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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 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  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. 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

  18. 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

  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. 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

  1. 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

  2. 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

  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. 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

  7. 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

  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. 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

  4. 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

  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. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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…

  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. 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.

  20. 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.

  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. 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…

  5. 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.

  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

    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 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

  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. 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

  4. 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.

  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. 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…

  11. 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)

  12. 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)

  13. 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)

  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. 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…

  20. 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

  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. 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.

  5. 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.

  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. 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.

  12. 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.

  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. 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

  1. 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

  2. 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

  3. 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

  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. 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

  11. 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

  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. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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....

  5. 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.

  6. 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;...

  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. 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

  11. 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

  12. 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

  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 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

  7. 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

  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. 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.

  16. 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

  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. 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.

  7. 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

  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. 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

  18. 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

  19. 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,…

  20. 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)

  1. 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…

  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

  11. Enhanced early innate and T cell-mediated responses in subjects immunized with Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909).

    PubMed

    Minang, Jacob T; Inglefield, Jon R; Harris, Andrea M; Lathey, Janet L; Alleva, David G; Sweeney, Diane L; Hopkins, Robert J; Lacy, Michael J; Bernton, Edward W

    2014-11-28

    NuThrax™ (Anthrax Vaccine Adsorbed with CPG 7909 Adjuvant) (AV7909) is in development. Samples obtained in a phase Ib clinical trial were tested to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity. Subjects received two intramuscular doses of commercial BioThrax(®) (Anthrax Vaccine Adsorbed, AVA), or two intramuscular doses of one of four formulations of AV7909. IP-10, IL-6, and C-reactive protein (CRP) levels were elevated 24-48 h after administration of AV7909 formulations, returning to baseline by Day 7. AVA (no CPG 7909) resulted in elevated IL-6 and CRP, but not IP-10. Another marker of CpG, transiently decreased absolute lymphocyte counts (ALCs), correlated with transiently increased IP-10. Cellular recall responses to anthrax protective antigen (PA) or PA peptides were assessed by IFN-γ ELISpot assay performed on cryopreserved PBMCs obtained from subjects prior to immunization and 7 days following the second immunization (study day 21). One-half of subjects that received AV7909 with low-dose (0.25mg/dose) CPG 7909 possessed positive Day 21 T cell responses to PA. In contrast, positive T cell responses occurred at an 11% average rate (1/9) for AVA-treated subjects. Differences in cellular responses due to dose level of CPG 7909 were not associated with differences in humoral anti-PA IgG responses, which were elevated for recipients of AV7909 compared to recipients of AVA. Serum markers at 24 or 48 h (i.e. % ALC decrease, or increase in IL-6, IP-10, or CRP) correlated with the humoral (antibody) responses 1 month later, but did not correlate with cellular ELISpot responses. In summary, biomarkers of early responses to CPG 7909 were confirmed, and adding a CpG adjuvant to a vaccine administered twice resulted in increased T cell effects relative to vaccine alone. Changes in early biomarkers correlated with subsequent adaptive humoral immunity but not cellular immunity. PMID:24530403

  12. Is it time to retire the A.V. Hill Model?: A rebuttal to the article by Professor Roy Shephard.

    PubMed

    Noakes, Timothy D

    2011-04-01

    philosophies of how science should be conducted according to either the Kuhnian or the Popperian philosophies of scientific discovery. My conclusion is that the dominance of an authoritarian Kuhnian philosophy, which refuses to admit genuine error or "the need to alter one's course of belief or action," explains why there is little appetite in the exercise sciences for the acceptance of genuinely novel ideas such as the CGM. Furthermore, to advance the case for the CGM, I now include evidence from more than 30 studies, which, in my opinion, can only be interpreted according to a model of exercise regulation where the CNS, acting in an anticipatory manner, regulates the exercise behaviour by altering skeletal muscle recruitment, specifically to ensure that homeostasis is maintained during exercise. Since few, if any, of those studies can be explained by the 'brainless' A.V. Hill Cardiovascular Model on which Professor Shephard bases his arguments, I argue that it is now the appropriate time to retire that model. Perhaps this will bring to an end the charade that holds either (i) that the brain plays no part in the regulation of exercise performance; or, conversely, (ii) that the role of the brain is already so well defined that further research by other scientists is unnecessary. However, this cannot occur in a discipline that is dominated by an authoritarian Kuhnian philosophy. PMID:21425886

  13. Og4C3 circulating antigen, anti-Brugia malayi IgG and IgG4 titers in Wuchereria bancrofti infected patients, according to their parasitological status.

    PubMed

    Chanteau, S; Glaziou, P; Luquiaud, P; Plichart, C; Moulia-Pelat, J P; Cartel, J L

    1994-09-01

    This study involved 221 microfilaremic (Mf+), 302 amicrofilaremic (Mf-) antigen positive (AG+) and 1454 Mf-antigen negative (AG-) individuals living in endemic villages. Whatever the group considered, antigen and antibody titers were widely distributed. Og4C3 antigen, detected both in Mf- and Mf+ patients, was significantly higher in Mf+ patients. The Mf parasitological status did not significantly influence the antifilarial antibodies levels in the infected AG+ individuals, although IgG4 was more discriminant. In the supposedly uninfected individuals (Mf-AG-), anti-filarial IgG and IgG4 could be detected in a large proportion of the group. Og4C3 circulating antigen test was confirmed to be a good marker of active Wuchereria bancrofti infection. PMID:7899800

  14. Bioavailability assessment of toxic metals using the technique "acid-volatile sulfide (AVS)-simultaneously extracted metals (SEM)" in marine sediments collected in Todos os Santos Bay, Brazil.

    PubMed

    Silva, Jucelino B; Nascimento, Rodrigo A; de Oliva, Sergio T; de Oliveira, Olívia M C; Ferreira, Sergio L C

    2015-10-01

    This paper reports the bioavailability of the metals (cadmium, copper, zinc, lead, and nickel) in sediment samples collected in seven stations from the São Paulo Estuary, Todos os Santos Bay, Brazil. The bioavailability was determined by employing the technique "acid-volatile sulfide (AVS) and simultaneously extracted metal (SEM)". The elements cadmium, copper, lead, and zinc were determined using differential pulse anodic stripping voltammetry (DPASV), while nickel was quantified utilizing electrothermal atomic absorption spectrometry (ET AAS). The accuracy of these methods was confirmed using a certified reference material of estuarine sediment (NIST 1646). The sulfide was quantified using potentiometry with selective electrode and the organic matter determination employing an indirect volumetric method using potassium dichromate and iron(II) sulfate solutions. The bioavailability of the metals was estimated by relationship between the concentration of AVS and the sum of the concentrations of the simultaneously extracted metals (ΣSEM), considering a significant toxicity when (ΣSEM)/(AVS) is higher than 1. The bioavailability values in the seven stations studied varied from 0.93 to 1.31 (June, 2014) and from 0.34 to 0.58 (September, 2014). These results demonstrated a critical condition of toxicity (bioavailability >1) in six of the seven sediment samples collected during the rainy season (June, 2014). In the other period (September, 2014), the bioavailability was always lower than 1 for all sediment samples collected in the seven stations. The individual values of the concentrations of the five metals were compared with the parameters PEL (probable effects level) and TEL (threshold effects level), which are commonly employed for characterization of ecological risk in environmental systems. This comparison revealed that all metals have concentrations lower than the PEL and only zinc and lead in some stations have contents higher than the TEL. The

  15. Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.

    PubMed

    Hopkins, Robert J; Kalsi, Gurdyal; Montalvo-Lugo, Victor M; Sharma, Mona; Wu, Yukun; Muse, Derek D; Sheldon, Eric A; Hampel, Frank C; Lemiale, Laurence

    2016-04-19

    AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax(®) (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥0.56) to be ≥40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine. PMID:26979136

  16. Absolute quantification of Pru av 2 in sweet cherry fruit by liquid chromatography/tandem mass spectrometry with the use of a stable isotope-labelled peptide.

    PubMed

    Ippoushi, Katsunari; Sasanuma, Motoe; Oike, Hideaki; Kobori, Masuko; Maeda-Yamamoto, Mari

    2016-08-01

    Pru av 2, a pathogenesis-related (PR) protein present in the sweet cherry (Prunus avium L.) fruit, is the principal allergen of cherry and one of the chief causes of pollen food syndrome (oral allergy syndrome). In this study, a quantitative assay for this protein was developed with the use of the protein absolute quantification (AQUA) method, which consists of liquid chromatography/tandem mass spectrometry (LC/MS/MS) employing TGC[CAM]STDASGK[(13)C6,(15)N2], a stable isotope-labelled internal standard (SIIS) peptide. This assay gave a linear relationship (r(2)>0.99) in a concentration range (2.3-600fmol/μL), and the overall coefficient of variation (CV) for multiple tests was 14.6%. Thus, the contents of this allergenic protein in sweet cherry products could be determined using this assay. This assay should be valuable for allergological investigations of Pru av 2 in sweet cherry and detection of protein contamination in foods. PMID:26988485

  17. Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua

    PubMed Central

    Li, Shun-Ji; Hopkins, Richard J.; Zhao, Yi-Pei; Zhang, Yun-Xuan; Hu, Jue; Chen, Xu-Yang; Xu, Zhi; Huang, Guo-Hua

    2016-01-01

    Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 ± 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 ± 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis. PMID:26878829

  18. Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua.

    PubMed

    Li, Shun-Ji; Hopkins, Richard J; Zhao, Yi-Pei; Zhang, Yun-Xuan; Hu, Jue; Chen, Xu-Yang; Xu, Zhi; Huang, Guo-Hua

    2016-01-01

    Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 ± 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 ± 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis. PMID:26878829

  19. Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen

    PubMed Central

    2004-01-01

    Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called ‘P-loop’ region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy. PMID:15330760

  20. Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

    PubMed Central

    Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

    2003-01-01

    Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

  1. Rolling-leaf14 is a 2OG-Fe (II) oxygenase family protein that modulates rice leaf rolling by affecting secondary cell wall formation in leaves.

    PubMed

    Fang, Likui; Zhao, Fangming; Cong, Yunfei; Sang, Xianchun; Du, Qing; Wang, Dezhong; Li, Yunfeng; Ling, Yinghua; Yang, Zhenglin; He, Guanghua

    2012-06-01

    As an important agronomic trait, leaf rolling in rice (Oryza sativa L.) has attracted much attention from plant biologists and breeders. Moderate leaf rolling increases the amount of photosynthesis in cultivars and hence raises grain yield. Here, we describe the map-based cloning of the gene RL14, which was found to encode a 2OG-Fe (II) oxygenase of unknown function. rl14 mutant plants had incurved leaves because of the shrinkage of bulliform cells on the adaxial side. In addition, rl14 mutant plants displayed smaller stomatal complexes and decreased transpiration rates, as compared with the wild type. Defective development could be rescued functionally by the expression of wild-type RL14. RL14 was transcribed in sclerenchymatous cells in leaves that remained wrapped inside the sheath. In mature leaves, RL14 accumulated mainly in the mesophyll cells that surround the vasculature. Expression of genes related to secondary cell wall formation was affected in rl14-1 mutants, and cellulose and lignin content were altered in rl14-1 leaves. These results reveal that the RL14 gene affects water transport in leaves by affecting the composition of the secondary cell wall. This change in water transport results in water deficiency, which is the major reason for the abnormal shape of the bulliform cells. PMID:22329407

  2. Measuring Vertical Profiles of Wind, Temperature and Humidity within the Atmospheric Boundary Layer using the Research UAVs 'M2AV Carolo'

    NASA Astrophysics Data System (ADS)

    Bange, J.; Martin, S.

    2009-09-01

    The measurement of vertical profiles is important to characterise the vertical structure of the atmospheric boundary layer (ABL). For instance, the dependence of the potential temperature on altitude defines the thermal stratification. The mechanical shear (i.e. the variation of wind speed and direction) produces turbulence and turbulent fluxes. The top of the ABL is required for scaling approaches (e.g. Deardorff scaling in the convective boundary layer, local scaling in the stable boundary layer). The Meteorological Mini Aerial Vehicles (M²AV) are self-constructed, automatically operating research aircraft of 6 kg in weight (including 1.5 kg scientific payload) and 2 m wingspan. These systems are capable of performing turbulence measurements (wind vector, temperature and humidity) and are used as a new instrument for measuring vertical profiles of the lower troposphere. Compared to a radiosonde, the spatial resolution of the M²AV is significantly higher. Especially the wind measurement is significantly more accurate compared to radiosonde data when using an aircraft that is equipped with a proper flow sensor (mainly a five-hole probe). It is important to maintain flow angles (sideslip and angle of attack) within the calibration range (typically 10 to 20 degree). This limits the vertical speed (the rate of climb and descent) of the research aircraft. In general there are two approaches to measure vertical profiles with research aircraft. Instantaneous profiles (slant flight pattern) are suitable if only little time is available, if the ABL is very in-stationary (or the aircraft is slow), if the dependence of the profile on time is requested (repeated slant flight patterns over one location) or if the dependence of the profile on the location is requested (saw-tooth pattern). For mean profiles (horizontal straight and level flights 'legs' at several altitudes within the ABL) it is necessary to use fast sensors. If the response time is too large, the vertical

  3. Improved longitudinal [(18)F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction.

    PubMed

    Brendel, Matthias; Högenauer, Marcus; Delker, Andreas; Sauerbeck, Julia; Bartenstein, Peter; Seibyl, John; Rominger, Axel

    2015-03-01

    Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [(18)F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [(18)F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (-18%) and MCI (-10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis

  4. Redox Mechanisms of AVS022, an Oriental Polyherbal Formula, and Its Component Herbs in Protection against Induction of Matrix Metalloproteinase-1 in UVA-Irradiated Keratinocyte HaCaT Cells

    PubMed Central

    Pluemsamran, Thanyawan; Tripatara, Pinpat; Phadungrakwittaya, Rattana; Akarasereenont, Pravit; Laohapand, Tawee

    2013-01-01

    Ayurved Siriraj HaRak (AVS022) formula has been used for topical remedy of dermatologic disorders. Oxidative stress induced by ultraviolet (UV) A irradiation could be implicated in photoaged skin through triggering matrix metalloproteinase-1 (MMP-1). We, therefore, explored the antioxidant mechanisms by which AVS022 formulation and its individual components protected against UVA-dependent MMP-1 upregulation in keratinocyte HaCaT cells. TLC analysis revealed the presence of multiple phenolics including gallic acid (GA) in the AVS022 extracts. We demonstrated that pretreatment with the whole formula and individual herbal components except T. triandra protected against increased MMP-1 activity in irradiated HaCaT cells. Moreover, all herbal extracts and GA, used as the reference compound, were able to reverse cytotoxicity, oxidant production, glutathione (GSH) loss, and inactivation of catalase and glutathione peroxidase (GPx). F. racemosa was observed to yield the strongest abilities to abolish UVA-mediated induction of MMP-1 and impairment of antioxidant defenses including GSH and catalase. Our observations suggest that upregulation of endogenous antioxidants could be the mechanisms by which AVS022 and its herbal components suppressed UVA-stimulated MMP-1 in HaCaT cells. In addition, pharmacological actions of AVS022 formula may be attributed to the antioxidant potential of its components, in particular F. racemosa, and several phenolics including GA. PMID:24171043

  5. Acid Volatile Sulfides (avs) and the Bioavailability of Trace Metals in the Channel of the SÃO Francisco River, Sepetiba Bay - de Janeiro-Brazil

    NASA Astrophysics Data System (ADS)

    Monte, Christiane; Rodrigues, Ana Paula; Marinho, Matheus; Quaresma, Tássia; Machado, Wilson

    2014-05-01

    Sepetiba Bay has 430 Km2 of internal and 2,500 Km2 area of the drainage basin (Lacerda et al., 2007), located 60 km west of the city of Rio de Janeiro. Sepetiba Bay has 430 Km2 of internal and 2,500 Km2 area of the drainage basin (Lacerda et al., 2007), located 60 km west of the city of Rio de Janeiro.The San Francisco channel comes from the Guandu River and empties into Sepetiba Bay and is the main contributor of freshwater to the estuarine system. The Guandu River system/channel of San Francisco receives contribution of domestic and industrial effluents, which go largely to Sepetiba Bay. This work aimed to evaluate the .This work aimed to evaluate the ratio SEM/AVS as a way of predicting bioavailability trace metals from industrial sewage, mainly, in the estuarine system of Sepetiba. This model is based on the property of some Divalent metal cations (Cd, Cu, Ni, Pb and Zn), by presenting a low solubility constant, are removed from the soluble fraction by precipitation, forming secondary metal sulfides. Were held four transects, made up of three points each, the coast line to the center of the Bay. The surface sediment was collected with a van Veen sampler type ,packed in glass jars and kept frozen until analysis.The determination of SEM/AVS followed the methodology described by Allen et al. (1991). The variation between sulfide 159.88 ± 0.05 µmol/g on 12 points. The metals that entered the sum of simultaneous extraction were: Cd, Cu, Ni, Pb and Zn ranging from: 6.47 ± 0.11 µmol/g on sum.The means (± standard deviation) ratio SEM/AVS per transect were: 1.04 ± 1.20 (transect 1); 0.48 ± 0.53 (transect 2); 1.26 ± 1.32 (transect 3) and 0.18 ± 0.14 (transect 4). Only transects 1 and 3 had higher results than 1 , meaning that there are more divalent metal sulfides in the environment. This means that only the sulfides would not be capable of complex and may reflect the potential bioavailability of these in the aquatic environment. There is no statistical

  6. Navier-Stokes simulation of external/internal transonic flow on the forebody/inlet of the AV-8B Harrier II

    NASA Technical Reports Server (NTRS)

    Mysko, Stephen J.; Chyu, Wei J.; Stortz, Michael W.; Chow, Chuen-Yen

    1993-01-01

    In this work, the computation of combined external/internal transonic flow on the complex forebody/inlet configuration of the AV-8B Harrier II is performed. The actual aircraft has been measured and its surface and surrounding domain, in which the fuselage and inlet have a common wall, have been described using structured grids. The 'thin-layer' Navier-Stokes equations were used to model the flow along with the Chimera embedded multi-block technique. A fully conservative, alternating direction implicit (ADI), approximately factored, partially fluxsplit algorithm was employed to perform the computation. Comparisons to some experimental wind tunnel data yielded good agreement for flow at zero incidence and angle of attack. The aim of this paper is to provide a methodology or computational tool for the numerical solution of complex external/internal flows.

  7. The development of a monoclonal antibody recognizing the Drosophila melanogaster phosphorylated histone H2A variant (γ-H2AV).

    PubMed

    Lake, Cathleen M; Holsclaw, Julie Korda; Bellendir, Stephanie P; Sekelsky, Jeff; Hawley, R Scott

    2013-09-01

    The recognition of DNA double-strand breaks (DSBs) using a phospho-specific antibody to the histone 2A variant has become the gold standard assay for DNA damage detection. Here we report on the development of the first monoclonal antibody to the phospho-specific form of Drosophila H2AV and characterize the specificity of this antibody to programmed DSBs in oocytes and rereplication sites in endocycling cells by immunofluorescence assays and to DSBs resulting from irradiation in both cell culture and whole tissue by Western blot assays. These studies show that the antibody derived in the study is highly specific for this modification that occurs at DSB sites, and therefore will be a new useful tool within the Drosophila community for the study of DNA damage response, DSB repair, meiotic recombination and chemical agents that cause DNA damage. PMID:23833215

  8. Modeling the influence of the VV delay for CRT on the electrical activation patterns in absence of conduction through the AV node

    NASA Astrophysics Data System (ADS)

    Romero, D. A.; Sebastián, Rafael; Plank, Gernot; Vigmond, Edward J.; Frangi, Alejandro F.

    2008-03-01

    From epidemiological studies, it has been shown that 0.2% of men and 0.1% of women suffer from a degree of atrioventricular (AV) block. In recent years, the palliative treatment for third degree AV block has included Cardiac Resynchronization Therapy (CRT). It was found that patients show more clinical improvement in the long term with CRT compared with single chamber devices. Still, an important group of patients does not improve their hemodynamic function as much as could be expected. A better understanding of the basis for optimizing the devices settings (among which the VV delay) will help to increase the number of responders. In this work, a finite element model of the left and right ventricles was generated using an atlas-based approach for their segmentation, which includes fiber orientation. The electrical activity was simulated with the electrophysiological solver CARP, using the Ten Tusscher et al. ionic model for the myocardium, and the DiFrancesco-Noble for Purkinje fibers. The model is representative of a patient without dilated or ischemic cardiomyopathy. The simulation results were analyzed for total activation times and latest activated regions at different VV delays and pre-activations (RV pre-activated, LV pre-activated). To optimize the solution, simulations are compared against the His-Purkinje network activation (normal physiological conduction), and interventricular septum activation (as collision point for the two wave fronts). The results were analyzed using Pearson's coefficient of correlation for point to point comparisons between simulation cases. The results of this study contribute to gain insight on the VV delay and how its adjustment might influence response to CRT and how it can be used to optimize the treatment.

  9. Contribution of Individual Ebp Pilus Subunits of Enterococcus faecalis OG1RF to Pilus Biogenesis, Biofilm Formation and Urinary Tract Infection

    PubMed Central

    Sillanpää, Jouko; Chang, Chungyu; Singh, Kavindra V.; Montealegre, Maria Camila; Nallapareddy, Sreedhar R.; Harvey, Barrett R.; Ton-That, Hung; Murray, Barbara E.

    2013-01-01

    The endocarditis and biofilm-associated pilus (Ebp) operon is a component of the core genome of Enterococcus faecalis that has been shown to be important for biofilm formation, adherence to host fibrinogen, collagen and platelets, and in experimental endocarditis and urinary tract infection models. Here, we created single and double deletion mutants of the pilus subunits and sortases; next, by combining western blotting, immunoelectron microscopy, and using ebpR in trans to increase pilus production, we identified EbpA as the tip pilin and EbpB as anchor at the pilus base, the latter attached to cell wall by the housekeeping sortase, SrtA. We also confirmed EbpC and Bps as the major pilin and pilin-specific sortase, respectively, both required for pilus polymerization. Interestingly, pilus length was increased and the number of pili decreased by deleting ebpA, while control overexpression of ebpA in trans restored wild-type levels, suggesting a dual role for EbpA in both initiation and termination of pilus polymerization. We next investigated the contribution of each pilin subunit to biofilm formation and UTI. Significant reduction in biofilm formation was observed with deletion of ebpA or ebpC (P<0.001) while ebpB was found to be dispensable; a similar result was seen in kidney CFUs in experimental UTI (ΔebpA, ΔebpC, P≤0.0093; ΔebpB, non-significant, each vs. OG1RF). Hence, our data provide important structural and functional information about these ubiquitous E. faecalis pili and, based on their demonstrated importance in biofilm and infection, suggest EbpA and EbpC as potential targets for antibody-based therapeutic approaches. PMID:23874774

  10. L'Anti-Atlas occidental du Maroc: étude sédimentologique et reconstitutions paléogéographiques au Cambrien inférieur

    NASA Astrophysics Data System (ADS)

    Benssaou, M.; Hamoumi, N.

    2001-04-01

    L'étude lithostratigraphique en sédimentologique des formations du Cambrien inférieur de l'Anti-Atlas occidental (Maroc) a permis de mettre en évidence la diversité extrême des faciès allant des faciès continentaux jusqu'au faciès franchement marins. La répartition verticale de ces faciès ainsi que leurs associations ont permis de (i) proposer un nouveau découpage de la succession en formations lithostratigraphiques, (ii) reconstituer les milieux de dépôt (système fluviatile, lacs, fan-deltas, milieu littoral, plate-forme dominée par des constructions stromatolitiques et récifales et plate-forme dominée par les tempêtes) et (iii) établir des modèles paléogéographiques retraçant les différentes étapes d'évolution de ce bassin qui fait partie de la plate-forme nord-gondwanienne au Cambrien inférieur. Lithostratigraphical and sedimentological studies of the Early Cambrian formations in the western Anti-Atlas (Morocco) evidence their large diversity of facies ranging from continental to clearly marine. Vertical distribution and associations of facies afford opportunities to (i) suggest a new classification of the sedimentary sequence in terms of lithostratigraphic formations, (ii) restore the depositional environments (fluvial system, lake, delta fan, coast, stromatolite and reef-dominated platform, tempest-dominated platform), and (iii) establish palæogeographic models displaying the different evolutionary stages of this basin that constituted a part of the Lower Cambrian north-Gondwanian platform.

  11. Increasing the probability of long-range (1 month) SPI index forecasts based on SL-AV model for the Russian territory.

    NASA Astrophysics Data System (ADS)

    Utkuzova, Dilyara; Khan, Valentina; Donner, Reik

    2016-04-01

    taken from CPC_CAMS archive) was integrated with MSLP atmospheric pressure field (from ERA Interim achieve) to create special type of SPI combined maps. As a basic seasonal forecasting model we took the SL-AV (Semi-implicit semi-Lagrangian vorticity-divergence dynamical core) model (Tolstykh, 2010) which runs in Hydrometcentre of Russia and has ALADIN/LACE parameterization. Skill scores of SPI calculation based on SL-AV hindcasts showed that it is necessary to use statistical methodology which can increase one month SPI index predictability. Calculations showed that for a new scheme the best predictors are pressure fields on the H500 and MSLP levels. This data was taken from SL-AV model hindcasts for all North Eurasian territory. The main idea of cross-correlation analysis between SPI data and pressure was to show interconnections between precipitation and pressure in different areas and detect the informative prognostic predictors (areas) for each SPI. Then using all information which was extracted before the regression analysis was done. This analysis helped to reconstruct forecasting SPI for the territory of Russia in two ways - deterministic and probabilistic. The resulting forecasts skill scores for both types of predictions are acceptable and scheme can be used in operational precipitation forecasts with one month in advance.

  12. Enhanced multi-protocol analysis via intelligent supervised embedding (EMPrAvISE): detecting prostate cancer on multi-parametric MRI

    NASA Astrophysics Data System (ADS)

    Viswanath, Satish; Bloch, B. Nicholas; Chappelow, Jonathan; Patel, Pratik; Rofsky, Neil; Lenkinski, Robert; Genega, Elizabeth; Madabhushi, Anant

    2011-03-01

    Currently, there is significant interest in developing methods for quantitative integration of multi-parametric (structural, functional) imaging data with the objective of building automated meta-classifiers to improve disease detection, diagnosis, and prognosis. Such techniques are required to address the differences in dimensionalities and scales of individual protocols, while deriving an integrated multi-parametric data representation which best captures all disease-pertinent information available. In this paper, we present a scheme called Enhanced Multi-Protocol Analysis via Intelligent Supervised Embedding (EMPrAvISE); a powerful, generalizable framework applicable to a variety of domains for multi-parametric data representation and fusion. Our scheme utilizes an ensemble of embeddings (via dimensionality reduction, DR); thereby exploiting the variance amongst multiple uncorrelated embeddings in a manner similar to ensemble classifier schemes (e.g. Bagging, Boosting). We apply this framework to the problem of prostate cancer (CaP) detection on 12 3 Tesla pre-operative in vivo multi-parametric (T2-weighted, Dynamic Contrast Enhanced, and Diffusion-weighted) magnetic resonance imaging (MRI) studies, in turn comprising a total of 39 2D planar MR images. We first align the different imaging protocols via automated image registration, followed by quantification of image attributes from individual protocols. Multiple embeddings are generated from the resultant high-dimensional feature space which are then combined intelligently to yield a single stable solution. Our scheme is employed in conjunction with graph embedding (for DR) and probabilistic boosting trees (PBTs) to detect CaP on multi-parametric MRI. Finally, a probabilistic pairwise Markov Random Field algorithm is used to apply spatial constraints to the result of the PBT classifier, yielding a per-voxel classification of CaP presence. Per-voxel evaluation of detection results against ground truth for Ca

  13. Recommendations for a Standardized Avian Coronavirus (AvCoV) Nomenclature: Outcome from Discussions Within the Framework of the European Union COST Action FA1207: "Towards Control of Avian Coronaviruses: Strategies for Vaccination, Diagnosis and Surveillance".

    PubMed

    2016-06-01

    Viruses within the Coronaviridae family show variations within their genome sequences, especially within the major structural protein, the Spike (S) glycoprotein gene. Therefore, many different antigenic forms, serotypes, or variant strains of avian coronaviruses (AvCoV) exist worldwide. Only a few of them, the so called protectotypes, cross protect against different serotypes. New serotypes arise by recombination or spontaneous mutations. From time to time, antigenic virus variants appear which differ significantly from known serotypes. The result of this variability is an inconsistent nomenclature and classification of virus strains. Furthermore, there are currently no standard classification methods defined. Within the framework of the COST Action FA1207 "Towards control of avian coronaviruses: strategies for diagnosis, surveillance, and vaccination" (working groups "Molecular virology" and "Epidemiology"), we aimed at defining and developing a unified and internationally standardized nomenclature and classification of AvCoVs. We recommend the use of "CoV Genus/AvCov/host/country/specimen id/year" to refer to AvCoV strains. PMID:27309279

  14. Burning mechanism and regression rate of RX-35-AU and RX-35-AV as a function of HMX particle size measured by the hybrid closed bomb-strand burner

    SciTech Connect

    Tao, W.C.; Costantino, M.S.; Ornellas, D.L.

    1990-04-01

    In this study, the average surface regression rate of two HMX-based cast explosives, RX-35-AU and RX-35-AV, is measured to pressures above 750 MPa using a hybrid closed bomb-strand burner. The hybrid design allows the simultaneous measurement of pressure and regression rate over a large range of pressures in each experiment. Nitroglycerin/Triacetin (75/25) and polyethylene glycol (PEG) are used as the energetic plasticizer and polymeric binder, respectively, in both formulations. The HMX solids loading in each formulation is 50 wt %, consisting of a narrow particle size distribution of 6--8 {mu}m for RX-35-AU and 150--177 {mu}m for RX-35-AV. Of special interest are the regression rate and burning mechanism as a function of the initial particle size distribution and the mechanical properties fo the cast explosives. In general, the regression rate for the larger particle size formulation, RX-35-AV, is two to three times faster compared to that for RX-35-AU. Up to 750 MPa and independent of the initial confinement pressure, RX-35-AU exhibits a planar burning mechanism with the regression rate obeying the classical aP{sup n} formalism. For RX-35-AV, however, the burning behavior is erratic for samples ignited at 200 MPa confinement pressure. At confinement pressures above 400 MPa, the regression exhibits more of a planar burning mechanism. The unstable combustion behavior for RX-35-AV at lower confinement pressures is related to several mechanisms: (1) an abrupt increase in surface area due to particle fracture and subsequent translation and rotation, resulting in debonding and creating porosity, (2) thixotropic'' separation of the binder and nitramine, causing the significantly greater fracture damage to the nitramine during the loading cycle, (3) microscopic damage to the nitramine crystals that increase its intrinsic burning rate. 12 refs., 8 figs., 2 tabs.

  15. Transcriptomes analysis of Aeromonas molluscorum Av27 cells exposed to tributyltin (TBT): Unravelling the effects from the molecular level to the organism

    PubMed Central

    Cruz, Andreia; Rodrigues, Raquel; Pinheiro, Miguel; Mendo, Sónia

    2015-01-01

    Aeromonas molluscorum Av27 cells were exposed to 0, 5 and 50 μM of TBT and the respective transcriptomes were obtained by pyrosequencing. Gene Ontology revealed that exposure to 5 μM TBT results in a higher number of repressed genes in contrast with 50 μM of TBT, where the number of over-expressed genes is greater. At both TBT concentrations, higher variations in gene expression were found in the functional categories associated with enzymatic activities, transport/binding and oxidation-reduction. A number of proteins are affected by TBT, such as the acriflavin resistance protein, several transcription-related proteins, several Hsps, ABC transporters, CorA and ZntB and other outer membrane efflux proteins, all of these involved in cellular metabolic processes, important to maintain overall cell viability. Using the STRING tool, several proteins with unknown function were related with others involved in degradation processes, such as the pyoverdine chromophore biosynthetic protein, that has been described as playing a role in the Sn–C cleavage of organotins. This approach has allowed a better understanding of the molecular effects of exposure of bacterial cells to TBT. Furthermore it contributes to the knowledge of the functional genomic aspects of bacteria exposed to this pollutant. Furthermore, the transcriptomic data gathered, and now publically available, constitute a valuable resource for comparative genome analysis. PMID:26171931

  16. Transcriptomes analysis of Aeromonas molluscorum Av27 cells exposed to tributyltin (TBT): Unravelling the effects from the molecular level to the organism.

    PubMed

    Cruz, Andreia; Rodrigues, Raquel; Pinheiro, Miguel; Mendo, Sónia

    2015-08-01

    Aeromonas molluscorum Av27 cells were exposed to 0, 5 and 50 μM of TBT and the respective transcriptomes were obtained by pyrosequencing. Gene Ontology revealed that exposure to 5 μM TBT results in a higher number of repressed genes in contrast with 50 μM of TBT, where the number of over-expressed genes is greater. At both TBT concentrations, higher variations in gene expression were found in the functional categories associated with enzymatic activities, transport/binding and oxidation-reduction. A number of proteins are affected by TBT, such as the acriflavin resistance protein, several transcription-related proteins, several Hsps, ABC transporters, CorA and ZntB and other outer membrane efflux proteins, all of these involved in cellular metabolic processes, important to maintain overall cell viability. Using the STRING tool, several proteins with unknown function were related with others involved in degradation processes, such as the pyoverdine chromophore biosynthetic protein, that has been described as playing a role in the Sn-C cleavage of organotins. This approach has allowed a better understanding of the molecular effects of exposure of bacterial cells to TBT. Furthermore it contributes to the knowledge of the functional genomic aspects of bacteria exposed to this pollutant. Furthermore, the transcriptomic data gathered, and now publically available, constitute a valuable resource for comparative genome analysis. PMID:26171931

  17. The influence of isoleucine and arginine on biological activity and peptide-membrane interactions of antimicrobial peptides from the bactericidal domain of AvBD4.

    PubMed

    Hu, Wan-Ning; Jiao, Wen-Jing; Ma, Zhi; Dong, Na; Ma, Qing-Quan; Shao, Chang-Xuan; Shan, An-Shan

    2013-11-01

    In this study, the influence of isoleucine and arginine on the biological activity and peptide-membrane interactions of linear avian β-defensin-4 (RL38) analogs was investigated. Results of biological activities showed that the antimicrobial activities of AvBD-4 analogs were closely related to hydrophobicity and amphipathicity. The peptide GLI19 with high hydrophobicity value and amphipathicity displayed broad spectrum antimicrobial activity against both gram-negative and gram-positive, whereas GLR19 with increasing multiple charges only exhibited activity against gram-negative. The interaction between peptides and the liposome membrane demonstrated that the peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which supported the antimicrobial activity data. The outer membranes assay further demonstrated that GLI19 had a greater capacity than the other tested peptides to penetrate the cell membrane at a low concentration. Collectively, the peptides derived from the bactericidal domain of linear β- defensins by truncation and hydrophobic amino acid substitution may be effective high-potential antibacterial agents. PMID:23746111

  18. Current Trends in AV Technology.

    ERIC Educational Resources Information Center

    Ely, Donald P.

    Beginning with a clarification of the difference between the product and the process approach to audiovisual (educational) technology, a series of levels or categories of media use are presented: (1) the tool level; (2) the data level; (3) the behavior control level; (4) the meaning level; (5) the research level; and (6) the systems level. Using…

  19. AV from A to Z.

    ERIC Educational Resources Information Center

    Buchanan, Gale

    1979-01-01

    Audiovisual aids as effective classroom supplements to instruction may be purchased, rented, or made in the school graphics and other departments. The author discusses various kinds of equipment, such as films, projectors, records, tapes, and recorders, in-house production and use, and lists free or inexpensive film rental sources. (MF)

  20. Reference Readiness for AV Questions.

    ERIC Educational Resources Information Center

    Drolet, Leon L., Jr.

    1981-01-01

    Reviews 50 reference tools which librarians can use to answer almost any audiovisual question including queries on trivia, equipment selection, biographical information, and motion picture ratings. (LLS)

  1. Audiovisual heritage preservation in Earth and Space Science Informatics: Videos from Free and Open Source Software for Geospatial (FOSS4G) conferences in the TIB|AV-Portal.

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    continues to grow - and so does the number of topics to be addressed at conferences. Up to now, commercial Web 2.0 platforms like Youtube and Vimeo were used. However, these platforms lack capabilities for long-term archiving and scientific citation, such as persistent identifiers that permit the citation of specific intervals of the overall content. To address these issues, the scientific library community has started to implement improved multimedia archiving and retrieval services for scientific audiovisual content which fulfil these requirements. Using the reference case of the OSGeo conference video recordings, this paper gives an overview over the new and growing collection activities by the German National Library of Science and Technology for audiovisual content in Geoinformatics/ESSI in the TIB|AV Portal for audiovisual content. Following a successful start in 2014 and positive response from the OSGeo Community, the TIB acquisition strategy for OSGeo video material was extended to include German, European, North-American and global conference content. The collection grows steadily by new conference content and also by harvesting of past conference videos from commercial Web 2.0 platforms like Youtube and Vimeo. This positions the TIB|AV-Portal as a reliable and concise long-term resource for innovation mining, education and scholarly research within the ESSI context both within Academia and Industry.

  2. Spectroscopic studies of Cepheids in Circinus (AV Cir, BP Cir) and Triangulum Australe (R TrA, S TrA, U TrA, LR TrA)

    NASA Astrophysics Data System (ADS)

    Usenko, I. A.; Kniazev, A. Yu.; Berdnikov, L. N.; Kravtsov, V. V.

    2014-12-01

    Based on high-resolution spectra taken with the 1.9-m telescope of the South African Astronomical Observatory, we have determined the atmospheric parameters and chemical composition for three small-amplitude (AV Cir, BP Cir, and LR TrA), two classical (R TrA and S TrA), and one double-mode (U TrA) Cepheids. The averaged atmospheric parameters have been estimated for three Cepheids (AV Cir, BP Cir, and U TrA) observed at various pulsation phases. In all Cepheids, except U TrA, the metallicity has turned out to be higher than the solar one by 0.1-0.2 dex. The abundances of the key elements of the evolution of yellow supergiants (C, O, Na, Mg, Al) show that these objects have already passed the first dredge-up, while those of the remaining elements are nearly solar. Comparison of our results on the Cepheids from the list (except U TrA) with those of other authors shows significant differences in C and O abundance estimates for AV Cir, R TrA, S TrA, and LR TrA. For AV Cir and BP Cir, the H α line profiles are symmetric but with a slight asymmetry in the core at approximately the same phase near 0{·/ P } 7: on the "blue" side for AV Cir and on the "red" one for BP Cir. BP Cir exhibits a distinct asymmetry in the absorption lines of neutral atoms and ions at various pulsation phases, which can be explained by nonradial first-overtone pulsations. The constancy of the H α absorption line profiles with pulsation phase for AV Cir and BP Cir may suggest the presence of a hydrogen envelope around them. For the double-mode Cepheid U TrA, an asymmetry is observed in the cores of the H α line and the absorption lines of neutral atoms and ions at various pulsation phases, which can be explained by nonradial pulsations in the Cepheid's atmosphere. The absorption lines of neutral atoms and ions of metals in LR TrA closely resemble those in the well-known Cepheid BG Cru: secondary "blue" and "red" components whose line depths vary with pulsation phase are noticeable. This Cepheid

  3. Correlation of amyloid PET ligand florbetapir F 18 (18F-AV-45) binding with β-amyloid aggregation and neuritic plaque deposition in postmortem brain tissue

    PubMed Central

    Choi, Seok Rye; Schneider, Julie A.; Bennett, David A.; Beach, Thomas G.; Bedell, Barry J.; Zehntner, Simone P.; Krautkramer, Michael; Kung, Hank F.; Skovronsky, Daniel M.; Hefti, Franz; Clark, Christopher M.

    2011-01-01

    Background Florbetapir F 18 (18F-AV-45) is a positron emission tomography (PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. The present study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and β-amyloid density measured by established neuropathological methods. Methods The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 subjects with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of β-amyloid identified by silver staining, thioflavin S staining, and immunohistochemistry. Results There were strong quantitative correlations between florbetapir F 18 tissue binding and both β-amyloid plaques identified by light microscopy (sliver staining and thioflavin S fluorescence) and by immunohistochemical measurements of β-amyloid using three antibodies recognizing different epitopes of the β-amyloid peptide (Aβ). Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusion Florbetapir F 18 selectively binds β-amyloid in human brain tissue. The binding intensity was quantitatively correlated with the density of β-amyloid plaques identified by standard neuropathological techniques and correlated with the density of Aβ measured by immunohistochemistry. Since β-amyloid plaques are a defining neuropathological feature for Alzheimer’s disease, these results support the use of florbetapir F 18 as an amyloid PET ligand to identify the presence of AD pathology in patients with signs and symptoms of progressive late-life cognitive

  4. Gender and ethnic differences in a case-control study of dyslipidemia: using the apolipoprotein A-V gene as an exemplar in cardiovascular genetics.

    PubMed

    Wung, Shu-Fen; Aouizerat, Bradley E

    2003-01-01

    Common, complex genetic disorders such as coronary heart disease (CHD) frequently show large population differences, contributing to health disparities. It is also well known that CHD risk factor profiles and the frequency of coronary events differ by gender. Study of premature CHD has revealed that apolipoproteins are important discriminating factors for distinguishing individuals with CHD. Recent findings indicated that apolipoprotein A-V (APOA-V) gene promoter polymorphisms are an important determinant of plasma triglycerides (TG) and lipoprotein cholesterol, and a risk factor for CHD. Variations in APOA-V may have varying impacts in different ethnic groups. The purpose of this interdisciplinary genetic research project was to determine (1) the association of the APOA-V polymorphisms with lipoprotein profiles, and (2) the gender and ethnic differences in the T-1131C promoter polymorphism of the APOA-V gene in individuals with dyslipidemia versus controls. Results indicate that the minor -1131C allele (CC homozygotes + CT heterozygotes) was associated with elevated plasma TG (p = 0.007), very low density lipoprotein (VLDL)-TG (p = 0.019), LDL-TG (p = 0.004), high-density-lipoprotein (HDL)-TG (p < 0.001), and VLDL-cholesterol (p = 0.008). We found a striking elevation in the frequency of the minor C allele in Asians (p < 0.001) compared to Europeans. We also found a significant difference in genotype frequency between men and women in Asians (p = 0.031) and Europeans (p < 0.01). Remarkably, Asian women with the C allele have a 36% increase in TG compared to Asian women homozygous for the T allele. In summary, we found significant ethnic-specific and gender-based differences in the frequency of the minor allele of the -1131 APOA-V gene promoter polymorphism. Identification of genetic variations among ethnic groups and between genders may have significant potential for a better understanding of the development of cardiovascular disease. PMID:14959997

  5. Endocytosis of apolipoprotein A-V by members of the low density lipoprotein receptor and the VPS10p domain receptor families.

    PubMed

    Nilsson, Stefan K; Christensen, Stine; Raarup, Merete K; Ryan, Robert O; Nielsen, Morten S; Olivecrona, Gunilla

    2008-09-19

    Apolipoprotein A-V (apoA-V) is present in low amounts in plasma and has been found to modulate triacylglycerol levels in humans and in animal models. ApoA-V displays affinity for members of the low density lipoprotein receptor (LDL-R) gene family, known as the classical lipoprotein receptors, including LRP1 and SorLA/LR11. In addition to LDL-A binding repeats, the mosaic receptor SorLA/LR11 also possesses a Vps10p domain. Here we show that apoA-V also binds to sortilin, a receptor from the Vsp10p domain gene family that lacks LDL-A repeats. Binding of apoA-V to sortilin was competed by neurotensin, a ligand that binds specifically to the Vps10p domain. To investigate the biological fate of receptor-bound apoA-V, binding experiments were conducted with cultured human embryonic kidney cells transfected with either SorLA/LR11 or sortilin. Compared with nontransfected cells, apoA-V binding to SorLA/LR11- and sortilin-expressing cells was markedly enhanced. Internalization experiments, live imaging studies, and fluorescence resonance energy transfer analyses demonstrated that labeled apoA-V was rapidly internalized, co-localized with receptors in early endosomes, and followed the receptors through endosomes to the trans-Golgi network. The observed decrease of fluorescence signal intensity as a function of time during live imaging experiments suggested ligand uncoupling in endosomes with subsequent delivery to lysosomes for degradation. This interpretation was supported by experiments with (125)I-labeled apoA-V, demonstrating clear differences in degradation between transfected and nontransfected cells. We conclude that apoA-V binds to receptors possessing LDL-A repeats and Vsp10p domains and that apoA-V is internalized into cells via these receptors. This could be a mechanism by which apoA-V modulates lipoprotein metabolism in vivo. PMID:18603531

  6. Comparison of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson’s Disease

    PubMed Central

    Wang, Julie L.; Oya, Shunichi; Parhi, Ajit K.; Lieberman, Brian P.; Ploessl, Karl; Hou, Catherine; Kung, Hank F.

    2010-01-01

    Introduction The utility of [18F]FPBM (2-(2′-((dimethylamino)methyl)-4′-(3-[18F]-fluoropropoxy)phenylthio)benzenamine), a selective serotonin transporter (SERT) tracer, and [18F]AV-133 ((+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine), a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model. Methods PET imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (rats #1-3) were performed with [18F]FPBM and [18F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [18F]FPBM and the dopamine transporter ligand, [125I]IPT, for confirmation. Results PET image analysis showed varying levels of SERT binding reduction (rat #1 = −11%, rat #2 = −4%, rat #3 = −43%; n = 2) and a clear and definitive loss of VMAT2 binding (rat #1 = −87%, rat #2 = −72%, and rat #3 = −91%; n = 1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (PCA, p-chloroamphetamine) showed a significant reduction of uptake in the cortex and hypothalamus regions of the brain. Conclusion The preliminary data suggest that [18F]FPBM and [18F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain. PMID:20447560

  7. The role of the Na+/Ca2+ exchanger, INa and ICaL in the genesis of dofetilide-induced torsades de pointes in isolated, AV-blocked rabbit hearts

    PubMed Central

    Farkas, Attila S; Makra, Péter; Csík, Norbert; Orosz, Szabolcs; Shattock, Michael J; Fülöp, Ferenc; Forster, Tamás; Csanády, Miklós; Papp, Julius Gy; Varró, András; Farkas, András

    2009-01-01

    Background and purpose: The Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide-induced TdP. Experimental approach: Effects of SEA0400 (1 µmol·L−1) on dofetilide-induced TdP was studied in isolated, Langendorff-perfused, atrioventricular (AV)-blocked rabbit hearts. To verify the relevance of the model, lidocaine (30 µmol·L−1) and verapamil (750 nmol·L−1) were also tested against dofetilide-induced TdP. Key results: Acute AV block caused a chaotic idioventricular rhythm and strikingly increased beat-to-beat variability of the RR and QT intervals. SEA0400 exaggerated the dofetilide-induced increase in the heart rate-corrected QT interval (QTc) and did not reduce the incidence of dofetilide-induced TdP [100% in the SEA0400 + dofetilide group vs. 75% in the dofetilide (100 nmol·L−1) control]. In the second set of experiments, verapamil further increased the dofetilide-induced QTc prolongation and neither verapamil nor lidocaine reduced the dofetilide-induced increase in the beat-to-beat variability of the QT interval. However, lidocaine decreased and verapamil prevented the development of dofetilide-induced TdP as compared with the dofetilide control (TdP incidence: 13%, 0% and 88% respectively). Conclusions and implications: Na+/Ca2+ exchanger does not contribute to dofetilide-induced TdP, whereas Na+ and Ca2+ channel activity is involved in TdP genesis in isolated, AV-blocked rabbit hearts. Neither QTc prolongation nor an increase in the beat-to-beat variability of the QT interval is a sufficient prerequisite of TdP genesis in rabbit hearts. PMID:19222480

  8. The A/V Club Next Generation

    ERIC Educational Resources Information Center

    Tech & Learning, 2009

    2009-01-01

    Engaging the digital natives isn't as daunting as one thinks. This article describes how three classrooms do it. One of these is in Brevard Public Schools in Viera, Florida. Pete Episcopo, the digital-media artist of the school, wanted to share his love of all things digital and teach essential 21st-century skills so students could be better…

  9. A/V Alternatives for Interesting Homework.

    ERIC Educational Resources Information Center

    Kersten, Fred

    1993-01-01

    Describes the use of audiovisual materials and equipment as part of music education homework. Recommends using audiotapes and videotapes of music accompanied by analytical questions to be completed by students. Predicts that new instructional technology will improve the effectiveness of this approach. (CFR)

  10. The Learning A-V Awards 1982.

    ERIC Educational Resources Information Center

    Abraham, Lisanne

    1982-01-01

    Teachers, audiovisual librarians, and curriculum specialists evaluated educational films and filmstrips for "Learning" magazine and selected 39 outstanding examples. Their choices are categorized under: (1) language arts/reading; (2) social studies; (3) science; (4) music; (5) values and guidance; (6) health and safety; and (7) computer science.…

  11. AV Instruction Media and Methods; Third Edition.

    ERIC Educational Resources Information Center

    Brown, James W., Ed.; And Others

    In addition to updating material covered in the second edition and providing more illustrative material, this edition attempts to offer a systematic approach to the integration of instructional aids into the curriculum. It discusses the use of significant new developments in instructional technology-multimedia packages or kits, programed…

  12. The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles

    PubMed Central

    Ullal, Pranav; McDonald, Nathan A.; Chen, Jun-Song; Lo Presti, Libera; Roberts-Galbraith, Rachel H.; Gould, Kathleen L.

    2015-01-01

    Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation. PMID:26553932

  13. Physical, Structural and Operational Vulnerability of Critical Facilities in Valle de Chalco Solidaridad, Estado de Mexico, Mexico. Case of study: Avándaro, San Isidro and El Triunfo

    NASA Astrophysics Data System (ADS)

    Garcia Payne, D. G.; Novelo-Casanova, D. A.; Ponce-Pacheco, A. B.; Espinosa-Campos, O.; Huerta-Parra, M.; Reyes-Pimentel, T.; Rodriguez, F.; Benitez-Olivares, I.

    2010-12-01

    Valle de Chalco Solidaridad is located in Mexico City Metropolitan Area in Estado de Mexico, Mexico. In this town there is a sewage canal called “La Compañía”. A wall of this canal collapsed on February 5, 2010 due to heavy rains creating the flooding of four surrounding communities. It is important to point out that this area is frequently exposed to floods. In this work, we consider a critical facility as an essential structure for performance, health care and welfare within a community or/and as a place that can be used as shelter in case of emergency or disaster. Global vulnerability (the sum of the three measured vulnerabilities) of the 25 critical facilities identified in the locations of Avándaro, San Isidro and El Triunfo was assessed using the Community Vulnerability Assessment Tool developed by the National Oceanic and Atmospheric Administration (NOAA). For each critical facility we determined its operational, structural and physical vulnerabilities. For our analysis, we considered the four main natural hazards to which Valle de Chalco is exposed: earthquakes, floods, landslides and sinking. We considered five levels of vulnerability using a scale from 1 to 5, where values range from very low to very high vulnerability, respectively. A critical facilities database was generated by collecting general information for three categories: schools, government and church. Each facility was evaluated considering its location in relation to identified high-risk areas. Our results indicate that in average, the global vulnerability of all facilities is low, however, there are particular cases in which this global vulnerability is high. The average operational vulnerability of the three communities is moderate. The global structural vulnerability (sum of the structural vulnerability for the four analyzed hazards) is moderate. In particular, the structural vulnerability to earthquakes is low, to landslides is very low, to flooding is moderate and to sinking is

  14. Audiovisual Media and the Disabled. AV in Action 1.

    ERIC Educational Resources Information Center

    Nederlands Bibliotheek en Lektuur Centrum, The Hague (Netherlands).

    Designed to provide information on public library services to the handicapped, this pamphlet contains case studies from three different countries on various aspects of the provision of audiovisual services to the disabled. The contents include: (1) "The Value of Audiovisual Materials in a Children's Hospital in Sweden" (Lis Byberg); (2) "Danish…

  15. 15 CFR 740.15 - Aircraft and vessels (AVS).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... approved by the Federal Aviation Administration pursuant to 14 CFR part 129 of the regulations of the... Statistics Regulations (15 CFR part 30), except that an SED or AES record is not required when any of the... requirements of the Foreign Trade Statistics Regulations (15 CFR part 30), except that an SED or AES record...

  16. 15 CFR 740.15 - Aircraft and vessels (AVS).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... approved by the Federal Aviation Administration pursuant to 14 CFR part 129 of the regulations of the... Statistics Regulations (15 CFR part 30), except that an SED or AES record is not required when any of the... requirements of the Foreign Trade Statistics Regulations (15 CFR part 30), except that an SED or AES record...

  17. 15 CFR 740.15 - Aircraft and vessels (AVS).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... approved by the Federal Aviation Administration pursuant to 14 CFR part 129 of the regulations of the... Statistics Regulations (15 CFR part 30), except that an SED or AES record is not required when any of the... requirements of the Foreign Trade Statistics Regulations (15 CFR part 30), except that an SED or AES record...

  18. 15 CFR 740.15 - Aircraft and vessels (AVS).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... approved by the Federal Aviation Administration pursuant to 14 CFR part 129 of the regulations of the... Statistics Regulations (15 CFR part 30), except that an SED or AES record is not required when any of the... requirements of the Foreign Trade Statistics Regulations (15 CFR part 30), except that an SED or AES record...

  19. 15 CFR 740.15 - Aircraft and vessels (AVS).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... approved by the Federal Aviation Administration pursuant to 14 CFR part 129 of the regulations of the... Statistics Regulations (15 CFR part 30), except that an SED or AES record is not required when any of the... requirements of the Foreign Trade Statistics Regulations (15 CFR part 30), except that an SED or AES record...

  20. A-V INSTRUCTION, MATERIALS AND METHODS. SECOND EDITION.

    ERIC Educational Resources Information Center

    BROWN, JAMES W.; AND OTHERS

    A DISCUSSION OF LEARNING AND COMMUNICATION THEORIES AND OF TEACHER AIMS FOR ACTIVE STUDENT LEARNING INTRODUCES A COMPREHENSIVE AND ILLUSTRATED DISCUSSION OF SOURCES AND METHODS FOR THE USE OF A WIDE VARIETY OF TEACHER AIDS. INFORMATION IS DETAILED ON THE SELECTION, LOCATION, USE, AND EVALUATION OF READY-MADE MATERIALS, FREE AND INEXPENSIVE…

  1. Aviation System Technology Advanced Research Program - AvSTAR

    NASA Technical Reports Server (NTRS)

    Denery, Dallas G.

    2001-01-01

    The objectives of this presentation is to provide the research and development by 2007 necessary to: complete the development of technology for tomorrow (Free-Flight); provide the foundations for setting the direction for the future (Beyond Free-Flight). The goals are to establish tomorrow's as well as the future's Air transportation system.

  2. Cataloging, Processing, Administering AV Materials. A Model for Wisconsin Schools.

    ERIC Educational Resources Information Center

    Little, Robert D., Ed.

    The objective of this cataloging manual is to recommend specific methods for cataloging audiovisual materials for use in individual school media centers. The following types of audiovisual aids are included: educational games, filmstrips, flat graphics, kits, models, motion pictures, realia, records, slides, sound filmstrips, tapes,…

  3. The Best Science Books & A-V Materials for Children.

    ERIC Educational Resources Information Center

    O'Connell, Susan M., Ed.; And Others

    Some scientists and science educators believe that the most effective strategy for raising science literacy among future workers and voters is to focus on the youngest members of the public. The reviews in this publication were undertaken to increase public understanding and appreciation of the importance and promise of the methods of science in…

  4. Transportation System After Next & Comments on AvSTAR Planning

    NASA Technical Reports Server (NTRS)

    Pearce, Robert

    2001-01-01

    The purpose of this presentation is to define and identify: the role of transportation in supporting future US needs, trends, system after next, supporting research and education, priority investments, and barriers.

  5. Avβ3 integrin: Pathogenetic role in osteotropic tumors.

    PubMed

    Stucci, Stefania; Tucci, Marco; Passarelli, Anna; Silvestris, Franco

    2015-10-01

    The interplay of cancer cells and accessory cells within the microenvironment drives signals regulating the proliferation, migration and skeleton colonization. Osteotropism of tumor cells depends on chemokine activation, production of soluble factors and defective gene expression that cooperate within the metastatic niche to the bone resorbing functions of osteoclasts. Adhesion of cancer cells to the extracellular matrix is regulated by integrins as αvβ3 that enhances their invasiveness, pro-tumor angiogenesis and skeleton invasion. Therefore, αvβ3 signaling is implicated in enhancing osteotropism of breast and prostate cancers as well as of multiple myeloma. Targeting of αvβ3 has been adopted to restrain the tumor progression in several cancer models leading to improvement of overall survival as effect of the reduction of both tumor burden and osteotropism by malignant cells. Here, we review both the role of αvβ3 in malignant osteoclastogenesis and its potential targeting to restrain the bone colonization by skeleton invading cancers. PMID:26126493

  6. Ninteenth International Cosmic Ray Conference. OG Sessions, Volume 1

    NASA Technical Reports Server (NTRS)

    Jones, F. C. (Compiler)

    1985-01-01

    Contributed papers addressing cosmic ray origin and galactic phenomena are compiled. The topic areas covered in this volume include gamma ray bursts, gamma rays from point sources, and diffuse gamma ray emission.

  7. Information Gathering Document 0321-1437-30-R-OG

    SciTech Connect

    Hollister, R

    2009-07-15

    Fines and turnings from machining depleted uranium (Dep-U), natural uranium (Nat-U), and Thorium-232, and stainless steel and aluminum. This IGO allows only small, oxidizable pieces of Dep-U/Nat-U/Th-232, with regulated metal contaminants below regulatory limits. Fines and turnings will be in 30 gallon vented drums immersed in mineral oil. The 30 gallon drums will be overpacked in 55 gallon vented drums. The waste will be stored on site until sent for stabilization & disposal with approved TSOFs.

  8. Ninteenth International Cosmic Ray Conference. OG Sessions, Volume 2

    NASA Technical Reports Server (NTRS)

    Jones, F. C. (Compiler)

    1985-01-01

    Contributed papers addressing cosmic ray origin and galactic phenomena are compiled. Topic areas include the composition, spectra, and anisotropy of cosmic ray nuclei with energies and 1 TeV, isotopes, antiprotons and related subjects, and electrons, positrons, and measurements of synchrotron radiation.

  9. Nineteenth International Cosmic Ray Conference. OG Sessions, Volume 3

    NASA Technical Reports Server (NTRS)

    Jones, F. C. (Compiler)

    1985-01-01

    Papers submitted for presentation at the 19th International Cosmic Ray Conference are compiled. This volume addresses cosmic ray sources and acceleration, interstellar propagation and nuclear interactions, and detection techniques and instrumentation.

  10. An ID2-dependent mechanism for VHL inactivation in cancer.

    PubMed

    Lee, Sang Bae; Frattini, Veronique; Bansal, Mukesh; Castano, Angelica M; Sherman, Dan; Hutchinson, Keino; Bruce, Jeffrey N; Califano, Andrea; Liu, Guangchao; Cardozo, Timothy; Iavarone, Antonio; Lasorella, Anna

    2016-01-14

    Mechanisms that maintain cancer stem cells are crucial to tumour progression. The ID2 protein supports cancer hallmarks including the cancer stem cell state. HIFα transcription factors, most notably HIF2α (also known as EPAS1), are expressed in and required for maintenance of cancer stem cells (CSCs). However, the pathways that are engaged by ID2 or drive HIF2α accumulation in CSCs have remained unclear. Here we report that DYRK1A and DYRK1B kinases phosphorylate ID2 on threonine 27 (Thr27). Hypoxia downregulates this phosphorylation via inactivation of DYRK1A and DYRK1B. The activity of these kinases is stimulated in normoxia by the oxygen-sensing prolyl hydroxylase PHD1 (also known as EGLN2). ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2α ubiquitylation and degradation. Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2α ubiquitylation. In glioblastoma, ID2 positively modulates HIF2α activity. Conversely, elevated expression of DYRK1 phosphorylates Thr27 of ID2, leading to HIF2α destabilization, loss of glioma stemness, inhibition of tumour growth, and a more favourable outcome for patients with glioblastoma. PMID:26735018

  11. Microbial problems in connection with storage of jet fuel in rock caverns. Development of a process for purification of corrosive jet fuel). Mikrobiella problem vid bergrumslagring av jetbraensle. Utveckling av process foer rening av korrosivt jetbraensle

    SciTech Connect

    Roffey, R.

    1985-06-01

    The literature concerning desulfurization is summarized. Investigations concerning the use of different compounds in order to purify corrosive jet fuel are described. A process for purification of corrosive jet fuel with 1-5 mg/l elemental sulphur was developed which is based on powdered silver as adsorbent. The capacity for adsorption was determined. On the basis of the data obtained, a scale-up was carried out to a full scale plant. The plant was planned for a capacity of 100 - 300 mT fuel/hour and so that it can be constructed as a mobile unit enabling it to be transported to various storage plants.

  12. Report on the 1984 AV Media Survey. I.E.T. Paper No. 261.

    ERIC Educational Resources Information Center

    Grundin, Hans U.

    This survey questioned almost 6,000 students concerning media use for 16 new and seven continuing courses at the British Open University. Student access to and use of various types of media are detailed, and helpfulness, irrelevance, and difficulty ratings for various components and services in the new courses are presented. Brief feedback…

  13. Cataloging, Processing, Administering AV Materials. A Model for Wisconsin Schools. Revised, 1974.

    ERIC Educational Resources Information Center

    Little, Robert David, Ed.; And Others

    The Wisconsin Association of School Librarians has produced a manual for standardized processing of all nonprint media, based on two principles: (1) the media should be centralized, organized, and administered for maximum access; and (2) content is more important than form. Definitions, cataloging, processing, housing, circulation, and care are…

  14. High Output Cardiac Failure Resolving after Repair of AV Fistula in a Six-Month-Old

    PubMed Central

    Teomete, Uygar; Gugol, Rubee Anne; Neville, Holly; Dandin, Ozgur; Young, Ming-Lon

    2016-01-01

    Background. Acquired AVF in pediatrics are commonly caused by iatrogenic means, including arterial or venous punctures. These fistulae can cause great hemodynamic stress on the heart as soon as they are created. Case. A six-month-old 25-week gestation infant was referred for respiratory distress. Initial exam revealed tachypnea, tachycardia, and hypertension. There was a bruit noted on her left arm. An ultrasound showed an arteriovenous fistula. Its location, however, precluded intervention because of the high risk for limb-loss. An echocardiogram showed evidence of pulmonary hypertension that was treated with sildenafil and furosemide. However, no improvement was seen. On temporary manual occlusion of the fistula, the patient was noted to have increased her blood pressure and decreased her heart rate, suggesting significant hemodynamic effect of the fistula. The fistula was subsequently ligated and the patient clinically and echocardiographically improved. Conclusion. A patient in high output cardiac failure or pulmonary artery hypertension, especially prematüre patients with preexisting lung disease, should be probed for history of multiple punctures, trauma, or surgery and should have prompt evaluation for AVF. If it can be diagnosed and repaired, most of the cases have been shown to decrease the stress on the heart and reverse the pathologic hemodynamics. PMID:26885434

  15. 45 CFR 156.135 - AV calculation for determining level of coverage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... TO HEALTH CARE ACCESS HEALTH INSURANCE ISSUER STANDARDS UNDER THE AFFORDABLE CARE ACT, INCLUDING... expected spending for health care costs in a benefit year so that: (i) Any current year HSA contributions...-specific calculations; and (5) Contains claims data on health care services typically offered in the...

  16. Development of an 8000 bps voice codec for AvSat

    NASA Technical Reports Server (NTRS)

    Clark, Joseph F.

    1988-01-01

    Air-mobile speech communication applications share robustness and noise immunity requirements with other mobile applications. The quality requirements are stringent, especially in the cockpit where air safety is involved. Based on these considerations, a decision was made to test an intermediate data rate such as 8.0 and 9.6 kb/s as proven technologies. A number of vocoders and codec technologies were investigated at rates ranging from 2.4 kb/s up to and including 9.6 kb/s. The proven vocoders operating at 2.4 and 4.8 kb/s lacked the noise immunity or the robustness to operate reliably in a cabin noise environment. One very attractive alternative approach was Spectrally Encoded Residual Excited LPC (SE-RELP) which is used in a multi-rate voice processor (MRP) developed at the Naval Research Lab (NRL). The MRP uses SE-RELP at rates of 9.6 and 16 kb/s. The 9.6 kb/s rate can be lowered to 8.0 kb/s without loss of information by modifying the frame. An 8.0 kb/s vocoder was developed using SE-RELP as a demonstrator and testbed. This demonstrator is implemented in real time using two Compaq 2 portable computers, each equipped with an ARIEL DSP016 Data Acquisition Processor.

  17. Development of an 8000 bps voice codec for AvSat

    NASA Astrophysics Data System (ADS)

    Clark, Joseph F.

    1988-05-01

    Air-mobile speech communication applications share robustness and noise immunity requirements with other mobile applications. The quality requirements are stringent, especially in the cockpit where air safety is involved. Based on these considerations, a decision was made to test an intermediate data rate such as 8.0 and 9.6 kb/s as proven technologies. A number of vocoders and codec technologies were investigated at rates ranging from 2.4 kb/s up to and including 9.6 kb/s. The proven vocoders operating at 2.4 and 4.8 kb/s lacked the noise immunity or the robustness to operate reliably in a cabin noise environment. One very attractive alternative approach was Spectrally Encoded Residual Excited LPC (SE-RELP) which is used in a multi-rate voice processor (MRP) developed at the Naval Research Lab (NRL). The MRP uses SE-RELP at rates of 9.6 and 16 kb/s. The 9.6 kb/s rate can be lowered to 8.0 kb/s without loss of information by modifying the frame. An 8.0 kb/s vocoder was developed using SE-RELP as a demonstrator and testbed. This demonstrator is implemented in real time using two Compaq 2 portable computers, each equipped with an ARIEL DSP016 Data Acquisition Processor.

  18. ASASSN-16av: Discovery of A Type Ia Supernova in NGC 3926 NED02

    NASA Astrophysics Data System (ADS)

    Holoien, T. W.-S.; Bersier, D.; Stanek, K. Z.; Kochanek, C. S.; Brown, J. S.; Godoy-Rivera, D.; Basu, U.; Shappee, B. J.; Prieto, J. L.; Dong, Subo; Chen, Ping; Brimacombe, J.

    2016-01-01

    During the ongoing All Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin"), using data from the quadruple 14-cm "Brutus" telescope in Haleakala, Hawaii, we discovered a new type Ia supernova in the galaxy NGC 3926 NED02.

  19. Geologic mapping of the Av-2 Bellicia quadrangle of asteroid 4 Vesta

    NASA Astrophysics Data System (ADS)

    Ruesch, O.; Hiesinger, H.; Schmedemann, N.; Kneissl, T.; Blewett, D. T.; Williams, D. A.; Russell, C. T.; Raymond, C. A.

    2012-04-01

    One of the largest asteroids in the Main Belt, the asteroid Vesta, is currently observed by the Dawn spacecraft [1]. In contrast to previously in-situ explored asteroids [2-7] Vesta is most probably an intact protoplanet and spectroscopic observations suggest a basaltic nature for its crust [8]. The Dawn Framing Camera [9] has acquired visible images that allow geologic mapping of its surface. Within the Dawn Mapping Working Group we focused on the north-eastern quadrangle (21° N-60° N and 0° E-90° E). Unfortunately, illumination conditions limited the observation from 21° N to 45° N and only with low incidence angle. The morphology of the study area is characterized by impact craters and smooth ejecta blankets typical for the northern hemisphere of Vesta. Using a lunar-like production function and chronology function [10], the crater size-frequency distribution (CSFD) indicates an old surface age with possible resurfacing events. A distinctive pattern in the CSFD for <10km craters is observed, but to fully understand its origin, further investigations are needed. Dark-rayed ejecta are observed, and overall distinctive albedo features are rare when compared to the equatorial terrains. For the study area we find that the visible-NIR spectral measurements, characterized by pyroxenes absorption bands [11], are neither related to volcanic/magmatic morphologic features (e.g., lava flows, dykes) nor to albedo features. Instead, the pyroxene signatures are associated with an old, cratered surface with a homogeneous albedo. [1] Russell et al., (2007) Earth Moon Planets, 10. [2] Carr et al., (1994) Icarus 107, 61-71. [3] Thomas et al., (1999) Icarus 140, 17-27. [4] Robinson et al., (2002) M&PS 37, 1651-1684. [5] Sullivan et al., (1996) Icarus 120,119-139. [6] Fujiwara et al., (2006) Science 312,1330. [7] Sierks et al., (2011) Science 334, 487. [8] Pieters et al., (2011) Space Sci. Rev. [9] Sierks et al., (2011) Space Sci Rev. [10] Neukum et al., (2011) EPSC-DPS2011-501-1. [11] Coradini et al., (2011) EPSC-DPS2011-740-6.

  20. High Output Cardiac Failure Resolving after Repair of AV Fistula in a Six-Month-Old.

    PubMed

    Teomete, Uygar; Gugol, Rubee Anne; Neville, Holly; Dandin, Ozgur; Young, Ming-Lon

    2016-01-01

    Background. Acquired AVF in pediatrics are commonly caused by iatrogenic means, including arterial or venous punctures. These fistulae can cause great hemodynamic stress on the heart as soon as they are created. Case. A six-month-old 25-week gestation infant was referred for respiratory distress. Initial exam revealed tachypnea, tachycardia, and hypertension. There was a bruit noted on her left arm. An ultrasound showed an arteriovenous fistula. Its location, however, precluded intervention because of the high risk for limb-loss. An echocardiogram showed evidence of pulmonary hypertension that was treated with sildenafil and furosemide. However, no improvement was seen. On temporary manual occlusion of the fistula, the patient was noted to have increased her blood pressure and decreased her heart rate, suggesting significant hemodynamic effect of the fistula. The fistula was subsequently ligated and the patient clinically and echocardiographically improved. Conclusion. A patient in high output cardiac failure or pulmonary artery hypertension, especially prematüre patients with preexisting lung disease, should be probed for history of multiple punctures, trauma, or surgery and should have prompt evaluation for AVF. If it can be diagnosed and repaired, most of the cases have been shown to decrease the stress on the heart and reverse the pathologic hemodynamics. PMID:26885434

  1. Environmental Technology Verification Report: Grouts for Wastewater Collection Systems, Avanti International AV-118 Acrylic Chemical Grout

    EPA Science Inventory

    Municipalities are discovering rapid degradation of infrastructures in wastewater collection and treatment facilities due to the infiltration of water from the surrounding environments. Wastewater facilities are not only wet, but also experience hydrostatic pressure conditions un...

  2. High throughput VLSI architecture for multiresolution integer motion estimation in high definition AVS video encoder

    NASA Astrophysics Data System (ADS)

    Yin, HaiBing; Qi, Honggang; Xu, Hao; Xie, Xiaodong; Gao, Wen

    2010-07-01

    This paper proposes a hardware friendly multi-resolution motion estimation algorithm and VLSI architecture for high definition MPEG-like video encoder hardware implementation. By parallel searching and utilizing the high correlation in multi-resolution reference pixels, huge throughput and computation due to large search window are alleviated considerably. Sixteen way parallel processing element arrays with configurable multiplying technologies achieve fast search with regular data access and efficient data reuse. Also, the parallel arrays can be efficiently reused at three hierarchical levels for sequential motion vector refinement. The modified algorithm reaches a good balance between implementation complexity and search performance. Also, the logic circuit and on-chip SRAM consumption of the VLSI architecture are moderate.

  3. Motion Pictures and Video Cassettes 1971. AV-USA Supplement 2.

    ERIC Educational Resources Information Center

    Hope, Thomas W.

    The financial status of the motion picture and of the video cassette industry in 1970 are reviewed. Based on production rates and income of these industries, trends are discovered. Figures on local origination of television programing and commercials are also included. The section on video cassettes includes the following information: the current…

  4. Four New A-V Ideas for Solo Learners. Individualization Through Automation

    ERIC Educational Resources Information Center

    Nation's Schools, 1972

    1972-01-01

    Describes four innovative programs in Omaha, Nebraska -- an individualized physical education program; Condon, Oregon -- a self-instructional welding package; Jackson, Mississippi -- a mechanized typing instruction program for the elementary grades; and Red Bank, New Jersey -- a computerized phonics program for the primary grades. (EA)

  5. Storage, Handling and Preservation of Audiovisual Materials. AV in Action 3.

    ERIC Educational Resources Information Center

    Thompson, Anthony Hugh

    Designed to provide the librarian with suggestions and guidelines for storing and preserving audiovisual materials, this pamphlet is divided into four major chapters: (1) Normal Use Storage Conditions; (2) Natural Lifetime, Working Lifetime and Long-Term Storage; (3) Handling; and (4) Shelving of Normal Use Materials. Topics addressed include:…

  6. A Comparison of Interaction in AV-based and Internet-based Distance Courses.

    ERIC Educational Resources Information Center

    Landis, Melodee

    2001-01-01

    Describes a study conducted at the University of Nebraska at Omaha that used questionnaires and interviews to compare and contrast the interaction that occurred in distance learning courses offered via two-way, fully interactive audio-video classrooms and online instruction through the Internet or World Wide Web. (Author/LRW)

  7. Using Asynchronous AV Communication Tools to Increase Academic Self-Efficacy

    ERIC Educational Resources Information Center

    Girasoli, Anthony J.; Hannafin, Robert D.

    2008-01-01

    Technology-enhanced learning environments (TELEs) deliver instructional content and provide an array of scaffolding features designed to support independent student learning. TELEs also support teacher efforts to guide student inquiry within these sometimes complex environments. Self-efficacy, defined by Bandura [Bandura, A. (1994). Self-efficacy.…

  8. The Black Box Theater and AV/IT Convergence: Creating the Classroom of the Future.

    ERIC Educational Resources Information Center

    Valenti, Mark S.

    2002-01-01

    Describes "black box" classrooms, which incorporate audiovisual and information technologies to provide an inherently flexible learning environment. Details various technological components of such classrooms. (EV)

  9. MISR Level 1A CCD Science data, all cameras (MIL1A_V2)

    NASA Technical Reports Server (NTRS)

    Diner, David J. (Principal Investigator)

    The Level 1A data are raw MISR data that are decommutated, reformatted 12-bit Level 0 data shifted to byte boundaries, i.e., reversal of square-root encoding applied and converted to 16 bit, and annotated (e.g., with time information). These data are used by the Level 1B1 processing algorithm to generate calibrated radiances. The science data output preserves the spatial sampling rate of the Level 0 raw MISR CCD science data. CCD data are collected during routine science observations of the sunlit portion of the Earth. Each product represents one 'granule' of data. A 'granule' is defined to be the smallest unit of data required for MISR processing. Also, included in the Level 1A product are pointers to calibration coefficient files provided for Level 1B processing. [Location=GLOBAL] [Temporal_Coverage: Start_Date=2000-02-24; Stop_Date=] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180].

  10. Aetervinning av faerg och ridaevatten med ultrafiltrering (recycling of paint and water curtains with ultrafiltration)

    SciTech Connect

    Fortkamp, U.; Allard, A.S.; Ekengren, O.

    1997-12-01

    Painting in spray booths causes overspray that is collected by a water curtain. The mixture of water and paint is commonly treated by means of precipitation. By means of this method, water can be used again but a paint sludge is created. Within this project, it was investigated how the paint as well as the water can be recycled. Separation by membrane filtration was tested for different paints in laboratory scale (0.2 liter volume). It was possible to separate all tested paints from the water and to concentrate it. At large scale (15 to 75 liters volume), an emulsion paint and a dispersion paint were tested. Under the tested conditions, it was slightly easier to concentrate the emulsion paint than the dispersion paint. It was possible to concentrate the paints to the original dry substance percentage. An important aspect of membrane filtration is cleaning of the membrane when the performance decreases. It was possible to clean all the tested membranes, but in many cases it was difficult. A ceramic membrane and a membrane of polyaramide showed the best results with regard to flux and cleaning of the membrane under the tested conditions. During the performance of the project two new applications of membrane filtration of paint were found. The method can be used for waste minimization by only separating the paint in an easy way at low costs. A third application is treating cleaning water from paint manufacturing.

  11. Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models

    PubMed Central

    Souchet, Benoit; Guedj, Fayçal; Penke-Verdier, Zsuza; Daubigney, Fabrice; Duchon, Arnaud; Herault, Yann; Bizot, Jean-Charles; Janel, Nathalie; Créau, Nicole; Delatour, Benoit; Delabar, Jean M.

    2015-01-01

    Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long-term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models. PMID:26539088

  12. Pharmacological correction of excitation/inhibition imbalance in Down syndrome mouse models.

    PubMed

    Souchet, Benoit; Guedj, Fayçal; Penke-Verdier, Zsuza; Daubigney, Fabrice; Duchon, Arnaud; Herault, Yann; Bizot, Jean-Charles; Janel, Nathalie; Créau, Nicole; Delatour, Benoit; Delabar, Jean M

    2015-01-01

    Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long-term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models. PMID:26539088

  13. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Dr. Rand Swanson

    2003-04-28

    This seventh quarterly technical report discusses the progress made on a machine vision technique for determining coal content and ore grades. Considerable progress has been made on coal analysis. Naval Research Laboratory (NRL) target recognition software has been tested and incorporated into the system. This software decreases analysis time considerably and is more intuitive to use. Work with board-level computers has proceeded well; ultimately this will make the technology more compact and fieldable. Work with talc will be delayed because the graduate student working on this project is leaving the program. Ongoing work is devoted to more detailed coal analysis, improving the software interface, and developing procedures and a users manual.

  14. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Rand Swanson

    2004-10-22

    This thirteenth quarterly technical report describes data collection at the Stillwater Mine and an additional improvement to the lighting system. The data collection system was returned to the Stillwater Mine during this reporting period and a large amount of data was collected. The data will be analyzed and correlated with fire assays in the next reporting period. The majority of work done this quarter has been devoted to collecting data from cores scanned in the Stillwater Mining Company core room. This work is somewhat tedious and tiresome, but essential to: (1) obtain enough data to reliably determine the correlation between assay results and spectral imaging results; (2) find bugs and glitches in the system that arise only periodically or after long periods of use; and (3) obtain data on the natural (and man-made) variations in the Stillwater ore that may confuse the machine vision algorithms.

  15. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Dr. Rand Swanson

    2003-07-21

    This eighth quarterly technical report discusses the progress made on a machine vision technique for determining coal content and preparations for Year-3 system deployment. Classification maps for coal have been generated and shown to two coal-mining executives. An application for licensing high-speed hyperspectral data analysis software from the Naval Research Laboratory (NRL) has been made. Both Western Energy and Stillwater Mining Company have offered platforms for Year-3 deployment. Barretts Minerals has expressed renewed interest in using Resonon's machine vision system for identifying dolomite in their talc ore and have agreed to provide samples to the Montana Tech team.

  16. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Dr. Rand Swanson

    2002-10-24

    This fifth quarterly technical report discusses the progress made on a machine vision technique for determining coal content and ore grades. Recent work has been devoted to implementing new hardware and examining defects in titanium sponge, a new application for the machine vision system. With the improvements in hardware and software, the data collection is much improved. Early results from data taken on titanium sponge defects indicate that some defects will be relatively easy to identify, but others will be much more difficult. Consequently, additional work is required with software algorithms for target recognition. Ongoing work will be divided into several fronts, which include data collection and analysis, improving the target recognition capabilities, and improving the electronic interface.

  17. Gocad2OGS: Workflow to Integrate Geo-structural Information into Numerical Simulation Models

    NASA Astrophysics Data System (ADS)

    Fischer, Thomas; Walther, Marc; Naumov, Dmitri; Sattler, Sabine; Kolditz, Olaf

    2015-04-01

    The investigation of fluid circulation in the Thuringian syncline is one of the INFLUINS project's targets. A 3D geo-structural model including 12 stratigraphic layers and 54 fault zones is created by geologists in the first step using the Gocad software. Within the INFLUINS project a ground-water flow simulation is used to check existing hypotheses and to gain new ideas of the underground fluid flow behaviour. We used the scientific, platform independent, open source software OpenGeoSys that implements the finite element method to solve the governing equations describing fluid flow in porous media. The geo-structural Gocad model is not suitable for the FEM numerical analysis. Therefore it is converted into an unstructured grid satisfying all mesh quality criteria required for the ground-water flow simulation. The resulting grid is stored in an open data format given by the Visualization Toolkit (vtk). In this work we present a workflow to convert geological structural models, created using the Gocad software, into a simulation model that is easy to use from numerical simulation software. We tested our workflow with the 3D geo-structural model of the Thuringian syncline and were able to setup and to evaluate a hydrogeological simulation model successfully.

  18. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Rand Swanson

    2004-01-23

    This tenth quarterly technical report discusses the progress made on a machine vision technique for ore grading based on hyperspectral imaging. A graduate student at Montana Tech has successfully defended her thesis related to this project. Arrangements with Stillwater Mining Company to deploy a machine vision system in their core room have been completed. Designs for they system that will be installed next quarter have been drawn and parts are being machined. Presentations on the spectral imaging system developed during this effort have been made to Stillwater Mining Company and at a remote sensing symposium at Montana State University.

  19. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Rand Swanson

    2003-04-27

    This eleventh quarterly technical report discusses the installation of a spectral machine vision system in the Stillwater mine's core room. In brief, the system has been fabricated, installed, and preliminary measurements have been made. A first round of refinements has been made, included replacing a bad bearing and applying filters to the lighting. A high-speed Spectral Angle Mapper (SAM) program was written to classify the cores in real time. This program identifies sulfides in the core sample quite well, but also produces false positives at boundaries and breaks in the core. Additionally, bright reflections from facets within the ore occasionally saturate the camera. Overall, the project is on schedule, but additional refinement in the algorithm and lighting is required to obtain more accurate results.

  20. Phenological tracking og agricultural feilds investigated by using dual polarimetry tanDEM-X images

    NASA Astrophysics Data System (ADS)

    Mirzaee, S.; Motagh, M.; Arefi, H.; Nooryazdan, A.

    2015-04-01

    Remote sensing plays a key role in monitoring and assessing environmental changes. Because of its special imaging characteristics such as high-resolution, capabilities to obtain data in all weather conditions and sensitivity to geometrical and dielectric properties of the features, Synthetic Aperture Radar (SAR) technology has become a powerful technique to detect small scale changes related to earth surface.SAR images contain the information of both phase and intensity in different modes like single, dual and full polarimetric states which are important in order to extract information about various targets. In this study we investigate phenological changes in an agricultural region using high-resolution X-band SAR data. The case study is located in Doroud region of Lorestan province, west of Iran. The purpose is to investigate the ability of copolar and interferometric coherence extracted from TanDEM-X dual polarimetry (HH/VV) in bistatic StripMap mode for tracking the phenological changes of crops during growing season. The data include 11 images acquired between 12.06.2012 and 02.11.2012 and 6 images acquired between 30.05.2013 and 04.08.2013 in the CoSSC format. Results show that copolar coherence is almost able to follow phenological changes but interferometric coherence has a near constant behaviour with fluctuations mainly related to baseline variations.

  1. A parallelization scheme to simulate reactive transport in the subsurface environment with OGS#IPhreeqc

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    This technical paper presents an efficient and performance-oriented method to model reactive mass transport processes in environmental and geotechnical subsurface systems. The open source scientific software packages OpenGeoSys and IPhreeqc have been coupled, to combine their individual strengths and features to simulate thermo-hydro-mechanical-chemical coupled processes in porous and fractured media with simultaneous consideration of aqueous geochemical reactions. Furthermore, a flexible parallelization scheme using MPI (Message Passing Interface) grouping techniques has been implemented, which allows an optimized allocation of computer resources for the node-wise calculation of chemical reactions on the one hand, and the underlying processes such as for groundwater flow or solute transport on the other hand. The coupling interface and parallelization scheme have been tested and verified in terms of precision and performance.

  2. A kind of integrated method discuss of fOG signal processing circuit

    NASA Astrophysics Data System (ADS)

    Lu, Jun; Pan, Xin; Ying, Jiaju; Liu, Jie

    2014-12-01

    In view of the circuit miniaturization need in project application of fiber optic gyroscope(FOG), a new integrated technical scheme adopting system in package(SIP) for signal processing circuit of FOG was put forward. At first, the principle on signal processing circuit of FOG was analyzed, and the technical scheme adopting SIP based on low-temperature co-fired substrate technology was presented according to circuit characteristic and actual condition. Secondly, under the prerequisite of the concept introduction of SIP and LTCC, the SIP prototype of signal processing circuit of FOG was trialed produced,and it passed through the debug test. This SIP modular is an overall circuit complete integrated the signal processing circuit of FOG, and only a potentiometer and EPROM do not case outside. The testing results indicate that SIP is a kind of feasible scheme that carries out miniaturization for signal processing circuit of FOG.

  3. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Dr. Rand Swanson

    2002-04-25

    This third quarterly technical report discusses the progress made on a machine vision technique for determining coal content and ore grades. The work done this quarter has utilized a miniature imaging spectrometer. Procedures to collect and process the spectral and spatial data from the imaging spectrometer have been established, and software routines have been employed to use this data to differentiate sulfides from background rock in platinum/palladium core samples. These sulfides are indicator minerals for high-grade platinum/palladium ore. Mappings of the sulfides generated with this procedure have been quite accurate. Samples of coal have also been obtained and preliminary measurements with the imaging spectrometer have been made.

  4. Handels- og Kontorfunktionaerernes Forbund i Danmark v. Dansk Arbejdsgiverforening [17 October 1989].

    PubMed

    1989-01-01

    The plaintiff employee's Danish union challenged as contrary to Sex Discrimination Directive 75/117 the salary practice of the defendant employer, which resulted in male employees receiving an average wage 6.85% higher than that received by female employees in the same job category. The difference resulted from a system of supplements paid to employees on the basis of mobility, vocational training, and length of service. The court held that when an employer applies a system of remuneration that is totally lacking in transparency, the employer is required to prove that the system does not discriminate against women if it is shown that the system results in women receiving average pay less than that received by men. It also ruled that pay differentials based on seniority were acceptable and that pay differentials based on mobility and vocational training were acceptable only if it was shown that such mobility or vocational training was important to the performance of specific tasks entrusted to an employee. PMID:12344117

  5. A REAL TIME COAL CONTENT ORE GRADE (C2OG) SENSOR

    SciTech Connect

    Dr. Rand Swanson

    2002-01-31

    The overall approach of this effort is to spectrally image ore or coal, and then use the spectral content (i.e., the particular colors of the ore or coal) to differentiate between the ore or coal grades. Currently, experts with practiced eyes do just this to identify the grade of platinum/palladium ore from the Stillwater Mine in south-central Montana. Additionally, trained eyes can identify high-sulfur and high-ash coal visually. The premise of this effort is that machine vision can accomplish this same differentiation. During the first quarter, machine vision results using a digital color camera did not correlate as well with assay results for platinum/palladium ore as would be required for a commercial device. One of the possible reasons for this is that the digital camera did not provide enough spectral information to obtain good differentiation between the sulfides associated with high-grade platinum/palladium ore and background interference, most notably yellow grease that contaminates some of the sample and green colored rock. The second quarter efforts have largely been devoted to implementing an imaging spectrometer for machine vision. In brief, modifying an imaging spectrometer that was designed for remote sensing from a Remotely Controlled (RC) airplane has done this. The imaging spectrometer provides 320 spectral channels, allowing for much better spectral resolution that can be obtained with a digital color camera, which provides 3 spectral channels. Preliminary results, as discussed below in more detail, are encouraging. The technical portion of the report below is organized into subsections as dictated by the DoE contract for this effort. These sections are: Experimental Apparatus, Experimental and Operating Data, Data Reduction, and Hypothesis and Conclusions. Partners in this effort are: Montana Tech of the University of Montana, Stillwater Mining Co., Western Syncoal, and the Montana Board of Research and Commercialization.

  6. Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.

    PubMed

    Esvan, Yannick J; Zeinyeh, Wael; Boibessot, Thibaut; Nauton, Lionel; Théry, Vincent; Knapp, Stefan; Chaikuad, Apirat; Loaëc, Nadège; Meijer, Laurent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-08-01

    The design and synthesis of new pyrido[3,4-g]quinazoline derivatives is described as well as their protein kinase inhibitory potencies toward five CMGC family members (CDK5, CK1, GSK3, CLK1 and DYRK1A). The interest for this original tricyclic heteroaromatic scaffold as modulators of CLK1/DYRK1A activity was validated by nanomolar potencies (compounds 12 and 13). CLK1 co-crystal structures with two inhibitors revealed the binding mode of these compounds within the ATP-binding pocket. PMID:27128181

  7. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1.

    PubMed

    Schneider, Philipp; Bayo-Fina, Juan Miguel; Singh, Rajeev; Kumar Dhanyamraju, Pavan; Holz, Philipp; Baier, Aninja; Fendrich, Volker; Ramaswamy, Annette; Baumeister, Stefan; Martinez, Elisabeth D; Lauth, Matthias

    2015-01-01

    The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome patients paradoxically display reduced Hh signalling activity. Here we find that DYRK1A stimulates GLI transcription factor activity through phosphorylation of general nuclear localization clusters. In contrast, in vivo and in vitro experiments reveal that DYRK1A kinase can also function as an inhibitor of endogenous Hh signalling by negatively regulating ABLIM proteins, the actin cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific small-molecule antagonist represents a novel and powerful inhibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo. PMID:26310823

  8. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1

    PubMed Central

    Schneider, Philipp; Miguel Bayo-Fina, Juan; Singh, Rajeev; Kumar Dhanyamraju, Pavan; Holz, Philipp; Baier, Aninja; Fendrich, Volker; Ramaswamy, Annette; Baumeister, Stefan; Martinez, Elisabeth D.; Lauth, Matthias

    2015-01-01

    The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome patients paradoxically display reduced Hh signalling activity. Here we find that DYRK1A stimulates GLI transcription factor activity through phosphorylation of general nuclear localization clusters. In contrast, in vivo and in vitro experiments reveal that DYRK1A kinase can also function as an inhibitor of endogenous Hh signalling by negatively regulating ABLIM proteins, the actin cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific small-molecule antagonist represents a novel and powerful inhibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo. PMID:26310823

  9. Diagnostic test for prenatal identification of Down's syndrome and mental retardation and gene therapy therefor

    SciTech Connect

    Smith, Desmond J.; Rubin, Edward M.

    2000-01-01

    A a diagnostic test useful for prenatal identification of Down syndrome and mental retardation. A method for gene therapy for correction and treatment of Down syndrome. DYRK gene involved in the ability to learn. A method for diagnosing Down's syndrome and mental retardation and an assay therefor. A pharmaceutical composition for treatment of Down's syndrome mental retardation.

  10. Microdeletion of the Down syndrome critical region at 21q22.

    PubMed

    Fujita, Hideki; Torii, Chiharu; Kosaki, Rika; Yamaguchi, Shinya; Kudoh, Jun; Hayashi, Kumiko; Takahashi, Takao; Kosaki, Kenjiro

    2010-04-01

    The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G-banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice. PMID:20358607

  11. Microbial problems in connection with storage of jet fuel in rock caverns. Methods to inhibit development of corrosive fuel. Mikrobiella problem vid bergrumslagring av jetbraensle. Inhiberingsmetoder foer att foerhindra uppkomst av korrosivt braensle

    SciTech Connect

    Norqvist, A.; Edlund, A.; Roffey

    1986-04-01

    Problems with long-term storage of jet fuel in rock caverns have during the last years been observed. The problems have mainly been concerned with the accumulation of corrosive compounds in the fuel. Studies in laboratory model systems were carried out in order to understand which factors are important in causing the problems. The rate of groundwater leaking in, the oxygen and sulfate concentration in the bedwater, the amount of sediment, and the temperature were shown to be some of the more-important factors. With the aim to find some suitable methods to prevent the problems from arising, studies in model systems were also carried out. Oxygenation of the bedwater or addition of a biodegradable biocide gave positive effects resulting in reduction of microbial activities and no development of corrosive fuel.

  12. SAR Aircrew--HH-3F Avionics and HH-3F Flight Preparation. ACH3AV-0442. Second Edition, Revised.

    ERIC Educational Resources Information Center

    Coast Guard Inst., Oklahoma City, OK.

    This document contains two U.S. Coast Guard self-study pamphlets that provide training in helicopter flight preparation and avionics duties. Each pamphlet consists of a number of lessons that include objectives, information illustrated with line drawings and/or photographs, and self-quizzes with answers. The avionics course covers the following…

  13. GB-InSAR monitoring and observational method for landslide emergency management: the Montaguto earthflow (AV, Italy)

    NASA Astrophysics Data System (ADS)

    Ferrigno, F.; Gigli, G.; Fanti, R.; Casagli, N.

    2015-12-01

    On 10 March 2010, due to the heavy rainfall that occurred on the previous days, the Montaguto earthflow reactivated, involving the road SS 90 "Delle Puglie", as had happened previously in May 2005 and in September 2009, and reaching the Roma-Bari railway. This determined a special attention of the National Civil Protection Department and a widespread monitoring and analysis program was initiated. A monitoring activity using GB-InSAR (Ground Based Interferometric Synthetic Aperture Radar) system began, in order to investigate the landslide kinematics, to plan urgent safety measures for risk mitigation and to design long term stabilization work. In this paper the GB-InSAR monitoring system results and its applications in the Observational Method (OM) approach are presented. The paper also highlights how the OM based on the GB-InSAR technique can produce savings in cost and time on engineering projects, without compromising safety, and how it can also benefit the geotechnical community by increasing scientific knowledge. This study focuses on the very much active role played by the monitoring activities, in both the design and plan modifications; with a special consideration for the emergency phase.

  14. A QoS aware resource allocation strategy for 3D A/V streaming in OFDMA based wireless systems.

    PubMed

    Chung, Young-Uk; Choi, Yong-Hoon; Park, Suwon; Lee, Hyukjoon

    2014-01-01

    Three-dimensional (3D) video is expected to be a "killer app" for OFDMA-based broadband wireless systems. The main limitation of 3D video streaming over a wireless system is the shortage of radio resources due to the large size of the 3D traffic. This paper presents a novel resource allocation strategy to address this problem. In the paper, the video-plus-depth 3D traffic type is considered. The proposed resource allocation strategy focuses on the relationship between 2D video and the depth map, handling them with different priorities. It is formulated as an optimization problem and is solved using a suboptimal heuristic algorithm. Numerical results show that the proposed scheme provides a better quality of service compared to conventional schemes. PMID:25250377

  15. IFLA General Conference, 1987. Division on Bibliographic Control. Bibliography and Round Table on A/V Media Section. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    The two papers in this section focus on the bibliographic control of sound recordings, primarily phonograph records. In the first, "The National Discography for the United Kingdom," Christopher Roads discusses the problem of lack of easily accessible and up-to-date information about the growing collection of new sound recordings as they are being…

  16. 76 FR 419 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-05

    ... found on a trim tab fitting assembly. The cause of the cracking was identified as stress corrosion. This... Register on October 1, 2010 (75 FR 60659). That NPRM proposed to correct an unsafe condition for the... tab fitting assembly. The cause of the cracking was identified as stress corrosion. This condition,...

  17. 76 FR 61638 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... Procedures (44 FR 11034, February 26, 1979), (3) Will not have a significant economic impact, positive or... the basic requirements of this proposed AD. The average labor rate is $85 per work-hour. Based on....-- Task description-- Identified in-- 328-100 airplanes Task 27-10-00-09...... Visual Check of 328...

  18. A QoS Aware Resource Allocation Strategy for 3D A/V Streaming in OFDMA Based Wireless Systems

    PubMed Central

    Chung, Young-uk; Choi, Yong-Hoon; Park, Suwon; Lee, Hyukjoon

    2014-01-01

    Three-dimensional (3D) video is expected to be a “killer app” for OFDMA-based broadband wireless systems. The main limitation of 3D video streaming over a wireless system is the shortage of radio resources due to the large size of the 3D traffic. This paper presents a novel resource allocation strategy to address this problem. In the paper, the video-plus-depth 3D traffic type is considered. The proposed resource allocation strategy focuses on the relationship between 2D video and the depth map, handling them with different priorities. It is formulated as an optimization problem and is solved using a suboptimal heuristic algorithm. Numerical results show that the proposed scheme provides a better quality of service compared to conventional schemes. PMID:25250377

  19. 77 FR 12163 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... Register on August 31, 2011 (76 FR 54145). That NPRM proposed to correct an unsafe condition for the... requested we revise the Cost of Compliance section of the NPRM (76 FR 54145, August 31, 2011). The commenter... a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February...

  20. 76 FR 58094 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-20

    ... was published in the Federal Register on December 2, 2010 (75 FR 75159), and proposed to supersede AD 2008-10-51, Amendment 39-15535 (73 FR 30752, May 29, 2008). That NPRM proposed to correct an unsafe... paragraph (h) of the NPRM (75 FR 75159, December 2, 2010). GCT DO Airworthiness Office stated that, based...

  1. 76 FR 54145 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ... rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will... lever could not be operated as intended during the landing roll-out. * * * Recurrence of such an event... past with Dornier 328-100 aeroplanes, where the power lever could not be operated as intended...

  2. Hypotension and AV block after diesel exhaust exposure in heart failure-prone rats: role of gaseous and particulate components

    EPA Science Inventory

    Acute inhalations ofdiesel engine exhaust (DE) and fine particulate matter (PM2.5) have been demonstrated to provoke adverse cardiac events in humans with preexisting heart disease. Electrophysiologic dysfunction and autonomic imbalance are among the mechanisms widely held to und...

  3. The East Asian Resource & Education Program at Yale. A Catalogue of A.V. Materials, Resources, and Organizations.

    ERIC Educational Resources Information Center

    White, Caryn

    This document consists of an annotated bibliography of publications, audio visual materials, and other items available through Yale University's East Asian Resource and Education Program. The document begins with a discussion of the program, its goals and objectives, teacher and school projects, publications, and special events. There is also a…

  4. 78 FR 52872 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ... AD. Discussion On July 17, 2008, we issued AD 2008-14-16, Amendment 39-15611 (73 FR 40955, July 17... (73 FR 40955, July 17, 2008), we received reports that certain fasteners which were installed as part... $15,191 $531,685 actions from AD 2008-14-16, hour = $3230. Amendment 39-15611 (73 FR 40955, July...

  5. A chicory cytochrome P450 mono-oxygenase CYP71AV8 for the oxidation of (+)-valencene.

    PubMed

    Cankar, Katarina; van Houwelingen, Adèle; Bosch, Dirk; Sonke, Theo; Bouwmeester, Harro; Beekwilder, Jules

    2011-01-01

    Chicory (Cichorium intybus L.), which is known to have a variety of terpene-hydroxylating activities, was screened for a P450 mono-oxygenase to convert (+)-valencene to (+)-nootkatone. A novel P450 cDNA was identified in a chicory root EST library. Co-expression of the enzyme with a valencene synthase in yeast, led to formation of trans-nootkatol, cis-nootkatol and (+)-nootkatone. The novel enzyme was also found to catalyse a three step conversion of germacrene A to germacra-1(10),4,11(13)-trien-12-oic acid, indicating its involvement in chicory sesquiterpene lactone biosynthesis. Likewise, amorpha-4,11-diene was converted to artemisinic acid. Surprisingly, the chicory P450 has a different regio-specificity on (+)-valencene compared to germacrene A and amorpha-4,11-diene. PMID:21115006

  6. 75 FR 75159 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-02

    ... proposed AD. Discussion On June 3, 2008, we issued AD 2008-10-51, Amendment 39-15535 (73 FR 30752, May 29... Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic.... 106(g), 40113, 44701. Sec. 39.13 2. The FAA amends Sec. 39.13 by removing Amendment 39-15535 (73...

  7. CONCENTRATION DEPENDENT ACCUMULATION OF [3H]-DELTAMETHRIN IN SODIUM CHANNEL N AV1.2 EXPRESSING XENOPUS LAEVIS OOCYTES.

    EPA Science Inventory

    Disruption of neuronal voltage-sensitive sodium channels (VSSCs) by pyrethroid insecticides such as deltamethrin (DLT) has been widely studied using Xenopus laevis oocytes transfected with VSSC. However, the extent of pyrethroid accumulation in VSSC-expressing oocytes is unknown....

  8. Produce Live News Broadcasts Using Standard AV Equipment: A Success Story from the Le Center High School in Minnesota.

    ERIC Educational Resources Information Center

    Rostad, John

    1997-01-01

    Describes the production of news broadcasts on video by a high school class in Le Center, Minnesota. Topics include software for Apple computers, equipment used, student responsibilities, class curriculum, group work, communication among the production crew, administrative and staff support, and future improvements. (LRW)

  9. 75 FR 60659 - Airworthiness Directives; 328 Support Services GmbH (Type Certificate Previously Held by AvCraft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-01

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or..., notify your principal maintenance inspector (PMI) or principal avionics inspector (PAI), as...

  10. Genetic dissection of the Down syndrome critical region.

    PubMed

    Jiang, Xiaoling; Liu, Chunhong; Yu, Tao; Zhang, Li; Meng, Kai; Xing, Zhuo; Belichenko, Pavel V; Kleschevnikov, Alexander M; Pao, Annie; Peresie, Jennifer; Wie, Sarah; Mobley, William C; Yu, Y Eugene

    2015-11-15

    Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr. By dividing the Setd4-Mx2 region into complementary Setd4-Kcnj6 and Kcnj15-Mx2 intervals, we started an unbiased dissection through generating and analyzing Dp(16)1Yey/Df(16Setd4-Kcnj6)Yey and Dp(16)1Yey/Df(16Kcnj15-Mx2)Yey mice. Surprisingly, the Dp(16)1Yey-associated cognitive phenotypes were not rescued by either deletion in the compound mutants, suggesting the possible presence of at least one causative gene in each of the two regions. The partial rescue by a Dyrk1a mutation in a compound mutant carrying Dp(16)1Yey and the Dyrk1a mutation confirmed the causative role of Dyrk1a, whereas the absence of a similar rescue by Df(16Dyrk1a-Kcnj6)Yey in Dp(16)1Yey/Df(16Dyrk1a-Kcnj6)Yey mice demonstrated the importance of Kcnj6. Our results revealed the high levels of complexities of gene actions and interactions associated with the Setd4/Cbr1-Fam3b/Mx2 region as well as their relationship with developmental cognitive deficits in DS. PMID:26374847

  11. GO2OGS: a versatile workflow to integrate complex geological information with fault data into numerical simulation models

    NASA Astrophysics Data System (ADS)

    Fischer, T.; Walther, M.; Sattler, S.; Naumov, D.; Kolditz, O.

    2015-08-01

    We offer a versatile workflow to convert geological models built with the software Paradigm™ GOCAD© into the open-source VTU format for the usage in numerical simulation models. Tackling relevant scientific questions or engineering tasks often involves multidisciplinary approaches. Conversion workflows are needed as a way of communication between the diverse tools of the various disciplines. Our approach offers an open-source, platform independent, robust, and comprehensible method that is potentially useful for a multitude of similar environmental studies. With two application examples in the Thuringian Syncline, we show how a heterogeneous geological GOCAD model including multiple layers and faults can be used for numerical groundwater flow modelling. The presented workflow offers the chance to incorporate increasingly detailed data, utilizing growing availability of computational power to simulate numerical models.

  12. Hip Hop Culture's OGs: A Narrative Inquiry into the Intersection of Hip Hop Culture, Black Males and Their Schooling Experiences

    ERIC Educational Resources Information Center

    Buchanan, Ian P.

    2013-01-01

    Using a critical race lens, this narrative study employs a focus group design to explore the intersections between black males, hip hop culture and schooling experiences. To provide a sociocultural grounding, this study first reviews the research literature around hip hop culture.s sociocultural development and its impact as a culture force that…

  13. The formation of pentagon-heptagon pair defect by the reconstruction og vacancy defects in carbon nanotube

    SciTech Connect

    Lee, G.D.; Wang, C.Z.; Yoon, E.; Hwang, N.M.; Ho, K.M.

    2008-01-29

    The reconstruction process of vacancy hole in carbon nanotube is investigated by tight-binding molecular dynamics simulations and by ab initio total energy calculations. In the molecular dynamics simulation, a vacancy hole is found to reconstruct into two separated pentagon-heptagon pair defects. As the result of reconstruction, the radius of the carbon nanotube is reduced and the chirality of the tube is partly changed. During the vacancy hole healing process, the formation of pentagonal and heptagonal rings is proceeded by the subsequent Stone-Wales.

  14. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

    PubMed

    O'Roak, Brian J; Vives, Laura; Fu, Wenqing; Egertson, Jarrett D; Stanaway, Ian B; Phelps, Ian G; Carvill, Gemma; Kumar, Akash; Lee, Choli; Ankenman, Katy; Munson, Jeff; Hiatt, Joseph B; Turner, Emily H; Levy, Roie; O'Day, Diana R; Krumm, Niklas; Coe, Bradley P; Martin, Beth K; Borenstein, Elhanan; Nickerson, Deborah A; Mefford, Heather C; Doherty, Dan; Akey, Joshua M; Bernier, Raphael; Eichler, Evan E; Shendure, Jay

    2012-12-21

    Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands. We discovered 27 de novo events in 16 genes, 59% of which are predicted to truncate proteins or disrupt splicing. We estimate that recurrent disruptive mutations in six genes-CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1-may contribute to 1% of sporadic ASDs. Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the importance of a β-catenin-chromatin-remodeling network to ASD etiology. PMID:23160955

  15. Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives.

    PubMed

    Giraud, Francis; Alves, Georges; Debiton, Eric; Nauton, Lionel; Théry, Vincent; Durieu, Emilie; Ferandin, Yoan; Lozach, Olivier; Meijer, Laurent; Anizon, Fabrice; Pereira, Elisabeth; Moreau, Pascale

    2011-07-14

    The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents. PMID:21623630

  16. MiR-1246

    PubMed Central

    Liao, Jun-Ming; Zhou, Xiang; Zhang, Yu; Lu, Hua

    2012-01-01

    Since the discovery of miRNAs, a number of miRNAs have been identified as p53’s transcriptional targets. Most of them are involved in regulation of the known p53 functions, such as cell cycle, apoptosis and senescence. Our recent study revealed miR-1246 as a novel target of p53 and its analogs p63 and p73 to suppress the expression of DYRK1A and consequently activate NFAT, both of which are associated with Down syndrome and possibly with tumorigenesis. This finding suggests that miR-1246 might serve as a likely link of the p53 family with Down syndrome. Here, we provide some prospective views on the potential role of the p53 family in Down syndrome via miR-1246 and propose a new p53-miR-1246-DYRK1A-NFAT pathway in cancer. PMID:22751441

  17. Targeted next-generation sequencing in the diagnosis of neurodevelopmental disorders.

    PubMed

    Okamoto, N; Miya, F; Tsunoda, T; Kato, M; Saitoh, S; Yamasaki, M; Shimizu, A; Torii, C; Kanemura, Y; Kosaki, K

    2015-09-01

    We developed a next-generation sequencing (NGS) based mutation screening strategy for neurodevelopmental diseases. Using this system, we screened 284 genes in 40 patients. Several novel mutations were discovered. Patient 1 had a novel mutation in ACTB. Her dysmorphic feature was mild for Baraitser-Winter syndrome. Patient 2 had a truncating mutation of DYRK1A. She lacked microcephaly, which was previously assumed to be a constant feature of DYRK1A loss of function. Patient 3 had a novel mutation in GABRD gene. She showed Rett syndrome like features. Patient 4 was diagnosed with Noonan syndrome with PTPN11 mutation. He showed complete agenesis of corpus callosum. We have discussed these novel findings. PMID:25156961

  18. Synthesis and preliminary in vitro kinase inhibition evaluation of new diversely substituted pyrido[3,4-g]quinazoline derivatives.

    PubMed

    Zeinyeh, Wael; Esvan, Yannick J; Nauton, Lionel; Loaëc, Nadège; Meijer, Laurent; Théry, Vincent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-09-01

    The synthesis of new diversely substituted pyrido[3,4-g]quinazolines is described. The inhibitory potencies of prepared compounds toward a panel of five CMGC protein kinases (CDK5, CLK1, DYRK1A, CK1, GSK3), that are known to play a potential role in Alzheimer's disease, were evaluated. The best overall kinase inhibition profile was found for nitro compound 4 bearing an ethyl group at the 5-position. PMID:27469128

  19. The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions

    PubMed Central

    Ritterhoff, Stefanie; Farah, Carla M; Grabitzki, Julia; Lochnit, Günter; Skurat, Alexander V; Schmitz, Michael Lienhard

    2010-01-01

    Protein kinases are organized in hierarchical networks that are assembled and regulated by scaffold proteins. Here, we identify the evolutionary conserved WD40-repeat protein Han11 as an interactor of the kinase homeodomain-interacting protein kinase 2 (HIPK2). In vitro experiments showed the direct binding of Han11 to HIPK2, but also to the kinases DYRK1a, DYRK1b and mitogen-activated protein kinase kinase kinase 1 (MEKK1). Han11 was required to allow coupling of MEKK1 to DYRK1 and HIPK2. Knockdown experiments in Caenorhabditis elegans showed the relevance of the Han11 orthologs Swan-1 and Swan-2 for the osmotic stress response. Downregulation of Han11 in human cells lowered the threshold and amplitude of HIPK2- and MEKK1-triggered signalling events and changed the kinetics of kinase induction. Han11 knockdown changed the amplitude and time dependence of HIPK2-driven transcription in response to DNA damage and also interfered with MEKK1-triggered gene expression and stress signalling. Impaired signal transmission also occurred upon interference with stoichiometrically assembled signalling complexes by Han11 overexpression. Collectively, these experiments identify Han11 as a novel scaffold protein regulating kinase signalling by HIPK2 and MEKK1. PMID:20940704

  20. Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors.

    PubMed

    Pagano, Mario A; Poletto, Giorgia; Di Maira, Giovanni; Cozza, Giorgio; Ruzzene, Maria; Sarno, Stefania; Bain, Jenny; Elliott, Matthew; Moro, Stefano; Zagotto, Giuseppe; Meggio, Flavio; Pinna, Lorenzo A

    2007-01-01

    Abnormally high constitutive activity of protein kinase CK2, levels of which are elevated in a variety of tumours, is suspected to underlie its pathogenic potential. The most widely employed CK2 inhibitor is 4,5,6,7-tetrabromobenzotriazole (TBB), which exhibits a comparable efficacy toward another kinase, DYRK1 a. Here we describe the development of a new class of CK2 inhibitors, conceptually derived from TBB, which have lost their potency toward DYRK1 a. In particular, tetrabromocinnamic acid (TBCA) inhibits CK2 five times more efficiently than TBB (IC50 values 0.11 and 0.56 microM, respectively), without having any comparable effect on DYRK1 a (IC50 24.5 microM) or on a panel of 28 protein kinases. The usefulness of TBCA for cellular studies has been validated by showing that it reduces the viability of Jurkat cells more efficiently than TBB through enhancement of apoptosis. Collectively taken, the reported data support the view that suitably derivatized tetrabromobenzene molecules may provide powerful reagents for dissecting the cellular functions of CK2 and counteracting its pathogenic potentials. PMID:17133643

  1. Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model.

    PubMed

    Stringer, Megan; Abeysekera, Irushi; Dria, Karl J; Roper, Randall J; Goodlett, Charles R

    2015-11-01

    Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function. PMID:26363314

  2. Hologram QSAR Models of a Series of 6-Arylquinazolin-4-Amine Inhibitors of a New Alzheimer’s Disease Target: Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase-1A Enzyme

    PubMed Central

    Leal, Felipe Dias; da Silva Lima, Camilo Henrique; de Alencastro, Ricardo Bicca; Castro, Helena Carla; Rodrigues, Carlos Rangel; Albuquerque, Magaly Girão

    2015-01-01

    Dual specificity tyrosine-phosphorylation-regulated kinase-1A (DYRK1A) is an enzyme directly involved in Alzheimer’s disease, since its increased expression leads to β-amyloidosis, Tau protein aggregation, and subsequent formation of neurofibrillary tangles. Hologram quantitative structure-activity relationship (HQSAR, 2D fragment-based) models were developed for a series of 6-arylquinazolin-4-amine inhibitors (36 training, 10 test) of DYRK1A. The best HQSAR model (q2 = 0.757; SEcv = 0.493; R2 = 0.937; SE = 0.251; R2pred = 0.659) presents high goodness-of-fit (R2 > 0.9), as well as high internal (q2 > 0.7) and external (R2pred > 0.5) predictive power. The fragments that increase and decrease the biological activity values were addressed using the colored atomic contribution maps provided by the method. The HQSAR contribution map of the best model is an important tool to understand the activity profiles of new derivatives and may provide information for further design of novel DYRK1A inhibitors. PMID:25756379

  3. AIDS-related primary cardiac lymphoma with right-sided heart failure and high-grade AV block: insights from magnetic resonance imaging.

    PubMed

    Llitjos, J-F; Redheuil, A; Puymirat, E; Vedrenne, G; Danchin, N

    2014-04-01

    A 44-year-old patient, with personal history of AIDS, was referred to our emergency unit with tachycardia and moderate signs of right-sided heart failure. The cardiac MRI study showed an impairment of the right ventricular free and inferior wall and the interventricular septum. The mass was characterized by notable heterogeneity with mixed areas of hypo- and hypersignal intensity in SSFP and T2-weighted images with fat saturation. There was global hyperenhancement of the mass after gadolinium contrast injection on T1-weighted images with and without fat saturation. The entire right coronary artery was included into the infiltrative mass. One day after the admission, the patient suddenly presented a paroxysmal third degree atrioventricular block, permanently corrected by an implanted cardiac pacemaker. Endomyocardial biopsy conformed the diagnosis of B-cell lymphoma. The patient died 4months after the diagnosis of acute heart failure with multi-organ dysfunction, after a short period of improvement under chemotherapy. We present this case to highlight the importance to consider that a large, solitary, right atrial mass in conjunction with pericardial effusion in a patient with HIV infection should lead to consider, as soon as possible, the diagnosis of lymphoma. MRI has explained the conduction disorders by showing the septal extension of the mass, and by demonstrating right coronary artery involvement. PMID:23830566

  4. Resonant-convergent PCM response theory for the calculation of second harmonic generation in makaluvamines A-V: pyrroloiminoquinone marine natural products from poriferans of genus Zyzzya.

    PubMed

    Milne, Bruce F; Norman, Patrick

    2015-05-28

    The first-order hyperpolarizability, β, has been calculated for a group of marine natural products, the makaluvamines. These compounds possess a common cationic pyrroloiminoquinone structure that is substituted to varying degrees. Calculations at the MP2 level indicate that makaluvamines possessing phenolic side chains conjugated with the pyrroloiminoquinone moiety display large β values, while breaking this conjugation leads to a dramatic decrease in the calculated hyperpolarizability. This is consistent with a charge-transfer donor-π-acceptor (D-π-A) structure type, characteristic of nonlinear optical chromophores. Dynamic hyperpolarizabilities calculated using resonance-convergent time-dependent density functional theory coupled to polarizable continuum model (PCM) solvation suggest that significant resonance enhancement effects can be expected for incident radiation with wavelengths around 800 nm. The results of the current work suggest that the pyrroloiminoquinone moiety represents a potentially useful new chromophore subunit, in particular for the development of molecular probes for biological imaging. The introduction of solvent-solute interactions in the theory is conventionally made in a density matrix formalism, and the present work will provide detailed account of the approximations that need to be introduced in wave function theory and our program implementation. The program implementation as such is achieved by a mere combination of existing modules from previous developments, and it is here only briefly reviewed. PMID:25584854

  5. Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer’s disease dementia, mild cognitive impairment, and normal aging

    PubMed Central

    Johnson, KA; Sperling, RA; Gidicsin, C; Carmasin, J; Maye, J; Coleman, RE; Reiman, EM; Sabbagh, MN; Sadowsky, CH; Fleisher, AS; Doraiswamy, PM; Carpenter, AP; Clark, CM; Joshi, AD; Lu, M; Grundman, M; Mintun, MA; Pontecorvo, MJ; Skovronsky, DM

    2013-01-01

    Objective To evaluate the performance characteristics of florbetapir F 18 PET in patients with Alzheimer’s disease dementia (AD), mild cognitive impairment (MCI) and healthy control subjects (HC). Methods Florbetapir PET was acquired in 184 subjects (45 AD, 60 MCI, and 79 HC) within a multi-center phase 2 study. Amyloid burden was assessed visually and quantitatively and classified as positive or negative. Results Florbetapir PET was visually rated amyloid positive in 76% of AD, 38% of MCI and 14% of HC. 84% of AD, 42% of MCI, and 23% of HC were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and APOE ε4 carrier status. Interpretation The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate potential value of florbetapir F 18 PET as an adjunct to clinical diagnosis. PMID:23375563

  6. The Future Is Now: The Era of Downloadable AV Has Dawned--Here's How It's Working in the Real Library World

    ERIC Educational Resources Information Center

    Kim, Ann

    2006-01-01

    This article discusses the possible answers to most librarians' questions and how advanced and hi-technology help them in the library world. Many of the answers to librarians' questions regarding digital media depend upon community/patron awareness and library resources. In this article, the author presents some quoted statements from electronic…

  7. A novel smart supramolecular organic gelator exhibiting dual-channel responsive sensing behaviours towards fluoride ion via gel-gel states.

    PubMed

    Mehdi, Hassan; Pang, Hongchang; Gong, Weitao; Dhinakaran, Manivannan Kalavathi; Wajahat, Ali; Kuang, Xiaojun; Ning, Guiling

    2016-07-01

    A novel smart supramolecular organic gelator G-16 containing anion and metal-coordination ability has been designed and synthesized. It shows excellent and robust gelation capability as a strong blue fluorescent supramolecular organic gel OG in DMF. Addition of Zn(2+) produced Zn(2+)-coordinated supramolecular metallogel OG-Zn. Organic gel OG and organometallic gel OG-Zn exhibited efficient and different sensing behaviors towards fluoride ion due to the variation in self-assembling nature. Supramolecular metallogel OG-Zn displayed specific selectivity for fluoride ion and formed OG-Zn-F with dramatic color change from blue to blue green in solution and gel to gel states. Furthermore after directly addition of fluoride into OG produced fluoride containing organic gel OG-F with drastically modulation in color from blue to greenish yellow fluorescence via strong aggregation-induced emission (AIE) property. A number of experiments were conducted such as FTIR, (1)H NMR, and UV/Vis spectroscopies, XRD, SEM and rheology. These results revealed that the driving forces involved in self-assembly of OG, OG-Zn, OG-Zn-F and OG-F were hydrogen bonding, metal coordination, π-π interactions, and van der Waal forces. In contrast to the most anion responsive gels, particularly fluoride ion responsive gels showed gel-sol state transition on stimulation by anions, the gel state of OG and OG-Zn did not show any gel-to-sol transition during the whole F(-) response process. PMID:27193611

  8. GO2OGS 1.0: a versatile workflow to integrate complex geological information with fault data into numerical simulation models

    NASA Astrophysics Data System (ADS)

    Fischer, T.; Naumov, D.; Sattler, S.; Kolditz, O.; Walther, M.

    2015-11-01

    We offer a versatile workflow to convert geological models built with the ParadigmTM GOCAD© (Geological Object Computer Aided Design) software into the open-source VTU (Visualization Toolkit unstructured grid) format for usage in numerical simulation models. Tackling relevant scientific questions or engineering tasks often involves multidisciplinary approaches. Conversion workflows are needed as a way of communication between the diverse tools of the various disciplines. Our approach offers an open-source, platform-independent, robust, and comprehensible method that is potentially useful for a multitude of environmental studies. With two application examples in the Thuringian Syncline, we show how a heterogeneous geological GOCAD model including multiple layers and faults can be used for numerical groundwater flow modeling, in our case employing the OpenGeoSys open-source numerical toolbox for groundwater flow simulations. The presented workflow offers the chance to incorporate increasingly detailed data, utilizing the growing availability of computational power to simulate numerical models.

  9. Re-oxidation Kinetics of Flash-Reduced Iron Particles in H2-H2O(g) Atmosphere Relevant to a Novel Flash Ironmaking Process

    NASA Astrophysics Data System (ADS)

    Yuan, Zhixue; Sohn, Hong Yong; Olivas-Martinez, Miguel

    2013-12-01

    A novel flash ironmaking process based on hydrogen-containing reduction gases is under development at the University of Utah. The goal of this work was to study the possibility of the re-oxidation of iron particles in a H2-H2O gas mixture in the lower part of the flash reactor from the kinetic point of view. The last stage of hydrogen reduction of iron oxide, i.e., the reduction of wustite, is limited by equilibrium. As the reaction mixture cools down, the re-oxidation of iron could take place because of the decreasing equilibrium constant and the high reactivity of the freshly reduced fine iron particles. The effects of temperature and H2O partial pressure on the re-oxidation rate were examined in the temperature range of 823 K to 973 K (550 °C to 700 °C) and H2O contents of 40 to 100 pct. The nucleation and growth kinetics model was shown to best describe the re-oxidation kinetics. The partial pressure dependence with respect to water vapor was determined to be of first order, and the activation energy of re-oxidation reaction was 146 kJ/mol. A complete rate equation that adequately represents the experimental data was developed.

  10. A parallelization scheme to simulate reactive transport in the subsurface environment with OGS#IPhreeqc 5.5.7-3.1.2

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    The open-source scientific software packages OpenGeoSys and IPhreeqc have been coupled to set up and simulate thermo-hydro-mechanical-chemical coupled processes with simultaneous consideration of aqueous geochemical reactions faster and easier on high-performance computers. In combination with the elaborated and extendable chemical database of IPhreeqc, it will be possible to set up a wide range of multiphysics problems with numerous chemical reactions that are known to influence water quality in porous and fractured media. A flexible parallelization scheme using MPI (Message Passing Interface) grouping techniques has been implemented, which allows an optimized allocation of computer resources for the node-wise calculation of chemical reactions on the one hand and the underlying processes such as for groundwater flow or solute transport on the other. This technical paper presents the implementation, verification, and parallelization scheme of the coupling interface, and discusses its performance and precision.

  11. Paléogéographie du Jurassique supérieur au sud du choot El Hodna, Algérie

    NASA Astrophysics Data System (ADS)

    Aissaoui, D. M.

    The Upper Jurassic outcrops as isolated mounts along the southern end of chott el Hodna, Algeria. They consist mainly on shallow platform deposited limestones immediately north (Bout Taleb) and east (Aures) of chott el Hodna, the carbonates of the same age are pelagic and deposited within basin or external platform respectively. Detailed study of Meharga-Fnoud series demonstrates that the shallow carbonate sedimentation in this sector is interrupted by periodic emersions as indicated by vadose diagenesis (birds-eyes, opened burrows, evaporite and dolomite, vadose silts etc). The proposed paleogeography locates the internal jurassic shoreline near the present southern limit of chott el Hodna. Each maximal extension of the emersion leads to the formation of a tidal flat whose origin is not associated with a reefal nor a sedimentary barrier. The emersions are mainly favored by the large dimension and the absence of significant submarine relief within the Jurassic platform. Each emersion starts in the north then progrades southwards by lateral accretions. Its progression is interrupted by deep tectonic reactivation which provokes marine transgression over the tidal flat. One of the main interest of the Jurassic paleogeography in this region concerns the association between the tidal flat and an extensive dolomitization which may transform limestones precursors into good reservoirs.

  12. Work Programme, 2001.

    ERIC Educational Resources Information Center

    European Centre for the Development of Vocational Training, Thessaloniki (Greece).

    This publication presents the work program for 2001 for the European Center for the Development of Vocational Training (CEDEFOP) set in the framework of four operational guidelines (OGs). The section on each OG contains an introduction including CEDEFOP's aims, followed by descriptions of research projects relevant to the OG. Each of the 11…

  13. Operational Group Sandy technical progress report

    USGS Publications Warehouse

    Department of the Interior Strategic Science Group

    2013-01-01

    This report documents results from the March 2013 deployment of the OGS. It includes background information on Hurricane Sandy and the federal response; the OGS methodology; scenarios for Hurricane Sandy’s impact on coastal communities and urban ecosystems; potential interventions to improve regional resilience to future major storms; a discussion of scenario results; and lessons learned about the OGS process.

  14. Two Grammatical Models of Modern English. The Old and the New from A to Z. Germanic Linguistic Series.

    ERIC Educational Resources Information Center

    Stuurman, Frits

    Case studies provide detailed comparisons, arranged alphabetically by title for ease of reference, of 26 problems in Modern English grammar, from both the old grammar (OG) and new grammar (NG) viewpoints. This A-Z approach juxtaposes contributions made by OG and NG to the description of Modern English grammar. Part I surveys large OG and NG…

  15. HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation.

    PubMed

    Siepi, Francesca; Gatti, Veronica; Camerini, Serena; Crescenzi, Marco; Soddu, Silvia

    2013-06-01

    HIPK2 (homeodomain-interacting protein kinase-2) binds to and phosphorylates, at Ser and Thr residues, a large number of targets involved in cell division and cell fate decision in response to different physiological or stress stimuli. Inactivation of HIPK2 has been observed in human and mouse cancers supporting its role as a tumor suppressor. Despite the biological relevance of this kinase, very little is known on how HIPK2 becomes catalytically active. Based on sequence homologies, HIPK2 has been taxonomically classified as a subfamily member of the dual-specificity tyrosine-regulated kinases (DYRKs) and the activation-loop Y354 of HIPK2 has been found phosphorylated in different cells; however, the relevance of this Y phosphorylation is presently unknown. Here, we show that HIPK2, which is extensively phosphorylated at S/T sites throughout its functional domains, becomes catalytically active by autophosphorylation at the activation-loop Y354. In particular, we found that, in analogy to DYRKs, HIPK2-Y354 phosphorylation is an autocatalytic event and its prevention, through Y354 substitution with non-phosphorylatable amino acids or by using the kinase inhibitor purvalanol A, induces a strong reduction of the HIPK2 S/T-kinase activity on different substrates. Interestingly, at variance from DYRKs, inhibition of HIPK2-Y354 phosphorylation induces a strong out-of-target Y-kinase activity in cis and a strong cytoplasmic relocalization of the kinase. Together, these results demonstrate that the catalytic activity, substrate specificity, and subcellular localization of HIPK2 are regulated by autophosphorylation of its activation-loop Y354. PMID:23485397

  16. HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation

    PubMed Central

    Siepi, Francesca; Gatti, Veronica; Camerini, Serena; Crescenzi, Marco; Soddu, Silvia

    2013-01-01

    HIPK2 (homeodomain-interacting protein kinase-2) binds to and phosphorylates, at Ser and Thr residues, a large number of targets involved in cell division and cell fate decision in response to different physiological or stress stimuli. Inactivation of HIPK2 has been observed in human and mouse cancers supporting its role as a tumor suppressor. Despite the biological relevance of this kinase, very little is known on how HIPK2 becomes catalytically active. Based on sequence homologies, HIPK2 has been taxonomically classified as a subfamily member of the dual-specificity tyrosine-regulated kinases (DYRKs) and the activation-loop Y354 of HIPK2 has been found phosphorylated in different cells; however, the relevance of this Y phosphorylation is presently unknown. Here, we show that HIPK2, which is extensively phosphorylated at S/T sites throughout its functional domains, becomes catalytically active by autophosphorylation at the activation-loop Y354. In particular, we found that, in analogy to DYRKs, HIPK2-Y354 phosphorylation is an autocatalytic event and its prevention, through Y354 substitution with non-phosphorylatable amino acids or by using the kinase inhibitor purvalanol A, induces a strong reduction of the HIPK2 S/T-kinase activity on different substrates. Interestingly, at variance from DYRKs, inhibition of HIPK2-Y354 phosphorylation induces a strong out-of-target Y-kinase activity in cis and a strong cytoplasmic relocalization of the kinase. Together, these results demonstrate that the catalytic activity, substrate specificity, and subcellular localization of HIPK2 are regulated by autophosphorylation of its activation-loop Y354. PMID:23485397

  17. Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins.

    PubMed

    Akue-Gedu, Rufine; Debiton, Eric; Ferandin, Yoan; Meijer, Laurent; Prudhomme, Michelle; Anizon, Fabrice; Moreau, Pascale

    2009-07-01

    The synthesis of new meridianin derivatives substituted at the C-5 position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. These compounds were tested for their kinase inhibitory potencies toward five kinases (CDK5/p25, CK1delta/epsilon, GSK-3alpha/beta, Dyrk1A and Erk2) as well as their in vitro antiproliferative activities toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 and PA 1). PMID:19477650

  18. Site-specific Proteasome Phosphorylation Controls Cell Proliferation and Tumorigenesis

    PubMed Central

    Guo, Xing; Wang, Xiaorong; Wang, Zhiping; Banerjee, Sourav; Yang, Jing; Huang, Lan; Dixon, Jack E.

    2015-01-01

    Despite the fundamental importance of proteasomal degradation in cells, little is known about whether and how the 26S proteasome itself is regulated in coordination with various physiological processes. Here we show that the proteasome is dynamically phosphorylated during cell cycle at Thr25 of the 19S subunit Rpt3. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrate that blocking Rpt3-Thr25 phosphorylation markedly impairs proteasome activity and impedes cell proliferation. Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation. Importantly, loss of the single phosphorylation of Rpt3-Thr25 or knockout of DYRK2 significantly inhibits tumor formation by proteasome-addicted human breast cancer cells in mice. These findings define an important mechanism for proteasome regulation and demonstrate the biological significance of proteasome phosphorylation in regulating cell proliferation and tumorigenesis. PMID:26655835

  19. Loss of the mammalian DREAM complex deregulates chondrocyte proliferation.

    PubMed

    Forristal, Chantal; Henley, Shauna A; MacDonald, James I; Bush, Jason R; Ort, Carley; Passos, Daniel T; Talluri, Srikanth; Ishak, Charles A; Thwaites, Michael J; Norley, Chris J; Litovchick, Larisa; DeCaprio, James A; DiMattia, Gabriel; Holdsworth, David W; Beier, Frank; Dick, Frederick A

    2014-06-01

    Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes. PMID:24710275

  20. Novel factors modulating human β-cell proliferation.

    PubMed

    Shirakawa, J; Kulkarni, R N

    2016-09-01

    β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. PMID:27615134

  1. Loss of the Mammalian DREAM Complex Deregulates Chondrocyte Proliferation

    PubMed Central

    Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Bush, Jason R.; Ort, Carley; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; Norley, Chris J.; Litovchick, Larisa; DeCaprio, James A.; DiMattia, Gabriel; Holdsworth, David W.; Beier, Frank

    2014-01-01

    Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes. PMID:24710275

  2. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21

    PubMed Central

    Hibaoui, Youssef; Grad, Iwona; Letourneau, Audrey; Sailani, M Reza; Dahoun, Sophie; Santoni, Federico A; Gimelli, Stefania; Guipponi, Michel; Pelte, Marie Françoise; Béna, Frédérique; Antonarakis, Stylianos E; Feki, Anis

    2014-01-01

    Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A ( DYRK1A) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. PMID:24375627

  3. Altered regulation of tau phosphorylation in a mouse model of down syndrome aging

    PubMed Central

    Sheppard, Olivia; Plattner, Florian; Rubin, Anna; Slender, Amy; Linehan, Jacqueline M.; Brandner, Sebastian; Tybulewicz, Victor L.J.; Fisher, Elizabeth M.C.; Wiseman, Frances K.

    2012-01-01

    Down syndrome (DS) results from trisomy of human chromosome 21 (Hsa21) and is associated with an increased risk of Alzheimer's disease (AD). Here, using the unique transchromosomic Tc1 mouse model of DS we investigate the influence of trisomy of Hsa21 on the protein tau, which is hyperphosphorylated in Alzheimer's disease. We show that in old, but not young, Tc1 mice increased phosphorylation of tau occurs at a site suggested to be targeted by the Hsa21 encoded kinase, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A). We show that DYRK1A is upregulated in young and old Tc1 mice, but that young trisomic mice may be protected from accumulating aberrantly phosphorylated tau. We observe that the key tau kinase, glycogen synthase kinase3-β (GSK-3β) is aberrantly phosphorylated at an inhibitory site in the aged Tc1 brain which may reduce total glycogen synthase kinase3-β activity. It is possible that a similar mechanism may also occur in people with DS. PMID:21843906

  4. Evaluation of the National School Lunch Program Application/Verification Pilot Projects, Volume IV: Analysis of Pilot Operations and Costs. Nutrition Assistance Program Report Series. Report No. CN-04-AV6

    ERIC Educational Resources Information Center

    Burghardt, John; Tasse, Tania; Ohls, James

    2004-01-01

    This report is the forth in the series of evaluations of the National School Lunch Program. The findings presented here are the result of an analysis of pilot project operations and costs for two alternatives to the current application-based certification process--Up-Front Documentation and Graduated Verification--that were tested in 12 public…

  5. High-resolution oscillator strength measurements for the A(v') - X(0) bands of carbon monoxide with 11 less than or equal to v' less than or equal to 14

    NASA Technical Reports Server (NTRS)

    Smith, Peter L.; Stark, G.; Yoshino, K.; Ito, K.

    1994-01-01

    Band oscillator strengths (f-values) for four bands of the Fourth Positive system (A (1)Pi - Chi(sup 1) Sigma(+)) of CO have been determined from high-resolution (lambda/Delta lambda approximately equal to 150,000) absorption spectra. The bands, (14, 0) through (11, 0), are at wavelengths between 121 and 127 nm. Our f-values for the (11, 0) and (12, 0) bands support those of Chan, Cooper, & Brion (1993), which have been shown to be consistent with observations of CO in the clouds in the line of sight to zeta Oph. Our f-values for the (13, 0) and (14, 0) bands are the first directly measured values for these bands.

  6. Sma Barn Pa Daghem: En studie av personalens samspel med barn och foraldrar vid lamning, hamtning och fri lek (Infants at Day Care: A Study of Staff Interaction with Children and Their Parents during Leaving, Collecting and Free Play).

    ERIC Educational Resources Information Center

    Lothigius, Anita Holmstedt

    This thesis presents a picture of how staff interact with infants (age group 1-3 years old) and parents at three day care centers. The study focused on the situations of leaving and collecting the children and the children's time of free play both in and outdoors. The theoretical content has an attachment/psycho-dynamical perspective with emphasis…

  7. IFLA General Conference 1988. Division of Management and Technology. Section on Information Technology; Section on Statistics; Section on Library Buildings and Equipment; Section on Conservation; Round Table on Management of Library Associations; Round Table on AV Media.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    The 15 papers in this compilation focus on library nagement and technology, including information technology, statistics, buildings and equipment, and conservation: (1) "Information Control: OSI (Open Systems Interconnection) and Networking Strategies" (Neil McClean, United Kingdom); (2) "OSI in Australia: Potential, Planning, Progress" (Rona…

  8. America's Revolutionary Period, 1760-1785; A Bibliography of the Holdings of The Sarah Byrd Askew Library and the AV Center of The William Paterson College of New Jersey.

    ERIC Educational Resources Information Center

    Job, Amy G.

    This annotated bibliography lists more than 850 book and nonbook materials concerning the Revolutionary War period. Entries are listed under the following categories: Revolution--general works, special geographic areas, and special miscellaneous topics; American and British forces; bibliographies and sources; biography; campaigns and battles;…

  9. Evaluation of the National School Lunch Program Application/Verification Pilot Projects: Volume I: Impacts on Deterrence, Barriers, and Accuracy. Nutrition Assistance Program Report Series. Report No. CN-04-AV1

    ERIC Educational Resources Information Center

    Burghardt, John; Gleason, Philip; Sinclair, Michael; Cohen, Rhoda; Hulsey, Lara; Milliner-Waddell, Julita

    2004-01-01

    The U.S. Department of Agriculture (USDA) sponsored the NSLP Application/Verification Pilot Projects to test ways to improve the process for certifying students for free or reduced-price meals. This report presents findings on the impacts of two alternatives to the current application based certification process--Up-Front Documentation and…

  10. Evaluation of the National School Lunch Program Application/Verification Pilot Projects: Volume II: Data Collection, Study Methods and Supplementary Tables on Certification Impacts. Nutrition Assistance Program Report Series. Report No. CN-04-AV2

    ERIC Educational Resources Information Center

    Burghardt, John; Gleason, Philip; Sinclair, Michael; Cohen, Rhoda; Hulsey, Lara; Milliner-Waddell, Julita

    2004-01-01

    This is Volume II of the report on the evaluation of the NSLP Application Verification Pilot Projects. It supplements Volume I, which presents the evaluation findings. Volume II has two objectives: (1) to provide a detailed description of the methods used to conduct the study; and (2) to present tabulations that supplement and extend the analyses…

  11. Replacement of a severe chronic post-traumatic aneurysm of the ascending aorta with aortic valve conduit--reconstruction of the anterior mitral valve ring and implantation of A-V sequential/biventricular pacemaker.

    PubMed

    Mensah, O-W; Friedl, A; Fried, A; Jepsen, M; Auricchio, A; Klein, H; Huth, C

    2005-08-01

    We present the case of a 23-year-old African professional footballer who was admitted on April 1, 1999 to the Cardiology Department of the University Hospital in Magdeburg, on an emergency basis, from a regional lung clinic. According to the history, he was involved in a collision with an opposing player during a football match in his country (in Africa). He lost consciousness for a short time, but continued playing to the end of the match. About two months later he was invited by a German football club for a check-up, with the view to ultimately playing for the club. The team did not find him physically fit enough to play professional football, so he decided to go to Paris by bus on March 31, 1999. During the journey he suddenly became cardio-pulmonary decompensated and had to undergo cardio-pulmonary resuscitation (CPR). He was intubated and placed on a respirator and immediately transferred to a nearby lung clinic. From the lung clinic he was transferred to the Intensive Care Unit of the Cardiology Department of the Magdeburg University Hospital, on April 1, 1999 as an emergency case. He was intensively treated with catecholamines, intravenous ACE inhibitors and diuretics. His clinical condition did not improve appreciably. His chest X-ray showed extreme dilatation of the right and left heart as well as extreme pulmonary congestion. PMID:16037867

  12. Hur arbetar forskollarare med bild? En studie av fem forskollarare som leder barn i bildaktiviteter (How Do Preschool Teachers Work with Art Activities? A Study of Five Preschool Teachers Leading Children in Art Activities).

    ERIC Educational Resources Information Center

    Skoog, Eva

    Art education has traditionally played an important role in the Swedish preschool. The subject includes a variety of activities, and different aims have been stressed from both aesthetic and pedagogical points of view. This study sought to describe and analyze how preschool teachers work with children in art activities. The investigation used a…

  13. The 2-oxoglutarate supply exerts significant control on the lysine synthesis flux in Saccharomyces cerevisiae.

    PubMed

    Quezada, Héctor; Marín-Hernández, Alvaro; Arreguín-Espinosa, Roberto; Rumjanek, Franklin D; Moreno-Sánchez, Rafael; Saavedra, Emma

    2013-11-01

    To determine the extent to which the supply of the precursor 2-oxoglutarate (2-OG) controls the synthesis of lysine in Saccharomyces cerevisiae growing exponentially in high glucose, top-down elasticity analysis was used. Three groups of reactions linked by 2-OG were defined. The 2-OG supply group comprised all metabolic steps leading to its formation, and the two 2-OG consumer groups comprised the enzymes and transporters involved in 2-OG transformation into lysine and glutamate and their further utilization for protein synthesis and storage. Various 2-OG steady-state concentrations that produced different fluxes to lysine and glutamate were attained using yeast mutants with increasing activities of Krebs cycle enzymes and decreased activities of Lys synthesis enzymes. The elasticity coefficients of the three enzyme groups were determined from the dependence of the amino acid fluxes on the 2-OG concentration. The respective degrees of control on the flux towards lysine (flux control coefficients) were determined from their elasticities, and were 1.1, 0.41 and -0.52 for the 2-OG producer group and the Lys and Glu branches, respectively. Thus, the predominant control exerted by the 2-OG supply on the rate of lysine synthesis suggests that over-expression of 2-OG producer enzymes may be a highly effective strategy to enhance Lys production. PMID:24034837

  14. Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life

    PubMed Central

    Gillespie, Joseph J.; Williams, Kelly; Shukla, Maulik; Snyder, Eric E.; Nordberg, Eric K.; Ceraul, Shane M.; Dharmanolla, Chitti; Rainey, Daphne; Soneja, Jeetendra; Shallom, Joshua M.; Vishnubhat, Nataraj Dongre; Wattam, Rebecca; Purkayastha, Anjan; Czar, Michael; Crasta, Oswald; Setubal, Joao C.; Azad, Abdu F.; Sobral, Bruno S.

    2008-01-01

    Background Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular α-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs). Methodology/Principal Findings We present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (∼1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions. Conclusion/Significance Collectively, we determined the relative conservation and distribution of 14354 predicted

  15. Nouveaux restes aviens du Néogène de la Sperrgebiet (Namibie): Complément à la biostratigraphie avienne des éolianites du désert de Namib

    NASA Astrophysics Data System (ADS)

    Senut, Brigitte; Dauphin, Yannicke; Pickford, Martin

    1998-11-01

    Two new types of fossil ratite eggshells discovered in aeolianites at Karingarab (Sperrgebiet, Namibia) exhibit morphologies intermediate between those of types already described. They help to refine the biochronology of the aeolianites of the Namib Desert.

  16. Smaborns Dagpasning: Et Problem for Foraeldre og Kommuner. (Day-Care of Pre-School Children: A Problem to Parents and Local Authorities. With an English Summary). Publication No. 103.

    ERIC Educational Resources Information Center

    Gronhoj, Bodil

    Survey data were collected for the purposes of describing and comparing various forms of day care provision for preschool children within Danish municipalities with different day care provision and different degrees of urbanization. Information concerning the family background of subjects, parental assessment of different aspects of day care and…

  17. Différenciation paléogéographique à l'Ordovicien supérieur dans le Tafilalt (Anti-Atlas oriental, Maroc) sous l'interaction de la glaciation et de la tectonique

    NASA Astrophysics Data System (ADS)

    El Maazouz, Brahim; Hamoumi, Naima

    2007-07-01

    The Tafilalt domain, which corresponded, during the Lower and Middle Ordovician, to a storm and/or tide-dominated epeiric shelf with east-west- to ENE-WSW-trending isopachs, such as the whole 'Anti-Atlasic basin', recorded major palaeogeographical changes during the Upper Ordovician. An extensional tectonic event resulted in the individualization of two sub-basins: the 'Khabt-El-Hejar sub-basin' and the 'western Tafilalt sub-basin', where new environments developed under the interplay between tectonics and glaciation. In the northeastern Tafilalt sub-basin took place an isolated carbonate platform, where Bryozoan mounds nucleated, and a mixed siliciclastic carbonate high-energy peritidal littoral. In the 'western Tafilalt sub-basin', the siliciclastic shelf was structured in half-graben, where sediments from the Saharan glacier and the carbonate platform of the Khabt-El-Hejar sub-basin accumulated in fan deltas.

  18. L'Arenig Llanvirn du Haut Atlas occidental et central (Maroc). Environnements sédimentaires, paléogéographie et contrôle de la sédimentation

    NASA Astrophysics Data System (ADS)

    Chacrone, Choukri; Hamoumi, Naïma

    2005-09-01

    The sedimentological study of Arenig-Llanvirn successions of Aït Lahsen (western High Atlas), Tizi-n-Tichka and Imini (central High Atlas) allow us to recognise two independent epeiric seas. In the western High Atlas, the sedimentation occurred in a wave- and storm-influenced delta, alimented by a source situated at the present-day location of the Argana corridor, under the control of sea-level fluctuations and subsidence. In the central High Atlas, the sedimentation occurred in an influenced tide and episodic storm delta, alimented by sources situated at the present-day location of the Siroua and Ouzellagh Massifs under the control of sea-level fluctuations and tectonics. To cite this article: C. Chacrone, N. Hamoumi, C. R. Geoscience 337 (2005).

  19. Nonselective and polarization effects in time-resolved optogalvanic spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhechev, D.; Steflekova, V.

    2016-02-01

    Three interfering effects in optogalvanic (OG) spectroscopy are identified in a hollow cathode discharge (HCD) - OG detector. The laser beam is found to generate two nonselective processes, namely photoelectron emission (PE) from the cathode surface with a sub-breakdown bias applied, and nonresonant space ionization. The convolution of these galvanic contributions was determined experimentally as an instrumental function and a deconvolution procedure to determine the actual OG signal was developed. Specific plasma conductance is detected dependent on the polarization of the laser beam irradiating. Linearly/circularly polarized light beam is found to induce OG signals differ in amplitude (and their shape parameters in the time-resolved OG signals (TROGS)). The phenomena coherence and specific conductance are found to be in causal relationship. The additional conductance due to coherent states of atoms manifests itself as an intrinsic instrumental property of OG detector.

  20. Energy balance-dependent regulation of ovine glucose 6-phosphate dehydrogenase protein isoform expression.

    PubMed

    Triantaphyllopoulos, Kostas A; Laliotis, George P; Bizelis, Iosif A

    2014-01-01

    G6PDH is the rate-limiting enzyme of the pentose phosphate pathway and one of the principal source of NADPH, a major cellular reductant. Importantly, in ruminant's metabolism the aforementioned NADPH provided, is utilized for de novo fatty acid synthesis. Previous work of cloning the ovine (Ovis aries) og6pdh gene has revealed the presence of two cDNA transcripts (og6pda and og6pdb), og6pdb being a product of alternative splicing not similar to any other previously reported.(1) In the current study the effect of energy balance in the ovine G6PDH protein expression was investigated, shedding light on the biochemical features and potential physiological role of the oG6PDB isoform. Changes in energy balance leads to protein expression changes in both transcripts, to the opposite direction and not in a proportional way. Negative energy balance was not in favor of the presence of any particular isoform, while both protein expression levels were not significantly different (P > 0.05). In contrast, at the transition point from negative to positive and on the positive energy balance, there is a significant increase of oG6PDA compared with oG6PDB protein expression (P < 0.001). Both oG6PDH protein isoforms changed significantly toward the positive energy balance. oG6PDA is escalating, while oG6PDB is falling, under the same stimulus (positive energy balance alteration). This change is also positively associated with increasing levels in enzyme activity, 4 weeks post-weaning in ewes' adipose tissue. Furthermore, regression analysis clearly demonstrated the linear correlation of both proteins in response to the WPW, while energy balance, enzyme activity, and oG6PDA relative protein expression follow the same escalating trend; in contrast, oG6PDB relative protein expression falls in time, similar to both transcripts accumulation pattern, as reported previously.(2.) PMID:24575366

  1. Structural Underpinnings of Nitrogen Regulation by the Prototypical Nitrogen-Responsive Transcriptional Factor NrpR

    SciTech Connect

    Wisedchaisri, Goragot; Dranow, David M.; Lie, Thomas J.; Bonanno, Jeffrey B.; Patskovsky, Yury; Ozyurt, Sinem A.; Sauder, J. Michael; Almo, Steven C.; Wasserman, Stephen R.; Burley, Stephen K.; Leigh, John A.; Gonen, Tamir

    2010-11-29

    Plants and microorganisms reduce environmental inorganic nitrogen to ammonium, which then enters various metabolic pathways solely via conversion of 2-oxoglutarate (2OG) to glutamate and glutamine. Cellular 2OG concentrations increase during nitrogen starvation. We recently identified a family of 2OG-sensing proteins - the nitrogen regulatory protein NrpR - that bind DNA and repress transcription of nitrogen assimilation genes. We used X-ray crystallography to determine the structure of NrpR regulatory domain. We identified the NrpR 2OG-binding cleft and show that residues predicted to interact directly with 2OG are conserved among diverse classes of 2OG-binding proteins. We show that high levels of 2OG inhibit NrpRs ability to bind DNA. Electron microscopy analyses document that NrpR adopts different quaternary structures in its inhibited 2OG-bound state compared with its active apo state. Our results indicate that upon 2OG release, NrpR repositions its DNA-binding domains correctly for optimal interaction with DNA thereby enabling gene repression.

  2. A reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors

    PubMed Central

    Leung, Ivanhoe K. H.; Demetriades, Marina; Hardy, Adam P.; Lejeune, Clarisse; Smart, Tristan J.; Szöllössi, Andrea; Kawamura, Akane; Schofield, Christopher J.; Claridge, Timothy D. W.

    2015-01-01

    The human 2-oxoglutarate (2OG) dependent oxygenases belong to a family of structurally related enzymes that play important roles in many biological processes. We report that competition-based NMR methods, using 2OG as a reporter ligand, can be used for quantitative and site-specific screening of ligand binding to 2OG oxygenases. The method was demonstrated using hypoxia inducible factor (HIF) hydroxylases and histone demethylases, and KD values were determined for inhibitors that compete with 2OG at the metal centre. This technique is also useful as a screening or validation tool for inhibitor discovery, as exemplified by work with protein-directed dynamic combinatorial chemistry (DCC). PMID:23234607

  3. Treadmill walking is not equivalent to overground walking for the study of walking smoothness and rhythmicity in older adults.

    PubMed

    Row Lazzarini, Brandi S; Kataras, Theodore J

    2016-05-01

    Treadmills are appealing for gait studies, but some gait mechanics are disrupted during treadmill walking. The purpose of this study was to examine the effects of speed and treadmill walking on walking smoothness and rhythmicity of 40 men and women between the ages of 70-96 years. Gait smoothness was examined during overground (OG) and treadmill (TM) walking by calculating the harmonic ratio from linear accelerations measured at the level of the lumbar spine. Rhythmicity was quantified as the stride time standard deviation. TM walking was performed at two speeds: a speed matching the natural OG walk speed (TM-OG), and a preferred TM speed (PTM). A dual-task OG condition (OG-DT) was evaluated to determine if TM walking posed a similar cognitive challenge. Statistical analysis included a one-way Analysis of Variance with Bonferroni corrected post hoc comparisons and the Wilcoxon signed rank test for non-normally distributed variables. Average PTM speed was slower than OG. Compared to OG, those who could reach the TM-OG speed (74.3% of sample) exhibited improved ML smoothness and rhythmicity, and the slower PTM caused worsened vertical and AP smoothness, but did not affect rhythmicity. PTM disrupted smoothness and rhythmicity differently than the OG-DT condition, likely due to reduced speed. The use of treadmills for gait smoothness and rhythmicity studies in older adults is problematic; some participants will not achieve OG speed during TM walking, walking at the TM-OG speed artificially improves rhythmicity and ML smoothness, and walking at the slower PTM speed worsens vertical and AP gait smoothness. PMID:27131175

  4. Aqueous leaf extract of Ocimum gratissimum improves hematological parameters in alloxan-induced diabetic rats via its antioxidant properties

    PubMed Central

    Shittu, Shehu-Tijani Toyin; Oyeyemi, Wahab A; Lasisi, Taye J; Shittu, Seyid Alli-Siise; Lawal, Temitope T; Olujobi, Samuel T

    2016-01-01

    Objective: This study was designed to investigate the effects of Ocimum gratissimum (OG) on hematological parameters and oxidative stress in diabetic rats. Materials and Methods: Twenty-five male rats (150–200 g) were randomly grouped into five as control, normal + OG, diabetic untreated, diabetic + OG, and diabetic + glibenclamide groups. Diabetes was induced by 100 mg/kg of alloxan monohydrate in the diabetic untreated and diabetic + OG groups followed by treatment with distilled water and 400 mg/kg OG, respectively, whereas control, normal + OG, and diabetic + glibenclamide groups were treated with distilled water, 400 mg/kg OG, and 5 mg/kg glibenclamide, respectively. Body weight and fasting blood glucose level were monitored weekly. After 28 days of treatments, under anesthesia induced by 50 mg/kg sodium thiopental i.p., blood samples were obtained for hematological analysis, malondialdehyde (MDA) level determination, and superoxide dismutase (SOD) activity. Data were compared using analysis of variance and Student's t-test. Results: There was a significant decrease in the fasting blood glucose of the diabetic + OG animals compared to the diabetic untreated and the initial reduction in weight observed in this group was reversed at the end of the experiments. Packed cell volume, red blood cell count, and hemoglobin concentration were significantly increased (P < 0.05) in the diabetic + OG when compared with the untreated group. The MDA concentration was significantly lowered (P < 0.01) in the diabetic + OG group when compared with diabetic untreated while SOD activity was significantly reduced in the diabetic untreated group. Conclusion: It was concluded that OG reverses anemia secondary to alloxan-induced diabetes mellitus in rats probably via its antioxidant activity. PMID:27127737

  5. Vascular Access for Hemodialysis

    MedlinePlus

    ... short-term use. [ Top ] What is an arteriovenous fistula? An AV fistula is a connection, made by a vascular surgeon, ... vessel surgery. The surgeon usually places an AV fistula in the forearm or upper arm. An AV ...

  6. The Role of Mirk Kinase in Sarcomas

    PubMed Central

    Friedman, Eileen

    2011-01-01

    Targeting the tyrosine kinase KIT in gastrointestinal stromal tumors has led to improved treatment. Other kinases might serve as therapeutic targets in the more common forms of sarcoma. The kinase Mirk/dyrk1B is highly expressed in the vast majority of osteosarcomas and rhabdomyosarcomas and mediates their growth, as depletion of Mirk led to tumor cell apoptosis. Mirk is known to increase the expression of a series of antioxidant genes, which scavenge reactive oxygen species (ROS) within various tumor cells, mediating their survival. As a result, depleting Mirk led to increased levels of damaging ROS. Tumor cells depleted of Mirk were also sensitized to low levels of chemotherapeutic drugs that increase ROS levels. In contrast, Mirk expression is quite low in most normal cells, and Mirk depletion or embryonic knockout of Mirk did not detectably affect cell survival. Thus targeting Mirk for intervention in sarcomas might spare most normal tissues. PMID:21559261

  7. Synthesis and biological evaluation of new 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles as PI3Kα inhibitors.

    PubMed

    Bruel, Amélie; Logé, Cédric; Tauzia, Marie-Ludivine de; Ravache, Myriam; Le Guevel, Rémy; Guillouzo, Christiane; Lohier, Jean-François; Oliveira Santos, Jana Sopkova-de; Lozach, Olivier; Meijer, Laurent; Ruchaud, Sandrine; Bénédetti, Hélène; Robert, Jean-Michel

    2012-11-01

    A series of novel 5-benzylated 4-oxo-3,4-dihydro-5H-pyridazino[4,5-b]indoles was synthesized through a newly developed approach. All these compounds were evaluated against DYRK1A, CDK5 and PI3Kα and showed promising inhibitory activities against PI3Kα with most IC(50) values in the micromolar range. Among them, compound 18 was strongly considered as the most interesting compound with an IC(50) value of 0.091 μM. This series exhibited also significant anti-proliferative effects in various human cancer cell lines including those resulting in activation of the PI3K pathway. PMID:23063566

  8. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences

    PubMed Central

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C.; Rattei, Thomas; Mende, Daniel R.; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-01

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de. PMID:26582926

  9. VERTICAL STRATIFICATION OF SOIL WATER STORAGE AND RELEASE DYNAMICS IN PACIFIC NORTHWEST CONIFEROUS FORESTS

    EPA Science Inventory

    abstract for journal article We characterized vertical variation in the seasonal depletion of stored soil moisture in old-growth ponderosa pine (OG-PP, xeric), and young and old-growth Douglas-fir (Y-DF, OG-DF, mesic) forests to evaluate changes in water availability for root up...

  10. 40 CFR 432.125 - New source performance standards (NSPS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 1 mg/L (ppm). 2 Maximum of 400.... 1 Ammonia (as N) 8.0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20...

  11. 40 CFR 432.15 - New source performance standards (NSPS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the... standards for BOD5, fecal coliform, O&G, and TSS are the same as the corresponding limitations specified in... standards for BOD5, fecal coliform, O&G, and TSS are the same as the limitations specified in §...

  12. 40 CFR 432.125 - New source performance standards (NSPS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 1 mg/L (ppm). 2 Maximum of 400.... 1 Ammonia (as N) 8.0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20...

  13. 40 CFR 432.125 - New source performance standards (NSPS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 1 mg/L (ppm). 2 Maximum of 400.... 1 Ammonia (as N) 8.0 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20...

  14. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences.

    PubMed

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C; Rattei, Thomas; Mende, Daniel R; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-01

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de. PMID:26582926

  15. The low temperature oxidation of lithium thin films on HOPG by O2 and H2O

    NASA Astrophysics Data System (ADS)

    Wulfsberg, Steven M.; Koel, Bruce E.; Bernasek, Steven L.

    2016-09-01

    Lithiated graphite and lithium thin films have been used in fusion devices. In this environment, lithiated graphite will undergo oxidation by background gases. In order to gain insight into this oxidation process, thin (< 15 monolayer (ML)) lithium films on highly ordered pyrolytic graphite (HOPG) were exposed to O2(g) and H2O(g) in an ultra-high vacuum chamber. High resolution electron energy loss spectroscopy (HREELS) was used to identify the surface species formed during O2(g) and H2O(g) exposure. Auger electron spectroscopy (AES) was used to obtain the relative oxidation rates during O2(g) and H2O(g) exposure. AES showed that as the lithium film thickness decreased from 15 to 5 to 1 ML, the oxidation rate decreased for both O2(g) and H2O(g). HREELS showed that a 15 ML lithium film was fully oxidized after 9.7 L (L) of O2(g) exposure and Li2O was formed. HREELS also showed that during initial exposure (< 0.5 L) H2O(g), lithium hydride and lithium hydroxide were formed on the surface of a 15 ML lithium film. After 0.5 L of H2O(g) exposure, the H2O(g) began to physisorb, and after 15 L of H2O(g) exposure, the 15 ML lithium film was not fully oxidized.

  16. 40 CFR 432.15 - New source performance standards (NSPS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the..., fecal coliform, O&G, and TSS are the same as the corresponding limitations specified in § 432.12(a)(1... standards for BOD5, fecal coliform, O&G, and TSS are the same as the limitations specified in §...

  17. 40 CFR 432.125 - New source performance standards (NSPS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 1 mg/L (ppm). 2 Maximum of 400 MPN or CFU per... 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 Total Nitrogen 147 103 1...

  18. 40 CFR 432.15 - New source performance standards (NSPS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the..., fecal coliform, O&G, and TSS are the same as the corresponding limitations specified in § 432.12(a)(1... standards for BOD5, fecal coliform, O&G, and TSS are the same as the limitations specified in §...

  19. 40 CFR 432.125 - New source performance standards (NSPS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 1 mg/L (ppm). 2 Maximum of 400 MPN or CFU per... 4.0 BOD5 26 16 Fecal Coliform (2) (3) O&G (as HEM) 14 8.0 TSS 30 20 Total Nitrogen 147 103 1...

  20. 40 CFR 432.45 - New source performance standards (NSPS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the..., fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.42(a)(1); and standards... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  1. 40 CFR 432.45 - New source performance standards (NSPS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the..., fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.42(a)(1); and standards... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  2. Reading and Spelling Gains Following One Year of Orton-Gillingham Intervention in Singaporean Students with Dyslexia

    ERIC Educational Resources Information Center

    Lim, Lois; Oei, Adam C.

    2015-01-01

    Despite the widespread use of Orton-Gillingham (OG) based approaches to dyslexia remediation, empirical support documenting its effectiveness is lacking. Recently, Chia and Houghton demonstrated the effectiveness of the OG approach for remediation of dyslexia in Singapore. As a conceptual replication and extension of that research, we report…

  3. Dissection of the C-terminal region of E1A redefines the roles of CtBP and other cellular targets in oncogenic transformation.

    PubMed

    Cohen, M J; Yousef, A F; Massimi, P; Fonseca, G J; Todorovic, B; Pelka, P; Turnell, A S; Banks, L; Mymryk, J S

    2013-09-01

    Human adenovirus E1A makes extensive connections with the cellular protein interaction network. By doing so, E1A can manipulate many cellular programs, including cell cycle progression. Through these reprogramming events, E1A functions as a growth-promoting oncogene and has been used extensively to investigate mechanisms contributing to oncogenesis. Nevertheless, it remains unclear how the C-terminal region of E1A contributes to oncogenic transformation. Although this region is required for transformation in cooperation with E1B, it paradoxically suppresses transformation in cooperation with activated Ras. Previous analysis has suggested that the interaction of E1A with CtBP plays a pivotal role in both activities. However, some C-terminal mutants of E1A retain CtBP binding and yet exhibit defects in transformation, suggesting that other targets of this region are also necessary. To explore the roles of these additional factors, we performed an extensive mutational analysis of the C terminus of E1A. We identified key residues that are specifically required for binding all known targets of the C terminus of E1A. We further tested each mutant for the ability to both localize to the nucleus and transform primary rat cells in cooperation with E1B-55K or Ras. Interaction of E1A with importin α3/Qip1, dual-specificity tyrosine-regulated kinase 1A (DYRK1A), HAN11, and CtBP influenced transformation with E1B-55K. Interestingly, the interaction of E1A with DYRK1A and HAN11 appeared to play a role in suppression of transformation by activated Ras whereas interaction with CtBP was not necessary. This unexpected result suggests a need for revision of current models and provides new insight into transformation by the C terminus of E1A. PMID:23864635

  4. Validation of microarray data in human lymphoblasts shows a role of the ubiquitin-proteasome system and NF-kB in the pathogenesis of Down syndrome

    PubMed Central

    2013-01-01

    Background Down syndrome (DS) is a complex disorder caused by the trisomy of either the entire, or a critical region of chromosome 21 (21q22.1-22.3). Despite representing the most common cause of mental retardation, the molecular bases of the syndrome are still largely unknown. Methods To better understand the pathogenesis of DS, we analyzed the genome-wide transcription profiles of lymphoblastoid cell lines (LCLs) from six DS and six euploid individuals and investigated differential gene expression and pathway deregulation associated with trisomy 21. Connectivity map and PASS-assisted exploration were used to identify compounds whose molecular signatures counteracted those of DS lymphoblasts and to predict their therapeutic potential. An experimental validation in DS LCLs and fetal fibroblasts was performed for the most deregulated GO categories, i.e. the ubiquitin mediated proteolysis and the NF-kB cascade. Results We show, for the first time, that the level of protein ubiquitination is reduced in human DS cell lines and that proteasome activity is increased in both basal conditions and oxidative microenvironment. We also provide the first evidence that NF-kB transcription levels, a paradigm of gene expression control by ubiquitin-mediated degradation, is impaired in DS due to reduced IkB-alfa ubiquitination, increased NF-kB inhibitor (IkB-alfa) and reduced p65 nuclear fraction. Finally, the DSCR1/DYRK1A/NFAT genes were analysed. In human DS LCLs, we confirmed the presence of increased protein levels of DSCR1 and DYRK1A, and showed that the levels of the transcription factor NFATc2 were decreased in DS along with a reduction of its nuclear translocation upon induction of calcium fluxes. Conclusions The present work offers new perspectives to better understand the pathogenesis of DS and suggests a rationale for innovative approaches to treat some pathological conditions associated to DS. PMID:23830204

  5. A kinase shRNA screen links LATS2 and the pRB tumor suppressor

    PubMed Central

    Tschöp, Katrin; Conery, Andrew R.; Litovchick, Larisa; DeCaprio, James A.; Settleman, Jeffrey; Harlow, Ed; Dyson, Nicholas

    2011-01-01

    pRB-mediated inhibition of cell proliferation is a complex process that depends on the action of many proteins. However, little is known about the specific pathways that cooperate with the Retinoblastoma protein (pRB) and the variables that influence pRB's ability to arrest tumor cells. Here we describe two shRNA screens that identify kinases that are important for pRB to suppress cell proliferation and pRB-mediated induction of senescence markers. The results reveal an unexpected effect of LATS2, a component of the Hippo pathway, on pRB-induced phenotypes. Partial knockdown of LATS2 strongly suppresses some pRB-induced senescence markers. Further analysis shows that LATS2 cooperates with pRB to promote the silencing of E2F target genes, and that reduced levels of LATS2 lead to defects in the assembly of DREAM (DP, RB [retinoblastoma], E2F, and MuvB) repressor complexes at E2F-regulated promoters. Kinase assays show that LATS2 can phosphorylate DYRK1A, and that it enhances the ability of DYRK1A to phosphorylate the DREAM subunit LIN52. Intriguingly, the LATS2 locus is physically linked with RB1 on 13q, and this region frequently displays loss of heterozygosity in human cancers. Our results reveal a functional connection between the pRB and Hippo tumor suppressor pathways, and suggest that low levels of LATS2 may undermine the ability of pRB to induce a permanent cell cycle arrest in tumor cells. PMID:21498571

  6. A kinase shRNA screen links LATS2 and the pRB tumor suppressor.

    PubMed

    Tschöp, Katrin; Conery, Andrew R; Litovchick, Larisa; Decaprio, James A; Settleman, Jeffrey; Harlow, Ed; Dyson, Nicholas

    2011-04-15

    pRB-mediated inhibition of cell proliferation is a complex process that depends on the action of many proteins. However, little is known about the specific pathways that cooperate with the Retinoblastoma protein (pRB) and the variables that influence pRB's ability to arrest tumor cells. Here we describe two shRNA screens that identify kinases that are important for pRB to suppress cell proliferation and pRB-mediated induction of senescence markers. The results reveal an unexpected effect of LATS2, a component of the Hippo pathway, on pRB-induced phenotypes. Partial knockdown of LATS2 strongly suppresses some pRB-induced senescence markers. Further analysis shows that LATS2 cooperates with pRB to promote the silencing of E2F target genes, and that reduced levels of LATS2 lead to defects in the assembly of DREAM (DP, RB [retinoblastoma], E2F, and MuvB) repressor complexes at E2F-regulated promoters. Kinase assays show that LATS2 can phosphorylate DYRK1A, and that it enhances the ability of DYRK1A to phosphorylate the DREAM subunit LIN52. Intriguingly, the LATS2 locus is physically linked with RB1 on 13q, and this region frequently displays loss of heterozygosity in human cancers. Our results reveal a functional connection between the pRB and Hippo tumor suppressor pathways, and suggest that low levels of LATS2 may undermine the ability of pRB to induce a permanent cell cycle arrest in tumor cells. PMID:21498571

  7. Interaction of CtBP with adenovirus E1A suppresses immortalization of primary epithelial cells and enhances virus replication during productive infection

    SciTech Connect

    Subramanian, T.; Zhao, Ling-jun; Chinnadurai, G.

    2013-09-01

    Adenovirus E1A induces cell proliferation, oncogenic transformation and promotes viral replication through interaction with p300/CBP, TRRAP/p400 multi-protein complex and the retinoblastoma (pRb) family proteins through distinct domains in the E1A N-terminal region. The C-terminal region of E1A suppresses E1A/Ras co-transformation and interacts with FOXK1/K2, DYRK1A/1B/HAN11 and CtBP1/2 (CtBP) protein complexes. To specifically dissect the role of CtBP interaction with E1A, we engineered a mutation (DL→AS) within the CtBP-binding motif, PLDLS, and investigated the effect of the mutation on immortalization and Ras cooperative transformation of primary cells and viral replication. Our results suggest that CtBP–E1A interaction suppresses immortalization and Ras co-operative transformation of primary rodent epithelial cells without significantly influencing the tumorigenic activities of transformed cells in immunodeficient and immunocompetent animals. During productive infection, CtBP–E1A interaction enhances viral replication in human cells. Between the two CtBP family proteins, CtBP2 appears to restrict viral replication more than CtBP1 in human cells. - Highlights: • Adenovirus E1A C-terminal region suppresses E1A/Ras co-transformation. • This E1A region binds with FOXK, DYRK1/HAN11 and CtBP cellular protein complexes. • We found that E1A–CtBP interaction suppresses immortalization and transformation. • The interaction enhances viral replication in human cells.

  8. Sunitinib activates Axl signaling in renal cell cancer.

    PubMed

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

  9. Detection of induced seismicity due to oil and gas extraction in the northern Gulf of Mexico, USA

    NASA Astrophysics Data System (ADS)

    Fadugba, Oluwaseun Idowu

    Drilling operations and extraction of oil and gas (O&G) may lead to subsurface slumping or compression of sediments due to reduced vertical principal stress which may lead to small earthquakes at the drilling site. O&G extraction is common in the northern Gulf of Mexico (NGM) and only thirty-five earthquakes of magnitudes between 2.3 and 6.0 have been recorded in the area from 1974 to the present. The purpose of this research is to detect more earthquakes using stacks of seismic data from the Transportable USArray (TA) from 2011 to 2013, and determine the spatiotemporal relationship between the detected earthquakes and O&G extraction. Five new small offshore earthquakes, that may be associated with the offshore O&G production, have been detected in the data. Spatial correlation of the epicenters with offshore drilling sites shows that the earthquakes may be due to the O&G extraction.

  10. The use of the osmole gap as a screening test for the presence of exogenous substances.

    PubMed

    Purssell, Roy A; Lynd, Larry D; Koga, Yoshikata

    2004-01-01

    The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing serious adverse outcomes. The quantitative measurement of specific serum levels of these substances using gas chromatography is expensive, time consuming and generally only available at major tertiary-care facilities. Therefore, because these toxic substances are osmotically active and the measurement of serum osmolality is easily performed and more readily available, the presence of an osmole gap (OG) has been adopted as an alternative screening test. By definition, the OG is the difference between the measured serum osmolality determined using the freezing point depression (Osm(m)) and the calculated serum molarity (Mc), which is estimated from the known and readily measurable osmotically active substances in the serum, in particular sodium, urea, glucose, and potassium and ethanol (alcohol). Thus, the OG=Osm(m)-Mc, and an OG above a specific threshold (the threshold of positivity) suggests the presence of unmeasured osmotically active substances, which could be indicative of a toxic exposure. The objectives of this study were to review the principles of evaluating screening tests, the theory behind the OG as a screening test and the literature upon which the adoption of the OG as a screening test has been based. This review revealed that there have been numerous equations derived and proposed for the estimation of the Mc, with the objective of developing empirical evidence of the best equation for the determination of the OG and ultimately the utility of OG as a screening test. However, the methods and statistical analysis employed have generally been inconsistent with recommended guidelines for screening test evaluation and although many equations have been derived, they have not been appropriately validated. Specific evidence of the clinical utility of the OG requires that a threshold of positivity be

  11. The most important single factor influencing learning is what the learner already knows - What do the learner know about clouds, precipitation, wind and greenhouse effect; a short review of research from 1883 to 2009

    NASA Astrophysics Data System (ADS)

    Hansen, P. J. K.

    2009-09-01

    English environmental educators Edward Boyes and Martin Stanisstreet, staring up in 1992 and writing more than a dozen articles and book chapters - often together with researchers from other countries. Common features of Hansen, Boyes and Stanisstreet and many other researchers' discoveries up to present, are that students on all levels still exchange or confuse the greenhouse effect with the effects of the ozone layer, and many thinks that the greenhouse effect is not necessary for life on the Erath. The greenhouse effect and related topics came into secondary curriculum during the 1990-ies in many countries. The presentation will discuss some ideas of how to teach him accordingly at secondary education. Ausubel, D. P. 1968: Educational Psychology: A Cognitive View. Holt, Rinehart and Winston Inc. New York. Ausubel, D. P., J. D. Novak og H. Hanesian 1978: Educational Psychology. A Cognitive View. Second Edition. Holt, Rinehart and Winston, New York, Chicago, San Francisco, Dallas, Montreal, Toronto, London, Sydney. Hall, G. S. 1883: The Contents of Children's Minds. Princeton Review. Vol.XI, 1883, s.249-272. Piaget, J. 1930: The Child's Conception of Physical Causality. Kegan Paul, Trench, Trubner & Co.LTD, London. New York: Harcourt Brace & Company. Oversettelse av La causalité physique chez l'enfant fra 1927. Piaget, J. 1977: The Child's Conception of the World. 2. Edition. Paladin, London. Oversettelse av La représentation du monde chez l'enfant fra 1926. Boyes, E. og M. Stanisstreet 1992: Students' Perceptions of Global Warming. International Journal of Environmental Studies. 1992, Vol.42, s.287-300. Hansen, P. J. K. 1989: Spørsmål om vær og meteorologi til elever i 9.klasse i Oslo-området i 1989. Oslo lærerhøgskoles skriftserie. Hefte nr.2/92, Oslo (Nå Høgskolen i Oslo, Avdeling for lærerutdanning). 1.opplag 1989, Oslo lærerhøgskole, Oslo. Hansen, P. J. K. 2009: Knowledge about the greenhouse effect and the effects of the ozone layer among Norwegian

  12. The most important single factor influencing learning is what the learner already knows - What do the learner know about clouds, precipitation, wind and greenhouse effect; a short review of research from 1883 to 2009

    NASA Astrophysics Data System (ADS)

    Hansen, P. J. K.

    2009-09-01

    English environmental educators Edward Boyes and Martin Stanisstreet, staring up in 1992 and writing more than a dozen articles and book chapters - often together with researchers from other countries. Common features of Hansen, Boyes and Stanisstreet and many other researchers' discoveries up to present, are that students on all levels still exchange or confuse the greenhouse effect with the effects of the ozone layer, and many thinks that the greenhouse effect is not necessary for life on the Erath. The greenhouse effect and related topics came into secondary curriculum during the 1990-ies in many countries. The presentation will discuss some ideas of how to teach him accordingly at secondary education. Ausubel, D. P. 1968: Educational Psychology: A Cognitive View. Holt, Rinehart and Winston Inc. New York. Ausubel, D. P., J. D. Novak og H. Hanesian 1978: Educational Psychology. A Cognitive View. Second Edition. Holt, Rinehart and Winston, New York, Chicago, San Francisco, Dallas, Montreal, Toronto, London, Sydney. Hall, G. S. 1883: The Contents of Children's Minds. Princeton Review. Vol.XI, 1883, s.249-272. Piaget, J. 1930: The Child's Conception of Physical Causality. Kegan Paul, Trench, Trubner & Co.LTD, London. New York: Harcourt Brace & Company. Oversettelse av La causalité physique chez l'enfant fra 1927. Piaget, J. 1977: The Child's Conception of the World. 2. Edition. Paladin, London. Oversettelse av La représentation du monde chez l'enfant fra 1926. Boyes, E. og M. Stanisstreet 1992: Students' Perceptions of Global Warming. International Journal of Environmental Studies. 1992, Vol.42, s.287-300. Hansen, P. J. K. 1989: Spørsmål om vær og meteorologi til elever i 9.klasse i Oslo-området i 1989. Oslo lærerhøgskoles skriftserie. Hefte nr.2/92, Oslo (Nå Høgskolen i Oslo, Avdeling for lærerutdanning). 1.opplag 1989, Oslo lærerhøgskole, Oslo. Hansen, P. J. K. 2009: Knowledge about the greenhouse effect and the effects of the ozone layer among Norwegian

  13. Morphology and structure of extremely red objects at z ∼ 1 in the CANDELS-COSMOS field

    NASA Astrophysics Data System (ADS)

    Fang, Guan-Wen; Ma, Zhong-Yang; Chen, Yang; Kong, Xu

    2015-06-01

    Using high-resolution HST/Wide Field Camera 3 F125W imaging from the CANDELS-COSMOS field, we report the structural and morphological properties of extremely red objects (EROs) at z ∼ 1. Based on the UVJ color criteria, we separate EROs into two types: old passive galaxies (OGs) and dusty star-forming galaxies (DGs). For a given stellar mass, we find that the mean size of OGs (DGs) is smaller by a factor of ∼ 2 (1.5) than that of present-day early-type (late-type) galaxies at a rest-frame optical wavelength. We derive the average effective radii of OGs and DGs, corresponding to 2.09 ± 1.13 kpc and 3.27 ± 1.14 kpc, respectively. Generally, the DGs are heterogeneous, with mixed features including bulges, disks and irregular structures, with relatively high M20, large size and low G. By contrast, OGs have elliptical-like compact morphologies with lower M20, smaller size and higher G, indicating a more concentrated and symmetric spatial extent of the stellar population distribution in OGs than DGs. These findings imply that OGs and DGs have different evolutionary processes, and that the minor merger scenario is the most likely mechanism for the structural properties of OGs. However, the size evolution of DGs is possibly due to the secular evolution of galaxies. Supported by the National Natural Science Foundation of China.

  14. A comparison of surgical procedures and postoperative cares for minimally invasive laparoscopic gastrectomy and open gastrectomy in gastric cancer

    PubMed Central

    Tang, Hong-Na; Hu, Jun-Hong

    2015-01-01

    Minimally invasive, laparoscopic gastrectomy (LG) has assumed an ever-expanding role in gastric cancer treatment. Accumulating data so far seem to suggest that LG is at least a viable alternative of conventional open gastrectomy (OG) in different contexts. However, even though reviews and meta-analyses have compared the advantages and limitations of each option, it is still controversial whether LG is a better alternative to OG, especially in advanced gastric cancer (AGC). The major goal of this study is to evaluate the readouts of LG, in comparison with OG. A literature search was performed for studies published from 2009 to 2013. Medical records of 20868 gastric cancer patients from 32 independent studies were reviewed and analyzed. All 32 studies concluded that LG is at least comparable with OG. LG is superior to OG in offering less blood loss, shorter hospital stay, and lower risk of complications, although LG is probably inferior in operative time, and not different from OG in mortality. Considering the merits and the potential future technical improvement, it is reasonable to speculate that LG may eventually replace OG in most clinical contexts. PMID:26379823

  15. Decolourization of the azo dye Orange G in aqueous solution via a heterogeneous Fenton-like reaction catalysed by goethite.

    PubMed

    Wu, Honghai; Dou, Xiaowen; Deng, Dayi; Guan, Yufeng; Zhang, Liguo; He, Guangping

    2012-01-01

    Decolourization of the azo dye Orange G (OG) was investigated by using goethite/H2O2 as a heterogeneous Fenton-like reagent. Five principle operational parameters, namely pH, ion strength, concentrations ofgoethite (alpha-FeOOH) and hydrogen peroxide (H2O2), and reaction temperature, were taken into account to investigate how these controlling factors mediated OG decolourization. Goethite surfaces catalysed a Fenton-like reaction responsible for decolourizing OG following pseudo-first-order kinetics (R2 > 0.964). This process was effective but seriously impacted by the medium pH and the dosages of both alpha-FeOOH and H2O2. The decolourization efficiencies of OG increased with the decrease of solution pH and NaCl (chloride ion) concentration and/or the increase of H2O2. The acidic aqueous medium conditions were likely favourable due to the surface adsorption of the negatively charged OG leading to the promotion of decolourizing OG. The apparent activation energy (E) for this reaction was 42.18 kJ mol(-1), a relatively low value. This is consistent with the OG decolourization being enhanced with the reaction temperature increase. PMID:22988614

  16. Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases

    PubMed Central

    Nangia-Makker, Pratima; Raz, Tirza; Tait, Larry; Shekhar, Malathy P.V.; Li, Hong; Balan, Vitaly; Makker, Hemanckur; Fridman, Rafael; Maddipati, Krishnarao; Raz, Avraham

    2013-01-01

    Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast comedo-ductal carcinoma in situ (comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide and recombinant galectin-3 as MMP substrates. Mice fed on OG-supplemented drinking water showed no adverse effects compared with control. These data suggest that OG is non-toxic and that the anti-cancer therapeutic activity of OG may in part be contributed by its MMP inhibitory activity. PMID:23380593

  17. Land-use change effects on soil quality in Montilla-Moriles DO, Southern Spain

    NASA Astrophysics Data System (ADS)

    Martín-Carrillo, M.; Parras-Alcántara, L.; Lozano-García, B.

    2013-02-01

    The agricultural Mediterranean areas are dedicated to arable crops (AC), but in the last few decades, a significant number of AC has a land use change (LUC) to olive grove cultivations (OG) and vineyards (V). A field study was conducted to determine the long-term effects (46 yr) of LUC (AC by OG and V) and to determine soil organic carbon (SOC), total nitrogen (TN), C:N ratio and their stratification across the soil entire profile, in Montilla-Moriles denomination of origin (DO), in Calcic-Chromic Luvisols (LVcc/cr), an area under semiarid Mediterranean conditions. The experimental design consisted of studying the LUC on one farm between 1965 and 2011. Originally, only AC was farmed in 1965, but OG and V were farmed up to now (2011). This LUC principally affected the thickness horizon, texture, bulk density, pH, organic matter, organic carbon, total nitrogen and C:N ratio. The LUC had a negative impact in the soil, affecting the SOC and TN stocks. The conversion from AC to V and OG involved the loss of the SOC stock (52.7% and 64.9% to V and OG, respectively) and the loss of the TN stock (42.6% and 38.1% to V and OG, respectively). With respect to the soil quality, the effect was opposite; 46 yr after LUC improved the soil quality, increasing the stratification ratio (in V and OG) of SOC, TN and C:N ratio.

  18. Impacts of land use change in soil carbon and nitrogen in a Mediterranean agricultural area (Southern Spain)

    NASA Astrophysics Data System (ADS)

    Parras-Alcántara, L.; Martín-Carrillo, M.; Lozano-García, B.

    2013-05-01

    The agricultural Mediterranean areas are dedicated to arable crops (AC), but in the last decades, a significant number of AC has led to a land use change (LUC) to olive grove (OG) and vineyards (V). A field study was conducted to determine the long-term effects (46 years) of LUC (AC by OG and V) and to determine soil organic carbon (SOC), total nitrogen (TN), C : N ratio and their stratification across the soil entire profile, in Montilla-Moriles denomination of origin (D.O.), in Calcic-Chromic Luvisols (LVcc/cr), an area under semiarid Mediterranean conditions. The experimental design consisted of studying the LUC on one farm between 1965 and 2011. Originally, only AC was farmed in 1965, but OG and V were farmed up to now (2011). This LUC principally affected the horizon thickness, texture, bulk density, pH, organic matter, organic carbon, total nitrogen and C : N ratio. The LUC had a negative impact in the soil, affecting the SOC and TN stocks. The conversion from AC to V and OG involved the loss of the SOC stock (52.7% and 64.9% to V and OG respectively) and the loss of the TN stock (42.6% and 38.1% to V and OG respectively). With respect to the stratification ratios (SRs), the effects were opposite; 46 years after LUC increased the SRs (in V and OG) of SOC, TN and C : N ratio.

  19. Studies of DNA Aptamer OliGreen and PicoGreen Fluorescence Interactions in Buffer and Serum.

    PubMed

    Bruno, John G; Sivils, Jeffrey C

    2016-07-01

    Spectrofluorometric and emission peak titration and timed studies of OliGreen (OG) and PicoGreen (PG) were conducted in Tris EDTA (TE) buffer, pooled rat and fetal bovine serum with two different aptamers of 72 and 192 bases in length to determine if OG or PG were suitable for aptamer pharmacokinetic (PK) studies in sera. Results indicated that OG and PG detected the single-stranded (ss) and double-stranded (ds) stem-loop structures of the two aptamers quite well in TE with reliable standard curves having exponential character (or several linear detection regions) up to 1 μg/ml of aptamer DNA with detection limits of ~1 ng/ml. The intensity of OG and PG staining appeared to correlate with the number and percentage of ss and ds bases in each aptamer. OG and PG fluorescence in pooled rat serum or fetal bovine serum (FBS) did not titer as a function of DNA aptamer concentration from 1 μg/ml to 1 ng/ml. This lack of OG or PG aptamer assays in serum is contrary to most published reports of OG or PG assays for ss antisense oligonucleotides, ds PCR amplicons or other types of DNA in serum or plasma. Further studies suggested that the lack of OG and PG assay titration in serum might not be entirely due to aptamer degradation from nucleases in serum since the fluorescence signals in serum appeared relatively stable over time from 30 min to 4 hours. A hypothesis is presented which attributes the inability of OG or PG to assay aptamers in serum to a combination of high blue-green autofluorescence in serum with possible serum nuclease degradation of aptamers over time and the changing aptamer to serum protein ratio coupled to nonspecific binding of serum proteins to aptamers thereby possibly changing aptamer conformations as a function of aptamer concentration during titration experiments. PMID:27209004

  20. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus PII signal transduction protein

    PubMed Central

    Fokina, Oleksandra; Chellamuthu, Vasuki-Ranjani; Forchhammer, Karl; Zeth, Kornelius

    2010-01-01

    PII proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by PII and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis, N-acetyl-glutamate kinase (NAGK), is a major PII target, whose activity responds to 2-OG via PII. Here we show structures of the Synechococcus elongatus PII protein in complex with ATP, Mg2+, and 2-OG, which clarify how 2-OG affects PII–NAGK interaction. PII trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per PII trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a Mg2+ ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the PII target. Structures of PII trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which PII senses effectors in a wide range of concentrations. PMID:21041661

  1. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus PII signal transduction protein.

    PubMed

    Fokina, Oleksandra; Chellamuthu, Vasuki-Ranjani; Forchhammer, Karl; Zeth, Kornelius

    2010-11-16

    P(II) proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by P(II) and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis, N-acetyl-glutamate kinase (NAGK), is a major P(II) target, whose activity responds to 2-OG via P(II). Here we show structures of the Synechococcus elongatus P(II) protein in complex with ATP, Mg(2+), and 2-OG, which clarify how 2-OG affects P(II)-NAGK interaction. P(II) trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per P(II) trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a Mg(2+) ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the P(II) target. Structures of P(II) trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which P(II) senses effectors in a wide range of concentrations. PMID:21041661

  2. Use of benzo analogs to enhance antimycotic activity of kresoxim methyl for control of aflatoxigenic fungal pathogens

    PubMed Central

    Kim, Jong H.; Mahoney, Noreen; Chan, Kathleen L.; Campbell, Bruce C.; Haff, Ronald P.; Stanker, Larry H.

    2014-01-01

    The aim of this study was to examine two benzo analogs, octylgallate (OG) and veratraldehyde (VT), as antifungal agents against strains of Aspergillus parasiticus and A.flavus (toxigenic or atoxigenic). Both toxigenic and atoxigenic strains used were capable of producing kojic acid, another cellular secondary product. A. fumigatus was used as a genetic model for this study. When applied independently, OG exhibits considerably higher antifungal activity compared to VT. The minimum inhibitory concentrations (MICs) of OG were 0.3–0.5 mM, while that of VT were 3.0–5.0 mM in agar plate-bioassays. OG or VT in concert with the fungicide kresoxim methyl (Kre-Me; strobilurin) greatly enhanced sensitivity of Aspergillus strains to Kre-Me. The combination with OG also overcame the tolerance of A. fumigatus mitogen-activated protein kinase (MAPK) mutants to Kre-Me. The degree of compound interaction resulting from chemosensitization of the fungi by OG was determined using checkerboard bioassays, where synergistic activity greatly lowered MICs or minimum fungicidal concentrations. However, the control chemosensitizer benzohydroxamic acid, an alternative oxidase inhibitor conventionally applied in concert with strobilurin, did not achieve synergism. The level of antifungal or chemosensitizing activity was also “compound—strain” specific, indicating differential susceptibility of tested strains to OG or VT, and/or heat stress. Besides targeting the antioxidant system, OG also negatively affected the cell wall-integrity pathway, as determined by the inhibition of Saccharomyces cerevisiae cell wall-integrity MAPK pathway mutants. We concluded that certain benzo analogs effectively inhibit fungal growth. They possess chemosensitizing capability to increase efficacy of Kre-Me and thus, could reduce effective dosages of strobilurins and alleviate negative side effects associated with current antifungal practices. OG also exhibits moderate antiaflatoxigenic activity. PMID

  3. Nanopore Detection of 8-Oxoguanine in the Human Telomere Repeat Sequence

    PubMed Central

    2015-01-01

    The human telomere repeat sequence 5′-TTAGGG-3′ is a hot spot for oxidation at guanine, yielding 8-oxo-7,8-dihydroguanine (OG), a biomarker of oxidative stress. Telomere shortening resulting from oxidation will ultimately induce cellular senescence. In this study, α-hemolysin (α-HL) nanopore technology was applied to detect and quantify OG in the human telomeric DNA sequence. This repeat sequence adopts a basket G-quadruplex in the NaCl electrolyte used for analysis that enters the α-HL channel, slowly unfolds, and translocates. The basket fold containing OG disrupts the structure, leading to >10× increase in the unfolding kinetics without yielding a detectable current pattern. Therefore, detection of OG with α-HL required labeling of OG with aminomethyl-[18-crown-6] using a mild oxidant. The labeled OG yielded a pulse-like signal in the current vs time trace when the DNA strand was electrophoretically passed through α-HL in NaCl electrolyte. However, the rate of translocation was too slow using NaCl salts, leading us to further refine the method. A mixture of NH4Cl and LiCl electrolytes induced the propeller fold that unravels quickly outside the α-HL channel. This electrolyte allowed observation of the labeled OG, while providing a faster recording of the currents. Lastly, OG distributions were probed with this method in a 120-mer stretch of the human telomere sequence exposed to the cellular oxidant 1O2. Single-molecule profiles determined the OG distributions to be random in this context. Application of the method in nanomedicine can potentially address many questions surrounding oxidative stress and telomere attrition observed in various disease phenotypes including prostate cancer and diabetes. PMID:25768204

  4. Basic characterization of avian β-defensin genes in the Japanese quail, Coturnix japonica.

    PubMed

    Ishige, Taichiro; Hara, Hiromi; Hirano, Takashi; Mannen, Hideyuki; Kono, Tomohiro; Hanzawa, Kei

    2016-03-01

    In this study, we identified a cluster of 14 avian β-defensins (AvBD; approximately 66 kbp) in the Japanese quail, Coturnix japonica. Except for AvBD12 (CjAvBD12) and -13, the CjAvBDs coding sequences exhibited greater than 78.0% similarity to the respective orthologous chicken AvBD genes (GgAvBD). The putative amino acid sequence encoded by each CjAvBD contained six cysteine residues and the GXC (X1-2) motif considered essential for the β-defensin family. Each CjAvBDs also formed a sub-group with the respective orthologous genes of various bird species in a phylogenetic tree analysis. Synteny between the CjAvBD cluster and GgAvBD cluster was confirmed. The CjAvBD cluster was mapped on the long-arm end of chromosome 3 by linkage analysis based on single nucleotide polymorphisms (SNPs) of CjAvBD1 and CjAvBD12 (approximately 46 kbp), as well as GgAvBD cluster. We also confirmed that CjAvBD1, -4, -5, -9, and -10 are transcribed in 20 tissues, including immune and digestive tissues. However, our experimental data indicated that the CjAvBD cluster lacks the AvBD3 and -7 loci, whereas the CjAvBD101α, -101β, and -101θ loci arose from gene duplication of the AvBD6 orthologous locus in the CjAvBD cluster after differentiation between Coturnix - Gallus. PMID:26338292

  5. The reverse J arteriovenous graft configuration for hemodialysis access: rationale, technique, and outcomes.

    PubMed

    Cull, David L; Carsten, Christopher G; Kalbaugh, Corey A; York, John W; Campbell, Ted R; Cass, Anna L; Taylor, Spence M

    2008-07-01

    The long-term survival of patients on hemodialysis is often limited by the exhaustion of vascular access sites. A fundamental principle of vascular access surgery is that the arteriovenous (AV) access be placed as far distally in the arm as possible. This principle enhances the secondary patency of the AV grafts by preserving the proximal veins for AV graft revision and provides venous outflow for a new AV access to be placed more proximally in the extremity. The standard straight and looped AV graft configurations violate this principle by bypassing long segments of vein in the extremity that could be used for AV graft revision or new AV graft placement. We have developed a novel AV graft configuration that preserves venous outflow and enhances the longevity of each AV access site. The purpose of this review is to describe the reverse J AV graft technique and to report our outcomes with the procedure. Between February 2004 and April 2007, 26 AV grafts were placed using the reverse J configuration. Eighteen (69%) AV grafts were placed in the upper arm, 7 (27%) were placed in the forearm, and 1 (4%) was placed in the thigh. Median follow-up was 320 days. The secondary AV graft patency was 90 per cent at 6 months, 84 per cent at 12 months, and 84 per cent at 18 months. Five AV grafts were subsequently revised to a loop configuration. Overall patient survival was 85 per cent at 6 months, 68 per cent at 12 months, and 62 per cent at 18 months. Compared with the standard straight and looped AV graft configurations, the reverse J AV graft configuration preserves the length of venous outflow in the extremity for AV graft revision or new AV graft placement. Therefore, the reverse J configuration enhances the secondary patency of AV graft patency and AV access site longevity. PMID:18646480

  6. Podzol development in S Norway - a soil chronosequence of 31 pedons covering soil ages from 85 to 9650 years

    NASA Astrophysics Data System (ADS)

    Sauer, Daniela; Svendgård-Stokke, Siri; Sperstad, Ragnhild; Sørensen, Rolf; Fuchs, Markus; Gebers, Henrik; Schülli-Maurer, Isabelle

    2013-04-01

    horizons. The mineralogical composition of the parent material is dominated by quartz and feldspars, whereby the feldspar grains show features of proceeding weathering with time. In addition to podzolisation features, illuvial clay is observed below the Bs horizons. Apparently, the sand is sufficiently buffered during the first millennia of soil formation so that acidification proceeds slowly enough to allow for clay translocation prior to podzolisation. Reference Sørensen, R., Høeg, H.I., Henningsmoen, K.E., Skog, G., Labowsky, S.F., Stabell, B. (2012): Utviklingen av det senglasiale og tidlig preboreale landskapet og vegetasjonen omkring steinalderboplassene ved Pauler, Larvik kommune, Vestfold. In: Jaksland, L. (Ed.), E18 Brunlaneprospektet. Varia 79. Kulturhistorisk Museum, University of Oslo.

  7. Micromorphological changes over time observed in the Vestfold Podzol chronosequence, SE Norway

    NASA Astrophysics Data System (ADS)

    Sauer, Daniela; Musztyfaga, Elżbieta; Sørensen, Rolf; Svendgård-Stokke, Siri; Rennert, Thilo; Sperstad, Ragnhild; Fuchs, Markus

    2016-04-01

    addition, micromorphological analysis shows that clay translocation took place prior to strong acidification and podzolisation in many profiles. In some rare cases, clay coatings are observed even on top of spodic material, suggesting that - at least to minor extent - translocation of coarse clay may take place even contemporarily to podzolisation. This apparent contradiction can be explained by different depths of mobilisation of metal-organic complexes and clay. Apparently, even when the upper, strongly acid part of the soils is already subject to podzolisation, acidification and Al saturation at some depth are still not as advanced as further up in the profile and still allow for clay mobilisation. In addition, cappings of coarse clay and fine silt on top of larger grains suggest that water flushing through the coarse voids of the sandy material, e.g., after snow-melt, may sweep down also clay particles in a not completely dispersed state. In this way, clay translocation might take place also outside the pH range that is usually considered suitable for clay migration. Reference Sørensen, R., Høeg, H.I., Henningsmoen, K.E., Skog, G., Labowsky, S.F., Stabell, B., 2012. Utviklingen av det senglasiale og tidlig preboreale landskapet og vegetasjonen omkring steinalderboplassene ved Pauler, Larvik kommune, Vestfold. In: Jaksland, L. (Ed.), E18 Brunlaneprospektet. Varia 79. Kulturhistorisk Museum, University of Oslo.

  8. Overview of Ground Station 1 of the NASA space communications and navigation program

    NASA Astrophysics Data System (ADS)

    Roberts, W. T.; Antsos, D.; Croonquist, A.; Piazzolla, S.; Roberts, L. C.; Garkanian, V.; Trinh, T.; Wright, M. W.; Rogalin, R.; Wu, J.; Clare, L.

    2016-03-01

    Optical Ground Station 1 (OGS1) is the first of a new breed of dedicated ground terminals to support NASA's developing space-based optical communications infrastructure. It is based at NASA's Optical Communications Telescope Laboratory (OCTL) at the Table Mountain Observatory near Wrightwood, CA. The system will serve as the primary ground station for NASA's Laser Communications Relay Demonstration (LCRD) experiment. This paper presents an overview of the OCTL telescope facility, the OGS1 ground-based optical communications systems, and the networking and control infrastructure currently under development. The OGS1 laser safety systems and atmospheric monitoring systems are also briefly described.

  9. Severe suppression of Frzb/sFRP3 transcription in osteogenic sarcoma.

    PubMed

    Mandal, Deendayal; Srivastava, Alok; Mahlum, Eric; Desai, Dinakar; Maran, Avudaiappan; Yaszemski, Michael; Jalal, Syed M; Gitelis, Steven; Bertoni, Franco; Damron, Tim; Irwin, Ronald; O'connor, Mary; Schwartz, Herbert; Bolander, Mark E; Sarkar, Gobinda

    2007-01-15

    Deciphering the molecular basis of cancer is critical for developing novel diagnostic and therapeutic strategies. To better understand the early molecular events involving osteogenic sarcoma (OGS), we have initiated a program to identify potential tumor suppressor genes. Expression profiling of total RNA from ten normal bone cell lines and eleven OGS-derived cell lines by microarray showed 135-fold lower expression of FRZB/sFRP3 mRNA in OGS cells compared to bone cells; this down-regulation of Frzb/sFRP3 mRNA expression was found to be serum-independent. Subsequently, fourteen OGS biopsy specimens showed nine-fold down-regulation of Frzb/sFRP3 mRNA expression compared to expression in eight normal bone specimens as determined by microarray. FRZB /sFRP3 protein level was also found to be at a very low level in 4/4 OGS cell lines examined. Quantitation by RT-PCR indicated approximately 70% and approximately 90% loss of Frzb/sFRP3 mRNA expression in OGS biopsy specimens and OGS-derived cell lines respectively, compared to expression in bone (p<0.0001). Hybridization experiments of a cDNA microarray containing paired normal and tumor specimens from nineteen different organs did not show any significant difference in the level of Frzb/sFRP3 mRNA expression between the normal and the corresponding tumor tissues. Exogenous expression of FRZB/sFRP3 mRNA in two OGS-derived cell lines lacking endogenous expression of the mRNA produced abundant mRNA from the exogenous gene, eliminating degradation as a possibility for very low level of FRZB/sFRP3 mRNA in OGS specimens. Results from PCR-based experiments suggest that the FRZB/sFRP3 gene is not deleted in OGS cell lines, however, karyotyping shows gross abnormalities involving chromosome 2 (location of the FRZB gene) in five of twelve OGS-derived cell lines. Together, these data suggest a tumor-suppressive potential for FRZB/sFRP3 in OGS. PMID:17079093

  10. Bedomning Av Kommunikativ Formaga Hos Personer Med Utvecklingsstorning. Teknik, Kommunikation, Handikapp Forskningsrapport nr 12 (Assessment of the Communicative Ability in Persons with Mental Retardation. Technology, Communication, Disability Research Report No. 12). TeleCommunity, RACE 2033 (Research in Advanced Communications Technologies in Europe).

    ERIC Educational Resources Information Center

    Brodin, Jane; Thurfjell, Fredrik

    This report was developed as part of a Swedish study to examine whether videotelephones can be used to develop the communicative ability of individuals with mental retardation and whether access to telecommunications increased the possibilities of social integration. Communication was viewed as sharing a feeling, action, or experience with another…

  11. Agreement between the Regents of the University of California (Los Alamos National Laboratory (LANL)) and the A.V. Topchiev Institute of Petrochemical Synthesis (TIPS), the Russian Academy of Sciences, Number 8992Q0004-35. Final report, Task order 001: Subprogram PTMSP and Subprogram Predictions.

    SciTech Connect

    1995-12-31

    In order to develop the conditions for preparing polymers with different molecular masses, the authors continued their investigation of TMSP (1-(trimethylsilyl)-1-propyne) polymerization catalyzed by TaCl{sub 5} and TaCl{sub 5}/BuLi at various ratios of VTMS (regulator of molecular mass of the polymer) : catalyst. They also studied the effect of the structure of silahydrocarbon on the process of TMSP polymerization. To this end, they carried out polymerization of TMSP in the presence of additives of vinylphenyldimethylsilane and vinylallyldimethylsilane. The conditions of experiments and the results obtained are shown. The method for controlling the molecular mass of PTMSP makes it possible to prepare PTMSP suitable for manufacture of both flat membranes and hollow fibers. The paper also describes the experimental study of PTMSP gas permeability, gas sorption in PTMSP, and a computer program for the prediction of all gas permeability parameters of polymers.

  12. Studenters fritids--och motionsvanor i Umea och Madison. Ett bidrag till forstaelsen av Pierre Bourdieus vetenskapliga metodologi. Akademiska avhanlingar, Pedagogiska institutionen Nr. 58 (Leisure and Exercise Habits among Students in Umea and Madison. A Contribution to the Understanding of Pierre Bourdieu's Scientific Methodology. Academic Dissertation, Faculty of Social Sciences No. 58).

    ERIC Educational Resources Information Center

    Lofgren, Kent

    This study, presented in Swedish with an English summary, analyzed differences between student groups at Umea University, Sweden, and the University of Wisconsin-Madison in terms of study situations, experiences of the university environment, exercise and sports activities, and the connections between study and leisure time activities. The study…

  13. 40 CFR 432.117 - Effluent limitations attainable by the application of the best control technology for...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... BOD5, TSS, O&G (as HEM), and fecal coliform are the same as the corresponding limitation specified...

  14. 40 CFR 432.127 - Effluent limitations attainable by the application of the best control technology for...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... BOD5, TSS, O&G (as HEM), and fecal coliform are the same as the corresponding limitation specified...

  15. Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases*

    PubMed Central

    Markolovic, Suzana; Wilkins, Sarah E.; Schofield, Christopher J.

    2015-01-01

    The post-translational hydroxylation of prolyl and lysyl residues, as catalyzed by 2-oxoglutarate (2OG)-dependent oxygenases, was first identified in collagen biosynthesis. 2OG oxygenases also catalyze prolyl and asparaginyl hydroxylation of the hypoxia-inducible factors that play important roles in the adaptive response to hypoxia. Subsequently, they have been shown to catalyze N-demethylation (via hydroxylation) of Nϵ-methylated histone lysyl residues, as well as hydroxylation of multiple other residues. Recent work has identified roles for 2OG oxygenases in the modification of translation-associated proteins, which in some cases appears to be conserved from microorganisms through to humans. Here we give an overview of protein hydroxylation catalyzed by 2OG oxygenases, focusing on recent discoveries. PMID:26152730

  16. What Is Coronary Angiography?

    MedlinePlus

    ... OG-rah-fee) is a test that uses dye and special x rays to show the insides ... the coronary arteries. Overview During coronary angiography, special dye is released into the bloodstream. The dye makes ...

  17. Chemistry union unveils names of four new elements

    NASA Astrophysics Data System (ADS)

    Johnston, Hamish

    2016-07-01

    The periodic table could soon be graced by four new symbols – Nh, Mc, Ts and Og – after the International Union of Pure and Applied Chemistry (IUPAC) unveiled its proposed names for the four most recently discovered elements.

  18. International Space Station United States Orbital Segment Oxygen Generation System On-Orbit Operational Experience

    NASA Technical Reports Server (NTRS)

    Erickson, Robert J.; Howe, John, Jr.; Kulp, Galen W.; VanKeuren, Steven P.

    2008-01-01

    The International Space Station (ISS) United States Orbital Segment (USOS) Oxygen Generation System (OGS) was originally intended to be installed in ISS Node 3. The OGS rack delivery was accelerated, and it was launched to ISS in July of 2006 and installed in the US Laboratory Module. Various modification kits were installed to provide its interfaces, and the OGS was first activated in July of 2007 for 15 hours, In October of 2007 it was again activated for 76 hours with varied production rates and day/night cycling. Operational time in each instance was limited by the quantity of feedwater in a Payload Water Reservoir (PWR) bag. Feedwater will be provided by PWR bag until the USOS Water Recovery System (WRS) is delivered to SS in fall of 2008. This paper will discuss operating experience and characteristics of the OGS, as well as operational issues and their resolution.

  19. Effects of feeding wheat straw or orchardgrass at ad libitum or restricted intake during the dry period on postpartum performance and lipid metabolism.

    PubMed

    Litherland, N B; Weich, W D; Hansen, W P; Linn, J G

    2012-12-01

    The objectives of this study were to investigate the effects of forage source [wheat straw (WS) or orchardgrass hay (OG)] and total amount of diet dry matter fed [ad libitum or restricted to 70% of predicted dry matter intake (DMI)] prepartum on postpartum performance. The study design was a 2×2 factorial design with 10 cows per treatment. Treatments were WS total mixed ration (TMR) ad libitum, OG TMR ad libitum, WS TMR restricted, and OG TMR restricted. The WS TMR (dry matter basis) contained 30% WS, 20.7% corn silage, 10.0% alfalfa hay, 18.2% ground corn, 16.8% soybean meal, and 4.3% molasses mineral mix (14.7% CP, 1.5 Mcal/kg of net energy for lactation, 37.0% neutral detergent fiber). The OG TMR contained 30% OG, 46.2% corn silage, 10.0% alfalfa hay, 9.5% soybean meal, and 4.3% molasses (14.2% CP, 1.5 Mcal/kg of net energy for lactation, 41.0% neutral detergent fiber). Cows received 1 lactation diet after calving (17.7% CP, 1.6 Mcal/kg of net energy for lactation, 27.3% neutral detergent fiber). Total diet DMI prepartum was higher for ad libitum than for restricted as designed, but forage source had no effect on DMI. Total tract apparent digestibilities of DM and NDF were greater for OG than for WS. Postpartum DMI expressed as a percentage of body weight for the first week of lactation was higher for ad libitum than for restricted diets. Postpartum DMI during the first 30 d of lactation was higher for OG than for WS, but no effect was observed for the amount fed prepartum. Milk yield during the first week of lactation was higher for OG than for WS; however, during the first 30 d, 3.5% fat-corrected milk yield and yield of milk fat were highest for OG TMR restricted and WS TMR ad libitum. Prepartum treatments had a limited effect on pre- and postpartum lipid metabolism; however, cows fed WS TMR ad libitum had the highest postpartum β-hydroxybutyrate. Eating behavior was observed by 10-min video scans of 24-h video surveillance for 5d pre- and postpartum

  20. Investigation into the High Voltage Shutdown of the Oxygen Generator System in the International Space Station

    NASA Technical Reports Server (NTRS)

    Carpenter, Joyce E.; Gentry, Gregory J.; Diderich, Greg S.; Roy, Robert J.; Golden, John L.; VanKeuren, Steve; Steele, John W.; Rector, Tony J.; Varsik, Jerome D.; Montefusco, Daniel J.; Wilson, Mark E.; Worthy, Erica S.

    2012-01-01

    The Oxygen Generation System (OGS) Hydrogen Dome Assembly Orbital Replacement Unit (ORU) serial number 00001 suffered a cell stack high-voltage shutdown on July 5, 2010. The Hydrogen Dome Assembly ORU was removed and replaced with the on-board spare ORU serial number 00002 to maintain OGS operation. The Hydrogen Dome Assembly ORU was returned from ISS on STS-133/ULF-5 in March 2011 with test, teardown and evaluation (TT&E) and failure analysis to follow.

  1. 40 CFR 432.82 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart must achieve... Fecal Coliform (2) (3) O&G 4 0.22 0.11 TSS 0.74 0.37 1 Pounds per 1000 lbs (or g/kg) of finished product... pounds per year of finished products must achieve the limitations for BOD5, fecal coliform, O&G, and...

  2. 40 CFR 432.82 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart must achieve... Fecal Coliform (2) (3) O&G 4 0.22 0.11 TSS 0.74 0.37 1 Pounds per 1000 lbs (or g/kg) of finished product... pounds per year of finished products must achieve the limitations for BOD5, fecal coliform, O&G, and...

  3. 40 CFR 432.25 - New source performance standards (NSPS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specified in 40 CFR 122.29(d)(1) after which it must achieve the effluent limitations specified in §§ 432.22... standards for BOD5, fecal coliform, O&G, and TSS are the same as the limitations specified in § 432.22(a)(1... on-site, the standards for BOD5, fecal coliform, O&G, and TSS are the same as the...

  4. 40 CFR 432.25 - New source performance standards (NSPS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specified in 40 CFR 122.29(d)(1) after which it must achieve the effluent limitations specified in §§ 432.22... standards for BOD5, fecal coliform, O&G, and TSS are the same as the limitations specified in § 432.22(a)(1... on-site, the standards for BOD5, fecal coliform, O&G, and TSS are the same as the...

  5. 40 CFR 432.32 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... daily 1 Maximum monthly avg. 1 BOD 5 0.34 0.17 Fecal Coliform (2) (3) O&G 4 0.16 0.08 TSS 0.48 0.24 1... slaughtered on-site, the limitations for BOD5, fecal coliform, O&G, and TSS are the same as the...

  6. 40 CFR 432.12 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... daily 1 Maximum monthly avg. 1 BOD 5 0.24 0.12 Fecal Coliform (2) (3) O&G 4 0.12 0.06 TSS 0.40 0.20 1... animals on-site, the limitations for BOD5, fecal coliform, O&G, and TSS specified in paragraph (a)(1)...

  7. 40 CFR 432.82 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart must achieve... Fecal Coliform (2) (3) O&G 4 0.22 0.11 TSS 0.74 0.37 1 Pounds per 1000 lbs (or g/kg) of finished product... pounds per year of finished products must achieve the limitations for BOD5, fecal coliform, O&G, and...

  8. 40 CFR 432.32 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... daily 1 Maximum monthly avg. 1 BOD 5 0.34 0.17 Fecal Coliform (2) (3) O&G 4 0.16 0.08 TSS 0.48 0.24 1... slaughtered on-site, the limitations for BOD5, fecal coliform, O&G, and TSS are the same as the...

  9. 40 CFR 432.12 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... daily 1 Maximum monthly avg. 1 BOD 5 0.24 0.12 Fecal Coliform (2) (3) O&G 4 0.12 0.06 TSS 0.40 0.20 1... animals on-site, the limitations for BOD5, fecal coliform, O&G, and TSS specified in paragraph (a)(1)...

  10. 40 CFR 432.35 - New source performance standards (NSPS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specified in 40 CFR 122.29(d)(1) after which it must achieve the effluent limitations specified in §§ 432.32... standards for BOD5, fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.32(a)(1... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  11. 40 CFR 432.22 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... Regulatedparameter Maximum daily 1 Maximum monthly avg. 1 BOD5 0.42 0.21 Fecal Coliform (2) (3) O&G 4 0.16 0.08 TSS 0... slaughtered on-site, the limitations for BOD5, fecal coliform, O&G, and TSS are the same as the...

  12. 40 CFR 432.22 - Effluent limitations attainable by the application of the best practicable control technology...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...). Except as provided in 40 CFR 125.30 through 125.32, any existing point source subject to this subpart... Regulatedparameter Maximum daily 1 Maximum monthly avg. 1 BOD5 0.42 0.21 Fecal Coliform (2) (3) O&G 4 0.16 0.08 TSS 0... slaughtered on-site, the limitations for BOD5, fecal coliform, O&G, and TSS are the same as the...

  13. 40 CFR 432.45 - New source performance standards (NSPS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the... standards for BOD5, fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.42(a)(1... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  14. 40 CFR 432.35 - New source performance standards (NSPS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specified in 40 CFR 122.29(d)(1) after which it must achieve the effluent limitations specified in §§ 432.32... standards for BOD5, fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.32(a)(1... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  15. 40 CFR 432.45 - New source performance standards (NSPS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... expiration of the applicable time period specified in 40 CFR 122.29(d)(1) after which it must achieve the... standards for BOD5, fecal coliform, TSS, and O&G are the same as the limitations specified in § 432.42(a)(1... on-site, the standards for BOD5, fecal coliform, TSS, and O&G are the same as the...

  16. Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress.

    PubMed

    Ge, Jin-Fang; Gao, Wen-Chao; Cheng, Wen-Ming; Lu, Wei-Li; Tang, Jie; Peng, Lei; Li, Ning; Chen, Fei-Hu

    2014-01-01

    This study focused on the antidepressant potential of orcinol glucoside (OG) and its possible mechanisms of action. We established a depressed rat model using 3 consecutive weeks of chronic unpredictable mild stress (CUMS). The antidepressant-like effect of OG was revealed using the sucrose preference test, the open field test, the forced swimming test (FST), and the tail suspension test (TST). The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations and mRNA expression of corticotrophin-releasing hormone (CRH) in the hypothalamus. The protein expression levels of brain-derived neurotrophic factor (BDNF) and total phosphorylated-ERK1/2 were detected by western blot. The results showed that OG treatment (1.5, 3, or 6mg/kg) alleviated the depression-like behaviour of rats under CUMS, as indicated by the increased sucrose preference and the decreased immobility in both the FST and TST, although the rearing frequency in the open field test increased only in the group that received the lowest dose (1.5mg/kg OG). Rats that received OG treatment exhibited reduced serum CORT levels and CRH mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by OG treatment. Moreover, OG treatment upregulated the protein levels of BDNF and phosphorylated-ERK1/2 in the hippocampus, even above control levels. Our findings suggest that OG improved depressive behaviour in CUMS rats by downregulating HPA axis hyperactivity and increasing BDNF expression and ERK1/2 phosphorylation in the hippocampus. PMID:23838013

  17. Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection

    PubMed Central

    Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Das, Subhasis

    2009-01-01

    In the present study, methanol extract of Ocimum gratissimum Linn (ME-Og) was tested against nicotine-induced murine peritoneal macrophage in vitro. Phytochemical analysis of ME-Og shown high amount of flavonoid and phenolic compound present in it. The cytotoxic effect of ME-Og was studied in murine peritoneal macrophages at different concentrations (0.1 to 100 µg/ml) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) method. To establish the protective role of ME-Og against nicotine toxicity, peritoneal macrophages from mice were treated with nicotine (10 mM), nicotine + ME-Og (1 to 25 µg/ml) for 12 h in culture media. The significantly (p < 0.05) increased super oxide anion generation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, lipid peroxidation, protein carbonyls, oxidized glutathione levels were observed in nicotine-treated group as compared to control group; those were significantly (p < 0.05) reduced in ME-Og supplemented groups in concentration dependent manner. More over, significantly (p < 0.05) reduced antioxidant status due to nicotine exposure was effectively ameliorated by ME-Og supplementation in murine peritoneal macrophages. Among the different concentration of ME-Og, maximum protective effect was observed by 25 µg/ml, which does not produce significant cell cytotoxicity in murine peritoneal macrophages. These findings suggest the potential use and beneficial role of O. gratissimum as a modulator of nicotine-induced free radical generation, lipid-protein damage and antioxidant status in important immune cell, peritoneal macrophages. PMID:20716908

  18. Foot-Ground Reaction Force During Resistance Exercise in Parabolic Flight

    NASA Technical Reports Server (NTRS)

    Lee, Stuart M. C.; Cobb, Kendall; Loehr, James A.; Nguyen, Daniel; Schneider, Suzanne M.

    2003-01-01

    An interim Resistance Exercise Device (iRED) was designed to provide resistive exercise as a countermeasure to space flight-induced loss of muscle strength and endurance as well as decreased bone mineral density. The purpose of this project was to compare foot-ground reaction force during iRED exercise in normal gravity (l-g) versus micro gravity (O-g) achieved during parabolic flight. METHODS: Four subjects performed three exercises using the iRED (squat, heel raise, and deadlift) during I-g and O-g at a moderate intensity (60% of maximum strength during deadlift exercise). Foot-ground reaction force was measured in three axes (x,y,z) using a force plate, and the magnitude of the resultant force vector was calculated (r = X 2 + y2 + Z2 ). Range of motion (ROM) was measured using a linear encoder. Peak force (PkF) and total work (TW) were calculated using a customized computer program. Paired t-tests were used to test if significant differences (p.::::0.05) were observed between I-g and O-g exercise. RESULTS: PkF and TW measured in the resultant axis were significantly less in O-g for each of the exercises tested. During O-g, PkF was 42-46% and TW was 33- 37% of that measured during I-g. ROM and average time to complete each repetition were not different from I-g to O-g. CONCLUSIONS: When performing exercises in which body mass is a portion of the resistance during I-g, PkF and TW measured during resistive exercise were reduced approximately 60-70% during O-g. Thus, a resistive exercise device during O-g will be required to provided higher resistances to induce a similar training stimulus to that on Earth.

  19. Oxygen Generator System Mars In-Situ Propellant Production Precursor Flight

    NASA Technical Reports Server (NTRS)

    Sridhar, K. R.; Gottmann, M.; Baird, R. S.

    1999-01-01

    The 2001 Lander to Mars will carry the first ever ISRU payload to Mars. This payload, the Mars In-situ Propellant production Precursor (MIP), will demonstrate a variety of technologies that will be required for future ISRU Mars indigenous material processing plant designs. One of those technologies is that of extracting oxygen from the predominantly carbon dioxide atmosphere of Mars, a prerequisite for future sample return and human missions to Mars. The Oxygen Generator Subsystem (OGS) portion of the MIP will demonstrate this and is the focus of this paper. The primary objective of the OGS is to demonstrate the production of oxygen from Mars atmospheric gases. Secondary objectives are to measure the performance and reliability of oxygen generation hardware in actual mission environments over an extended time. Major constraints on the OGS design came from several sources. The Lander provides power to the system from solar power that is harnessed by photovoltaic arrays. This limited OGS to daytime only operations (six to eight hours) and a maximum power of 15W. The reliance on solar power necessitated thermal cycling of the OGS between Mars ambient and OGS operating temperatures. The Lander also limited the total mass of the MIP payload to 7.5 kg with a correspondingly small volume, and the OGS was one of six experiments in the MIP. Mass and volume were to be minimized. Another constraint was cost. Mission funding, as always, was tight. Cost was to be minimized. In short the OGS design had to be low power (<15 Watts), low mass (1 kg), low volume, low cost, and be capable of cyclical operations for an extended stay on Mars. After extensive research, a zirconia based solid oxide electrolyzer design was selected.

  20. Oxygen Generator System Mars In-Situ Propellant Production Precursor Flight

    NASA Technical Reports Server (NTRS)

    Sridhar, K. R.; Gottmann, M.; Baird, R. S.

    1999-01-01

    The 2001 Lander to Mars will carry the first ever In situ Resource Utilization (ISRU) payload to Mars. This payload, the Mars In-situ Propellant production Precursor (MIP), will demonstrate a variety of technologies that will be required for future ISRU Mars indigenous material processing plant designs. One of those technologies is that of extracting oxygen from the predominantly carbon dioxide atmosphere of Mars, a prerequisite for future sample return and human missions to Mars. The Oxygen Generator Subsystem (OGS) portion of the MIP will demonstrate this and is the focus of this paper. The primary objective of the OGS is to demonstrate the production of oxygen from Mars atmospheric gases. Secondary objectives are to measure the performance and reliability of oxygen generation hardware in actual mission environments over an extended time. Major constraints on the OGS design came from several sources. The Lander provides power to the system from solar power that is harnessed by photovoltaic arrays. This limited OGS to daytime only operations (six to eight hours) and a maximum power of 15W. The reliance on solar power necessitated thermal cycling of the OGS between Mars ambient and OGS operating temperatures. The Lander also limited the total mass of the MIP payload to 7.5 kg with a correspondingly small volume, and the OGS was one of six experiments in the MIP Mass and volume were to be minimized. Another constraint was cost. Mission funding, as always, was tight. Cost was to be minimized. In short the OGS design had to be low power (<15 Watts), low mass (1 kg), low volume, low cost, and be capable of cyclical operations for an extended stay on Mars. After extensive research, a zirconia based solid oxide electrolyzer design was selected.