertaken at the global and regional scales by subdividing Vesta into 15 quadrangles. Here, we report the mapping results for quadrangle Av-14, the Urbinia quadrangle of Vesta, derived from data acquired during the High Altitude Mapping Orbit (HAMO) and Survey orbit. Base materials for mapping include HAMO-derived monochrome (clear filter) Framing Camera (FC) mosaic (~70 m/pixel and a Digital Terrain Model (DTM) derived from Survey orbit FC data (450 m/pixel). We also use FC color ratio images (~250 m/pixel) from Survey orbit and Visible and InfraRed (VIR) hyperspectral images from Survey (700 m/pixel) and HAMO (200 m/pixel) orbits to provide information on surface composition and refine unit boundaries. The Av-14 Quadrangle covers the region between 21°-66°S latitude and 270°-360°E longitude. The quadrangle is named after crater Urbinia (D=24 km; 30°S, 276°E), which displays an ejecta blanket with moderate albedo and a smooth, lightly cratered surface. The map area is dominated by moderately cratered equatorial terrains and lightly cratered, but highly deformed, southern terrains. The topographic gradient of the map area is declined toward the south from the more elevated equatorial terrain to the relatively lower interior of the Rheasilivia impact basin. Av-14 contains two dominant terrains - (1) intermediately-cratered equatorial terrain bearing flat-floored, E-W-trending troughs, and (2) relatively lightly-cratered south polar terrain, which contains the Rheasilvia impact basin and related terrains. The northern part of the quadrangle is covered by the moderately cratered equatorial ridge-and-trough terrain

  12. Physical Characteristics of Asteroid-like Comet Nucleus C/2001 OG108 (LONEOS)

    NASA Technical Reports Server (NTRS)

    Abell, P. A.; Fernandez, Y. R.; Pravec, P.; French, L. M.; Farnham, T. L.; Gaffey, M. J.; Hardersen, P. S.; Kusnirak, P.; Sarounova, L.; Sheppard, S. S.

    2003-01-01

    For many years several investigators have suggested that some portion of the near-Earth asteroid population may actually be extinct cometary nuclei. Evidence used to support these hypotheses was based on: observations of asteroid orbits and associated meteor showers (e.g. 3200 Phaethon and the Geminid meteor shower); low activity of short period comet nuclei, which implied nonvolatile surface crusts (e.g. Neujmin 1, Arend-Rigaux); and detections of transient cometary activity in some near-Earth asteroids (e.g. 4015 Wilson-Harrington). Recent investigations have suggested that approximately 5-10% of the near- Earth asteroid population may be extinct comets. However if members of the near-Earth asteroid population are extinct cometary nuclei, then there should be some objects within this population that are near their final stages of evolution and so should demonstrate only low levels of activity. The recent detections of coma from near-Earth object 2001 OG108 have renewed interest in this possible comet-asteroid connection. This paper presents the first high quality ground-based near-infrared reflectance spectrum of a comet nucleus combined with detailed lightcurve and albedo measurements.

  13. The dependence of the AV prior for SN Ia on host mass and disc inclination

    NASA Astrophysics Data System (ADS)

    Holwerda, B. W.; Keel, W. C.; Kenworthy, M. A.; Mack, K. J.

    2015-08-01

    Type Ia supernovae (SNe Ia) are used as `standard candles' for cosmological distance scales. To fit their light-curve shape-absolute luminosity relation, one needs to assume an intrinsic colour and a likelihood of host galaxy extinction or a convolution of these, a colour distribution prior. The host galaxy extinction prior is typically assumed to be an exponential drop-off for the current supernova programmes (P(A_V) ∝ e^{-A_V/τ_0}). We explore the validity of this prior using the distribution of extinction values inferred when two galaxies accidentally overlap (an occulting galaxy pair). We correct the supernova luminosity distances from the SDSS-III supernova projects (SDSS-SN) by matching the host galaxies to one of three templates from occulting galaxy pairs based on the host galaxy mass and the AV-bias-prior-scale (τ0) relation from Jha et al. We find that introducing an AV prior that depends on host mass results in lowered luminosity distances for the SDSS-SN on average but it does not reduce the scatter in individual measurements. This points, in our view, to the need for many more occulting galaxy templates to match to SN Ia host galaxies to rule out this possible source of scatter in the SN Ia distance measurements. We match occulting galaxy templates based on both mass and projected radius and we find that one should match by stellar mass first with radius as a secondary consideration. We discuss the caveats of the current approach: the lack of enough radial coverage, the small sample of priors (occulting pairs with HST data), the effect of gravitationally interacting as well as occulting pairs, and whether an exponential distribution is appropriate. Our aim is to convince the reader that a library of occulting galaxy pairs observed with HST will provide sufficient priors to improve (optical) SN Ia measurements to the next required accuracy in cosmology.

  14. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    SciTech Connect

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate

  15. A Comparison of the AVS-9 and the Panoramic Night Vision Goggles During Rotorcraft Hover and Landing

    NASA Technical Reports Server (NTRS)

    Szoboszlay, Zoltan; Haworth, Loran; Simpson, Carol

    2000-01-01

    A flight test was conducted to assess any differences in pilot-vehicle performance and pilot opinion between the use of a current generation night vision goggle (the AVS-9) and one variant of the prototype panoramic night vision goggle (the PNVGII). The panoramic goggle has more than double the horizontal field-of-view of the AVS-9, but reduced image quality. Overall the panoramic goggles compared well to the AVS-9 goggles. However, pilot comment and data are consistent with the assertion that some of the benefits of additional field-of-view with the panoramic goggles were negated by the reduced image quality of the particular variant of the panoramic goggles tested.

  16. Chemometric formulation of bacterial consortium-AVS for improved decolorization of resonance-stabilized and heteropolyaromatic dyes.

    PubMed

    Kumar, Madhava Anil; Kumar, Vaidyanathan Vinoth; Premkumar, Manickam Periyaraman; Baskaralingam, Palanichamy; Thiruvengadaravi, Kadathur Varathachary; Dhanasekaran, Anuradha; Sivanesan, Subramanian

    2012-11-01

    A bacterial consortium-AVS, consisting of Pseudomonas desmolyticum NCIM 2112, Kocuria rosea MTCC 1532 and Micrococcus glutamicus NCIM 2168 was formulated chemometrically, using the mixture design matrix based on the design of experiments methodology. The formulated consortium-AVS decolorized acid blue 15 and methylene blue with a higher average decolorization rate, which is more rapid than that of the pure cultures. The UV-vis spectrophotometric, Fourier transform infra red spectrophotometric and high performance liquid chromatographic analysis confirm that the decolorization was due to biodegradation by oxido-reductive enzymes, produced by the consortium-AVS. The toxicological assessment of plant growth parameters and the chlorophyll pigment concentrations of Phaseolus mungo and Triticum aestivum seedlings revealed the reduced toxic nature of the biodegraded products. PMID:22940340

  17. Geologic Mapping of the Av-13 Tuccia Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Kneissl, T.; Schmedemann, N.; Neukum, G.; Williams, D. A.; Garry, W. B.; Yingst, R. A.; Ammannito, E.; Jaumann, R.; Pieters, C. M.; Russell, C. T.; Raymond, C. A.; Schenk, P.; Hiesinger, H.; McCord, T. B.; Buczkowski, D.; Nathues, A.; Reddy, V.; Büttner, I.; Krohn, K.; Preusker, F.

    2012-04-01

    NASA's Dawn spacecraft is spending one year in orbit around asteroid 4Vesta to characterize its geology, chemical and mineralogical composition, topography, shape, and internal structure. The Dawn Team is conducting geological mapping of the surface in the form of one global and 15 quadrangle maps, and here we report results from the mapping of Tuccia quadrangle Av-13. Mapping is based on a Framing Camera (FC) mosaic produced from High Altitude Mapping Orbit (HAMO) data with a spatial resolution of ~70 m/pixel, supplemented by a Digital Terrain Model (DTM: lateral spacing of 450 m/pixel and vertical accuracy of ~30 meters), FC color images, and Visible and InfraRed (VIR) hyperspectral images. The Av-13 Quadrangle covers the region between 21°-66°S latitude and 180°-270°E longitude. It shows mainly three different terrains: Vestalia Terra located in the north of the quadrangle, the Equatorial Cratered Terrain, and the Ridge-and-Groove Terrain which is part of the Rheasilvia Formation. The Tuccia impact crater which names quadrangle Av-13 is located at 40°S and 197°E and has a diameter of about 16 km. The bright-rayed crater on its rim has a diameter of ~3.4 km. The crater Vibidia is located at 27.9°S and 220.3°E and has a diameter of ~7.5 km. It is a bright-rayed crater, which, however, also excavated dark material visible on the crater floor and at the eastern crater rim. Outcrops of dark material are also located at the eastern crater wall of a 25km-diameter crater at 30.0°S and 228.0°E. Another interesting crater is located at 60°S and 200°E on a steep slope on the Rheasilvia ridge-and-groove terrain. This crater has a diameter of approximately 15 km and shows a sharp, undegraded crater rim in the north and a highly degraded/mantled crater rim in the south. Proposed formation processes for this irregular crater rim are: ballistic ejecta coverage of the southern rim, incomplete formation of the rim, as well as mass-wasting processes like slumping and

  18. Videos for Science Communication and Nature Interpretation: The TIB|AV-Portal as Resource.

    NASA Astrophysics Data System (ADS)

    Marín Arraiza, Paloma; Plank, Margret; Löwe, Peter

    2016-04-01

    Scientific audiovisual media such as videos of research, interactive displays or computer animations has become an important part of scientific communication and education. Dynamic phenomena can be described better by audiovisual media than by words and pictures. For this reason, scientific videos help us to understand and discuss environmental phenomena more efficiently. Moreover, the creation of scientific videos is easier than ever, thanks to mobile devices and open source editing software. Video-clips, webinars or even the interactive part of a PICO are formats of scientific audiovisual media used in the Geosciences. This type of media translates the location-referenced Science Communication such as environmental interpretation into computed-based Science Communication. A new way of Science Communication is video abstracting. A video abstract is a three- to five-minute video statement that provides background information about a research paper. It also gives authors the opportunity to present their research activities to a wider audience. Since this kind of media have become an important part of scientific communication there is a need for reliable infrastructures which are capable of managing the digital assets researchers generate. Using the reference of the usecase of video abstracts this paper gives an overview over the activities by the German National Library of Science and Technology (TIB) regarding publishing and linking audiovisual media in a scientifically sound way. The German National Library of Science and Technology (TIB) in cooperation with the Hasso Plattner Institute (HPI) developed a web-based portal (av.tib.eu) that optimises access to scientific videos in the fields of science and technology. Videos from the realms of science and technology can easily be uploaded onto the TIB|AV Portal. Within a short period of time the videos are assigned a digital object identifier (DOI). This enables them to be referenced, cited, and linked (e.g. to the

  19. 76 FR 42031 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    ... (76 FR 19721). That NPRM proposed to correct an unsafe condition for the specified products. The MCAI... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant... Services GmbH (Type Certificate Previously Held by AvCraft Aerospace GmbH; Fairchild Dornier GmbH;...

  20. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers.

    PubMed

    Smith, Ruben; Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet; Hansson, Oskar

    2016-09-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with (18)F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer's disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited (18)F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was (18)F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β ((18)F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that (18)F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  1. Balloon launched decelerator test program: Post-flight test report, BLDT vehicle AV-2, Viking 1975 project

    NASA Technical Reports Server (NTRS)

    Dickinson, D.; Hicks, F.; Schlemmer, J.; Michel, F.; Moog, R. D.

    1972-01-01

    The pertinent events concerned with the launch, float, and flight of balloon launched decelerator test vehicle AV-2 are discussed. The performance of the decelerator system is analyzed. Data on the flight trajectory and decelerator test points at the time of decelerator deployment are provided. A description of the time history of vehicle events and anomalies encounters during the mission is included.

  2. Do acid volatile sulfides (AVS) influence the accumulation of sediment-bound metals to benthic invertebrates under natural field conditions?

    PubMed

    De Jonge, Maarten; Dreesen, Freja; De Paepe, Josefina; Blust, Ronny; Bervoets, Lieven

    2009-06-15

    The present study evaluates the influence of acid volatile sulfides (AVS) on accumulation of sediment-bound metals in benthic invertebrates under natural field conditions. Natural sediments, pore water, surface water, and two species of widespread benthic invertebrates (Chironomus gr. thummi and Tubifex tubifex) were collected from 17 historical polluted Flemish lowland rivers and measured for metal concentrations. Different sediment characteristics were determined (AVS, organic matter, clay content) and multiple regression was used to study their relationship with accumulated metals in the invertebrates. Physical and chemical analysis of the field samples indicated low metal concentrations in the water and pore water, but very high metal concentrations in the sediment and the invertebrates, especially for Pb (5.99 micromol/ g). In general, metal accumulation in chironomids and tubificid worms was most strongly correlated with total metal concentrations in the sediment and sediment metal concentrations normalized for organic matter and clay content. Following the results of the linear regression model, AVS did not turn out to be a significant variable in describing variation in metal accumulation. Our study clearly demonstrates that, in addition to the results gained from experiments under lab conditions, benthic invertebrates can accumulate metals from unspiked field sediments even when there's an excess of AVS. PMID:19603670

  3. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

    PubMed Central

    Puschmann, Andreas; Schöll, Michael; Ohlsson, Tomas; van Swieten, John; Honer, Michael; Englund, Elisabet

    2016-01-01

    Tau positron emission tomography ligands provide the novel possibility to image tau pathology in vivo. However, little is known about how in vivo brain uptake of tau positron emission tomography ligands relates to tau aggregates observed post-mortem. We performed tau positron emission tomography imaging with 18F-AV-1451 in three patients harbouring a p.R406W mutation in the MAPT gene, encoding tau. This mutation results in 3- and 4-repeat tau aggregates similar to those in Alzheimer’s disease, and many of the mutation carriers initially suffer from memory impairment and temporal lobe atrophy. Two patients with short disease duration and isolated memory impairment exhibited 18F-AV-1451 uptake mainly in the hippocampus and adjacent temporal lobe regions, correlating with glucose hypometabolism in corresponding regions. One patient died after 26 years of disease duration with dementia and behavioural deficits. Pre-mortem, there was 18F-AV-1451 uptake in the temporal and frontal lobes, as well as in the basal ganglia, which strongly correlated with the regional extent and amount of tau pathology in post-mortem brain sections. Amyloid-β (18F-flutemetamol) positron emission tomography scans were negative in all cases, as were stainings of brain sections for amyloid. This provides strong evidence that 18F-AV-1451 positron emission tomography can be used to accurately quantify in vivo the regional distribution of hyperphosphorylated tau protein. PMID:27357347

  4. Balloon launched decelerator test program: Post-flight test report, BLDT vehicle AV-3, Viking 1975 project

    NASA Technical Reports Server (NTRS)

    Dickinson, D.; Hicks, F.; Schlemmer, J.; Michel, F.; Moog, R. D.

    1973-01-01

    The pertinent events concerned with the launch, float, and flight of balloon launched decelerator test vehicle AV-3 are discussed. The performance of the decelerator system is analyzed. Data on the flight trajectory and decelerator test points at the time of decelerator deployment are provided. A description of the time history of vehicle events and anaomalies encounters during the mission is included.

  5. Draft Genome Sequence of Bacillus alcalophilus AV1934, a Classic Alkaliphile Isolated from Human Feces in 1934.

    PubMed

    Attie, Oliver; Jayaprakash, Anitha; Shah, Hardik; Paulsen, Ian T; Morino, Masato; Takahashi, Yuka; Narumi, Issay; Sachidanandam, Ravi; Satoh, Katsuya; Ito, Masahiro; Krulwich, Terry A

    2014-01-01

    Bacillus alcalophilus AV1934, isolated from human feces, was described in 1934 before microbiome studies and recent indications of novel potassium ion coupling to motility in this extremophile. Here, we report draft sequences that will facilitate an examination of whether that coupling is part of a larger cycle of potassium ion-coupled transporters. PMID:25395643

  6. 76 FR 19721 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will... Services GmbH (Type Certificate Previously Held by AvCraft Aerospace GmbH; Fairchild Dornier GmbH; Dornier Luftfahrt GmbH) Model 328-100 and -300 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT....

  7. AV119, a natural sugar from avocado gratissima, modulates the LPS-induced proinflammatory response in human keratinocytes.

    PubMed

    Donnarumma, Giovanna; Paoletti, Iole; Buommino, Elisabetta; Fusco, Alessandra; Baudouin, Caroline; Msika, Philippe; Tufano, Maria Antonietta; Baroni, Adone

    2011-12-01

    Keratinocytes play an active role in innate immune responses by secreting a variety of cytokines and chemokines. The release of critical proinflammatory cytokines, which are necessary to activate the immune response, is induced by the stimulation of Toll-like receptors (TLRs) by molecules present on pathogenic micro-organisms such as lipopolysaccharide (LPS). AV119, a patented blend of avocado sugars, induced the aggregation of Malassezia furfur, a dimorphic, lipid-dependent yeast that is part of the normal human cutaneous commensal flora and inhibited its penetration into the keratinocytes. In the present study, the anti-inflammatory effects of AV119 were investigated in LPS-induced inflammation of human keratinocytes. In particular, we analysed the modulation of the LPS-induced expression of proinflammatory cytokines and heat shock protein 70 (HSP70) by AV119 and the involvement of TLR-4. Our data show that AV119 is able to modulate significantly the proinflammatory response in human keratinocytes, blocking the NF-kB activation in human keratinocytes. PMID:20936426

  8. Electronic band structures of AV(2) (A = Ta, Ti, Hf and Nb) Laves phase compounds.

    PubMed

    Charifi, Z; Reshak, Ali Hussain; Baaziz, H

    2009-01-14

    First-principles density functional calculations, using the all-electron full potential linearized augmented plane wave method, have been performed in order to investigate the structural and electronic properties for Laves phase AV(2) (A = Ta, Ti, Hf and Nb) compounds. The generalized gradient approximation and the Engel-Vosko-generalized gradient approximation were used. Our calculations show that these compounds are metallic with more bands cutting the Fermi energy (E(F)) as we move from Nb to Ta, Hf and Ti, consistent with the increase in the values of the density of states at the Fermi level N(E(F)). N(E(F)) is controlled by the overlapping of V-p/d, A-d and A-p states around the Fermi energy. The ground state properties of these compounds, such as equilibrium lattice constant, are calculated and compared with the available literature. There is a strong/weak hybridization between the states, V-s states are strongly hybridized with A-s states below and above E(F). Around the Fermi energy we notice that V-p shows strong hybridization with A-p states. PMID:21813979

  9. Unified transform architecture for AVC, AVS, VC-1 and HEVC high-performance codecs

    NASA Astrophysics Data System (ADS)

    Dias, Tiago; Roma, Nuno; Sousa, Leonel

    2014-12-01

    A unified architecture for fast and efficient computation of the set of two-dimensional (2-D) transforms adopted by the most recent state-of-the-art digital video standards is presented in this paper. Contrasting to other designs with similar functionality, the presented architecture is supported on a scalable, modular and completely configurable processing structure. This flexible structure not only allows to easily reconfigure the architecture to support different transform kernels, but it also permits its resizing to efficiently support transforms of different orders (e.g. order-4, order-8, order-16 and order-32). Consequently, not only is it highly suitable to realize high-performance multi-standard transform cores, but it also offers highly efficient implementations of specialized processing structures addressing only a reduced subset of transforms that are used by a specific video standard. The experimental results that were obtained by prototyping several configurations of this processing structure in a Xilinx Virtex-7 FPGA show the superior performance and hardware efficiency levels provided by the proposed unified architecture for the implementation of transform cores for the Advanced Video Coding (AVC), Audio Video coding Standard (AVS), VC-1 and High Efficiency Video Coding (HEVC) standards. In addition, such results also demonstrate the ability of this processing structure to realize multi-standard transform cores supporting all the standards mentioned above and that are capable of processing the 8k Ultra High Definition Television (UHDTV) video format (7,680 × 4,320 at 30 fps) in real time.

  10. Transient 2(nd) Degree Av Block Mobitz Type II: A Rare Finding in Dengue Haemorrhagic Fever.

    PubMed

    Nigam, Ashwini Kumar; Singh, Omkar; Agarwal, Ayush; Singh, Amit K; Yadav, Subhash

    2015-05-01

    Dengue has been a major problem as endemic occurs almost every year and causes a state of panic due to lack of proper diagnostic methods and facilities for proper management. Patients presenting with classical symptoms are easy to diagnose, however as a large number of cases occur every year, a number of cases diagnosed with dengue fever on occasion presents with atypical manifestations, which cause extensive evaluation of the patients, unnecessary referral to higher centre irrespective of the severity and therefore a rough idea of these manifestations must be present in the backdrop in order to prevent these problems. Involvement of cardiovascular system in dengue has been reported in previous studies, and they are usually benign and self-limited. The importance of study of conduction abnormalities is important as sometimes conduction blocks are the first sign of acute myocarditis in patients of Dengue Hemorrhagic Fever in shock. We present here a case of 2(nd) Degree Mobitz Type II atrioventricular AV block in a case of Dengue Hemorrhagic fever reverting to the normal rhythm in recovery phase and no signs thereafter on follow up. PMID:26155512

  11. Authentication of Angelica anomala Avé-Lall cultivars through DNA barcodes.

    PubMed

    He, Yang; Hou, Pei; Fan, Gang; Song, Zhen; Arain, Saima; Shu, Hao; Tang, Ce; Yue, Qinghong; Zhang, Yi

    2012-04-01

    Angelica anomala Avé-Lall (Chuanbaizhi in Chinese) is an important medicinal plant which can be used in traditional Chinese medicines; however, there are no authentic and universal methods to differentiate this Sichuan famous-region drug of A. anomala from a large number of non-famous-region and false drugs. It has been demonstrated that DNA barcoding is a molecular diagnostic method for species identification, which uses a single standardized DNA fragment. In this study, we tested five DNA barcoding candidates (matK, ITS, ITS2, rbcL, and psbA-trnH), and we found that ITS was the best candidate to authenticate the famous-region drug of A. anomala. Moreover, through comparative analysis of these five DNA barcodes between A. anomala and Angelica dahurica, we found that ITS had the most and ITS2 had more variable regions, but the psbA-trnH, rbcL, and matK regions were identical. Hence, we suggest ITS as the DNA barcoding to identify A. anomala and A. dahurica. Moreover, we are determined to adopt the A. anomala as the accurate Latin name of Chuanbaizhi. PMID:22397381

  12. A thermodynamic muscle model and a chemical basis for A.V. Hill's muscle equation.

    PubMed

    Baker, J E; Thomas, D D

    2000-05-01

    Direct measurements of a relationship between force and actin-myosin biochemistry in muscle suggest that molecular forces in active muscle rapidly equilibrate among. not within, individual myosin crossbridges [Baker et al. (1999) Biophys J 77: 2657 2664]. This observation suggests a thermodynamic model of muscle contraction in which muscle, not an individual myosin crossbridge, is treated as a near-equilibrium system. The general approach can be applied to any ensemble of molecular motors that undergo a physicochemical step against a constant external potential. In this paper we apply the model to a simple two-state crossbridge scheme like that proposed by A.F. Huxley (1957) [Prog Biophys 7: 255 317], and we immediately obtain A.V. Hill's muscle equation. We show that this equation accurately describes steady-state muscle mechanics, biochemistry and energetics. This thermodynamic model provides a novel description of force-dependent actin-myosin kinetics in muscle and provides precise chemical expressions for myosin cooperativity, myosinduty ratios, the number of working strokes per ATP hydrolyzed, muscle efficiency. and energy transfer. PMID:11032344

  13. Magnesium, Potassium and Phosphorus in Available Forms in Luvisols in the Vicinity of Głogów Copper Smelter

    NASA Astrophysics Data System (ADS)

    Jaworska, H.; Dąbkowska-Naskręt, H.; Różański, S.

    2016-02-01

    Region near Głogów is characterized as industrial—agricultural area, intensively used. Presented study was undertaken to estimate the impact of agricultural land use and the vicinity of Głogów copper smelter on the contents of available forms of magnesium, phosphorus and potassium in selected profiles of Luvisols. The following analysis were performed: soil particle-size distribution, pH, organic carbon contents, CaCO3 contents. The contents of available forms of phosphorus and potassium were determined by Egner- Riehm method and that of magnesium using Schachtschabel's method. The results of the study showed that the contents of available P is medium (III class of abundance), very low in K (V class) and for available Mg very low (V class) to medium for surface horizons and very high (I class of abundance) in other soil horizons. The soils, in spite of the elevated copper content in humus horizons, according to IUNG, were classified as uncontaminated soils, therefore, can be used in plant production for all types of crops.

  14. Overexpression of an Apocynum venetum DEAD-Box Helicase Gene (AvDH1) in Cotton Confers Salinity Tolerance and Increases Yield in a Saline Field

    PubMed Central

    Chen, Jie; Wan, Sibao; Liu, Huaihua; Fan, Shuli; Zhang, Yujuan; Wang, Wei; Xia, Minxuan; Yuan, Rui; Deng, Fenni; Shen, Fafu

    2016-01-01

    Soil salinity is a major environmental stress limiting plant growth and productivity. We have reported previously the isolation of an Apocynum venetum DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here, we report that the overexpression of AvDH1 driven by a constitutive cauliflower mosaic virus-35S promoter in cotton plants confers salinity tolerance. Southern and Northern blotting analyses showed that the AvDH1 gene was integrated into the cotton genome and expressed. In this study, the growth of transgenic cotton expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant to salt than the wild-type plants when grown in a growth chamber. The lower membrane ion leakage, along with increased activity of superoxide dismutase, in AvDH1 transgenic lines suggested that these characteristics may prevent membrane damage, which increases plant survival rates. In a saline field, the transgenic cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed cotton yields compared with wild-type plants, especially at high soil salinity levels. This study indicates that transgenic cotton expressing AvDH1 is a promising option for increasing crop productivity in saline fields. PMID:26779246

  15. First Case of Automatic His Potential Detection With a Novel Ultra High-density Electroanatomical Mapping System for AV Nodal Ablation

    PubMed Central

    Hilbert, Sebastian; Kosiuk, Jedrzej; John, Silke; Hindricks, Gerhard; Bollmann, Andreas

    2016-01-01

    A 74-year old was considered for atrioventricular (AV) nodal ablation in view of atrial fibrillation (AF) with poorly controlled ventricular rate despite being on amiodarone. Targeted AV nodal ablation was successfully performed after identifying the target site for ablation by reviewing an ultra high-density map of the His region produced by automatic electrogram annotation. PMID:25852249

  16. Geologic Mapping of the Av-8 Marcia Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Williams, D. A.; Hiesinger, H.; Schenk, P. M.; Jaumann, R.; Buczkowski, D. L.; McCord, T. B.; Yingst, R. A.; Garry, W. B.; Combe, J.-Ph.; Pieters, C. M.; Nathues, A.; Le Corre, L.; Reddy, V.; Roatsch, T.; Preusker, F.; Schmedemann, N.; Neukum, G.; Raymond, C. A.; Ammannito, E.; De Sanctis, M. C.

    2012-04-01

    NASA's Dawn spacecraft is spending one year in orbit of asteroid 4Vesta to characterize its geology, chemical and mineralogical composition, topography, shape, and internal structure. The Dawn Team is conducting geological mapping of the surface in the form of 15 quadrangle maps, and here we report results from the mapping of Marcia quadrangle Av-8. Mapping is based on a Framing Camera (FC) mosaic produced from High Altitude Mapping Orbit (HAMO) data with a spatial resolution of ~70 m/pixel, supplemented by a Digital Terrain Model (DTM: lateral spacing of 450 m/pixel and vertical accuracy of ~30 meters), FC color images, and Visible and InfraRed (VIR) hyperspectral images. Av-8 Marcia Quadrangle covers 144˚-216˚E longitude and ±21˚ latitude in the equatorial region of Vesta. This quadrangle is dominated by the 'Snowman' crater region, which is a low-albedo ejecta field containing impact craters Marcia, (68 km by 58 km), Calpurnia (54 km by 52 km), and Minucia (26 km by 23 km). A hill with a dark-rayed crater, named Aricia Tholus, is 42.5 km by 28 km. This quadrangle has all three of the dominant terrains found on Vesta: A heavily-cratered northern terrain with ancient troughs and grooves, an intermediately-cratered equatorial terrain bearing prominent flat-floored, E-W-trending troughs, and the relatively lightly-cratered south polar region, containing the Rheasilvia impact basin and related terrains. The low albedo ejecta field derived from the 'Snowman' craters, which we call Dark Crater Ejecta Material, mantles underlying older terrains. It has an obvious lower abundance of impact craters, indicative of a relatively younger age. A dark-rayed crater, occurring at ~14˚N, 180˚, excavates a darker unit from underneath the brighter ejecta. Images from the Low Altitude Mapping Orbit (LAMO) show dark materials exposed in the rim of crater Marcia, suggesting basaltic flows or intrusions underlie the ejecta. Bright and Dark Lobate Materials also occur in this quad

  17. Geologic Mapping of the Av-15 Rheasilvia Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Yingst, R. A.; Ammannito, E.; Berman, D.; De Sanctis, M. C.; Capaccioni, F.; Frigeri, A.; Jaumann, R.; Le Corre, L.; Mest, S.; Palomba, E.; Pieters, C. M.; Preusker, F.; Reddy, V.; Roatsch, T.; Russell, C. T.; Schenk, P. M.; Schmedemann, N.; Williams, D. A.; Tosi, F.; Zambon, F.

    2012-04-01

    NASA's Dawn spacecraft is spending one year in orbit around asteroid 4 Vesta to characterize its geology, chemical and mineralogical composition, topography, shape, and internal structure. The Dawn Team is conducting geological mapping of the surface in the form of one global and 15 quadrangle maps. Here we report results from the mapping of Rheasilvia quadrangle Av-15. Mapping is based on a Framing Camera (FC) mosaic produced from High Altitude Mapping Orbit (HAMO) data with a spatial resolution of ~70 m/pixel, supplemented by a Digital Terrain Model (DTM: lateral spacing of 450 m/pixel and vertical accuracy of ~30 meters), FC color images, and Visible and InfraRed (VIR) hyperspectral images. Av-15 Rheasilvia Quadrangle covers the southern pole of Vesta and stretches north to -21°S. Vesta has three dominant terrains: A heavily-cratered northern terrain with ancient troughs and grooves, an intermediately-cratered equatorial terrain bearing prominent flat-floored, E-W-trending troughs, and the relatively lightly-cratered south polar region, containing the Rheasilvia impact basin and related terrains. This quadrangle is dominated by the central mound complex of the Rheasilvia impact basin. Primary geologic features of this region include: (1) the Rheasilvia complex, including the central mound terrain, ridge-and-groove terrain, and smoother terrain; (2) slump material; and (3) impact craters and associated material. The Rheasilvia formation encompasses the central mound complex, two trends of ridges and grooves (only 5% of the quad area is covered by this terrain), and patches of smoother, less-cratered terrain on the mound itself. The mound, which covers nearly 60% of the quadrangle area, is ~22 km high and ~180 km wide, with a discontinuous bounding scarp and low crater density. The ridge-and groove terrain consists of ridges and grooves radiating approximately 90°-270°, and ridges and troughs or ridge and groove complexes that arch or curve as they extend out

  18. Simple pressure measurement is not reliable in detection of access stenosis in native AV fistulas.

    PubMed

    Portová, M; Horení, J; Kremenová, E; Nejedlý, B; Válek, M; Lopot, F

    2005-01-01

    Dynamic arterial and venous pressures (PA, PV) are used as the simplest tools to assess vascular access quality (VAQ). An increased PV over three consecutive dialyses is believed to indicate a stenosis, a rule devised for synthetic grafts (AVG) but not adequately validated for AV fistulas (AVF). In this study dynamic PV and static intra-access pressure (calculated by means of the simplified formula PIA=(PA+PV)/2) changes were evaluated in 46 accesses in which balloon angioplasty had to eventually be performed. The whole group consisted of 30 forearm AVF, 5 upper arm AVF and 11 AVG. Pressures were compared in each patient at a time of satisfactory access flow (QVA) and immediately before the angioplasty and pressure difference over that period (deltaPV, deltaPIA) evaluated. Despite a significant drop in QVA over the follow-up interval in both AVF and AVG, the mean deltaPV and deltaPIA in AVF were only several mm Hg and the chosen threshold limit of 20 mmHg was exceeded in approximately 10% of patients only. The results in the AVG group were, however, very different: The mean deltaPV and deltaPIA were close to 20 mmHg and almost 60% of patients in the AVG group exceeded this limit. Evaluation of PIA did not improve stenosis detection in either group. It is concluded that PV and/or PIA monitoring may be useful to detect a stenosis in AVG but not in AVF. PMID:16363412

  19. Apolipoprotein A-V gene therapy for disease prevention / treatment: a critical analysis

    PubMed Central

    Forte, Trudy M.; Sharma, Vineeta; Ryan, Robert O.

    2016-01-01

    Abstract Apolipoprotein (apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol (TG) homeostasis. Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipo­protein lipase-mediated TG hydrolysis, another portion is recovered intracellularly, in association with cytosolic lipid droplets. Loss of apoA-V function is positively correlated with elevated plasma TG and increased risk of car­diovascular disease. Single nucleotide polymorphisms (SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions. Likewise, rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction. Genetically engineered mouse mod­els and human population studies suggest that, in certain instances, supplementation with wild type (WT) apoA-V may have therapeutic benefit. It is hypothesized that individuals that manifest elevated plasma TG owing to deleter­ious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance. On the other hand, subjects with hypertriglyceridemia of independent origin (unrelated to apoA-V func­tion) may not respond to apoA-V augmentation in this manner. Improvement in the ability to identify individuals predicted to benefit, advances in gene transfer technology and the strong connection between HTG and heart disease, point to apoA-V supplementation as a viable disease prevention / therapeutic strategy. Candidates would include individuals that manifest chronic TG elevation, have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels. PMID:26679785

  20. The Drosophila histone variant H2A.V works in concert with HP1 to promote kinetochore-driven microtubule formation.

    PubMed

    Vernì, Fiammetta; Cenci, Giovanni

    2015-01-01

    Unlike other organisms that have evolved distinct H2A variants for different functions, Drosophila melanogaster has just one variant which is capable of filling many roles. This protein, H2A.V, combines the features of the conserved variants H2A.Z and H2A.X in transcriptional control/heterochromatin assembly and DNA damage response, respectively. Here we show that mutations in the gene encoding H2A.V affect chromatin compaction and perturb chromosome segregation in Drosophila mitotic cells. A microtubule (MT) regrowth assay after cold exposure revealed that loss of H2A.V impairs the formation of kinetochore-driven (k) fibers, which can account for defects in chromosome segregation. All defects are rescued by a transgene encoding H2A.V that lacks the H2A.X function in the DNA damage response, suggesting that the H2A.Z (but not H2A.X) functionality of H2A.V is required for chromosome segregation. We also found that loss of H2A.V weakens HP1 localization, specifically at the pericentric heterochromatin of metaphase chromosomes. Interestingly, loss of HP1 yielded not only telomeric fusions but also mitotic defects similar to those seen in H2A.V null mutants, suggesting a role for HP1 in chromosome segregation. We also show that H2A.V precipitates HP1 from larval brain extracts indicating that both proteins are part of the same complex. Moreover, we found that the overexpression of HP1 rescues chromosome missegregation and defects in the kinetochore-driven k-fiber regrowth of H2A.V mutants indicating that both phenotypes are influenced by unbalanced levels of HP1. Collectively, our results suggest that H2A.V and HP1 work in concert to ensure kinetochore-driven MT growth. PMID:25591068

  1. A Comparison of the AVS-9 and the Panoramic Night Vision Goggle During Rotorcraft Hover and Landing

    NASA Technical Reports Server (NTRS)

    Szoboszlay, Zoltan; Haworth, Loran; Simpson, Carol; Rutkowski, Michael (Technical Monitor)

    2001-01-01

    The purpose of this flight test was to measure any differences in pilot-vehicle performance and pilot opinion between the use of the current generation AVS-9 Night Vision Goggle and one variant of the prototype Panoramic Night Vision Goggle (the PNV.GII). The PNVGII has more than double the horizontal field-of-view of the AVS-9, but reduced image quality. The flight path of the AH-1S helicopter was used as a measure of pilot-vehicle performance. Also recorded were subjective measures of flying qualities, physical reserves of the pilot, situational awareness, and display usability. Pilot comment and data indicate that the benefits of additional FOV with the PNVGIIs are to some extent negated by the reduced image quality of the PNVGIIs.

  2. The GRB Detected by Avs-F Apparatus Onboard Coronas-F Satellite in 2001-2005 Years

    NASA Astrophysics Data System (ADS)

    Arkhangelskaja, Irene V.; Arkhangelskiy, Andrey I.; Glyanenko, Alexander S.; Kotov, Yuri D.; Kuznetsov, Sergey N.

    2008-09-01

    The AVS-F apparatus onboard CORONAS-F satellite operated from 31.07.2001 up to 06.12.2005. This instrument constitutes the system for data processing from two detectors: SONG-D (CsI(TI) detector Ø200 mm and 100 mm height, fully surrounded by plastic anticoincidence shield) and XSS-1 (CdTe detector 4.9 mm × 4.9 mm). Despite of this satellite was Solar-oriented, over 30 GRB during August 2001 - December 2005 period were registered in the energy band of ~0.1-20 MeV by preliminary data analysis. The characteristics of GRB detected by AVS-F device are discussed.

  3. Modularization and Validation of FUN3D as a CREATE-AV Helios Near-Body Solver

    NASA Technical Reports Server (NTRS)

    Jain, Rohit; Biedron, Robert T.; Jones, William T.; Lee-Rausch, Elizabeth M.

    2016-01-01

    Under a recent collaborative effort between the US Army Aeroflightdynamics Directorate (AFDD) and NASA Langley, NASA's general unstructured CFD solver, FUN3D, was modularized as a CREATE-AV Helios near-body unstructured grid solver. The strategies adopted in Helios/FUN3D integration effort are described. A validation study of the new capability is performed for rotorcraft cases spanning hover prediction, airloads prediction, coupling with computational structural dynamics, counter-rotating dual-rotor configurations, and free-flight trim. The integration of FUN3D, along with the previously integrated NASA OVERFLOW solver, lays the ground for future interaction opportunities where capabilities of one component could be leveraged with those of others in a relatively seamless fashion within CREATE-AV Helios.

  4. Geosciences Information for Teachers (GIFT) Workshops held in Conjunction with Alexander von Humboldt (AvH) EGU Conferences.

    NASA Astrophysics Data System (ADS)

    Laj, C. E.; Cifelli, F.

    2014-12-01

    Given the increasing success of the GIFT workshops held in conjunction with the General Assemblies, since 2010 EGU has also developed a series of GIFT workshops held in conjunction with AvH conferences. The Alexander von Humboldt Conference Series of the European Geosciences Union are a series of meetings held outside of Europe, in particular in South America, Africa or Asia, on selected topics of geosciences with a socio-economic impact for regions on these continents, jointly organised with the scientists and their institutes and the institutions of these regions. Associated GIFT workshops were held in Merida, Yucatan, on the theme of Climate Change, Natural Hazards and Societies (March 2010), then in Penang, Malaysia (June 2011) on the theme of Ocean Acidification, in November 2012 in Cusco (Peru) on the theme of Natural Disasters, Global Change and the Preservation of World Heritage Sites, finally in Istanbul (March 2014) on "High Impact Natural Hazards Related to the Euro-Mediterranean Region. The next GIFT workshop is already planned for October 2015 in Adis Ababa (Ethiopia) on the theme "Water". In each case, the GIFT workshop was held on the last two days of the AvH conference and reunited 40-45 teachers from the nation where the AvH was held. Keynote speakers from AvH were speakers to the GIFT workshops which also included hands-on activities animated by sciences educators. In 3 cases of the 4 cases, these GIFT workshops represented the first workshop specifically aimed at teachers held in the country, and therefore represents a significant Earth Sciences contribution to secondary education in non European countries.

  5. Geosciences Information for Teachers (GIFT) Workshops held in Conjunction with Alexander von Humboldt (AvH) EGU Conferences

    NASA Astrophysics Data System (ADS)

    Laj, Carlo; Cifelli, Francesca

    2015-04-01

    The Alexander von Humboldt Conference Series of the European Geosciences Union are a series of meetings held outside of Europe, in particular in South America, Africa or Asia, on selected topics of geosciences with a socio-economic impact for regions on these continents, jointly organised with the scientists and their institutes and the institutions of these regions. Given the increasing success of the GIFT workshops held in conjunction with the General Assemblies, since 2010 EGU has also developed a series of GIFT workshops held in conjunction with AvH conferences. Associated GIFT workshops were held in Merida, Yucatan, on the theme of Climate Change, Natural Hazards and Societies (March 2010), then in Penang, Malaysia (June 2011) on the theme of Ocean Acidification, in November 2012 in Cusco (Peru) on the theme of Natural Disasters, Global Change and the Preservation of World Heritage Sites, finally in Istanbul (March 2014) on "High Impact Natural Hazards Related to the Euro-Mediterranean Region. The next GIFT workshop is already planned for October 2015 in Adis Ababa (Ethiopia) on the theme "Water". In each case, the GIFT workshop was held on the last two days of the AvH conference and reunited 40-45 teachers from the nation where the AvH was held. Keynote speakers from AvH were speakers to the GIFT workshops which also included hands-on activities animated by sciences educators. These GIFT workshops represented the first workshops specifically aimed at teachers held in the country, and therefore represents a significant Earth Sciences contribution to secondary education in non European countries.

  6. The Dural AV-Fistula (DAVF), the Most Frequent Acquired Vascular Malformation of the Central Nervous System (CNS).

    PubMed

    Wanke, I; Rüfenacht, D A

    2015-10-01

    Acquired arteriovenous malformations, such as is the case with dural arteriovenous fistulae (DAVF), are the consequence of a pathological new arterial ingrowth into venous spaces that reaches directly the venous lumen, without interposition of a capillary network, thereby creating an AV-shunt.The following concise text will provide elements in regards to diagnosis, indication for treatment discussion and choice of endovascular treatment (EVT) method. PMID:26308245

  7. The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse

    PubMed Central

    Beardsley, Patrick M.; Shelton, Keith L.; Hendrick, Elizabeth; Johnson, Kirk W.

    2010-01-01

    Stress and renewed contact with drug (a “slip”) have been linked to persisting relapse of methamphetamine abuse. Human brain microglial activation has been linked with methamphetamine abuse, and inhibitors of glial cell activation, certain phosphodiesterase (PDE) inhibitors, and glial cell derived neurotrophic factor (GDNF) have been reported to modulate drug abuse effects. Our objective was to determine whether the glial cell attenuator, 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine (AV411, ibudilast), a non-selective PDE inhibitor and promoter of GDNF, could reduce stress- and methamphetamine prime-induced reinstatement of methamphetamine-seeking behavior. Male Long-Evans hooded rats were trained to lever press reinforced with 0.1 mg/kg i.v. methamphetamine infusion according to fixed-ratio 1 (FR1) reinforcement schedules during daily, 2-h experimental sessions. After performance had stabilized, lever pressing was extinguished for 12 consecutive sessions and doses of 0 (vehicle), 2.5 and 7.5 mg/kg AV411 were then administered intraperitoneally b.i.d. on the last two days of extinction and then once on the testday to separate groups of 12 rats. During testing, the rats were given 15 min of intermittent footshock or a 1 mg/kg i.p. methamphetamine prime followed by a 2-h reinstatement test session. AV411 significantly reduced response levels of footshock-induced (2.5 and 7.5 mg/kg) and prime-induced (7.5 mg/kg) reinstatement of extinguished methamphetamine-maintained responding. AV411 has properties consistent with the ability to attenuate relapse precipitated by stress and methamphetamine “slips” during abstinence. These results thus reinforce interest in atypical neurobiological mechanisms which could be exploited for developing novel medications for treating drug abuse disorders. PMID:20399770

  8. Re-entrant tachycardia using two bypass tracts and excluding AV node in short PR interval, normal QRS syndrome.

    PubMed Central

    Ward, D E; Camm, A J; Spurrell, R A

    1978-01-01

    In patients with the short PR interval, normal QRS complex syndrome, paroxysmal tachycardias are usually the result of circus movement involving the AV node and a partial or complete AV nodal bypass. We report 2 patients with this syndrome who suffered distressing rapid paroxysms of tachycardia but in whom there was evidence of a concealed direct VA connection. In both patients, tachycardia was initiated with critical AV prolongation distal to the His bundle, in response to programmed atrial premature stimuli. The constancy of the timing of the atrial echo from the onset of the QRS complex in the presence of a varying HV interval is evidence for involvement of the ventricles in the re-entry pathway. In addition, in both patients the appearance of left bundle-branch block during tachycardia was associated with appropriate prolongation of tachycardia cycle length consistent with the presence of a direct VA connection. The short AH interval during tachycardia and the absence of critical AH prolongation suggests the participation of a rapidly conducting pathway in the anterograde limb of the tachycardia circuit. PMID:708514

  9. Coastal surface sediment quality assessment in Leizhou Peninsula (South China Sea) based on SEM-AVS analysis.

    PubMed

    Li, Feng; Lin, Jin-qin; Liang, Yan-yan; Gan, Hua-yang; Zeng, Xiang-yun; Duan, Zhi-peng; Liang, Kai; Liu, Xing; Huo, Zhen-hai; Wu, Chang-hua

    2014-07-15

    Surface sediments from the coastal area of the Leizhou Peninsula in the South China Sea were collected and analyzed and the potential ecological risks in the area were assessed based on acid-volatile sulfide (AVS) model. The AVS levels are between 0.109 and 55.6 μmol g(-1), with the average at 4.45 μmol g(-1). The high AVS-concentration zones include the aquaculture areas of Liusha Bay and the densely populated areas of Zhanjiang Bay. The simultaneously extracted metals (SEM) range from 0.026 μmol g(-1) to 8.61 μmol g(-1), with the average at 0.843 μmol g(-1). Most of high SEM-concentration stations were located in ports or aquaculture zones. Most of the coastal surface sediments of the Leizhou Peninsula (90%) had no adverse biological effects according to the criterion proposed by USEPA (2005); while adverse effects were uncertain in some stations (8%); even in 2 stations (2%) adverse biological effects may be expected. PMID:24880682

  10. Secondary arteriovenous fistulas: converting prosthetic AV grafts to autogenous dialysis access.

    PubMed

    Slayden, Geoffrey C; Spergel, Lawrence; Jennings, William C

    2008-01-01

    As existing arteriovenous grafts (AVGs) fail, the National Kidney Foundation KDOQI Guidelines and the AV Fistula First Breakthrough Initiative ("Fistula First") project recommend that each patient be re-evaluated for conversion to an arteriovenous fistula (AVF). AVFs created following failure of an AVG have been termed secondary fistulas (SAVF). We review our experience and outcomes converting AVGs to SAVFs, utilizing the mature outflow vein of the AVG when possible, otherwise creating a new AVF at a remote site. We reviewed two groups of consecutive patients undergoing operations for vascular access at different centers. Group 1 had a SAVF protocol in place during the study period with specific criteria for timing SAVF construction. Patients from group 2 were referred for evaluation by nephrologists or dialysis nurses as access problems were recognized, without a formal protocol in place. All patients had preoperative ultrasound or contrast imaging in addition to physical examination. Indications for creating a SAVF were AVG thrombosis, dysfunction, erosion, bleeding, or steal syndrome involving the existing AVG. The simple presence of a functional AVG without evidence of dysfunction was not an indication for conversion to a SAVF. SAVFs were classified according to location and the potential for utilizing the existing mature AVG outflow vein. Group 1: 40 consecutive patients, age 26-78 (mean = 62), 42% were female; 55% were diabetic. These patients had 1-22 previous access operations (mean = 3). 92.5% underwent SAVF surgery prior to loss of the AVG, minimizing catheter use. Cumulative patency was 92.5% at 1 year and 87.5% at 2 years. Group 2: 102 consecutive patients, age 24-87 (mean = 55), 52% were female; 50% were diabetic. These patients had 1-50 previous access operations (mean = 3). Only 19.3% were referred for SAVF surgery prior to loss of the AVG or outflow vein. Cumulative patency was 94.4% at 1 year and 91.6% at 2 years. Failure, dysfunction, or

  11. Geologic Mapping of the Av-3 Caparronia Quadrangle of Asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Blewett, D. T.; Young, B. L.; Williams, D. A.; O'Brien, D. P.; Gaskell, R.; Yingst, R. A.; Garry, W. B.; Buczkowski, D. L.; Hiesinger, H.; McCord, T. B.; Combe, J.-Ph; Schenk, P. M.; Jaumann, R.; Pieters, C. M.; Nathues, A.; Le Corre, L.; Reddy, V.; De Sanctis, M.; Roatsch, T.; Preusker, F.

    2012-04-01

    NASA's Dawn spacecraft is spending one year in orbit around asteroid (4) Vesta to characterize its geology, chemical and mineralogical composition, topography, shape, and internal structure. The Dawn Team is conducting geological mapping of the surface in the form of 15 quadrangle maps, and here we report results from the mapping of Caparronia quadrangle Av-3. Mapping is based on a Framing Camera (FC) mosaic produced from High Altitude Mapping Orbit (HAMO) data with a spatial resolution of ~70 m/pixel, supplemented by a Digital Terrain Model (DTM: lateral spacing of 450 m/pixel and vertical accuracy of ~30 meters), FC color images, and Visible and InfraRed (VIR) hyperspectral images. The Caparronia Quadrangle extends from 90˚ to 180˚ E longitude and 21˚ to 66˚ N latitude. Vesta's rotation axis is tilted ~29˚ with respect to its orbital plane. Dawn arrived during northern winter, hence portions of Vesta north of ~45˚ N are in shadow and have not yet been imaged. Vesta has three dominant terrains: A heavily-cratered northern terrain with ancient troughs and grooves, an intermediately-cratered equatorial terrain bearing prominent flat-floored, E-W-trending troughs, and the relatively lightly-cratered south polar region, containing the Rheasilvia impact basin and related terrains. The Northern Cratered Trough terrain dominates the Caparronia quadrangle. Part of a NW-SE-trending trough enters the center of the sunlit part of the quad. Caparronia crater is centered at ~36˚ N, 167˚ E and is located near the eastern edge of the quad. The crater's elongation in the north-south direction is caused by slumping, likely as a result of the steep topography on which the crater formed. Smooth ejecta from Caparronia and two other relatively fresh craters can be mapped to a distance of roughly one crater radius from the crater rims, and to greater distances in places. In addition to morphology derived from FC clear filter images, we plan to take advantage of compositional

  12. The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using 18F-AV45: Is Amyloid the Principal Actor in the Disease?

    PubMed Central

    Beaufils, Emilie; Ribeiro, Maria Joao; Vierron, Emilie; Vercouillie, Johnny; Dufour-Rainfray, Diane; Cottier, Jean-Philippe; Camus, Vincent; Mondon, Karl; Guilloteau, Denis; Hommet, Caroline

    2014-01-01

    Background Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution. PMID:25538727

  13. Randomized, Double-Blind, Placebo-Controlled, Safety and Immunogenicity Study of 4 Formulations of Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909) in Healthy Adult Volunteers

    PubMed Central

    Hopkins, Robert J.; Daczkowski, Nancy F.; Kaptur, Paulina E.; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L.; Bernton, Edward

    2013-01-01

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax® (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18 to 50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA + 0.25 mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA + 0.25 mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909. PMID:23701746

  14. The risk assessment of heavy metals in Futian mangrove forest sediment in Shenzhen Bay (South China) based on SEM-AVS analysis.

    PubMed

    Chai, Minwei; Shen, Xiaoxue; Li, Ruili; Qiu, Guoyu

    2015-08-15

    The risks of heavy metal in Futian mangrove forest sediment were assessed using the acid-volatile sulfide (AVS) and simultaneously extracted metals (SEM) methods. The results indicated that AVS distributions were more variable than the SEM distributions at all 16 sampling sites. The positive correlation between AVS and SEM indicated that their similar formative and existing conditions and that AVS acted as an important carrier for SEM. The major SEM component was Zn (69.7.3-94.2%), whereas the Cd contribution (the most toxic metal present) to SEM was no more than 1%. The possible adverse effects caused by heavy metals at ten sampling sites may be due to higher levels of SEMs, rather than AVSs. The total organic carbon (TOC) was an important metal-binding phase in the sediments. Taking into account the TOC concentration, there were no adverse effects due to heavy metals in any of the Futian mangrove forest sediments. PMID:26028168

  15. British randomised controlled trial of AV and VV optimization (“BRAVO”) study: rationale, design, and endpoints

    PubMed Central

    2014-01-01

    Background Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources. Methods/Design BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014. Discussion If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented. Trial registration Clinicaltrials.gov NCT01258829 PMID:24693953

  16. Massive stars exploding in a He-rich circumstellar medium - IX. SN 2014av, and characterization of Type Ibn SNe

    NASA Astrophysics Data System (ADS)

    Pastorello, A.; Wang, X.-F.; Ciabattari, F.; Bersier, D.; Mazzali, P. A.; Gao, X.; Xu, Z.; Zhang, J.-J.; Tokuoka, S.; Benetti, S.; Cappellaro, E.; Elias-Rosa, N.; Harutyunyan, A.; Huang, F.; Miluzio, M.; Mo, J.; Ochner, P.; Tartaglia, L.; Terreran, G.; Tomasella, L.; Turatto, M.

    2016-02-01

    We present spectroscopic and photometric data of the Type Ibn supernova (SN) 2014av, discovered by the Xingming Observatory Sky Survey. Stringent pre-discovery detection limits indicate that the object was detected for the first time about 4 d after the explosion. A prompt follow-up campaign arranged by amateur astronomers allowed us to monitor the rising phase (lasting 10.6 d) and to accurately estimate the epoch of the maximum light, on 2014 April 23 (JD = 245 6771.1 ± 1.2). The absolute magnitude of the SN at the maximum light is MR = -19.76 ± 0.16. The post-peak light curve shows an initial fast decline lasting about three weeks, and is followed by a slower decline in all bands until the end of the monitoring campaign. The spectra are initially characterized by a hot continuum. Later on, the temperature declines and a number of lines become prominent mostly in emission. In particular, later spectra are dominated by strong and narrow emission features of He I typical of Type Ibn supernovae (SNe), although there is a clear signature of lines from heavier elements (in particular O I, Mg II and Ca II). A forest of relatively narrow Fe II lines is also detected showing P-Cygni profiles, with the absorption component blueshifted by about 1200 km s-1. Another spectral feature often observed in interacting SNe, a strong blue pseudo-continuum, is seen in our latest spectra of SN 2014av. We discuss in this paper the physical parameters of SN 2014av in the context of the Type Ibn SN variety.

  17. Single primitive ventricle with normally related great arteries and atresia of the left A-V valve.

    PubMed Central

    Coto, E O; Raggio, J M; Malo, P; Sainz, C; Aparisi, R; Gomez-Ullate, J M

    1978-01-01

    A child aged 2 years and 9 months was angiocardiographically diagnosed to have a single ventricle with normally related great arteries and atresia of the left A-V valve. A Blalock-Hanlon procedure and division of a large patent ductus arteriosus were followed by reduction in pulmonary artery pressure, but after operation the patient showed signs of left ventricular failure unresponsive to medical treatment, necessitating pulmonary artery banding. We have found only three similar published cases, and this is the only one with full angiographic documentation. Images PMID:725830

  18. Chemical Soil Degradation n the Area of the Głogów Copper Smelter Protective Forest/ Degradacja Ziemi Na Terenach Byłej Strefy Ochronnej Huty Miedzi Głogów

    NASA Astrophysics Data System (ADS)

    Kostecki, Jakub; Greinert, Andrzej; Drab, Michał; Wasylewicz, Róża; Walczak, Barbara

    2015-06-01

    Earth surface is under the continous influence of the environmental factors - both natural and anthropogenic. The significant impact on the environment can be noted in areas adjacent to the metal industry plants, in a consequence of pollutants emission, especially dusts containing the heavy metals, into the atmosphere,. In the surroundings of Głogów Copper Smelter (GCS) elevated amounts of copper and lead has been noted. In the soils of the test sites were found up to 5250 mg kg-1 Cu and 1290 mg kg-1 Pb. The forest litter contained 3.3-5.1 more Cu and 3.9-8.6 Pb than the humic horizon of the soil. Analyse of the different soils covering the GCS protective forest area let specify the stabilising role of particle size distribution, TOC content and the soil reaction to Cu and Pb migration in the environment. Powierzchnia ziemi jest nieustannnie narażona na oddziaływania o charakterze naturalnym i antropogenicznym. Znaczące oddziaływanie jest łatwo zauważalne na terenach przemysłowych. Szczególnie na obszarach objętych wydobyciem i przeróbką metali. Na terenach przyległych do Huty Miedzi Głogów stwierdzono wysoką koncentrację miedzi i ołowiu sięgającą 5250 mg kg-1 Cu i 1290 mg kg-1 Pb. Poziom ściółki leśnej zawierał 3,3-5,1 raza więcej Cu i 3,9-8,6 Pb niż poziom próchniczny analizowanych gleb. Analiza różnych gleb pokrywających las ochronny HMG pozwoliła wskazać na znaczącą rolę składu granulometrycznego, zawartości węgla organicznego oraz odczynu na stabilizację migracji Cu i Pb w środowisku.

  19. Large-scale atmospheric processes in the Arctic region reproduced by Sl-AV model and reanalysis data

    NASA Astrophysics Data System (ADS)

    Kulikova, Irina; Kruglova, Ekaterina; Khan, Valentina; Kiktev, Dmitry; Tischenko, Vladimir

    2015-04-01

    The variability of large-scale atmospheric processes in the Arctic region was analyzed on the base of the NCEP/DOE reanalysis data and seasonal hindcasts from global semi-Lagrangian model (SL-AV), developed in collaboration of Hydrometeorological Centre of Russia with Institute of Numerical Mathematics. Using the factor analysis it was shown that the model reproduces well the first major variability modes to explain 85-90% of the accumulated dispersion. Teleconnection indices as the quantitative characteristics of low-frequency variability are used to identify zonal and meridional flow regimes. Composite maps indicating the spatial distribution of anomalies of the main meteorological variables (500 hPa geopotential height, the sea level atmospheric pressure, the temperature at 850 hPa, 2m air temperature, precipitation, zonal and meridional wind component) for positive and negative phases of each index of atmospheric circulation are created. Average values of composite maps are accompanied with their statistical significance assessed using the "bootstrap" technique. Main characteristics of field configuration in Arctic region of cited above meteorological parameters corresponding to positive and negative phases of circulation indices are analyzed and discussed. Ability of SL-AV model to reproduce these characteristics at monthly and seasonal time scale is discussed as well. Results of this study are aimed to improve the quality of long-range forecasts and increase the "limit of predictability" and can be useful in the practice to develop monthly and seasonal weather forecasts for the Arctic region.

  20. Influence of reactive sulfide (AVS) and supplementary food on Ag, Cd and Zn bioaccumulation in the marine polychaete Neanthes arenaceodentata

    USGS Publications Warehouse

    Lee, J.-S.; Lee, B.-G.; Yoo, H.; Koh, C.-H.; Luoma, S.N.

    2001-01-01

    A laboratory bioassay determined the relative contribution of various pathways of Ag, Cd and Zn bioaccumulation in the marine polychaete Neanthes arenaceodentata exposed to moderately contaminated sediments. Juvenile worms were exposed for 25 d to experimental sediments containing 5 different reactive sulfide (acid volatile sulfides, AVS) concentrations (1 to 30 ??mol g-1), but with constant Ag, Cd, and Zn concentrations of 0.1, 0.1 and 7 ??mol g-1, respectively. The sediments were supplemented with contaminated food (TetraMin??) containing 3 levels of Ag-Cd-Zn (uncontaminated, 1?? or 5??1 metal concentrations in the contaminated sediment). The results suggest that bioaccumulation of Ag, Cd and Zn in the worms occurred predominantly from ingestion of contaminated sediments and contaminated supplementary food. AVS or dissolved metals (in porewater and overlying water) had a minor effect on bioaccumulation of the 3 metals in most of the treatments. The contribution to uptake from the dissolved source was most important in the most oxic sediments, with maximum contributions of 8% for Ag, 30% for Cd and 20% for Zn bioaccumulation. Sediment bioassays where uncontaminated supplemental food is added could seriously underestimate metal exposures in an equilibrated system; N. arenaceodentata feeding on uncontaminated food would be exposed to 40-60% less metal than if the food source was equilibrated (as occurs in nature). Overall, the results show that pathways of metal exposure are dynamically linked in contaminated sediments and shift as external geochemical characteristics and internal biological attributes vary.

  1. [Hemodynamic benefits of AV interval adjustment and heart rate increase during exercise in dual-chamber pacing as determined by Doppler].

    PubMed

    Sancho-Tello, M J; Salvador, A; Olagüe, J

    1990-01-01

    In order to determine the relative significance of ventricular rate increase and AV delay on exercise cardiac output, we have studied 10 patients (8 male and 2 female, 16-59 years) with complete chronic heart block treated with AV sequential pacing. Cardiac output variations (delta CO) were estimated by pulsed Doppler comparisons of the aortic flow velocity in the supine position, at rest and during bicycle exercise. The following pacing programs were tested: DDD with AV intervals of 50, 100 and 150 ms (DDD50 o DDDD100, DDD150), VVI at 70 ppm (VVI70), and VVI at the maximal available rate in this pacing mode-113 or 130 ppm depending on the PM type (VVIM). Exercise measurements in DDD mode were taken when that rate was reached. The delta CO was calculated as a percent change of the product flow velocity integral x heart rate, from that obtained with VVI70 mode at rest. At rest, the delta CO obtained with DDD pacing was 20.4 +/- 14.7% and the optimal AV delay was 50 ms in 1 patient, 100 ms in 3 patients and 150 ms in six. During exercise, the delta CO was higher in DDD and VVIM modes (82.0 +/- 30.8% and 56.2 +/- 37.6%, respectively; p less than 0.01) than in VVI70 mode (20.4 +/- 10.4%; p less than 0.005), the greatest delta CO was reached at DDD mode in 8 out of 10 patients (p less than 0.03). The optimal AV delays were 50 ms in 5 patients, 100 ms in 4 patients and 150 ms in one. Thus, DDD pacing with the optimal AV delay seems to obtain greater haemodynamic benefits during exercise than does rate-responsive pacing; the optimal exercise AV delay varies from patient to patient and is usually less than 150 ms. PMID:2236802

  2. Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense

    PubMed Central

    2013-01-01

    Background Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. Methods The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 μg/ml) and GA (up to 10 μg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. Results AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. Conclusions AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula. PMID:23826868

  3. Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages.

    PubMed

    Schwarz, Adam J; Yu, Peng; Miller, Bradley B; Shcherbinin, Sergey; Dickson, James; Navitsky, Michael; Joshi, Abhinay D; Devous, Michael D; Mintun, Mark S

    2016-05-01

    SEE THAL AND VANDENBERGHE DOI101093/BRAIN/AWW057 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-mortem Braak staging of neurofibrillary tau tangle topographical distribution is one of the core neuropathological criteria for the diagnosis of Alzheimer's disease. The recent development of positron emission tomography tracers targeting neurofibrillary tangles has enabled the distribution of tau pathology to be imaged in living subjects. Methods for extraction of classic Braak staging from in vivo imaging of neurofibrillary tau tangles have not yet been explored. Standardized uptake value ratio images were calculated from 80-100 minute (18)F-AV-1451 (also known as T807) positron emission tomography scans obtained from n = 14 young reference subjects (age 21-39 years, Mini-Mental State Examination 29-30) and n = 173 older test subjects (age 50-95 years) comprising amyloid negative cognitively normal (n = 42), clinically-diagnosed mild cognitive impairment (amyloid positive, n = 47, and amyloid negative, n = 40) and Alzheimer's disease (amyloid positive, n = 28, and amyloid negative, n = 16). We defined seven regions of interest in anterior temporal lobe and occipital lobe sections corresponding closely to those used as decision points in Braak staging. An algorithm based on the Braak histological staging procedure was applied to estimate Braak stages directly from the region of interest profiles in each subject. Quantitative region-based analysis of (18)F-AV-1451 images yielded region of interest and voxel level profiles that mirrored key features of neuropathological tau progression including profiles consistent with Braak stages 0 through VI. A simple set of decision rules enabled plausible Braak stages corresponding to stereotypical progression patterns to be objectively estimated in 149 (86%) of test subjects. An additional 12 (7%) subjects presented with predefined variant profiles (relative sparing of the hippocampus and/or occipital lobe). The estimated Braak

  4. Assessment of Multiple Risk Outcomes, Strengths, and Change with the START:AV: A Short-Term Prospective Study with Adolescent Offenders.

    PubMed

    Viljoen, Jodi L; Beneteau, Jennifer L; Gulbransen, Erik; Brodersen, Etta; Desmarais, Sarah L; Nicholls, Tonia L; Cruise, Keith R

    2012-01-01

    The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV; Nicholls, Viljoen, Cruise, Desmarais, & Webster, 2010; Viljoen, Cruise, Nicholls, Desmarais, & Webster, in preparation) is a clinical guide designed to assist in the assessment and management of adolescents' risk for adverse events (e.g., violence, general offending, suicide, victimization). In this initial validation study, START:AV assessments were conducted on 90 adolescent offenders (62 male, 28 female), who were prospectively followed for a 3-month period. START:AV assessments had good to excellent inter-rater reliability and strong concurrent validity with Structured Assessment of Violence Risk in Youth assessments (SAVRY; Borum, Bartel, & Forth, 2006). START:AV risk estimates and Vulnerability total scores predicted multiple adverse outcomes, including violence towards others, offending, victimization, suicidal ideation, and substance abuse. In addition, Strength total scores inversely predicted violence, offending, and street drug use. During the 3-month follow-up, risk estimates changed in at least one domain for 92% of youth, and 27% of youth showed reliable changes in Strength and/or Vulnerability total scores (reliable change index, 90% confidence interval; Jacobsen & Truax, 1991). While these findings are promising, a strong need exists for further research on the START:AV, the measurement of change, and on the role of strengths in risk assessment and treatment-planning. PMID:23436983

  5. Assessment of Multiple Risk Outcomes, Strengths, and Change with the START:AV: A Short-Term Prospective Study with Adolescent Offenders

    PubMed Central

    Viljoen, Jodi L.; Beneteau, Jennifer L.; Gulbransen, Erik; Brodersen, Etta; Desmarais, Sarah L.; Nicholls, Tonia L.; Cruise, Keith R.

    2012-01-01

    The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV; Nicholls, Viljoen, Cruise, Desmarais, & Webster, 2010; Viljoen, Cruise, Nicholls, Desmarais, & Webster, in preparation) is a clinical guide designed to assist in the assessment and management of adolescents’ risk for adverse events (e.g., violence, general offending, suicide, victimization). In this initial validation study, START:AV assessments were conducted on 90 adolescent offenders (62 male, 28 female), who were prospectively followed for a 3-month period. START:AV assessments had good to excellent inter-rater reliability and strong concurrent validity with Structured Assessment of Violence Risk in Youth assessments (SAVRY; Borum, Bartel, & Forth, 2006). START:AV risk estimates and Vulnerability total scores predicted multiple adverse outcomes, including violence towards others, offending, victimization, suicidal ideation, and substance abuse. In addition, Strength total scores inversely predicted violence, offending, and street drug use. During the 3-month follow-up, risk estimates changed in at least one domain for 92% of youth, and 27% of youth showed reliable changes in Strength and/or Vulnerability total scores (reliable change index, 90% confidence interval; Jacobsen & Truax, 1991). While these findings are promising, a strong need exists for further research on the START:AV, the measurement of change, and on the role of strengths in risk assessment and treatment-planning. PMID:23436983

  6. The Two-Component System GrvRS (EtaRS) Regulates ace Expression in Enterococcus faecalis OG1RF

    PubMed Central

    Singh, Kavindra V.; La Rosa, Sabina Leanti; Cohen, Ana Luisa V.; Murray, Barbara E.

    2014-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. PMID:25385790

  7. Application of PET2OGS to CO2 storage in a saline aquifer of the CO2CRC Otway project

    NASA Astrophysics Data System (ADS)

    Park, Chan-Hee; Shinn, Young Jae

    2014-05-01

    PET2OGS, a set of algorithms that integrate the static model (Petrel) with the dynamic model (OpenGeoSys), is applied to model CO2 storage in a saline aquifer. The Otway Basin is the first demonstration site of the deep geological storage of carbon dioxide as part of carbon capture and storage (CCS) technology in Australia. During Stage 2 of the CO2CRC Otway project, CO2 was injected into a saline aquifer along the injection interval of 1435 - 1450 m in a well. Upon conversion and adaption of the geological model into the dynamic model, the simulation of CO2 injection at 159 tone/day for 5 months is carried out for a hypothetical scenario. CO2 storage in each facies are analyzed for storage capacities. The discrete nature of CO2 plume behaviors known in multiphase flow in heterogeneous media is observed in the numerical simulation of CO2 storage. Sensitivity analysis of the storage capacity with respect to facies, porosity, and permeability is provided.

  8. Microwave-assisted solvothermal synthesis of spinel AV2O4 (M = Mg, Mn, Fe, and Co).

    PubMed

    Gutierrez, Arturo; Manthiram, Arumugam

    2014-08-18

    Lower-valent vanadium oxide spinels AV2O4 (A = Mg, Mn, Fe, and Co) consisting of A(2+) and V(3+) ions have been synthesized by a low-temperature microwave-assisted solvothermal (MW-ST) synthesis process in a tetraethylene glycol (TEG) medium. The oxides are formed within a short reaction time of 30 min at 300 °C. Subsequent postheat treatment of the oxides at elevated temperatures in inert or reducing atmospheres results in an instability of the spinel phase, especially CoV2O4 due to the ease of formation of metallic Co, demonstrating the advantage of the low-temperature MW-ST process in accessing these oxides. This MW-ST synthesis approach is attractive for synthesizing other lower-valent transition-metal oxides that are otherwise difficult to obtain by conventional synthesis methods and for subsequent study of their unique physical and chemical properties. PMID:25100260

  9. Deletion of one nucleotide within the homonucleotide tract present in the hsdS gene alters the DNA sequence specificity of type I restriction-modification system NgoAV.

    PubMed

    Adamczyk-Poplawska, Monika; Lower, Michal; Piekarowicz, Andrzej

    2011-12-01

    As a result of a frameshift mutation, the hsdS locus of the NgoAV type IC restriction and modification (RM) system comprises two genes, hsdS(NgoAV1) and hsdS(NgoAV2). The specificity subunit, HsdS(NgoAV), the product of the hsdS(NgoAV1) gene, is a naturally truncated form of an archetypal specificity subunit (208 N-terminal amino acids instead of 410). The presence of a homonucleotide tract of seven guanines (poly[G]) at the 3' end of the hsdS(NgoAV1) gene makes the NgoAV system a strong candidate for phase variation, i.e., stochastic addition or reduction in the guanine number. We have constructed mutants with 6 guanines instead of 7 and demonstrated that the deletion of a single nucleotide within the 3' end of the hsdS(NgoAV1) gene restored the fusion between the hsdS(NgoAV1) and hsdS(NgoAV2) genes. We have demonstrated that such a contraction of the homonucleotide tract may occur in vivo: in a Neisseria gonorrhoeae population, a minor subpopulation of cells appeared to have only 6 guanines at the 3' end of the hsdS(NgoAV1) gene. Escherichia coli cells carrying the fused gene and expressing the NgoAVΔ RM system were able to restrict λ phage at a level comparable to that for the wild-type NgoAV system. NgoAV recognizes the quasipalindromic interrupted sequence 5'-GCA(N(8))TGC-3' and methylates both strands. NgoAVΔ recognizes DNA sequences 5'-GCA(N(7))GTCA-3' and 5'-GCA(N(7))CTCA-3', although the latter sequence is methylated only on the complementary strand within the 5'-CTCA-3' region of the second recognition target sequence. PMID:21984785

  10. SU-D-9A-01: Listmode-Driven Optimal Gating (OG) Respiratory Motion Management: Potential Impact On Quantitative PET Imaging

    SciTech Connect

    Lee, K; Hristov, D

    2014-06-01

    Purpose: To evaluate the potential impact of listmode-driven amplitude based optimal gating (OG) respiratory motion management technique on quantitative PET imaging. Methods: During the PET acquisitions, an optical camera tracked and recorded the motion of a tool placed on top of patients' torso. PET event data were utilized to detect and derive a motion signal that is directly coupled with a specific internal organ. A radioactivity-trace was generated from listmode data by accumulating all prompt counts in temporal bins matching the sampling rate of the external tracking device. Decay correction for 18F was performed. The image reconstructions using OG respiratory motion management technique that uses 35% of total radioactivity counts within limited motion amplitudes were performed with external motion and radioactivity traces separately with ordered subset expectation maximization (OSEM) with 2 iterations and 21 subsets. Standard uptake values (SUVs) in a tumor region were calculated to measure the effect of using radioactivity trace for motion compensation. Motion-blurred 3D static PET image was also reconstructed with all counts and the SUVs derived from OG images were compared with SUVs from 3D images. Results: A 5.7 % increase of the maximum SUV in the lesion was found for optimal gating image reconstruction with radioactivity trace when compared to a static 3D image. The mean and maximum SUVs on the image that was reconstructed with radioactivity trace were found comparable (0.4 % and 4.5 % increase, respectively) to the values derived from the image that was reconstructed with external trace. Conclusion: The image reconstructed using radioactivity trace showed that the blurring due to the motion was reduced with impact on derived SUVs. The resolution and contrast of the images reconstructed with radioactivity trace were comparable to the resolution and contrast of the images reconstructed with external respiratory traces. Research supported by Siemens.

  11. OGS#PETSc approach for robust and efficient simulations of strongly coupled hydrothermal processes in EGS reservoirs

    NASA Astrophysics Data System (ADS)

    Watanabe, Norihiro; Blucher, Guido; Cacace, Mauro; Kolditz, Olaf

    2016-04-01

    A robust and computationally efficient solution is important for 3D modelling of EGS reservoirs. This is particularly the case when the reservoir model includes hydraulic conduits such as induced or natural fractures, fault zones, and wellbore open-hole sections. The existence of such hydraulic conduits results in heterogeneous flow fields and in a strengthened coupling between fluid flow and heat transport processes via temperature dependent fluid properties (e.g. density and viscosity). A commonly employed partitioned solution (or operator-splitting solution) may not robustly work for such strongly coupled problems its applicability being limited by small time step sizes (e.g. 5-10 days) whereas the processes have to be simulated for 10-100 years. To overcome this limitation, an alternative approach is desired which can guarantee a robust solution of the coupled problem with minor constraints on time step sizes. In this work, we present a Newton-Raphson based monolithic coupling approach implemented in the OpenGeoSys simulator (OGS) combined with the Portable, Extensible Toolkit for Scientific Computation (PETSc) library. The PETSc library is used for both linear and nonlinear solvers as well as MPI-based parallel computations. The suggested method has been tested by application to the 3D reservoir site of Groß Schönebeck, in northern Germany. Results show that the exact Newton-Raphson approach can also be limited to small time step sizes (e.g. one day) due to slight oscillations in the temperature field. The usage of a line search technique and modification of the Jacobian matrix were necessary to achieve robust convergence of the nonlinear solution. For the studied example, the proposed monolithic approach worked even with a very large time step size of 3.5 years.

  12. The North East Italy (NI) broadband seismic network run by OGS: experience in improving the long period performances

    NASA Astrophysics Data System (ADS)

    Pesaresi, D.

    2009-04-01

    experimented and routinely used by the world wide GEOFON seismic network and the German regional seismic network: examples and performances of a typical OGS installation will be shown.

  13. Vesta's north pole quadrangle Av-1 (Albana): Geologic map and the nature of the south polar basin antipodes

    NASA Astrophysics Data System (ADS)

    Blewett, David T.; Buczkowski, Debra L.; Ruesch, Ottaviano; Scully, Jennifer E.; O'Brien, David P.; Gaskell, Robert; Roatsch, Thomas; Bowling, Timothy J.; Ermakov, Anton; Hiesinger, Harald; Williams, David A.; Raymond, Carol A.; Russell, Christopher T.

    2014-12-01

    As part of systematic global mapping of Vesta using data returned by the Dawn spacecraft, we have produced a geologic map of the north pole quadrangle, Av-1 Albana. Extensive seasonal shadows were present in the north polar region at the time of the Dawn observations, limiting the ability to map morphological features and employ color or spectral data for determination of composition. The major recognizable units present include ancient cratered highlands and younger crater-related units (undivided ejecta, and mass-wasting material on crater floors). The antipode of Vesta's large southern impact basins, Rheasilvia and Veneneia, lie within or near the Av-1 quadrangle. Therefore it is of particular interest to search for evidence of features of the kind that are found at basin antipodes on other planetary bodies. Albedo markings known as lunar swirls are correlated with basin antipodes and the presence of crustal magnetic anomalies on the Moon, but lighting conditions preclude recognition of such albedo features in images of the antipode of Vesta's Rheasilvia basin. “Hilly and lineated terrain,” found at the antipodes of large basins on the Moon and Mercury, is not present at the Rheasilvia or Veneneia antipodes. We have identified small-scale linear depressions that may be related to increased fracturing in the Rheasilvia and Veneneia antipodal areas, consistent with impact-induced stresses (Buczkowski, D. et al. [2012b]. Analysis of the large scale troughs on Vesta and correlation to a model of giant impact into a differentiated asteroid. Geol. Soc. of America Annual Meeting. Abstract 152-4; Bowling, T.J. et al. [2013]. J. Geophys. Res. - Planets, 118. http://dx.doi.org/10.1002/jgre.20123). The general high elevation of much of the north polar region could, in part, be a result of uplift caused by the Rheasilvia basin-forming impact, as predicted by numerical modeling (Bowling, T.J. et al. [2013]. J. Geophys. Res. - Planets, 118. http://dx.doi.org/10.1002/jgre

  14. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    SciTech Connect

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  15. AVS: Experimental Tests of a New Process to Inductively Vitrify HLW Inside the Final Disposal Containers at Very High Waste Loadings

    SciTech Connect

    Powell, J.; Reich, M.; Jordan, J.; Ventre, L.; Barletta, R.; Manowitz, B.; Steinberg, M.; Grossman, W.; Maise, G.; Salzano, F.; Hess, C.; Ramsey, W. G.; Plodinec, M. J.

    2002-02-26

    The design and performance capabilities of the Advanced Vitrification System (AVS) are described, together with the results of experimental tests. The AVS is an in-can melting system in which high-level waste (HLW) is vitrified directly inside the final disposal container. The AVS container, or module, consists of an outer stainless steel canister and an alumina-lined, inner graphite crucible, which is thermally insulated from the outer stainless canister. The graphite crucible is inductively heated to very high temperatures (up to 1500 C) by an external low frequency (30 Hertz) alternating current (AC) transformer coil. The actively cooled outer stainless canister remains at near ambient temperature. The HLW/frit mixture is fed into the hot graphite crucible, where it is vitrified. After cooldown, the HLW/frit feed and off-gas pipes are disconnected from the top of the module, which is then sealed and readied for shipment or storage. All radioactively contaminated melter components inside the module are disposed of along with the vitrified waste. The graphite crucible also provides a geologically stable barrier for the vitrified product. The AVS potentially can double HLW loading over that obtained from Joule melters; lower vitrification costs by about half; reduce the number of disposal canisters required by about half; handle diverse waste feeds with high concentrations of problem elements such as chromium and zirconium; and reduce the time needed to vitrify a given inventory of HLW.

  16. 77 FR 1667 - Nelson S. Galgoul, Av. Edison Passess 909, Rio De Janeiro, R.J., Brazil 20531-070, Respondent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ..., the most recent being that of August 12, 2011 (76 FR 50,661 (Aug. 16, 2011)), has continued the... Bureau of Industry and Security Nelson S. Galgoul, Av. Edison Passess 909, Rio De Janeiro, R.J., Brazil... program from the United States to Iran via Brazil, without the required U.S. Government...

  17. Artificial vision by direct optic nerve electrode (AV-DONE) implantation in a blind patient with retinitis pigmentosa.

    PubMed

    Sakaguchi, Hirokazu; Kamei, Motohiro; Fujikado, Takashi; Yonezawa, Eiji; Ozawa, Motoki; Cecilia-Gonzalez, Carmen; Ustariz-Gonzalez, Orlando; Quiroz-Mercado, Hugo; Tano, Yasuo

    2009-01-01

    The purpose of this study was to evaluate the efficacy and safety of artificial vision by using a direct optic nerve electrode (AV-DONE) in a blind patient with retinitis pigmentosa (RP). This device, comprising three wire electrodes (0.05 mm in diameter), was implanted into the optic disc of a patient with RP with no light perception vision and the device was left implanted. Six months later, visual sensations were elicited by electrical stimulation through each electrode and the thresholds for the phosphene perception elicited by pulses of 0.25-ms duration/phase and a pulse frequency of 320 Hz were 30, 5, and 70 microA for each electrode. The phosphenes, which ranged in size from that of a match head to an apple, were round, oval, or linear, primarily yellow, and focally distributed. The area of the phosphenes changed when the electrical stimulation was supplied from different electrodes. No complications arose during the follow-up period. Localized visual sensations were produced in a blind patient with advanced RP, suggesting that our system could lead to the development of a useful visual prosthesis system. PMID:19894096

  18. 3DVIEWNIX-AVS: a software package for the separate visualization of arteries and veins in CE-MRA images.

    PubMed

    Lei, Tianhu; Udupa, Jayaram K; Odhner, Dewey; Nyúl, László G; Saha, Punam K

    2003-01-01

    Our earlier study developed a computerized method, based on fuzzy connected object delineation principles and algorithms, for artery and vein separation in contrast enhanced Magnetic Resonance Angiography (CE-MRA) images. This paper reports its current development-a software package-for routine clinical use. The software package, termed 3DVIEWNIX-AVS, consists of the following major operational parts: (1) converting data from DICOM3 to 3DVIEWNIX format, (2) previewing slices and creating VOI and MIP Shell, (3) segmenting vessel, (4) separating artery and vein, (5) shell rendering vascular structures and creating animations. This package has been applied to EPIX Medical Inc's CE-MRA data (AngioMark MS-325). One hundred and thirty-five original CE-MRA data sets (of 52 patients) from 6 hospitals have been processed. In all case studies, unified parameter settings produce correct artery-vein separation. The current package is running on a Pentium PC under Linux and the total computation time per study is about 3 min. The strengths of this software package are (1) minimal user interaction, (2) minimal anatomic knowledge requirements on human vascular system, (3) clinically required speed, (4) free entry to any operational stages, (5) reproducible, reliable, high quality of results, and (6) cost effective computer implementation. To date, it seems to be the only software package (using an image processing approach) available for artery and vein separation of the human vascular system for routine use in a clinical setting. PMID:12821028

  19. The AV Consultant

    ERIC Educational Resources Information Center

    Wadsworth, Raymond H.

    1976-01-01

    An audiovisual communications consultant involved in planning a new facility is able to translate the needs of educators into integrated systems, and relate these to the architects and engineers in terms of working drawings, specifications, system descriptions, functional schematics, and block diagrams. (Author/MLF)

  20. Bibliography of AV Materials.

    ERIC Educational Resources Information Center

    Friedstein, Harriet, Ed.

    1981-01-01

    Lists commercially available audiovisual materials by subject area. Includes title, producer (addresses given), catalog number, format (film, filmstrip, cassette, slides), and prices. Subject areas include: elements; equilibrium; gases; laboratory techniques and experiments; general chemistry; introductory materials (including mathematics); and…

  1. Bibliography of AV Materials.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1981

    1981-01-01

    Presented is the second part of a bibliographic listing of commercially available audiovisual materials for chemistry. Information includes producer (with addresses), catalog number, format (slides, cassettes, filmstrips, films), and price for items in these categories: matter and energy, nuclear chemistry, periodic table, solids and crystals,…

  2. Cholera in Pregnancy: Outcomes from a Specialized Cholera Treatment Unit for Pregnant Women in Léogâne, Haiti

    PubMed Central

    Ciglenecki, Iza; Bichet, Mathieu; Tena, Javier; Mondesir, Erneau; Bastard, Mathieu; Tran, Nguyen-Toan; Antierens, Annick; Staderini, Nelly

    2013-01-01

    Background The association between cholera in pregnancy and negative fetal outcome has been described since the 19th century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. Methods Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera treatment guidelines but with earlier, more intense fluid replacement. All women had intravenous access established at admission regardless of their hydration status, and all received antibiotic treatment. Data were collected on patient demographics, pregnancy and cholera status, and pregnancy outcome. In this analysis we calculated risk ratios for fetal death and performed logistic regression analysis to control for confounding factors. Results 263 pregnant women with cholera were hospitalized between December 2010 and July 2011. None died during hospitalization, 226 (86%) were discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton births, of whom 2 died within the first 5 days postpartum. The remaining 21 pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death was associated with factors reflecting severity of the cholera episode: after adjusting for confounding factors, the strongest risk factor for fetal death was severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration was 9.4, 95% CI 2.5–35.3, p = 0.005), followed by severe vomiting (adjusted risk ratio 5.1, 95% 1.1–23.8, p = 0.041). Conclusion This is the largest cohort of pregnant women with cholera described to date. The main risk factor identified for fetal death was severity of dehydration. Our experience suggests that establishing specialized multidisciplinary units which facilitate close follow-up of both pregnancy and dehydration

  3. Future-saving audiovisual content for Data Science: Preservation of geoinformatics video heritage with the TIB|AV-Portal

    NASA Astrophysics Data System (ADS)

    Löwe, Peter; Plank, Margret; Ziedorn, Frauke

    2015-04-01

    In data driven research, the access to citation and preservation of the full triad consisting of journal article, research data and -software has started to become good scientific practice. To foster the adoption of this practice the significance of software tools has to be acknowledged, which enable scientists to harness auxiliary audiovisual content in their research work. The advent of ubiquitous computer-based audiovisual recording and corresponding Web 2.0 hosting platforms like Youtube, Slideshare and GitHub has created new ecosystems for contextual information related to scientific software and data, which continues to grow both in size and variety of content. The current Web 2.0 platforms lack capabilities for long term archiving and scientific citation, such as persistent identifiers allowing to reference specific intervals of the overall content. The audiovisual content currently shared by scientists ranges from commented howto-demonstrations on software handling, installation and data-processing, to aggregated visual analytics of the evolution of software projects over time. Such content are crucial additions to the scientific message, as they ensure that software-based data-processing workflows can be assessed, understood and reused in the future. In the context of data driven research, such content needs to be accessible by effective search capabilities, enabling the content to be retrieved and ensuring that the content producers receive credit for their efforts within the scientific community. Improved multimedia archiving and retrieval services for scientific audiovisual content which meet these requirements are currently implemented by the scientific library community. This paper exemplifies the existing challenges, requirements, benefits and the potential of the preservation, accessibility and citability of such audiovisual content for the Open Source communities based on the new audiovisual web service TIB|AV Portal of the German National Library

  4. Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

    PubMed

    Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

    2015-12-01

    Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. PMID:26505974

  5. Test Characteristics of Neck Fullness and Witnessed Neck Pulsations in the Diagnosis of Typical AV Nodal Reentrant Tachycardia

    PubMed Central

    Sakhuja, Rahul; Smith, Lisa M; Tseng, Zian H; Badhwar, Nitish; Lee, Byron K; Lee, Randall J; Scheinman, Melvin M; Olgin, Jeffrey E; Marcus, Gregory M

    2011-01-01

    Summary Background Claims in the medical literature suggest that neck fullness and witnessed neck pulsations are useful in the diagnosis of typical AV nodal reentrant tachycardia (AVNRT). Hypothesis Neck fullness and witnessed neck pulsations have a high positive predictive value in the diagnosis of typical AVNRT. Methods We performed a cross sectional study of consecutive patients with palpitations presenting to a single electrophysiology (EP) laboratory over a 1 year period. Each patient underwent a standard questionnaire regarding neck fullness and/or witnessed neck pulsations during their palpitations. The reference standard for diagnosis was determined by electrocardiogram and invasive EP studies. Results Comparing typical AVNRT to atrial fibrillation (AF) or atrial flutter (AFL) patients, the proportions with neck fullness and witnessed neck pulsations did not significantly differ: in the best case scenario (using the upper end of the 95% confidence interval [CI]), none of the positive or negative predictive values exceeded 79%. After restricting the population to those with supraventricular tachycardia other than AF or AFL (SVT), neck fullness again exhibited poor test characteristics; however, witnessed neck pulsations exhibited a specificity of 97% (95% CI 90–100%) and a positive predictive value of 83% (95% CI 52–98%). After adjustment for potential confounders, SVT patients with witnessed neck pulsations had a 7 fold greater odds of having typical AVNRT, p=0.029. Conclusions Although neither neck fullness nor witnessed neck pulsations are useful in distinguishing typical AVNRT from AF or AFL, witnessed neck pulsations are specific for the presence of typical AVNRT among those with SVT. PMID:19479968

  6. Application of variable structure system theory to aircraft flight control. [AV-8A and the Augmentor Wing Jet STOL Research Aircraft

    NASA Technical Reports Server (NTRS)

    Calise, A. J.; Kadushin, I.; Kramer, F.

    1981-01-01

    The current status of research on the application of variable structure system (VSS) theory to design aircraft flight control systems is summarized. Two aircraft types are currently being investigated: the Augmentor Wing Jet STOL Research Aircraft (AWJSRA), and AV-8A Harrier. The AWJSRA design considers automatic control of longitudinal dynamics during the landing phase. The main task for the AWJSRA is to design an automatic landing system that captures and tracks a localizer beam. The control task for the AV-8A is to track velocity commands in a hovering flight configuration. Much effort was devoted to developing computer programs that are needed to carry out VSS design in a multivariable frame work, and in becoming familiar with the dynamics and control problems associated with the aircraft types under investigation. Numerous VSS design schemes were explored, particularly for the AWJSRA. The approaches that appear best suited for these aircraft types are presented. Examples are given of the numerical results currently being generated.

  7. Case report: Manual lymphatic drainage and kinesio taping in the secondary malignant breast cancer-related lymphedema in an arm with arteriovenous (A-V) fistula for hemodialysis.

    PubMed

    Chou, Ya-Hui; Li, Shu-Hua; Liao, Su-Fen; Tang, Hao-Wei

    2013-08-01

    Lymphedema is a dreaded complication of breast cancer treatment. The standard care for lymphedema is complex decongestive physiotherapy, which includes manual lymphatic drainage (MLD), short stretch bandaging, exercise, and skin care. The Kinesio Taping could help to improve lymphatic uptake. We reported a patient with unilateral secondary malignant breast cancer-related lymphedema and arteriovenous (A-V) fistula for hemodialysis happened in the same arm, and used kinesio taping, MLD, and exercise to treat this patient because no pressure could be applied to the A-V fistula. The 12-session therapy created an excellent effect. We do not think the kinesio taping could replace short stretch bandaging, but it could be another choice for contraindicating pressure therapy patients, and we should pay attention to wounds induced by kinesio tape. PMID:22879520

  8. Endovascular image-guided treatment of in-vivo model aneurysms with asymmetric vascular stents (AVS): evaluation with time-density curve angiographic analysis and histology

    PubMed Central

    Dohatcu, A.; Ionita, C. N.; Paciorek, A.; Bednarek, D. R.; Hoffmann, K. R.; Rudin, S.

    2008-01-01

    In this study, we compare the results obtained from Time-Density Curve (TDC) analysis of angiographic imaging sequences with histological evaluation for a rabbit aneurysm model treated with standard stents and new asymmetric vascular stents (AVS) placed by image-guided endovascular deployment. AVSs are stents having a low-porosity patch region designed to cover the aneurysm neck and occlude blood flow inside. To evaluate the AVSs, rabbits with elastase-induced aneurysm models (n=20) were divided into three groups: the first (n=10) was treated with an AVS, the second (n=5) with a non-patch standard coronary stent, and third was untreated as a control (n=5). We used TDC analysis to measure how much contrast media entered the aneurysm before and after treatment. TDCs track contrast-media-density changes as a function of time over the region of interest in x-ray DSA cine-sequences. After 28 days, the animals were sacrificed and the explanted specimens were histologically evaluated. The first group showed an average reduction of contrast flow into the aneurysm of 95% after treatment with an AVS with fully developed thrombus at 28 days follow-up. The rabbits treated with standard stents showed an increase in TDC residency time after treatment and partial-thrombogenesis. The untreated control aneurysms displayed no reduction in flow and were still patent at follow-up. The quantitative TDC analysis findings were confirmed by histological evaluation suggesting that the new AVS has great potential as a definitive treatment for cerebro-vascular aneurysms and that angiographic TDC analysis can provide in-vivo verification. PMID:18958295

  9. No proarrhythmic properties of the antibiotics Moxifloxacin or Azithromycin in anaesthetized dogs with chronic-AV block

    PubMed Central

    Thomsen, M B; Beekman, J D M; Attevelt, N J M; Takahara, A; Sugiyama, A; Chiba, K; Vos, M A

    2006-01-01

    Background & purpose: The therapeutically available quinolone antibiotic moxifloxacin has been used as a positive control for prolonging the QT interval in both clinical and non-clinical studies designed to assess the potential of new drugs to delay cardiac repolarization. Despite moxifloxacin prolonging QT, it has not been shown to cause torsades de pointes arrhythmias (TdP). Azithromycin is a macrolide antibiotic that has rarely been associated, clinically, with cases of proarrhythmia. As there is a lack of clinical data available, the cardiac safety of these drugs was assessed in a TdP-susceptible animal model by evaluating their repolarization and proarrhythmia effects. Experimental approach & Key results: In transfected HEK cells, the IC50s for I hERG were 45±6 and 856±259 μg ml-1 for moxifloxacin and azithromycin, respectively. Intravenous administration of 2 and 8 mg kg-1 moxifloxacin (total peak-plasma concentrations 4.6±1.5 and 22.9±6.8 μg ml-1) prolonged the QTc in 6 anaesthetized dogs with chronic AV block by 7±3 and 21±19%, respectively. Similar intravenous doses of azithromycin (total peak-plasma concentrations 5.4±1.3 and 20.8±4.9 μg ml-1) had no electrophysiological effects in the same dogs. The reference compound, dofetilide (25 μg kg-1 i.v.) caused QTc prolongation (29±15%) and TdP in all dogs. Beat-to-beat variability of repolarization (BVR), quantified as short-term variability of the left ventricular monophasic action potential duration, was only increased after dofetilide (1.8±0.7 to 3.8±1.5 ms; P<0.05). Conclusion & implications: As neither moxifloxacin nor azithromycin caused TdP or an increase in the BVR, we conclude that both drugs can be used safely in clinical situations. PMID:17088870

  10. In Vivo Imaging of Amyloid Deposition in Alzheimer’s Disease using the Novel Radioligand [18F]AV-45 (Florbetapir F 18)

    PubMed Central

    Wong, Dean F.; Rosenberg, Paul B.; Zhou, Yun; Kumar, Anil; Raymont, Vanessa; Ravert, Hayden T.; Dannals, Robert F.; Nandi, Ayon; Brašić, James R.; Ye, Weiguo; Hilton, John; Lyketsos, Constantine; Kung, Hank F.; Joshi, Abhinay D.; Skovronsky, Daniel M.; Pontecorvo, Michael J.

    2011-01-01

    Introduction An [18F] labeled PET amyloid (Aβ) imaging agent could facilitate clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer’s disease (AD) pathology. Here we present the results of the first clinical trial with [18F]AV-45 (Florbetapir F 18). Methods An open-label, multicenter, brain imaging, metabolism and safety study of [18F]AV-45 was performed on 16 patients with Alzheimer’s disease (AD: MMSE 19.3 +/− 3.1; Age 75.8 +/− 9.2) and 16 cognitively healthy controls (HC: MMSE 29.8 +/− 0.45; Age 72.5 +/− 11.6 ). Dynamic PET imaging was performed over a period of approximately 90 minutes following 10 mCi injection of the tracer. Standard uptake values (SUV) and cortical to cerebellum SUV ratios (SUVR) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps in a subset of subjects Results Valid PET imaging data were available for 11 AD and 15 HC subjects [18F]AV-45 accumulated in cortical regions expected to be high in amyloid deposition (e.g., precuneus, frontal and temporal cortex) of AD patients; minimal accumulation of tracer was seen in cortical regions of HC subjects. The cortical to cerebellar SUVR values in AD patients showed continual substantial increases through 30 minutes post-administration, reaching a plateau within 50 minutes. The 10 minute period from 50–60 minutes post administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/− 0.175 for patients with AD vs. 1.25 +/− 0.177 for HC subjects. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r= 0.58–0.88, p<0.005) and were significantly greater for AD patients than for HC subjects in cortical regions, but not in subcortical white matter or cerebellar regions. There were no clinically significant changes in vital signs, ECG or laboratory values. Conclusions