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Sample records for del gen mll

  1. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia.

    PubMed

    Grembecka, Jolanta; He, Shihan; Shi, Aibin; Purohit, Trupta; Muntean, Andrew G; Sorenson, Roderick J; Showalter, Hollis D; Murai, Marcelo J; Belcher, Amalia M; Hartley, Thomas; Hess, Jay L; Cierpicki, Tomasz

    2012-01-29

    Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are to our knowledge the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities. These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. They also selectively block proliferation and induce both apoptosis and differentiation of leukemia cells harboring MLL translocations. Identification of these compounds provides a new tool for better understanding MLL-mediated leukemogenesis and represents a new approach for studying the role of menin as an oncogenic cofactor of MLL fusion proteins. Our findings also highlight a new therapeutic strategy for aggressive leukemias with MLL rearrangements.

  2. Pharmacologic inhibition of the menin-MLL interaction blocks progression of MLL leukemia in vivo

    DOE PAGES

    Borkin, Dmitry; He, Shihan; Miao, Hongzhi; ...

    2015-03-26

    Chromosomal translocations affecting mixed lineage leukemia gene ( MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. In this paper, we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia. Finally, we demonstrate the efficacy of these compounds in primary samples derived from MLL leukemia patients. In conclusion, overall, we demonstrate that pharmacologic inhibitionmore » of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.« less

  3. Mll5 Is Required for Normal Spermatogenesis

    PubMed Central

    Yap, Damian B.; Walker, David C.; Prentice, Leah M.; McKinney, Steven; Turashvili, Gulisa; Mooslehner-Allen, Katrin; de Algara, Teresa Ruiz; Fee, John; de Tassigny, Xavier d'Anglemont; Colledge, William H.; Aparicio, Samuel

    2011-01-01

    Background Mll5 is currently a member of the Mll family of SET domain histone methyltransferase proteins but studies have also showed that it could be part of the SET3 branch of proteins. Recently, constitutive knock out animal studies have shown that Mll5 is required for proper haematopoietic stem cell differentiation, and loss of Mll5 results in synthetic lethality for genome de-methylation. Mll5 deficient male mice are infertile and here we analyse the consequences of Mll5 deficiency for spermatogenesis. Methodology/Principal Findings Mll5 deficient male mice, but not female mice, are infertile. Here we show using RNA in-situ hybridization that Mll5 is expressed in the germ cells of the testes of wild type mice. Consistent with the expression of Mll5, we demonstrate by electron microscopy, video microscopy and in vitro fertilisation techniques that Mll5 deficient mice have defects in terminal maturation and packaging of sperm. The defects seen include detachment of the acrosomal cap and impaired excess cytoplasm removal. Functional tests of sperm motility show a lack of progressive motility of spermatozoa from Mll5 deficient animals. None of these defects could be rescued by in vitro fertilization. Using microarray analysis we show that transcripts implicated in spermatogenesis are dysregulated. Conclusions/Significance Our data demonstrate a clear role of Mll5 in mammalian spermatogenesis at the level of terminal differentiation providing further support for its classification in the SET3 branch of proteins. Moreover, this study identifies Tlk2, Utx, Gpr64, Sult4a1, Rap2ip, Vstm2 and HoxA10 as possible Mll5 targets that together may account for the observed spermatozoa maturation defects. PMID:22069496

  4. A multicenter evaluation of comprehensive analysis of MLL translocations and fusion gene partners in acute leukemia using the MLL FusionChip device.

    PubMed

    Harrison, Christine J; Griffiths, Mike; Moorman, Fìona; Schnittger, Susanne; Cayuela, Jean-Michel; Shurtleff, Sheila; Gottardi, Enrico; Mitterbauer, Gerlinde; Colomer, Dolores; Delabesse, Eric; Castéras, Vincent; Maroc, Nicolas

    2007-02-01

    Rearrangements of the MLL gene are significant in acute leukemia. Among the most frequent translocations are t(4;11)(q21;q23) and t(9;11)(p22;q23), which give rise to the MLL-AFF1 and MLL-MLLT3 fusion genes (alias MLL-AF4 and MLL-AF9) in acute lymphoblastic and acute myeloid leukemia, respectively. Current evidence suggests that determining the MLL status of acute leukemia, including precise identification of the partner gene, is important in defining appropriate treatment. This underscores the need for accurate detection methods. A novel molecular diagnostic device, the MLL FusionChip, has been successfully used to identify MLL fusion gene translocations in acute leukemia, including the precise breakpoint location. This study evaluated the performance of the MLL FusionChip within a routine clinical environment, comprising nine centers worldwide, in the analysis of 21 control and 136 patient samples. It was shown that the assay allowed accurate detection of the MLL fusion gene, regardless of the breakpoint location, and confirmed that this multiplex approach was robust in a global multicenter trial. The MLL FusionChip was shown to be superior to other detection methods. The type of molecular information provided by MLL FusionChip gave an indication of the appropriate primers to design for disease monitoring of MLL patients following treatment.

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

    PubMed Central

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

    2009-01-01

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

  6. The MLL recombinome of acute leukemias in 2017.

    PubMed

    Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; Zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

    2018-02-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

  7. The MLL recombinome of acute leukemias in 2017

    PubMed Central

    Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. PMID:28701730

  8. The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability.

    PubMed

    Grey, William; Ivey, Adam; Milne, Thomas A; Haferlach, Torsten; Grimwade, David; Uhlmann, Frank; Voisset, Edwige; Yu, Veronica

    2018-01-01

    The Cdc28 protein kinase subunits, Cks1 and Cks2, play dual roles in Cdk-substrate specificity and Cdk-independent protein degradation, in concert with the E3 ubiquitin ligase complexes SCF Skp2 and APC Cdc20 . Notable targets controlled by Cks include p27 and Cyclin A. Here, we demonstrate that Cks1 and Cks2 proteins interact with both the Mll N and Mll C subunits of Mll1 (Mixed-lineage leukaemia 1), and together, the Cks proteins define Mll1 levels throughout the cell cycle. Overexpression of CKS1B and CKS2 is observed in multiple human cancers, including various MLL-rearranged (MLLr) AML subtypes. To explore the importance of MLL-Fusion Protein regulation by CKS1/2, we used small molecule inhibitors (MLN4924 and C1) to modulate their protein degradation functions. These inhibitors specifically reduced the proliferation of MLLr cell lines compared to primary controls. Altogether, this study uncovers a novel regulatory pathway for MLL1, which may open a new therapeutic approach to MLLr leukaemia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Structure of the MLL CXXC domain – DNA complex and its functional role in MLL-AF9 leukemia

    PubMed Central

    Cierpicki, Tomasz; Risner, Laurie E.; Grembecka, Jolanta; Lukasik, Stephen M.; Popovic, Relja; Omonkowska, Monika; Shultis, David S.; Zeleznik-Le, Nancy J.; Bushweller, John H.

    2010-01-01

    MLL (Mixed Lineage Leukemia) is the target of chromosomal translocations which cause leukemias with poor prognosis. All leukemogenic MLL fusion proteins retain the CXXC domain which binds to nonmethylated CpG DNA. We present the solution structure of the MLL CXXC domain in complex with DNA, showing for the first time how the CXXC domain distinguishes nonmethylated from methylated CpG DNA. Based on the structure, we designed point mutations which disrupt DNA binding. Introduction of these mutations into MLL-AF9 results in increased DNA methylation of specific CpG nucleotides in Hoxa9, increased H3K9 methylation, decreased expression of Hoxa9 locus transcripts, loss of immortalization potential, and inability to induce leukemia in mice. These results establish that DNA binding by the CXXC domain and protection against DNA methylation is essential for MLL fusion leukemia. They also provide support for this interaction as a potential target for therapeutic intervention. PMID:20010842

  10. The MLL recombinome of acute leukemias in 2013

    PubMed Central

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements. PMID:23628958

  11. Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis.

    PubMed

    Gan, T; Jude, C D; Zaffuto, K; Ernst, P

    2010-10-01

    The mixed lineage leukemia (MLL) gene is disrupted by chromosomal translocations in acute leukemia, producing a fusion oncogene with altered properties relative to the wild-type gene. Murine loss-of-function studies have shown an essential role for Mll in developing the haematopoietic system, yet studies using different conditional knockout models have yielded conflicting results regarding the requirement for Mll during adult steady-state haematopoiesis. In this study, we used a loxP-flanked Mll allele (Mll(F)) and a developmentally regulated, haematopoietic-specific VavCre transgene to reassess the consequences of Mll loss in the haematopoietic lineage, without the need for inducers of Cre recombinase. We show that VavCre;Mll mutants exhibit phenotypically normal fetal haematopoiesis, but rarely survive past 3 weeks of age. Surviving animals are anemic, thrombocytopenic and exhibit a significant reduction in bone marrow haematopoietic stem/progenitor populations, consistent with our previous findings using the inducible Mx1Cre transgene. Furthermore, the analysis of VavCre mutants revealed additional defects in B-lymphopoiesis that could not be assessed using Mx1Cre-mediated Mll deletion. Collectively, these data support the conclusion that Mll has an essential role in sustaining postnatal haematopoiesis.

  12. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia

    PubMed Central

    Placke, Theresa; Faber, Katrin; Nonami, Atsushi; Putwain, Sarah L.; Salih, Helmut R.; Heidel, Florian H.; Krämer, Alwin; Root, David E.; Barbie, David A.; Krivtsov, Andrei V.; Armstrong, Scott A.; Hahn, William C.; Huntly, Brian J.; Sykes, Stephen M.; Milsom, Michael D.; Scholl, Claudia

    2014-01-01

    Chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) trigger aberrant gene expression in hematopoietic progenitors and give rise to an aggressive subtype of acute myeloid leukemia (AML). Insights into MLL fusion-mediated leukemogenesis have not yet translated into better therapies because MLL is difficult to target directly, and the identity of the genes downstream of MLL whose altered transcription mediates leukemic transformation are poorly annotated. We used a functional genetic approach to uncover that AML cells driven by MLL-AF9 are exceptionally reliant on the cell-cycle regulator CDK6, but not its functional homolog CDK4, and that the preferential growth inhibition induced by CDK6 depletion is mediated through enhanced myeloid differentiation. CDK6 essentiality is also evident in AML cells harboring alternate MLL fusions and a mouse model of MLL-AF9–driven leukemia and can be ascribed to transcriptional activation of CDK6 by mutant MLL. Importantly, the context-dependent effects of lowering CDK6 expression are closely phenocopied by a small-molecule CDK6 inhibitor currently in clinical development. These data identify CDK6 as critical effector of MLL fusions in leukemogenesis that might be targeted to overcome the differentiation block associated with MLL-rearranged AML, and underscore that cell-cycle regulators may have distinct, noncanonical, and nonredundant functions in different contexts. PMID:24764564

  13. Expression of HOXB genes is significantly different in acute myeloid leukemia with a partial tandem duplication of MLL vs. a MLL translocation: a cross-laboratory study.

    PubMed

    Liu, Hsi-Che; Shih, Lee-Yung; May Chen, Mei-Ju; Wang, Chien-Chih; Yeh, Ting-Chi; Lin, Tung-Huei; Chen, Chien-Yu; Lin, Chih-Jen; Liang, Der-Cherng

    2011-05-01

    In acute myeloid leukemia (AML), the mixed lineage leukemia (MLL) gene may be rearranged to generate a partial tandem duplication (PTD), or fused to partner genes through a chromosomal translocation (tMLL). In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other studies enriches samples for analysis and yields more conclusive results. 2011 Elsevier Inc. All rights reserved.

  14. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4

    PubMed Central

    Dhar, Shilpa S.; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

    2012-01-01

    Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD4–6) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD4–6 reduce PHD4–6's binding ability and MLL4's catalytic activity. PHD4–6's binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD4–6's binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation. PMID:23249737

  15. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4.

    PubMed

    Dhar, Shilpa S; Lee, Sung-Hun; Kan, Pu-Yeh; Voigt, Philipp; Ma, Li; Shi, Xiaobing; Reinberg, Danny; Lee, Min Gyu

    2012-12-15

    Mixed-lineage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Lys 4 (H3K4me3), a hallmark of gene activation. However, how MLL4-deposited H3K4me3 interplays with other histone marks in epigenetic processes remains largely unknown. Here, we show that MLL4 plays an essential role in differentiating NT2/D1 stem cells by activating differentiation-specific genes. A tandem plant homeodomain (PHD(4-6)) of MLL4 recognizes unmethylated or asymmetrically dimethylated histone H4 Arg 3 (H4R3me0 or H4R3me2a) and is required for MLL4's nucleosomal methyltransferase activity and MLL4-mediated differentiation. Kabuki syndrome mutations in PHD(4-6) reduce PHD(4-6)'s binding ability and MLL4's catalytic activity. PHD(4-6)'s binding strength is inhibited by H4R3 symmetric dimethylation (H4R3me2s), a gene-repressive mark. The protein arginine methyltransferase 7 (PRMT7), but not PRMT5, represses MLL4 target genes by up-regulating H4R3me2s levels and antagonizes MLL4-mediated differentiation. Consistently, PRMT7 knockdown increases MLL4-catalyzed H3K4me3 levels. During differentiation, decreased H4R3me2s levels are associated with increased H3K4me3 levels at a cohort of genes, including many HOXA and HOXB genes. These findings indicate that the trans-tail inhibition of MLL4-generated H3K4me3 by PRMT7-regulated H4R3me2s may result from H4R3me2s's interference with PHD(4-6)'s binding activity and is a novel epigenetic mechanism that underlies opposing effects of MLL4 and PRMT7 on cellular differentiation.

  16. Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy.

    PubMed

    Wang, Zhi-Hui; Li, Dong-Dong; Chen, Wei-Lin; You, Qi-Dong; Guo, Xiao-Ke

    2018-01-15

    The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed. Copyright © 2017. Published by Elsevier Ltd.

  17. The super elongation complex (SEC) and MLL in development and disease

    PubMed Central

    Smith, Edwin; Lin, Chengqi; Shilatifard, Ali

    2011-01-01

    Transcriptional regulation at the level of elongation is vital for the control of gene expression and metazoan development. The mixed lineage leukemia (MLL) protein and its Drosophila homolog, Trithorax, which exist within COMPASS (complex of proteins associated with Set1)-like complexes, are master regulators of development. They are required for proper homeotic gene expression, in part through methylation of histone H3 on Lys 4. In humans, the MLL gene is involved in a large number of chromosomal translocations that create chimeric proteins, fusing the N terminus of MLL to several proteins that share little sequence similarity. Several frequent translocation partners of MLL were found recently to coexist in a super elongation complex (SEC) that includes known transcription elongation factors such as eleven-nineteen lysine-rich leukemia (ELL) and P-TEFb. Importantly, the SEC is required for HOX gene expression in leukemic cells, suggesting that chromosomal translocations involving MLL could lead to the overexpression of HOX and other genes through the involvement of the SEC. Here, we review the normal developmental roles of MLL and the SEC, and how MLL fusion proteins can mediate leukemogenesis. PMID:21460034

  18. MLL-ENL cooperates with SCF to transform primary avian multipotent cells.

    PubMed

    Schulte, Cathleen E; von Lindern, Marieke; Steinlein, Peter; Beug, Hartmut; Wiedemann, Leanne M

    2002-08-15

    The MLL gene is targeted by chromosomal translocations, which give rise to heterologous MLL fusion proteins and are associated with distinct types of acute lymphoid and myeloid leukaemia. To determine how MLL fusion proteins alter the proliferation and/or differentiation of primary haematopoietic progenitors, we introduced the MLL-AF9 and MLL-ENL fusion proteins into primary chicken bone marrow cells. Both fusion proteins caused the sustained outgrowth of immature haematopoietic cells, which was strictly dependent on stem cell factor (SCF). The renewing cells have a long in vitro lifespan exceeding the Hayflick limit of avian cells. Analysis of clonal cultures identified the renewing cells as immature, multipotent progenitors, expressing erythroid, myeloid, lymphoid and stem cell surface markers. Employing a two-step commitment/differentiation protocol involving the controlled withdrawal of SCF, the MLL-ENL-transformed progenitors could be induced to terminal erythroid or myeloid differentiation. Finally, in cooperation with the weakly leukaemogenic receptor tyrosine kinase v-Sea, the MLL-ENL fusion protein gave rise to multilineage leukaemia in chicks, suggesting that other activated, receptor tyrosine kinases can substitute for ligand-activated c-Kit in vivo.

  19. The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia.

    PubMed

    Emerenciano, Mariana; Meyer, Claus; Mansur, Marcela B; Marschalek, Rolf; Pombo-de-Oliveira, Maria S

    2013-04-01

    Acute leukaemia in early childhood - and mainly infant leukaemia (IL) - is characterized by acquired genetic alterations, most commonly by the presence of distinct MLL rearrangements (MLL-r). The aim of this study was to investigate possible correlations between clinical features and molecular analyses of a series of 545 childhood leukaemia (≤24 months of age) cases: 385 acute lymphoblastic leukaemia (ALL) and 160 acute myeloid leukaemia (AML). The location of the genomic breakpoints was determined in a subset of 30 MLL-r cases. The overall survival of the investigated cohort was 60·5%, as determined by the Kaplan-Meier method. Worse outcomes were associated with age at diagnosis ≤6 months (P < 0·001), high white blood cell count (P = 0·001), and MLL-r (P = 0·002) in ALL, while children with AML displayed a poorer outcome (P = 0·009) regardless of their age strata. Moreover, we present first evidence that MLL-r patients with poor outcome preferentially displayed chromosomal breakpoints within MLL intron 11. Based on the literature, most MLL-r IL display a breakpoint localization towards intron 11, which in turn may explain their worse clinical course. In summary, the MLL breakpoint localization is of clinical importance and should be considered as a novel outcome predictor for MLL-r patients. © 2013 Blackwell Publishing Ltd.

  20. Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

    PubMed

    Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S; Liang, Kaiwei; Takahashi, Yoh-Hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C Peter; Shilatifard, Ali

    2012-12-01

    Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers.

  1. Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4

    PubMed Central

    Herz, Hans-Martin; Mohan, Man; Garruss, Alexander S.; Liang, Kaiwei; Takahashi, Yoh-hei; Mickey, Kristen; Voets, Olaf; Verrijzer, C. Peter; Shilatifard, Ali

    2012-01-01

    Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo. Loss of Trr results in a global decrease of H3K4me1 and H3K27ac levels in various tissues. Assays with the cut wing margin enhancer implied a functional role for Trr in enhancer-mediated processes. A genome-wide analysis demonstrated that Trr is required to maintain the H3K4me1 and H3K27ac chromatin signature that resembles the histone modification patterns described for enhancers. Furthermore, studies in the mammalian system suggested a role for the Trr homolog Mll3 in similar processes. Since Trr and mammalian Mll3/4 complexes are distinguished by bearing a unique subunit, the H3K27 demethylase UTX, we propose a model in which the H3K4 monomethyltransferases Trr/Mll3/Mll4 and the H3K27 demethylase UTX cooperate to regulate the transition from inactive/poised to active enhancers. PMID:23166019

  2. The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

    PubMed

    Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

    2017-07-20

    Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

  3. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    PubMed

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements

    PubMed Central

    Middlemiss, Shiloh M.C.; Wen, Victoria W.; Clifton, Molly; Kwek, Alan; Liu, Bing; Mayoh, Chelsea; Bongers, Angelika; Karsa, Mawar; Pan, Sukey; Cruikshank, Sarah; Scandlyn, Marissa; Hoang, Wendi; Imamura, Toshihiko; Kees, Ursula R.; Gudkov, Andrei V.; Chernova, Olga B.

    2016-01-01

    There is an urgent need for the development of less toxic, more selective and targeted therapies for infants with leukemia characterized by translocation of the mixed lineage leukemia (MLL) gene. In this study, we performed a cell-based small molecule library screen on an infant MLL-rearranged (MLL-r) cell line, PER-485, in order to identify selective inhibitors for MLL-r leukemia. After screening initial hits for a cytotoxic effect against a panel of 30 cell lines including MLL-r and MLL wild-type (MLL-wt) leukemia, solid tumours and control cells, small molecule CCI-007 was identified as a compound that selectively and significantly decreased the viability of a subset of MLL-r and related leukemia cell lines with CALM-AF10 and SET-NUP214 translocation. CCI-007 induced a rapid caspase-dependent apoptosis with mitochondrial depolarization within twenty-four hours of treatment. CCI-007 altered the characteristic MLL-r gene expression signature in sensitive cells with downregulation of the expression of HOXA9, MEIS1, CMYC and BCL2, important drivers in MLL-r leukemia, within a few hours of treatment. MLL-r leukemia cells that were resistant to the compound were characterised by significantly higher baseline gene expression levels of MEIS1 and BCL2 in comparison to CCI-007 sensitive MLL-r leukemia cells. In conclusion, we have identified CCI-007 as a novel small molecule that displays rapid toxicity towards a subset of MLL-r, CALM-AF10 and SET-NUP214 leukemia cell lines. Our findings suggest an important new avenue in the development of targeted therapies for these deadly diseases and indicate that different therapeutic strategies might be needed for different subtypes of MLL-r leukemia. PMID:27317766

  5. Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia

    PubMed Central

    Li, Bin E.; Ernst, Patricia

    2015-01-01

    MLL1, located on human chromosome 11, is disrupted in distinct recurrent chromosomal translocations in several leukemia subsets. Studying the MLL1 gene and its oncogenic variants has provided a paradigm for understanding cancer initiation and maintenance through aberrant epigenetic gene regulation. Here we review the historical development of model systems to recapitulate oncogenic MLL1-rearrangement (MLL-r) alleles encoding mixed-lineage leukemia fusion proteins (MLL-FPs) or internal gene rearrangement products. These largely mouse and human cell/xenograft systems have been generated and used to understand how MLL-r alleles affect diverse pathways to result in a highly penetrant, drug-resistant leukemia. The particular features of the animal models influenced the conclusions of mechanisms of transformation. We discuss significant downstream enablers, inhibitors, effectors, and collaborators of MLL-r leukemia, including molecules that directly interact with MLL-FPs and endogenous mixed-lineage leukemia protein, direct target genes of MLL-FPs, and other pathways that have proven to be influential in supporting or suppressing the leukemogenic activity of MLL-FPs. The use of animal models has been complemented with patient sample, genome-wide analyses to delineate the important genomic and epigenomic changes that occur in distinct subsets of MLL-r leukemia. Collectively, these studies have resulted in rapid progress toward developing new strategies for targeting MLL-r leukemia and general cell-biological principles that may broadly inform targeting aberrant epigenetic regulators in other cancers. PMID:25264566

  6. MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma.

    PubMed

    Mater, David Van; Goodman, Barbara K; Wang, Endi; Gaca, Ana M; Wechsler, Daniel S

    2012-04-01

    Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.

  7. Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.

    PubMed

    Hannibal, Mark C; Buckingham, Kati J; Ng, Sarah B; Ming, Jeffrey E; Beck, Anita E; McMillin, Margaret J; Gildersleeve, Heidi I; Bigham, Abigail W; Tabor, Holly K; Mefford, Heather C; Cook, Joseph; Yoshiura, Koh-ichiro; Matsumoto, Tadashi; Matsumoto, Naomichi; Miyake, Noriko; Tonoki, Hidefumi; Naritomi, Kenji; Kaname, Tadashi; Nagai, Toshiro; Ohashi, Hirofumi; Kurosawa, Kenji; Hou, Jia-Woei; Ohta, Tohru; Liang, Deshung; Sudo, Akira; Morris, Colleen A; Banka, Siddharth; Black, Graeme C; Clayton-Smith, Jill; Nickerson, Deborah A; Zackai, Elaine H; Shaikh, Tamim H; Donnai, Dian; Niikawa, Norio; Shendure, Jay; Bamshad, Michael J

    2011-07-01

    Kabuki syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki syndrome is caused by mutations in MLL2, a gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin states. Here, we report on the screening of 110 families with Kabuki syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki syndrome. Copyright © 2011 Wiley-Liss, Inc.

  8. MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

    PubMed

    Makrythanasis, P; van Bon, B W; Steehouwer, M; Rodríguez-Santiago, B; Simpson, M; Dias, P; Anderlid, B M; Arts, P; Bhat, M; Augello, B; Biamino, E; Bongers, E M H F; Del Campo, M; Cordeiro, I; Cueto-González, A M; Cuscó, I; Deshpande, C; Frysira, E; Izatt, L; Flores, R; Galán, E; Gener, B; Gilissen, C; Granneman, S M; Hoyer, J; Yntema, H G; Kets, C M; Koolen, D A; Marcelis, C l; Medeira, A; Micale, L; Mohammed, S; de Munnik, S A; Nordgren, A; Psoni, S; Reardon, W; Revencu, N; Roscioli, T; Ruiterkamp-Versteeg, M; Santos, H G; Schoumans, J; Schuurs-Hoeijmakers, J H M; Silengo, M C; Toledo, L; Vendrell, T; van der Burgt, I; van Lier, B; Zweier, C; Reymond, A; Trembath, R C; Perez-Jurado, L; Dupont, J; de Vries, B B A; Brunner, H G; Veltman, J A; Merla, G; Antonarakis, S E; Hoischen, A

    2013-12-01

    Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Crystal Structure of Menin Reveals Binding Site for Mixed Lineage Leukemia (MLL) Protein

    SciTech Connect

    Murai, Marcelo J.; Chruszcz, Maksymilian; Reddy, Gireesh

    2014-10-02

    Menin is a tumor suppressor protein that is encoded by the MEN1 (multiple endocrine neoplasia 1) gene and controls cell growth in endocrine tissues. Importantly, menin also serves as a critical oncogenic cofactor of MLL (mixed lineage leukemia) fusion proteins in acute leukemias. Direct association of menin with MLL fusion proteins is required for MLL fusion protein-mediated leukemogenesis in vivo, and this interaction has been validated as a new potential therapeutic target for development of novel anti-leukemia agents. Here, we report the first crystal structure of menin homolog from Nematostella vectensis. Due to a very high sequence similarity, the Nematostellamore » menin is a close homolog of human menin, and these two proteins likely have very similar structures. Menin is predominantly an {alpha}-helical protein with the protein core comprising three tetratricopeptide motifs that are flanked by two {alpha}-helical bundles and covered by a {beta}-sheet motif. A very interesting feature of menin structure is the presence of a large central cavity that is highly conserved between Nematostella and human menin. By employing site-directed mutagenesis, we have demonstrated that this cavity constitutes the binding site for MLL. Our data provide a structural basis for understanding the role of menin as a tumor suppressor protein and as an oncogenic co-factor of MLL fusion proteins. It also provides essential structural information for development of inhibitors targeting the menin-MLL interaction as a novel therapeutic strategy in MLL-related leukemias.« less

  10. MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells

    PubMed Central

    Maethner, Emanuel; Garcia-Cuellar, Maria-Paz; Breitinger, Constanze; Takacova, Sylvia; Divoky, Vladimir; Hess, Jay L.; Slany, Robert K.

    2014-01-01

    Summary Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here we provide evidence that MLL-ENL also inhibits polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as scaffold that contacted the elongation machinery as well as the PRC1 (polycomb repressive complex 1) component CBX8. These interactions were mutually exclusive in vitro corresponding to an antagonistic behavior of MLL-ENL and CBX8 in vivo. CBX8 inhibited elongation in a specific reporter assay and this effect was neutralized by direct association with ENL. Correspondingly MLL-ENL defective in CBX8 binding could not fully activate gene loci necessary for transformation. Finally, we demonstrate dimerization of MLL-ENL as neomorphic activity that may augment polycomb inhibition and transformation. PMID:23623499

  11. A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia.

    PubMed

    Maroc, N; Morel, A; Beillard, E; De La Chapelle, A L; Fund, X; Mozziconacci, M-J; Dupont, M; Cayuela, J-M; Gabert, J; Koki, A; Fert, V; Hermitte, F

    2004-09-01

    Reciprocal rearrangements of the MLL gene are among the most common chromosomal abnormalities in both Acute Lymphoblastic and Myeloid Leukemia. The MLL gene, located on the 11q23 chromosomal band, is involved in more than 40 recurrent translocations. In the present study, we describe the development and validation of a biochip-based assay designed to provide a comprehensive molecular analysis of MLL rearrangements when used in a standard clinical pathology laboratory. A retrospective blind study was run with cell lines (n=5), and MLL positive and negative patient samples (n=31), to evaluate assay performance. The limits of detection determined on cell line data were 10(-1), and the precision studies yielded 100% repeatability and 98% reproducibility. The study shows that the device can detect frequent (AF4, AF6, AF10, ELL or ENL) as well as rare partner genes (AF17, MSF). The identified fusion transcripts can then be used as molecular phenotypic markers of disease for the precise evaluation of minimal residual disease by RQ-PCR. This biochip-based molecular diagnostic tool allows, in a single experiment, rapid and accurate identification of MLL gene rearrangements among 32 different fusion gene (FG) partners, precise breakpoint positioning and comprehensive screening of all currently characterized MLL FGs.

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

    PubMed

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

    2013-10-01

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

  13. Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia

    PubMed Central

    Wei, Junping; Wunderlich, Mark; Fox, Catherine; Alvarez, Sara; Cigudosa, Juan C.; Wilhelm, Jamie S.; Zheng, Yi; Cancelas, Jose A.; Gu, Yi; Jansen, Michael; DiMartino, Jorge F.; Mulloy, James C.

    2008-01-01

    Summary Faithful modeling of mixed lineage leukemia in murine cells has been difficult to achieve. We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid or mixed lineage leukemia in immunodeficient mice. Some leukemia stem cells (LSC) were multipotent and could be lineage directed by altering either the growth factors or the recipient strain of mouse, highlighting the importance of microenviromental cues. Other LSC were strictly lineage committed, demonstrating the heterogeneity of the stem cell compartment in MLL disease. Targeting the Rac signaling pathway by pharmacologic or genetic means resulted in rapid and specific apoptosis of MLL-AF9 cells, suggesting that the Rac signaling pathway may be a valid therapeutic target in MLL-rearranged AML. PMID:18538732

  14. Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases.

    PubMed

    Hubert, Amy; Henderson, Jordana M; Ross, Kelly G; Cowles, Martis W; Torres, Jessica; Zayas, Ricardo M

    2013-01-01

    Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5-1 and mll5-2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5-2 are required for regeneration and that set1, trr-1 and mll5-2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo.

  15. Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases

    PubMed Central

    Hubert, Amy; Henderson, Jordana M.; Ross, Kelly G.; Cowles, Martis W.; Torres, Jessica; Zayas, Ricardo M.

    2013-01-01

    Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5–1 and mll5–2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5–2 are required for regeneration and that set1, trr-1 and mll5–2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo. PMID:23235145

  16. Histone acetyltransferase activity of MOF is required for MLL-AF9 leukemogenesis

    PubMed Central

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

    2017-01-01

    Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore Mof inactivation suppressed leukemia development in a NUP98-HOXA9 driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. PMID:28202522

  17. Effective Targeting of the P53/MDM2 Axis in Preclinical Models of Infant MLL-Rearranged Acute Lymphoblastic Leukemia

    PubMed Central

    Richmond, Jennifer; Carol, Hernan; Evans, Kathryn; High, Laura; Mendomo, Agnes; Robbins, Alissa; Meyer, Claus; Venn, Nicola C.; Marschalek, Rolf; Henderson, Michelle; Sutton, Rosemary; Kurmasheva, Raushan T.; Kees, Ursula R.; Houghton, Peter J.; Smith, Malcolm A.; Lock, Richard B.

    2015-01-01

    Purpose While the overall cure rate for pediatric acute lymphoblastic leukemia (ALL) approaches 90%, infants with ALL harboring translocations in the mixed-lineage leukemia (MLL) oncogene (infant MLL-ALL) experience shorter remission duration and lower survival rates (∼50%). Mutations in the p53 tumor suppressor gene are uncommon in infant MLL-ALL, and drugs that release p53 from inhibitory mechanisms may be beneficial. The purpose of this study was to assess the efficacy of the orally available nutlin, RG7112, against patient-derived MLL-ALL xenografts. Experimental Design Eight MLL-ALL patient-derived xenografts were established in immune-deficient mice, and their molecular features compared with B-lineage ALL and T-ALL xenografts. The sensitivity of MLL-ALL xenografts to RG7112 was assessed in vitro and in vivo, and the ability of RG7112 to induce p53, cell cycle arrest and apoptosis in vivo was evaluated. Results Gene expression analysis revealed that MLL-ALL, B-lineage ALL and T-ALL xenografts clustered according to subtype. Moreover, genes previously reported to be over-expressed in MLL-ALL, including MEIS1, CCNA1, and members of the HOXA family, were significantly up-regulated in MLL-ALL xenografts, confirming their ability to recapitulate the clinical disease. Exposure of MLL-ALL xenografts to RG7112 in vivo caused p53 up-regulation, cell cycle arrest and apoptosis. RG7112 as a single agent induced significant regressions in infant MLL-ALL xenografts. Therapeutic enhancement was observed when RG7112 was assessed using combination treatment with an induction-type regimen (vincristine/dexamethasone/L-asparaginase) against an MLL-ALL xenograft. Conclusion The utility of targeting the p53-MDM2 axis in combination with established drugs for the management of infant MLL-ALL warrants further investigation. PMID:25573381

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

    PubMed

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

    2017-04-01

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

  19. Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.

    PubMed

    Morgado-Palacin, Isabel; Day, Amanda; Murga, Matilde; Lafarga, Vanesa; Anton, Marta Elena; Tubbs, Anthony; Chen, Hua Tang; Ergan, Aysegul; Anderson, Rhonda; Bhandoola, Avinash; Pike, Kurt G; Barlaam, Bernard; Cadogan, Elaine; Wang, Xi; Pierce, Andrew J; Hubbard, Chad; Armstrong, Scott A; Nussenzweig, André; Fernandez-Capetillo, Oscar

    2016-09-13

    Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AML(MLL) and in xenografts of a human AML-MLL cell line. We also found that inhibition of ATM, a kinase that senses DNA double-strand breaks, also promoted the survival of the AML(MLL) mice. Collectively, these data indicated that ATR or ATM inhibition represent potential therapeutic strategies for the treatment of AML, especially MLL-driven leukemias. Copyright © 2016, American Association for the Advancement of Science.

  20. Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

    PubMed Central

    Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko; Kuroki, Yoko; Hijikata, Atsushi; Takagi, Masatoshi; Tomizawa, Daisuke; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Kaneko, Akiko; Ono, Rintaro; Sato, Kaori; Suzuki, Nahoko; Fujiki, Saera; Koh, Katsuyoshi; Ishii, Eiichi; Shultz, Leonard D.; Ohara, Osamu; Mizutani, Shuki

    2015-01-01

    Translocation of the mixed-lineage leukemia (MLL) gene with AF4, AF9, or ENL results in acute leukemia with both lymphoid and myeloid involvement. We characterized leukemia-initiating cells (LICs) in primary infant MLL-rearranged leukemia using a xenotransplantation model. In MLL-AF4 patients, CD34+CD38+CD19+ and CD34−CD19+ cells initiated leukemia, and in MLL-AF9 patients, CD34−CD19+ cells were LICs. In MLL-ENL patients, either CD34+ or CD34− cells were LICs, depending on the pattern of CD34 expression. In contrast, in patients with these MLL translocations, CD34+CD38−CD19−CD33− cells were enriched for normal hematopoietic stem cells (HSCs) with in vivo long-term multilineage hematopoietic repopulation capacity. Although LICs developed leukemic cells with clonal immunoglobulin heavy-chain (IGH) rearrangement in vivo, CD34+CD38−CD19−CD33− cells repopulated recipient bone marrow and spleen with B cells, showing broad polyclonal IGH rearrangement and recipient thymus with CD4+ single positive (SP), CD8+ SP, and CD4+CD8+ double-positive (DP) T cells. Global gene expression profiling revealed that CD9, CD32, and CD24 were over-represented in MLL-AF4, MLL-AF9, and MLL-ENL LICs compared with normal HSCs. In patient samples, these molecules were expressed in CD34+CD38+ and CD34− LICs but not in CD34+CD38−CD19−CD33− HSCs. Identification of LICs and LIC-specific molecules in primary human MLL-rearranged acute lymphoblastic leukemia may lead to improved therapeutic strategies for MLL-rearranged leukemia. PMID:25538041

  1. MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis.

    PubMed

    Ali, Aamir; Veeranki, Sailaja Naga; Chinchole, Akash; Tyagi, Shweta

    2017-06-19

    Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. MicroRNA-106b~25 cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia

    PubMed Central

    Verboon, Lonneke J.; Obulkasim, Askar; de Rooij, Jasmijn D.E.; Katsman, Jenny E.; Sonneveld, Edwin; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Pieters, Rob; Cloos, Jacqueline; Kaspers, Gertjan J.L.; Klusmann, Jan-Henning; Zwaan, Christian Michel; Fornerod, Maarten; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    The most important reason for therapy failure in pediatric acute myeloid leukemia (AML) is relapse. In order to identify miRNAs that contribute to the clonal evolution towards relapse in pediatric AML, miRNA expression profiling of 127 de novo pediatric AML cases were used. In the diagnostic phase, no miRNA signatures could be identified that were predictive for relapse occurrence, in a large pediatric cohort, nor in a nested mixed lineage leukemia (MLL)-rearranged pediatric cohort. AML with MLL- rearrangements are found in 15-20% of all pediatric AML samples, and reveal a relapse rate up to 50% for certain translocation partner subgroups. Therefore, microRNA expression profiling of six paired initial diagnosis-relapse MLL-rearranged pediatric AML samples (test cohort) and additional eight paired initial diagnosis-relapse samples with MLL-rearrangements (validation cohort) was performed. A list of 53 differentially expressed miRNAs was identified of which the miR-106b~25 cluster, located in intron 13 of MCM7, was the most prominent. These differentially expressed miRNAs however could not predict a relapse in de novo AML samples with MLL-rearrangements at diagnosis. Furthermore, higher mRNA expression of both MCM7 and its upstream regulator E2F1 was found in relapse samples with MLL-rearrangements. In conclusion, we identified the miR-106b~25 cluster to be upregulated in relapse pediatric AML with MLL-rearrangements. PMID:27351222

  3. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription

    SciTech Connect

    Huang, Jing; Gurung, Buddha; Wan, Bingbing

    2013-04-08

    Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs. Menin interacts with many proteins and is involved in a variety of cellular processes. Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity. Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription. Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions asmore » an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis. A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins. Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.« less

  4. High-Affinity Small-Molecule Inhibitors of the Menin-Mixed Lineage Leukemia (MLL) Interaction Closely Mimic a Natural Protein-Protein Interaction

    SciTech Connect

    He, Shihan; Senter, Timothy J.; Pollock, Jonathan

    2014-10-02

    The protein–protein interaction (PPI) between menin and mixed lineage leukemia (MLL) plays a critical role in acute leukemias, and inhibition of this interaction represents a new potential therapeutic strategy for MLL leukemias. We report development of a novel class of small-molecule inhibitors of the menin–MLL interaction, the hydroxy- and aminomethylpiperidine compounds, which originated from HTS of ~288000 small molecules. We determined menin–inhibitor co-crystal structures and found that these compounds closely mimic all key interactions of MLL with menin. Extensive crystallography studies combined with structure-based design were applied for optimization of these compounds, resulting in MIV-6R, which inhibits the menin–MLL interactionmore » with IC 50 = 56 nM. Treatment with MIV-6 demonstrated strong and selective effects in MLL leukemia cells, validating specific mechanism of action. Our studies provide novel and attractive scaffold as a new potential therapeutic approach for MLL leukemias and demonstrate an example of PPI amenable to inhibition by small molecules.« less

  5. Structural and Biochemical Insights into MLL1 Core Complex Assembly

    SciTech Connect

    Avdic, Vanja; Zhang, Pamela; Lanouette, Sylvain

    2012-05-02

    Histone H3 Lys-4 methylation is predominantly catalyzed by a family of methyltransferases whose enzymatic activity depends on their interaction with a three-subunit complex composed of WDR5, RbBP5, and Ash2L. Here, we report that a segment of 50 residues of RbBP5 bridges the Ash2L C-terminal domain to WDR5. The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5s {beta}-propeller domain. RbBP5 engages in several hydrogen bonds and van der Waals contacts within a V-shaped cleft formed by the junction of two blades on WDR5. Mutational analysesmore » of both the WDR5 V-shaped cleft and RbBP5 residues reveal that the interactions between RbBP5 and WDR5 are important for the stimulation of MLL1 methyltransferase activity. Overall, this study provides the structural basis underlying the formation of the WDR5-RbBP5 subcomplex and further highlight the crucial role of WDR5 in scaffolding the MLL1 core complex.« less

  6. High resolution tip-tilt positioning system for a next generation MLL-based x-ray microscope

    DOE PAGES

    Xu, Weihe; Schlossberger, Noah; Xu, Wei; ...

    2017-11-15

    Multilayer Laue lenses (MLLs) are x-ray focusing optics with the potential to focus hard x-rays down to a single nanometer level. In order to achieve point focus, an MLL microscope needs to have the capability to perform tip-tilt motion of MLL optics and to hold the angular position for an extended period of time. Here, we present a 2D tip-tilt system that can achieve an angular resolution of over 100 microdegree with a working range of 4°, by utilizing a combination of laser interferometer and mini retroreflector. The linear dimensions of the developed system are about 30 mm in allmore » directions, and the thermal dissipation of the system during operation is negligible. Compact design and high angular resolution make the developed system suitable for MLL optics alignment in the next generation of MLL-based x-ray microscopes.« less

  7. High resolution tip-tilt positioning system for a next generation MLL-based x-ray microscope

    SciTech Connect

    Xu, Weihe; Schlossberger, Noah; Xu, Wei

    Multilayer Laue lenses (MLLs) are x-ray focusing optics with the potential to focus hard x-rays down to a single nanometer level. In order to achieve point focus, an MLL microscope needs to have the capability to perform tip-tilt motion of MLL optics and to hold the angular position for an extended period of time. Here, we present a 2D tip-tilt system that can achieve an angular resolution of over 100 microdegree with a working range of 4°, by utilizing a combination of laser interferometer and mini retroreflector. The linear dimensions of the developed system are about 30 mm in allmore » directions, and the thermal dissipation of the system during operation is negligible. Compact design and high angular resolution make the developed system suitable for MLL optics alignment in the next generation of MLL-based x-ray microscopes.« less

  8. How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum.

    PubMed

    Banka, Siddharth; Veeramachaneni, Ratna; Reardon, William; Howard, Emma; Bunstone, Sancha; Ragge, Nicola; Parker, Michael J; Crow, Yanick J; Kerr, Bronwyn; Kingston, Helen; Metcalfe, Kay; Chandler, Kate; Magee, Alex; Stewart, Fiona; McConnell, Vivienne P M; Donnelly, Deirdre E; Berland, Siren; Houge, Gunnar; Morton, Jenny E; Oley, Christine; Revencu, Nicole; Park, Soo-Mi; Davies, Sally J; Fry, Andrew E; Lynch, Sally Ann; Gill, Harinder; Schweiger, Susann; Lam, Wayne W K; Tolmie, John; Mohammed, Shehla N; Hobson, Emma; Smith, Audrey; Blyth, Moira; Bennett, Christopher; Vasudevan, Pradeep C; García-Miñaúr, Sixto; Henderson, Alex; Goodship, Judith; Wright, Michael J; Fisher, Richard; Gibbons, Richard; Price, Susan M; C de Silva, Deepthi; Temple, I Karen; Collins, Amanda L; Lachlan, Katherine; Elmslie, Frances; McEntagart, Meriel; Castle, Bruce; Clayton-Smith, Jill; Black, Graeme C; Donnai, Dian

    2012-04-01

    MLL2 mutations are detected in 55 to 80% of patients with Kabuki syndrome (KS). In 20 to 45% patients with KS, the genetic basis remains unknown, suggesting possible genetic heterogeneity. Here, we present the largest yet reported cohort of 116 patients with KS. We identified MLL2 variants in 74 patients, of which 47 are novel and a majority are truncating. We show that pathogenic missense mutations were commonly located in exon 48. We undertook a systematic facial KS morphology study of patients with KS at our regional dysmorphology meeting. Our data suggest that nearly all patients with typical KS facial features have pathogenic MLL2 mutations, although KS can be phenotypically variable. Furthermore, we show that MLL2 mutation-positive KS patients are more likely to have feeding problems, kidney anomalies, early breast bud development, joint dislocations and palatal malformations in comparison with MLL2 mutation-negative patients. Our work expands the mutation spectrum of MLL2 that may help in better understanding of this molecule, which is important in gene expression, epigenetic control of active chromatin states, embryonic development and cancer. Our analyses of the phenotype indicates that MLL2 mutation-positive and -negative patients differ systematically, and genetic heterogeneity of KS is not as extensive as previously suggested. Moreover, phenotypic variability of KS suggests that MLL2 testing should be considered even in atypical patients.

  9. ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia

    PubMed Central

    2014-01-01

    Background Acute leukemia in early age (EAL) is characterized by acquired genetic alterations such as MLL rearrangements (MLL-r). The aim of this case-controlled study was to investigate whether single nucleotide polymorphisms (SNPs) of IKZF1, ARID5B, and CEBPE could be related to the onset of EAL cases (<24 months-old at diagnosis). Methods The SNPs (IKZF1 rs11978267, ARID5B rs10821936 and rs10994982, CEBPE rs2239633) were genotyped in 265 cases [169 acute lymphoblastic leukemia (ALL) and 96 acute myeloid leukaemia (AML)] and 505 controls by Taqman allelic discrimination assay. Logistic regression was used to evaluate the association between SNPs of cases and controls, adjusted on skin color and/or age. The risk was determined by calculating odds ratios (ORs) with 95% confidence interval (CI). Results Children with the IKZF1 SNP had an increased risk of developing MLL-germline ALL in white children. The heterozygous/mutant genotype in ARID5B rs10994982 significantly increased the risk for MLL-germline leukemia in white and non-white children (OR 2.60, 95% CI: 1.09-6.18 and OR 3.55, 95% CI: 1.57-8.68, respectively). The heterozygous genotype in ARID5B rs10821936 increased the risk for MLL-r leukemia in both white and non-white (OR 2.06, 95% CI: 1.12-3.79 and OR 2.36, 95% CI: 1.09-5.10, respectively). Furthermore, ARID5B rs10821936 conferred increased risk for MLL-MLLT3 positive cases (OR 7.10, 95% CI:1.54-32.68). Our data do not show evidence that CEBPE rs2239633 confers increased genetic susceptibility to EAL. Conclusions IKZF1 and CEBPE variants seem to play a minor role in genetic susceptibility to EAL, while ARID5B rs10821936 increased the risk of MLL-MLLT3. This result shows that genetic susceptibility could be associated with the differences regarding MLL breakpoints and partner genes. PMID:24564228

  10. Acute leukaemia and myelodysplastic syndromes with chromosomal rearrangement involving 11q23 locus, but not MLL gene.

    PubMed

    Zuo, Wenli; Wang, Sa A; DiNardo, Courtney; Yabe, Mariko; Li, Shaoying; Medeiros, L Jeffrey; Tang, Guilin

    2017-03-01

    Chromosome 11q23 translocations, resulting in MLL (KMT2A ) rearrangement, have been well characterised in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). However, little is known of haematopoietic neoplasms associated with 11q23 translocation but without MLL rearrangement (11q23+/ MLL -). The aim of this study is to characterise such cases with 11q23+/ MLL -. We retrospectively searched our database for cases with haematopoietic malignancies with 11q23+/ MLL -. We identified nine patients, two with AML, two with B-lymphoblastic leukaemia (B-ALL); two with T-lymphoblastic leukaemia (T-ALL), two with myelodysplastic syndrome (MDS) and one with chronic myelomonocytic leukaemia (CMML). The translocations included t(X;11)(p11.2;q23), t(2;11)(p21;q23), t(6;11)(q27;q23), t(8;9;11)(q13;q13;q23), t(11;11)(p15;q23), t(11;14)(q23;q24) and t(11;15)(q23;q14). Five of six patients with acute leukaemia had received chemotherapy and detection of 11q23 translocation occurred at time of disease relapse. Both patients with MDS and the patient with CMML had 11q23 translocation detected at time of initial diagnosis, all three patients progressed to AML after >1 year on hypomethylating agent therapy. All patients received risk-adapted therapies, including stem cell transplant in five patients. At the last follow-up, eight patients died with a median overall survival of 14 months. 11q23+/ MLL - occurs rarely, involving different partner chromosomes and showing clinical and pathological features and disease subtypes different from those cases with MLL rearrangement. 11q23+/ MLL - appears to be associated with clonal evolution/disease progression in acute leukaemia, a high risk for AML progression in MDS/CMML and a high incidence of disease relapse. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation

    PubMed Central

    Jo, Stephanie Y.; Granowicz, Eric M.; Maillard, Ivan; Thomas, Dafydd

    2011-01-01

    Disruptor of telomeric silencing 1-like (Dot1l) is a histone 3 lysine 79 methyltransferase. Studies of constitutive Dot1l knockout mice show that Dot1l is essential for embryonic development and prenatal hematopoiesis. DOT1L also interacts with translocation partners of Mixed Lineage Leukemia (MLL) gene, which is commonly translocated in human leukemia. However, the requirement of Dot1l in postnatal hematopoiesis and leukemogenesis of MLL translocation proteins has not been conclusively shown. With a conditional Dot1l knockout mouse model, we examined the consequences of Dot1l loss in postnatal hematopoiesis and MLL translocation leukemia. Deletion of Dot1l led to pancytopenia and failure of hematopoietic homeostasis, and Dot1l-deficient cells minimally reconstituted recipient bone marrow in competitive transplantation experiments. In addition, MLL-AF9 cells required Dot1l for oncogenic transformation, whereas cells with other leukemic oncogenes, such as Hoxa9/Meis1 and E2A-HLF, did not. These findings illustrate a crucial role of Dot1l in normal hematopoiesis and leukemogenesis of specific oncogenes. PMID:21398221

  12. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study

    PubMed Central

    Ruppert, Amy S.; Marcucci, Guido; Mrózek, Krzysztof; Paschka, Peter; Langer, Christian; Baldus, Claudia D.; Wen, Jing; Vukosavljevic, Tamara; Powell, Bayard L.; Carroll, Andrew J.; Kolitz, Jonathan E.; Larson, Richard A.; Caligiuri, Michael A.; Bloomfield, Clara D.

    2007-01-01

    The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P = .39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P = .67 and P = .55, respectively). Thirteen MLL-PTD+ patients relapsed within 1.4 years of achieving CR. MLL-PTD+ patients who relapsed more often had other adverse CN-AML–associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD+ patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD. PMID:17341662

  13. Mutations in Mll2, an H3K4 Methyltransferase, Result in Insulin Resistance and Impaired Glucose Tolerance in Mice

    PubMed Central

    Schröter, David; Matthews, Helen C.; Bogani, Debora; Moir, Lee; Long, Anna; Church, Christopher; Hugill, Alison; Anstee, Quentin M.; Goldin, Rob; Thursz, Mark; Hollfelder, Florian; Cox, Roger D.

    2013-01-01

    We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5–14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level. PMID:23826075

  14. An Evolutionary Conserved Epigenetic Mark of Polycomb Response Elements Implemented by Trx/MLL/COMPASS.

    PubMed

    Rickels, Ryan; Hu, Deqing; Collings, Clayton K; Woodfin, Ashley R; Piunti, Andrea; Mohan, Man; Herz, Hans-Martin; Kvon, Evgeny; Shilatifard, Ali

    2016-07-21

    Polycomb response elements (PREs) are specific DNA sequences that stably maintain the developmental pattern of gene expression. Drosophila PREs are well characterized, whereas the existence of PREs in mammals remains debated. Accumulating evidence supports a model in which CpG islands recruit Polycomb group (PcG) complexes; however, which subset of CGIs is selected to serve as PREs is unclear. Trithorax (Trx) positively regulates gene expression in Drosophila and co-occupies PREs to antagonize Polycomb-dependent silencing. Here we demonstrate that Trx-dependent H3K4 dimethylation (H3K4me2) marks Drosophila PREs and maintains the developmental expression pattern of nearby genes. Similarly, the mammalian Trx homolog, MLL1, deposits H3K4me2 at CpG-dense regions that could serve as PREs. In the absence of MLL1 and H3K4me2, H3K27me3 levels, a mark of Polycomb repressive complex 2 (PRC2), increase at these loci. By inhibiting PRC2-dependent H3K27me3 in the absence of MLL1, we can rescue expression of these loci, demonstrating a functional balance between MLL1 and PRC2 activities at these sites. Thus, our study provides rules for identifying cell-type-specific functional mammalian PREs within the human genome. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Complete molecular remission in relapsed and refractory acute myeloid leukaemia with MLL-AF9 treated with chidamide-based chemotherapy.

    PubMed

    Lun, Y; Yang, J-J; Wu, Y

    2017-12-01

    The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy. Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor that is clinically active in relapsed and refractory peripheral T-cell lymphomas. To the best of our knowledge, successful reinduction treatment on relapsed MLL-AF9 by chidamide-based regimen has not been previously reported. © 2017 John Wiley & Sons Ltd.

  16. MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation

    PubMed Central

    Sebastian, Soji; Sreenivas, Prethish; Sambasivan, Ramkumar; Cheedipudi, Sirisha; Kandalla, Prashanth; Pavlath, Grace K.; Dhawan, Jyotsna

    2009-01-01

    Most cells in adult tissues are nondividing. In skeletal muscle, differentiated myofibers have exited the cell cycle permanently, whereas satellite stem cells withdraw transiently, returning to active proliferation to repair damaged myofibers. We have examined the epigenetic mechanisms operating in conditional quiescence by analyzing the function of a predicted chromatin regulator mixed lineage leukemia 5 (MLL5) in a culture model of reversible arrest. MLL5 is induced in quiescent myoblasts and regulates both the cell cycle and differentiation via a hierarchy of chromatin and transcriptional regulators. Knocking down MLL5 delays entry of quiescent myoblasts into S phase, but hastens S-phase completion. Cyclin A2 (CycA) mRNA is no longer restricted to S phase, but is induced throughout G0/G1, with activation of the cell cycle regulated element (CCRE) in the CycA promoter. Overexpressed MLL5 physically associates with the CCRE and impairs its activity. MLL5 also regulates CycA indirectly: Cux, an activator of CycA promoter and S phase is induced in RNAi cells, and Brm/Brg1, CCRE-binding repressors that promote differentiation are repressed. In knockdown cells, H3K4 methylation at the CCRE is reduced, reflecting quantitative global changes in methylation. MLL5 appears to lack intrinsic histone methyl transferase activity, but regulates expression of histone-modifying enzymes LSD1 and SET7/9, suggesting an indirect mechanism. Finally, expression of muscle regulators Pax7, Myf5, and myogenin is impaired in MLL5 knockdown cells, which are profoundly differentiation defective. Collectively, our results suggest that MLL5 plays an integral role in novel chromatin regulatory mechanisms that suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. PMID:19264965

  17. SON and its alternatively spliced isoforms control MLL complex-mediated H3K4me3 and transcription of leukemia-associated genes

    PubMed Central

    Kim, Jung-Hyun; Baddoo, Melody C.; Park, Eun Young; Stone, Joshua K.; Park, Hyeonsoo; Butler, Thomas W.; Huang, Gang; Yan, Xiaomei; Pauli-Behn, Florencia; Myers, Richard M.; Tan, Ming; Flemington, Erik K.; Lim, Ssang-Taek; Erin Ahn, Eun-Young

    2016-01-01

    SUMMARY Dysregulation of MLL complex-mediated histone methylation plays a pivotal role in gene expression associated with diseases, but little is known about cellular factors modulating MLL complex activity. Here, we report that SON, previously known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation. SON binds to DNA near transcription start sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and transcriptional repression. Importantly, alternatively spliced short isoforms of SON are markedly upregulated in acute myeloid leukemia. The short isoforms compete with full-length SON for chromatin occupancy, but lack the menin-binding ability, thereby antagonizing full-length SON function in transcriptional repression while not impairing full-length SON-mediated RNA splicing. Furthermore, overexpression of a short isoform of SON enhances replating potential of hematopoietic progenitors. Our findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpression as a marker indicating aberrant transcriptional initiation in leukemia. PMID:26990989

  18. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    PubMed Central

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

    2015-01-01

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  19. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    PubMed

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  20. Nm-scale spatial resolution x-ray imaging with MLL nanofocusing optics: instrumentational requirements and challenges

    SciTech Connect

    Nazaretski, E.; Yan, H.; Lauer, K.

    2016-08-30

    The Hard X-ray Nanoprobe (HXN) beamline at NSLS-II has been designed and constructed to enable imaging experiments with unprecedented spatial resolution and detection sensitivity. The HXN X-ray Microscope is a key instrument for the beamline, providing a suite of experimental capabilities which includes scanning fluorescence, diffraction, differential phase contrast and ptychography utilizing Multilayer Laue Lenses (MLL) and zoneplate (ZP) as nanofocusing optics. In this paper, we present technical requirements for the MLL-based scanning microscope, outline the development concept and present first ~15 x 15 nm 2 spatial resolution x-ray fluorescence images.

  1. Conformational Control of the Binding of the Transactivation Domain of the MLL Protein and c-Myb to the KIX Domain of CREB

    PubMed Central

    Korkmaz, Elif Nihal; Nussinov, Ruth; Haliloğlu, Türkan

    2012-01-01

    The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation domain of proto-oncogene protein c-Myb and the transactivation domain of the trithorax group protein mixed lineage leukemia (MLL) transcription factor lead to the biologically active ternary MLL∶KIX∶c-Myb complex which plays a role in Pol II-mediated transcription. The binding of the activation domain of MLL to KIX enhances c-Myb binding. Here we carried out molecular dynamics (MD) simulations for the MLL∶KIX∶c-Myb ternary complex, its binary components and KIX with the goal of providing a mechanistic explanation for the experimental observations. The dynamic behavior revealed that the MLL binding site is allosterically coupled to the c-Myb binding site. MLL binding redistributes the conformational ensemble of KIX, leading to higher populations of states which favor c-Myb binding. The key element in the allosteric communication pathways is the KIX loop, which acts as a control mechanism to enhance subsequent binding events. We tested this conclusion by in silico mutations of loop residues in the KIX∶MLL complex and by comparing wild type and mutant dynamics through MD simulations. The loop assumed MLL binding conformation similar to that observed in the KIX∶c-Myb state which disfavors the allosteric network. The coupling with c-Myb binding site faded, abolishing the positive cooperativity observed in the presence of MLL. Our major conclusion is that by eliciting a loop-mediated allosteric switch between the different states following the binding events, transcriptional activation can be regulated. The KIX system presents an example how nature makes use of conformational control in higher level regulation of transcriptional activity and thus cellular events. PMID:22438798

  2. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes.

    PubMed

    Dhar, Shilpa S; Zhao, Dongyu; Lin, Tao; Gu, Bingnan; Pal, Khusboo; Wu, Sarah J; Alam, Hunain; Lv, Jie; Yun, Kyuson; Gopalakrishnan, Vidya; Flores, Elsa R; Northcott, Paul A; Rajaram, Veena; Li, Wei; Shilatifard, Ali; Sillitoe, Roy V; Chen, Kaifu; Lee, Min Gyu

    2018-06-07

    Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. B-cell acute lymphoblastic leukemia with mature phenotype and MLL rearrangement: report of five new cases and review of the literature.

    PubMed

    Sajaroff, Elisa Olga; Mansini, Adrian; Rubio, Patricia; Alonso, Cristina Noemí; Gallego, Marta S; Coccé, Mariela C; Eandi-Eberle, Silvia; Bernasconi, Andrea Raquel; Ampatzidou, Maria; Paterakis, George; Papadhimitriou, Stefanos I; Petrikkos, Loizos; Papadakis, Vassilios; Polychronopoulou, Sophia; Rossi, Jorge G; Felice, Maria Sara

    2016-10-01

    The association between mature-B phenotype and MLL abnormalities in acute lymphoblastic leukemia (ALL) is a very unusual finding; only 14 pediatric cases have been reported so far. We describe the clinical and biological characteristics and outcome of five pediatric cases of newly diagnosed B lineage ALL with MLL abnormalities and mature immunophenotype based on light chain restriction and surface Ig expression. Blasts showed variable expression of CD10/CD34/TdT. MLL abnormalities with no MYC involvement were detected in all patients by G-banding, FISH, and/or RT-PCR. Three patients were treated according to Interfant protocol, one to ALLIC-09, and one received B-NHL-BFM-2004. All patients achieved complete remission and three of them relapsed. Despite the small cohort size, it could be postulated that B lineage ALL with MLL abnormalities and mature phenotype is a distinct entity that differs both from the typical Pro B ALL observed in infants and mature B-ALL with high MYC expression.

  4. Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid leukemia presenting with cardiorespiratory failure and meconium ileus.

    PubMed

    Gyárfás, Tobias; Wintgens, Juergen; Biskup, Wolfgang; Oschlies, Ilske; Klapper, Wolfram; Siebert, Reiner; Bens, Susanne; Haferlach, Claudia; Meisel, Roland; Kuhlen, Michaela; Borkhardt, Arndt

    2016-12-01

    Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of symptoms including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates. Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations are common in neonatal AML. A female neonate born at 34 weeks gestation presented with cardiorespiratory failure, hepatosplenomegaly, pancytopenia, and coagulopathy. She required intensive care treatment including mechanical ventilation, high-dose catecholamine therapy, and multiple transfusions. Small intestinal biopsy obtained during laparotomy for meconium ileus revealed an infiltrate by an undifferentiated monoblastic, MLL-rearranged leukemia. No other manifestations of leukemia could be detected. After spontaneous clinical remission, lasting 5 months without any specific treatment, the patient presented with leukemia cutis and full-blown monoblastic leukemia. MLL-AF10-rearranged AML could be re-diagnosed and successfully treated with chemotherapy and hematopoietic stem cell transplantation. Our patient exhibited a unique manifestation of neonatal MLL-AF10 rearranged AML with cardiorespiratory failure and intestinal infiltration. It highlights the importance of leukemia in the differential diagnosis of neonatal distress, congenital hematological abnormalities, and skin lesions.

  5. Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

    PubMed

    Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

    2015-11-01

    Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

  6. DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells.

    PubMed

    Klaus, Christine R; Iwanowicz, Dorothy; Johnston, Danielle; Campbell, Carly A; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Olhava, Edward J; Scott, Margaret Porter; Pollock, Roy M; Daigle, Scott R; Raimondi, Alejandra

    2014-09-01

    EPZ-5676 [(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol], a small-molecule inhibitor of the protein methyltransferase DOT1L, is currently under clinical investigation for acute leukemias bearing MLL-rearrangements (MLL-r). In this study, we evaluated EPZ-5676 in combination with standard of care (SOC) agents for acute leukemias as well as other chromatin-modifying drugs in cellular assays with three human acute leukemia cell lines: MOLM-13 (MLL-AF9), MV4-11 (MLL-AF4), and SKM-1 (non-MLL-r). Studies were performed to evaluate the antiproliferative effects of EPZ-5676 combinations in a cotreatment model in which the second agent was added simultaneously with EPZ-5676 at the beginning of the assay, or in a pretreatment model in which cells were incubated for several days in the presence of EPZ-5676 prior to the addition of the second agent. EPZ-5676 was found to act synergistically with the acute myeloid leukemia (AML) SOC agents cytarabine or daunorubicin in MOLM-13 and MV4-11 MLL-r cell lines. EPZ-5676 is selective for MLL-r cell lines as demonstrated by its lack of effect either alone or in combination in the nonrearranged SKM-1 cell line. In MLL-r cells, the combination benefit was observed even when EPZ-5676 was washed out prior to the addition of the chemotherapeutic agents, suggesting that EPZ-5676 sets up a durable, altered chromatin state that enhances the chemotherapeutic effects. Our evaluation of EPZ-5676 in conjunction with other chromatin-modifying drugs also revealed a consistent combination benefit, including synergy with DNA hypomethylating agents. These results indicate that EPZ-5676 is highly efficacious as a single agent and synergistically acts with other chemotherapeutics, including AML SOC drugs and DNA hypomethylating agents in MLL-r cells. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  7. Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model.

    PubMed

    Fu, Jen-Fen; Liang, Sung-Tzu; Huang, Ying-Jung; Liang, Kung-Hao; Yen, Tzung-Hai; Liang, Der-Cherng; Shih, Lee-Yung

    2017-03-01

    PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11 G503A . To study the impact of PTPN11 G503A cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared to the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 wt , the cells harboring PTPN11 G503A were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine. The cells harboring PTPN11 G503A autonomously differentiated into macrophages (1.8%) in the medium containing IL3. Further studies showed that the cells had an elevated (∼2.9-fold) Csf1 transcription level and secreted more (∼4.5-fold) M-CSF to the medium which can stimulate monocyte/macrophage differentiation of BM cells. Mice transplanted with the cells harboring PTPN11 G503A had a higher concentration of M-CSF in plasma. When mixed with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 wt , the cells harboring PTPN11 G503A had an increased competitive engraftment and clonal expansion in the BM and spleen of recipient mice, although no competitive growth advantage was observed in the in vitro co-culturing assays. The mice transplanted with the MLL/AF10(OM-LZ) cells harboring PTPN11 wt developed myelomonocytic leukemia, while those transplanted with the cells harboring PTPN11 G503A -induced monocytic leukemia in a shorter latency. Our results demonstrated that addition of PTPN11 G503A to MLL/AF10 affected cell proliferation, chemo-resistance, differentiation, in vivo BM recruitment/clonal expansion and accelerated disease progression. © 2016 UICC.

  8. Morus alba Leaf Lectin (MLL) Sensitizes MCF-7 Cells to Anoikis by Inhibiting Fibronectin Mediated Integrin-FAK Signaling through Ras and Activation of P38 MAPK

    PubMed Central

    Saranya, Jayaram; Shilpa, Ganesan; Raghu, Kozhiparambil G.; Priya, Sulochana

    2017-01-01

    Lectins are a unique class of carbohydrate binding proteins/glycoproteins, and many of them possess anticancer properties. They can induce cell cycle arrest and apoptosis, inhibit protein synthesis, telomerase activity and angiogenesis in cancer cells. In the present study, we have demonstrated the effect of Morus alba leaf lectin (MLL) on anoikis induction in MCF-7 cells. Anoikis induction in cancer cells has a significant role in preventing early stage metastasis. MLL treatment in monolayers of MCF-7 cells caused significant detachment of cells in a time and concentration dependent manner. The detached cells failed to re-adhere and grew even to culture plates coated with different matrix proteins. DNA fragmentation, membrane integrity studies, annexin V staining, caspase 9 activation and upregulation of Bax/Bad confirmed that the detached cells underwent apoptosis. Upregulation of matrix metalloproteinase 9 (MMP-9) caused a decrease in fibronectin (FN) production which facilitated the cells to detach by blocking the FN mediated downstream signaling. On treatment with MLL, we have observed downregulation of integrin expression, decreased phosphorylation of focal adhesion kinase (FAK), loss in FAK-integrin interaction and active Ras. MLL treatment downregulated the levels of phosphorylated Akt and PI3K. Also, we have studied the effect of MLL on two stress activated protein kinases p38 MAPK and JNK. p38 MAPK activation was found to be elevated, but there was no change in the level of JNK. Thus our study substantiated the possible antimetastatic effect of MLL by inducing anoikis in MCF-7 cells by activation of caspase 9 and proapoptotic Bax/Bad by blockage of FN mediated integrin/FAK signaling and partly by activation of p38 MAPK. PMID:28223935

  9. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

    SciTech Connect

    Karatas, Hacer; Li, Yangbing; Liu, Liu

    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis formore » their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.« less

  10. Enhancers of Polycomb EPC1 and EPC2 sustain the oncogenic potential of MLL leukemia stem cells

    PubMed Central

    Huang, Xu; Spencer, Gary J; Lynch, James T; Ciceri, Filippo; Somerville, Tim D D; Somervaille, Tim C P

    2013-01-01

    Through a targeted knockdown (KD) screen of chromatin regulatory genes we identified the EP400 complex components EPC1 and EPC2 as critical oncogenic co-factors in acute myeloid leukemia (AML). EPC1 and EPC2 were required for the clonogenic potential of human AML cells of multiple molecular subtypes. Focusing on MLL-mutated AML as an exemplar, Epc1 or Epc2 KD induced apoptosis of murine MLL-AF9 AML cells and abolished leukemia stem cell potential. By contrast, normal hematopoietic stem and progenitor cells (HSPC) were spared. Similar selectivity was observed for human primary AML cells versus normal CD34+ HSPC. In keeping with these distinct functional consequences, Epc1 or Epc2 KD induced divergent transcriptional consequences in murine MLL-AF9 granulocyte-macrophage progenitor-like (GMP) cells versus normal GMP, with a signature of increased MYC activity in leukemic but not normal cells. This was caused by accumulation of MYC protein and was also observed following KD of other EP400 complex genes. Pharmacological inhibition of MYC:MAX dimerization, or concomitant MYC KD, reduced apoptosis following EPC1 KD, linking the accumulation of MYC to cell death. Therefore EPC1 and EPC2 are components of a complex which directly or indirectly serves to prevent MYC accumulation and AML cell apoptosis, thus sustaining oncogenic potential. PMID:24166297

  11. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2007-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage (www.ncbi.nlm.nih.gov).

  12. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2006-01-01

    GenBank (R) is a comprehensive database that contains publicly available DNA sequences for more than 205 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the Web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at www.ncbi.nlm.nih.gov.

  13. GenBank

    PubMed Central

    Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Wheeler, David L.

    2007-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage (). PMID:17202161

  14. Taxonomic dissection of the genus Micrococcus: Kocuria gen. nov., Nesterenkonia gen. nov., Kytococcus gen. nov., Dermacoccus gen. nov., and Micrococcus Cohn 1872 gen. emend.

    PubMed

    Stackebrandt, E; Koch, C; Gvozdiak, O; Schumann, P

    1995-10-01

    The results of a phylogenetic and chemotaxonomic analysis of the genus Micrococcus indicated that it is significantly heterogeneous. Except for Micrococcus lylae, no species groups phylogenetically with the type species of the genus, Micrococcus luteus. The other members of the genus form three separate phylogenetic lines which on the basis of chemotaxonomic properties can be assigned to four genera. These genera are the genus Kocuria gen. nov. for Micrococcus roseus, Micrococcus varians, and Micrococcus kristinae, described as Kocuria rosea comb. nov., Kocuria varians comb. nov., and Kocuria kristinae comb. nov., respectively; the genus Nesterenkonia gen. nov. for Micrococcus halobius, described as Nesterenkonia halobia comb. nov.; the genus Nesterenkonia gen. nov. for Micrococcus halobius, described as Nesterenkonia halobia comb. nov.; the genus Dermacoccus gen. nov. for Micrococcus nishinomiyaensis, described as Dermacoccus nishinomiyaensis comb. nov.; and the genus Kytocossus gen. nov. for Micrococcus sedentarius, described as Kytococcus sedentarius comb. nov. M. luteus and M. lylae, which are closely related phylogenetically but differ in some chemotaxonomic properties, are the only species that remain in the genus Micrococcus Cohn 1872. An emended description of the genus Micrococcus is given [corrected].

  15. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2011-01-01

    GenBank® is a comprehensive database that contains publicly available nucleotide sequences for more than 380,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system that integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  16. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2009-01-01

    GenBank is a comprehensive database that contains publicly available nucleotide sequences for more than 300,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank(R) staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  17. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2005-01-01

    GenBank is a comprehensive database that contains publicly available DNA sequences for more than 165,000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  18. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2008-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 260 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  19. GenBank

    PubMed Central

    Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Wheeler, David L.

    2008-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 260 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov PMID:18073190

  20. Morel-Lavallee Lesion (MLL) Mimicking A Soft Tissue Neoplasm.

    PubMed

    Kumar, Sandeep; Hasan, Roumina; Kadavigere, Rajagopal; Maddukuri, Satish Babu; Puppala, Radha

    2015-04-01

    Morel-lavallee lesion (MLL) represents post traumatic subcutaneous cyst generally overlying bony prominences like greater trochanter, lower back, knee and scapula. A 51-year-old man presented with a swelling in left thigh since six years which was insidious in onset, gradually progressive in size and not associated with pain, fever or discharge. There was no history of trauma or any associated constitutional symptoms. Since there was no history of trauma recalled by the patient the clinical dilemma was between soft tissue sarcoma and cold abscess. We report a case of slow growing painless mass lesion of thigh, diagnosed on Magnetic Resonance Imaging (MRI) as morel lavallee lesion and describe its salient imaging features with treatment options.

  1. An Lnc RNA (GAS5)/SnoRNA-derived piRNA induces activation of TRAIL gene by site-specifically recruiting MLL/COMPASS-like complexes

    PubMed Central

    He, Xin; Chen, Xinxin; Zhang, Xue; Duan, Xiaobing; Pan, Ting; Hu, Qifei; Zhang, Yijun; Zhong, Fudi; Liu, Jun; Zhang, Hong; Luo, Juan; Wu, Kang; Peng, Gao; Luo, Haihua; Zhang, Lehong; Li, Xiaoxi; Zhang, Hui

    2015-01-01

    PIWI-interacting RNA (piRNA) silences the transposons in germlines or induces epigenetic modifications in the invertebrates. However, its function in the mammalian somatic cells remains unknown. Here we demonstrate that a piRNA derived from Growth Arrest Specific 5, a tumor-suppressive long non-coding RNA, potently upregulates the transcription of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a proapoptotic protein, by inducing H3K4 methylation/H3K27 demethylation. Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A). We have indicated a novel pathway for piRNAs to specially activate gene expression. Given that MLL3 or UTX are frequently mutated in various tumors, the piRNA/MLL3/UTX complex mediates the induction of TRAIL, and consequently leads to the inhibition of tumor growth. PMID:25779046

  2. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2010-01-01

    GenBank is a comprehensive database that contains publicly available nucleotide sequences for more than 300,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bi-monthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI homepage: www.ncbi.nlm.nih.gov.

  3. Pediatric acute myeloid leukemia with NPM1 mutations is characterized by a gene expression profile with dysregulated HOX gene expression distinct from MLL-rearranged leukemias.

    PubMed

    Mullighan, C G; Kennedy, A; Zhou, X; Radtke, I; Phillips, L A; Shurtleff, S A; Downing, J R

    2007-09-01

    Somatic mutations in nucleophosmin (NPM1) occur in approximately 35% of adult acute myeloid leukemia (AML). To assess the frequency of NPM1 mutations in pediatric AML, we sequenced NPM1 in the diagnostic blasts from 93 pediatric AML patients. Six cases harbored NPM1 mutations, with each case lacking common cytogenetic abnormalities. To explore the phenotype of the AMLs with NPM1 mutations, gene expression profiles were obtained using Affymetrix U133A microarrays. NPM1 mutations were associated with increased expression of multiple homeobox genes including HOXA9, A10, B2, B6 and MEIS1. As dysregulated homeobox gene expression is also a feature of MLL-rearranged leukemia, the gene expression signatures of NPM1-mutated and MLL-rearranged leukemias were compared. Significant differences were identified between these leukemia subtypes including the expression of different HOX genes, with NPM1-mutated AML showing higher levels of expression of HOXB2, B3, B6 and D4. These results confirm recent reports of perturbed HOX expression in NPM1-mutated adult AML, and provide the first evidence that the NPM1-mutated signature is distinct from MLL-rearranged AML. These findings suggest that mutated NPM1 leads to dysregulated HOX expression via a different mechanism than MLL rearrangement.

  4. Nucleoporin Nup98 associates with Trx/MLL and NSL histone-modifying complexes and regulates Hox gene expression.

    PubMed

    Pascual-Garcia, Pau; Jeong, Jieun; Capelson, Maya

    2014-10-23

    The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups). In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBD-R2/NSL [corrected] and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.

  5. Using GenBank.

    PubMed

    Wheeler, David

    2007-01-01

    GenBank(R) is a comprehensive database of publicly available DNA sequences for more than 205,000 named organisms and for more than 60,000 within the embryophyta, obtained through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Daily data exchange with the European Molecular Biology Laboratory (EMBL) in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases with taxonomy, genome, mapping, protein structure, and domain information and the biomedical journal literature through PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available through FTP. GenBank usage scenarios ranging from local analyses of the data available through FTP to online analyses supported by the NCBI Web-based tools are discussed. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  6. A case of pediatric B-Lymphoblastic leukemia presenting with a t(9;12)(p24;q11.2) involving JAK2 and concomitant MLL rearrangement with apparent insertion at 6q27

    PubMed Central

    2013-01-01

    Background B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in pediatric patients and the leading cause of cancer-related death in children and young adults. Translocations of 9p24 involving JAK2 (9p24) and gain-of-function mutations of JAK2 with subsequent activation of the JAK2 kinase have been described in several hematological malignancies including B-ALL. However, rearrangements involving JAK2 are rare in B-ALL as only few cases have been described in the literature. Findings Herein, we present a case of pediatric B-ALL whose conventional cytogenetics revealed an abnormal karyotype with a reciprocal translocation involving 9p24 (JAK2) and 12p11.2. Fluorescence in situ hybridization (FISH) studies using the RP11-927H16 Spectrum Green JAK2 probe on previously G-banded metaphases confirmed the involvement of JAK2 in this rearrangement. Further FISH studies on the same previously G-banded metaphases using the LSI MLL probe helped to characterize an insertion of MLL into 6q27 as an additional abnormality in this karyotype. FISH studies performed on interphase nuclei also revealed an abnormal clone with MLL rearrangements in 23.6% of the nuclei examined as well as an abnormal clonal population with a deletion of the 5'IGH@ region in 88.3% of the nuclei examined. Conclusions Rearrangements of 9p24 can result in constitutive activation of JAK2, and have been observed in B-ALL. Rearrangements of the MLL gene have also been described extensively in B-ALL. However, rearrangements of MLL with a partner at 6q27 and in conjunction with a translocation involving JAK2 have not been previously described. This case pinpoints the importance of FISH and conventional cytogenetics to characterize complex rearrangements in which JAK2 and MLL are involved. The therapeutic targeting of JAK2 and MLL in cases like this may be prognostically beneficial. PMID:24274401

  7. miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism

    PubMed Central

    Liu, Jun; Guo, Bo; Chen, Zhuo; Wang, Nayi; Iacovino, Michelina; Cheng, Jijun; Roden, Christine; Pan, Wen; Khan, Sajid; Chen, Suning; Kyba, Michael; Fan, Rong; Guo, Shangqin

    2017-01-01

    The hematopoietic stem cell–enriched miR-125 family microRNAs (miRNAs) are critical regulators of hematopoiesis. Overexpression of miR-125a or miR-125b is frequent in human acute myeloid leukemia (AML), and the overexpression of these miRNAs in mice leads to expansion of hematopoietic stem cells accompanied by perturbed hematopoiesis with mostly myeloproliferative phenotypes. However, whether and how miR-125 family miRNAs cooperate with known AML oncogenes in vivo, and how the resultant leukemia is dependent on miR-125 overexpression, are not well understood. We modeled the frequent co-occurrence of miR-125b overexpression and MLL translocations by examining functional cooperation between miR-125b and MLL-AF9. By generating a knock-in mouse model in which miR-125b overexpression is controlled by doxycycline induction, we demonstrated that miR-125b significantly enhances MLL-AF9–driven AML in vivo, and the resultant leukemia is partially dependent on continued overexpression of miR-125b. Surprisingly, miR-125b promotes AML cell expansion and suppresses apoptosis involving a non–cell-intrinsic mechanism. MiR-125b expression enhances VEGFA expression and production from leukemia cells, in part by suppressing TET2. Recombinant VEGFA recapitulates the leukemia-promoting effects of miR-125b, whereas knockdown of VEGFA or inhibition of VEGF receptor 2 abolishes the effects of miR-125b. In addition, significant correlation between miR-125b and VEGFA expression is observed in human AMLs. Our data reveal cooperative and dependent relationships between miR-125b and the MLL oncogene in AML leukemogenesis, and demonstrate a miR-125b-TET2-VEGFA pathway in mediating non–cell-intrinsic leukemia-promoting effects by an oncogenic miRNA. PMID:28053194

  8. An Fc-engineered CD19 antibody eradicates MRD in patient-derived MLL-rearranged acute lymphoblastic leukemia xenografts.

    PubMed

    Schewe, Denis M; Alsadeq, Ameera; Sattler, Cornelia; Lenk, Lennart; Vogiatzi, Fotini; Cario, Gunnar; Vieth, Simon; Valerius, Thomas; Rosskopf, Sophia; Meyersieck, Fabian; Alten, Julia; Schrappe, Martin; Gramatzki, Martin; Peipp, Matthias; Kellner, Christian

    2017-09-28

    Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, we tested an Fc-engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE). Patient-derived xenografts (PDX) of pediatric mixed-lineage leukemia gene ( MLL )-rearranged ALL were established in NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model. The majority of surviving mice remained polymerase chain reaction (PCR)-MRD negative after treatment. When antibody therapy was initiated in overt leukemia, antibody CD19-DE was still efficient in prolonging survival of xenografted mice in comparison with nontreated control animals, but the effects were less pronounced than in the MRD setting. Importantly, the combination of antibody CD19-DE and cytoreduction by chemotherapy (dexamethasone, vincristine, PEG-asparaginase) resulted in significantly improved survival rates in xenografted mice. Antibody CD19-DE treatment was also efficient in a randomized phase 2-like PDX trial using 13 MLL -rearranged BCP-ALL samples. Macrophage depletion by liposomal clodronate resulted in a reversal of the beneficial effects of CD19-DE, suggesting an important role for macrophages as effector cells. In support of this finding, CD19-DE was found to enhance phagocytosis of patient-derived ALL blasts by human macrophages in vitro. Thus, Fc-engineered CD19 antibodies may represent a promising treatment option for infants and children with MLL -rearranged BCP-ALL who have a poor outcome when treated with chemotherapy only. © 2017 by The American Society of Hematology.

  9. Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

    PubMed Central

    Driessen, Emma M.C.; van Roon, Eddy H.J.; Spijkers-Hagelstein, Jill A.P.; Schneider, Pauline; de Lorenzo, Paola; Valsecchi, Maria Grazia; Pieters, Rob; Stam, Ronald W.

    2013-01-01

    Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier results on the incidence of RAS mutations in Mixed Lineage Leukemia-rearranged acute lymphoblastic leukemia are inconclusive. Therefore, we studied frequencies and relation with clinical parameters of RAS mutations in a large cohort of infant acute lymphoblastic leukemia patients. Using conventional sequencing analysis, we screened neuroblastoma RAS viral (v-ras) oncogene homolog gene (NRAS), v-Ki-ras Kirsten rat sarcoma viral oncogene homolog gene (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) for mutations in a large cohort (n=109) of infant acute lymphoblastic leukemia patients and studied the mutations in relation to several clinical parameters, and in relation to Homeobox gene A9 expression and the presence of ALL1 fused gene 4-Mixed Lineage Leukemia (AF4-MLL). Mutations were detected in approximately 14% of all cases, with a higher frequency of approximately 24% in t(4;11)-positive patients (P=0.04). Furthermore, we identified RAS mutations as an independent predictor (P=0.019) for poor outcome in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia, with a hazard ratio of 3.194 (95% confidence interval (CI):1.211–8.429). Also, RAS-mutated infants have higher white blood cell counts at diagnosis (P=0.013), and are more resistant to glucocorticoids in vitro (P<0.05). Finally, we demonstrate that RAS mutations, and not the lack of Homeobox gene A9 expression nor the expression of AF4-MLL are associated with poor outcome in t(4;11)-rearranged infants. We conclude that the presence of RAS mutations in Mixed Lineage Leukemia

  10. TideGen LCOE Workbooks

    DOE Data Explorer

    Jarlath McEntee

    2016-03-21

    Workbooks showing Annualized Energy Production, Cost Breakdown Structure, Levelized Cost of Electricity for DOE Refernce Tidal Project 1) Baseline TidGen Power System 2) TidGen Power System with the application of Advanced Controls 3) Advanced TidGen Power System with several enhancements These files are provided as a zipped set. Files are linked together and must be viewed in the same folder.

  11. Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

    PubMed Central

    Cruickshank, M N; Ford, J; Cheung, L C; Heng, J; Singh, S; Wells, J; Failes, T W; Arndt, G M; Smithers, N; Prinjha, R K; Anderson, D; Carter, K W; Gout, A M; Lassmann, T; O'Reilly, J; Cole, C H; Kotecha, R S; Kees, U R

    2017-01-01

    To address the poor prognosis of mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (iALL), we generated a panel of cell lines from primary patient samples and investigated cytotoxic responses to contemporary and novel Food and Drug Administration-approved chemotherapeutics. To characterize representation of primary disease within cell lines, molecular features were compared using RNA-sequencing and cytogenetics. High-throughput screening revealed variable efficacy of currently used drugs, however identified consistent efficacy of three novel drug classes: proteasome inhibitors, histone deacetylase inhibitors and cyclin-dependent kinase inhibitors. Gene expression of drug targets was highly reproducible comparing iALL cell lines to matched primary specimens. Histone deacetylase inhibitors, including romidepsin (ROM), enhanced the activity of a key component of iALL therapy, cytarabine (ARAC) in vitro and combined administration of ROM and ARAC to xenografted mice further reduced leukemia burden. Molecular studies showed that ROM reduces expression of cytidine deaminase, an enzyme involved in ARAC deactivation, and enhances the DNA damage–response to ARAC. In conclusion, we present a valuable resource for drug discovery, including the first systematic analysis of transcriptome reproducibility in vitro, and have identified ROM as a promising therapeutic for MLL-rearranged iALL. PMID:27443263

  12. Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells

    PubMed Central

    Somervaille, Tim C. P.; Matheny, Christina J.; Spencer, Gary J.; Iwasaki, Masayuki; Rinn, John L.; Witten, Daniela M.; Chang, Howard Y.; Shurtleff, Sheila A.; Downing, James R.; Cleary, Michael L.

    2009-01-01

    Summary The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. PMID:19200802

  13. HoxBlinc RNA Recruits Set1/MLL Complexes to Activate Hox Gene Expression Patterns and Mesoderm Lineage Development.

    PubMed

    Deng, Changwang; Li, Ying; Zhou, Lei; Cho, Joonseok; Patel, Bhavita; Terada, Naohiro; Li, Yangqiu; Bungert, Jörg; Qiu, Yi; Huang, Suming

    2016-01-05

    Trithorax proteins and long-intergenic noncoding RNAs are critical regulators of embryonic stem cell pluripotency; however, how they cooperatively regulate germ layer mesoderm specification remains elusive. We report here that HoxBlinc RNA first specifies Flk1(+) mesoderm and then promotes hematopoietic differentiation through regulation of hoxb pathways. HoxBlinc binds to the hoxb genes, recruits Setd1a/MLL1 complexes, and mediates long-range chromatin interactions to activate transcription of the hoxb genes. Depletion of HoxBlinc by shRNA-mediated knockdown or CRISPR-Cas9-mediated genetic deletion inhibits expression of hoxb genes and other factors regulating cardiac/hematopoietic differentiation. Reduced hoxb expression is accompanied by decreased recruitment of Set1/MLL1 and H3K4me3 modification, as well as by reduced chromatin loop formation. Re-expression of hoxb2-b4 genes in HoxBlinc-depleted embryoid bodies rescues Flk1(+) precursors that undergo hematopoietic differentiation. Thus, HoxBlinc plays an important role in controlling hoxb transcription networks that mediate specification of mesoderm-derived Flk1(+) precursors and differentiation of Flk1(+) cells into hematopoietic lineages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. HoxBlinc RNA recruits Set1/MLL complexes to activate Hox gene expression patterns and mesoderm lineage development

    PubMed Central

    Deng, Changwang; Li, Ying; Zhou, Lei; Cho, Joonseok; Patel, Bhavita; Terada, Nao; Li, Yangqiu; Bungert, Jörg; Qiu, Yi; Huang, Suming

    2015-01-01

    Summary Trithorax proteins and long-intergenic noncoding RNAs are critical regulators of embryonic stem cell pluripotency; however, how they cooperatively regulate germ layer mesoderm specification remains elusive. We report here that HoxBlinc RNA first specifies Flk1+ mesoderm and then promotes hematopoietic differentiation through regulating hoxb gene pathways. HoxBlinc binds to the hoxb genes, recruits Setd1a/MLL1 complexes, and mediates long-range chromatin interactions to activate transcription of the hoxb genes. Depletion of HoxBlinc by shRNA-mediated KD or CRISPR-Cas9-mediated genetic deletion inhibits expression of hoxb genes and other factors regulating cardiac/hematopoietic differentiation. Reduced hoxb gene expression is accompanied by decreased recruitment of Set1/MLL1 and H3K4me3 modification, as well as by reduced chromatin loop formation. Re-expression of hoxb2-b4 genes in HoxBlinc-depleted embryoid bodies rescues Flk1+ precursors that undergo hematopoietic differentiation. Thus, HoxBlinc plays an important role in controlling hoxb transcription networks that mediate specification of mesoderm-derived Flk1+ precursors and differentiation of Flk1+ cells into hematopoietic lineages. PMID:26725110

  15. Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells

    PubMed Central

    Dai, Qian; Shen, Yang; Wang, Yan; Wang, Xin; Francisco, Joel Celio; Luo, Zhuojuan

    2017-01-01

    Abstract Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells. PMID:29036642

  16. A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex.

    PubMed

    Patel, Anamika; Vought, Valarie E; Dharmarajan, Venkatasubramanian; Cosgrove, Michael S

    2011-02-04

    Gene expression within the context of eukaryotic chromatin is regulated by enzymes that catalyze histone lysine methylation. Histone lysine methyltransferases that have been identified to date possess the evolutionarily conserved SET or Dot1-like domains. We previously reported the identification of a new multi-subunit histone H3 lysine 4 methyltransferase lacking homology to the SET or Dot1 family of histone lysine methyltransferases. This enzymatic activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell. Here, we report that the minimal complex required for WRAD enzymatic activity includes WDR5, RbBP5, and Ash2L and that DPY-30, although not required for enzymatic activity, increases the histone substrate specificity of the WRAD complex. We also show that WRAD requires zinc for catalytic activity, displays Michaelis-Menten kinetics, and is inhibited by S-adenosyl-homocysteine. In addition, we demonstrate that WRAD preferentially methylates lysine 4 of histone H3 within the context of the H3/H4 tetramer but does not methylate nucleosomal histone H3 on its own. In contrast, we find that MLL1 and WRAD are required for nucleosomal histone H3 methylation, and we provide evidence suggesting that each plays distinct structural and catalytic roles in the recognition and methylation of a nucleosome substrate. Our results indicate that WRAD is a new H3K4 methyltransferase with functions that include regulating the substrate and product specificities of the MLL1 core complex.

  17. Summary of CPAS Gen II Parachute Analysis

    NASA Technical Reports Server (NTRS)

    Morris, Aaron L.; Bledsoe, Kristin J.; Fraire, Usbaldo, Jr.; Moore, James W.; Olson, Leah M.; Ray, Eric

    2011-01-01

    The Orion spacecraft is currently under development by NASA and Lockheed Martin. Like Apollo, Orion will use a series of parachutes to slow its descent and splashdown safely. The Orion parachute system, known as the CEV Parachute Assembly System (CPAS), is being designed by NASA, the Engineering and Science Contract Group (ESCG), and Airborne Systems. The first generation (Gen I) of CPAS testing consisted of thirteen tests and was executed in the 2007-2008 timeframe. The Gen I tests provided an initial understanding of the CPAS parachutes. Knowledge gained from Gen I testing was used to plan the second generation of testing (Gen II). Gen II consisted of six tests: three singleparachute tests, designated as Main Development Tests, and three Cluster Development Tests. Gen II required a more thorough investigation into parachute performance than Gen I. Higher fidelity instrumentation, enhanced analysis methods and tools, and advanced test techniques were developed. The results of the Gen II test series are being incorporated into the CPAS design. Further testing and refinement of the design and model of parachute performance will occur during the upcoming third generation of testing (Gen III). This paper will provide an overview of the developments in CPAS analysis following the end of Gen I, including descriptions of new tools and techniques as well as overviews of the Gen II tests.

  18. AutoGen Version 5.0

    NASA Technical Reports Server (NTRS)

    Gladden, Roy E.; Khanampornpan, Teerapat; Fisher, Forest W.

    2010-01-01

    Version 5.0 of the AutoGen software has been released. Previous versions, variously denoted Autogen and autogen, were reported in two articles: Automated Sequence Generation Process and Software (NPO-30746), Software Tech Briefs (Special Supplement to NASA Tech Briefs), September 2007, page 30, and Autogen Version 2.0 (NPO- 41501), NASA Tech Briefs, Vol. 31, No. 10 (October 2007), page 58. To recapitulate: AutoGen (now signifying automatic sequence generation ) automates the generation of sequences of commands in a standard format for uplink to spacecraft. AutoGen requires fewer workers than are needed for older manual sequence-generation processes, and greatly reduces sequence-generation times. The sequences are embodied in spacecraft activity sequence files (SASFs). AutoGen automates generation of SASFs by use of another previously reported program called APGEN. AutoGen encodes knowledge of different mission phases and of how the resultant commands must differ among the phases. AutoGen also provides means for customizing sequences through use of configuration files. The approach followed in developing AutoGen has involved encoding the behaviors of a system into a model and encoding algorithms for context-sensitive customizations of the modeled behaviors. This version of AutoGen addressed the MRO (Mars Reconnaissance Orbiter) primary science phase (PSP) mission phase. On previous Mars missions this phase has more commonly been referred to as mapping phase. This version addressed the unique aspects of sequencing orbital operations and specifically the mission specific adaptation of orbital operations for MRO. This version also includes capabilities for MRO s role in Mars relay support for UHF relay communications with the MER rovers and the Phoenix lander.

  19. Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells.

    PubMed

    Dai, Qian; Shen, Yang; Wang, Yan; Wang, Xin; Francisco, Joel Celio; Luo, Zhuojuan; Lin, Chengqi

    2017-12-01

    Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression. Our studies also reveal that Zfp281 functions partially through recruiting the L1 regulators DNA hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s, leading to their balanced expression. In summary, our data indicate an instrumental role of Zfp281 in suppressing the young active L1s in mouse ES cells. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis.

    PubMed

    Dietrich, Philipp A; Yang, Chen; Leung, Halina H L; Lynch, Jennifer R; Gonzales, Estrella; Liu, Bing; Haber, Michelle; Norris, Murray D; Wang, Jianlong; Wang, Jenny Yingzi

    2014-11-20

    β-catenin is required for establishment of leukemic stem cells (LSCs) in acute myeloid leukemia (AML). Targeted inhibition of β-catenin signaling has been hampered by the lack of pathway components amenable to pharmacologic manipulation. Here we identified a novel β-catenin regulator, GPR84, a member of the G protein-coupled receptor family that represents a highly tractable class of drug targets. High GPR84 expression levels were confirmed in human and mouse AML LSCs compared with hematopoietic stem cells (HSCs). Suppression of GPR84 significantly inhibited cell growth by inducing G1-phase cell-cycle arrest in pre-LSCs, reduced LSC frequency, and impaired reconstitution of stem cell-derived mixed-lineage leukemia (MLL) AML, which represents an aggressive and drug-resistant subtype of AML. The GPR84-deficient phenotype in established AML could be rescued by expression of constitutively active β-catenin. Furthermore, GPR84 conferred a growth advantage to Hoxa9/Meis1a-transduced stem cells. Microarray analysis demonstrated that GPR84 significantly upregulated a small set of MLL-fusion targets and β-catenin coeffectors, and downregulated a hematopoietic cell-cycle inhibitor. Altogether, our data reveal a previously unrecognized role of GPR84 in maintaining fully developed AML by sustaining aberrant β-catenin signaling in LSCs, and suggest that targeting the oncogenic GPR84/β-catenin signaling axis may represent a novel therapeutic strategy for AML. © 2014 by The American Society of Hematology.

  1. Head-Worn Displays for NextGen

    NASA Technical Reports Server (NTRS)

    Bailey, Randall E.; Shelton, Kevin J.; Arthur, J. J.

    2011-01-01

    The operating concepts emerging under the Next Generation air transportation system (NextGen) require new technology and procedures - not only on the ground-side - but also on the flight deck. Flight deck display and decision support technologies are specifically targeted to overcome aircraft safety barriers that might otherwise constrain the full realization of NextGen. One such technology is the very lightweight, unobtrusive head-worn display (HWD). HWDs with an integrated head-tracking system are being researched as they offer significant potential benefit under emerging NextGen operational concepts. Two areas of benefit for NextGen are defined. First, the HWD may be designed to be equivalent to the Head-Up Display (HUD) using Virtual HUD concepts. As such, these operational credits may be provided to significantly more aircraft for which HUD installation is neither practical nor possible. Second, the HWD provides unique display capabilities, such as an unlimited field-of-regard. These capabilities may be integral to emerging NextGen operational concepts, eliminating safety issues which might otherwise constrain the full realization of NextGen. The paper details recent research results, current HWD technology limitations, and future technology development needed to realize HWDs as a enabling technology for NextGen.

  2. Review of the taxonomy of the genus Arthrobacter, emendation of the genus Arthrobacter sensu lato, proposal to reclassify selected species of the genus Arthrobacter in the novel genera Glutamicibacter gen. nov., Paeniglutamicibacter gen. nov., Pseudoglutamicibacter gen. nov., Paenarthrobacter gen. nov. and Pseudarthrobacter gen. nov., and emended description of Arthrobacter roseus.

    PubMed

    Busse, Hans-Jürgen

    2016-01-01

    In this paper, the taxonomy of the genus Arthrobacter is discussed, from its first description in 1947 to the present state. Emphasis is given to intrageneric phylogeny and chemotaxonomic characteristics, concentrating on quinone systems, peptidoglycan compositions and polar lipid profiles. Internal groups within the genus Arthrobacter indicated from homogeneous chemotaxonomic traits and corresponding to phylogenetic grouping and/or high 16S rRNA gene sequence similarities are highlighted. Furthermore, polar lipid profiles and quinone systems of selected species are shown, filling some gaps concerning these chemotaxonomic traits. Based on phylogenetic groupings, 16S rRNA gene sequence similarities and homogeneity in peptidoglycan types, quinone systems and polar lipid profiles, a description of the genus Arthrobacter sensu lato and an emended description of Arthrobacter roseus are provided. Furthermore, reclassifications of selected species of the genus Arthrobacter into novel genera are proposed, namely Glutamicibacter gen. nov. (nine species), Paeniglutamicibacter gen. nov. (six species), Pseudoglutamicibacter gen. nov. (two species), Paenarthrobacter gen. nov. (six species) and Pseudarthrobacter gen. nov. (ten species).

  3. Regulación del flujo sanguíneo uterino. II. Funciones de estrógeno y receptores estrogénicos α/β en acciones genómicas y no-genómicas del endotelio uterino *

    PubMed Central

    Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

    2015-01-01

    Resumen El embarazo está marcado por cambios y adaptaciones cardiovasculares que son importantes para el crecimiento y mantenimiento de la placenta y el feto. Durante este periodo, las adaptaciones vasculares uterinas manifiestan cambios clasificados como de corto o largo plazo los cuales están relacionados con adaptaciones vasodilatadoras, angiogénicas o de remodelación. El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsables por facilitar el incremento dramático en el fluido sanguíneo uterino necesario durante el embarazo. En ésta revisión bibliográfica se discuten la base estructural para la diversidad y selectividad funcional de los REs por el estrógeno, el papel de los REs sobre los efectos genómicos y no-genómicos en células endoteliales de arterias uterinas (CEAU). Estos temas integran el conocimiento científico sobre la regulación molecular de CEAU para mantener el incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113751

  4. RxGen General Optical Model Prescription Generator

    NASA Technical Reports Server (NTRS)

    Sigrist, Norbert

    2012-01-01

    RxGen is a prescription generator for JPL's in-house optical modeling software package called MACOS (Modeling and Analysis for Controlled Optical Systems), which is an expert optical analysis software package focusing on modeling optics on dynamic structures, deformable optics, and controlled optics. The objectives of RxGen are to simplify and automate MACOS prescription generations, reducing errors associated with creating such optical prescriptions, and improving user efficiency without requiring MACOS proficiency. RxGen uses MATLAB (a high-level language and interactive environment developed by MathWorks) as the development and deployment platform, but RxGen can easily be ported to another optical modeling/analysis platform. Running RxGen within the modeling environment has the huge benefit that variations in optical models can be made an integral part of the modeling state. For instance, optical prescription parameters determined as external functional dependencies, optical variations by controlling the in-/exclusion of optical components like sub-systems, and/or controlling the state of all components. Combining the mentioned capabilities and flexibilities with RxGen's optical abstraction layer completely eliminates the hindering aspects for requiring proficiency in writing/editing MACOS prescriptions, allowing users to focus on the modeling aspects of optical systems, i.e., increasing productivity and efficiency. RxGen provides significant enhancements to MACOS and delivers a framework for fast prototyping as well as for developing very complex controlled optical systems.

  5. FLT3-ITD and MLL-PTD influence the expression of MDR-1, MRP-1, and BCRP mRNA but not LRP mRNA assessed with RQ-PCR method in adult acute myeloid leukemia.

    PubMed

    Nasilowska-Adamska, Barbara; Solarska, Iwona; Paluszewska, Monika; Malinowska, Iwona; Jedrzejczak, Wieslaw W; Warzocha, Krzysztof

    2014-04-01

    Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed-lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations associated with leukemia which indicate unsatisfactory prognosis. Downstream regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA) in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid leukemia (AML) adult patients. The real-time quantitative polymerase chain reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP, and LRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. Significantly higher expressions of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05; p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p = 0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In univariate analysis, the high expression of MDR-1 mRNA (≥0.1317) negatively influenced the outcome of induction therapy (p = 0.05), whereas the high expression of BCRP mRNA (≥1.1487) was associated with a high relapse rate (RR) (p = 0.013). We found that the high expression of MDR-1 (≥0.1317), MRP-1 (≥0.8409), and BCRP mRNA (≥1.1487) significantly influenced disease-free survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA (≥1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and DFS (p = 0.002) in multivariate analysis. The significant correlation between the expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients requires further investigation.

  6. GenCade Version 1 Quick-Start Guide: How to Start a Successful GenCade Project

    DTIC Science & Technology

    2015-03-01

    Properly defining the inlets is a crucial part of a GenCade project and can be difficult. A user should become familiar with the Inlet Reservoir Model ( IRM ...GenCade Report 2 provide additional documentation on IRM variable names and functions. 3.9.4 Export data The data may easily be exported to a text

  7. Unleashing Gen Y: Marketing Mars to Millennials

    NASA Technical Reports Server (NTRS)

    Leahy, Bart D.; Hidalgo, Loretta; Kloberdanz, Cassie

    2007-01-01

    Space advocates need to engage Generation Y (born 1977-1999).This outreach is necessary to recruit the next generation of scientists and engineers to explore Mars. Space advocates in the non-profit, private, and government sectors need to use a combination of technical communication, marketing, and politics, to develop messages that resonate with Gen Y. Until now, space messages have been generated by and for college-educated white males; Gen Y is much more diverse, including as much as one third minorities. Young women, too, need to be reached. My research has shown that messages emphasizing technology, fun, humor, and opportunity are the best means of reaching the Gen Y audience of 60 million (US population is 300 million). The important things space advocates must avoid are talking down to this generation, making false promises, or expecting them to "wait their turn" before they can participate. This is the MTV generation! We need to find ways of engaging Gen Y now to build a future where human beings can live and work on the planet Mars. In addition to the messages themselves, advocates need to keep up with Gen Y' s social networking and use of iPods, cell phones, and the Internet. NASA and space advocacy groups can use these tools for "viral marketing," where young people share targeted space-related information via cell phones or the Internet because they like it. Overall, Gen Y is a socially dynamic and media-savvy group; advocates' space messages need to be sincere, creative, and placed in locations where Gen Y lives. Mars messages must be memorable!

  8. The Integrated Airport: Building a Successful NextGen Testbed

    SciTech Connect

    Frederick-Recascino, Christina; Sweigard, Doug; Lester, Wade

    2009-02-18

    This presentation will describe a unique public-private partnership - the Integrated Airport - that was created to engage in research and testing related to NextGen Technology deployment.  NextGen refers to the program that will be initiated to modernize the US National Airspace.  As with any major, multi-decade initiative, such as NextGen, integration of work efforts by multiple partners in the modernization is critical for success.  This talk will focus on the development of the consortium, how the consortium plans for NextGen initiatives, the series of technology demonstrations we have produced and plans for the future of NextGen testing and implementation. 

  9. The Integrated Airport: Building a Successful NextGen Testbed

    ScienceCinema

    Frederick-Recascino, Christina; Sweigard, Doug; Lester, Wade

    2018-01-24

    This presentation will describe a unique public-private partnership - the Integrated Airport - that was created to engage in research and testing related to NextGen Technology deployment.  NextGen refers to the program that will be initiated to modernize the US National Airspace.  As with any major, multi-decade initiative, such as NextGen, integration of work efforts by multiple partners in the modernization is critical for success.  This talk will focus on the development of the consortium, how the consortium plans for NextGen initiatives, the series of technology demonstrations we have produced and plans for the future of NextGen testing and implementation. 

  10. Factors Influencing Retention of Gen Y and Non-Gen Y Teachers Working at International Schools in Asia

    ERIC Educational Resources Information Center

    Fong, Hoi Wah Benny

    2018-01-01

    Quantitative studies on international-school teacher retention are few, especially studies that differentiate between Gen Y and non-Gen Y teachers. This article reports on the findings of a study that examined the relationship of job satisfaction factors to the likelihood of contract renewal by international-school teachers. Results from the study…

  11. J3Gen: A PRNG for Low-Cost Passive RFID

    PubMed Central

    Melià-Seguí, Joan; Garcia-Alfaro, Joaquin; Herrera-Joancomartí, Jordi

    2013-01-01

    Pseudorandom number generation (PRNG) is the main security tool in low-cost passive radio-frequency identification (RFID) technologies, such as EPC Gen2. We present a lightweight PRNG design for low-cost passive RFID tags, named J3Gen. J3Gen is based on a linear feedback shift register (LFSR) configured with multiple feedback polynomials. The polynomials are alternated during the generation of sequences via a physical source of randomness. J3Gen successfully handles the inherent linearity of LFSR based PRNGs and satisfies the statistical requirements imposed by the EPC Gen2 standard. A hardware implementation of J3Gen is presented and evaluated with regard to different design parameters, defining the key-equivalence security and nonlinearity of the design. The results of a SPICE simulation confirm the power-consumption suitability of the proposal. PMID:23519344

  12. Dedicated Caravan Sites for French Gens du Voyage

    PubMed Central

    2017-01-01

    Abstract In France, gens du voyage (“people who travel” or “travellers”) is a term used by the government to categorize various itinerant populations, the majority of which are diverse Romani groups. People categorized as gens du voyage are legally required to reside in particular locations called “dedicated caravan sites.” Parliamentary debates about these dedicated caravan sites have clarified that one of the objectives of such sites is to help fulfill the gens du voyage’s right to health. However, there is a significant gap between the officially stated goals of such sites and the reality of life within them. This paper draws on research finding that the conditions in most dedicated caravan sites do not conform with the rights of gens du voyage to acceptable sanitary conditions and other underlying determinants of health. PMID:29302165

  13. Next Gen One Portal Usability Evaluation

    NASA Technical Reports Server (NTRS)

    Cross, E. V., III; Perera, J. S.; Hanson, A. M.; English, K.; Vu, L.; Amonette, W.

    2018-01-01

    Each exercise device on the International Space Station (ISS) has a unique, customized software system interface with unique layouts / hierarchy, and operational principles that require significant crew training. Furthermore, the software programs are not adaptable and provide no real-time feedback or motivation to enhance the exercise experience and/or prevent injuries. Additionally, the graphical user interfaces (GUI) of these systems present information through multiple layers resulting in difficulty navigating to the desired screens and functions. These limitations of current exercise device GUI's lead to increased crew time spent on initiating, loading, performing exercises, logging data and exiting the system. To address these limitations a Next Generation One Portal (NextGen One Portal) Crew Countermeasure System (CMS) was developed, which utilizes the latest industry guidelines in GUI designs to provide an intuitive ease of use approach (i.e., 80% of the functionality gained within 5-10 minutes of initial use without/limited formal training required). This is accomplished by providing a consistent interface using common software to reduce crew training, increase efficiency & user satisfaction while also reducing development & maintenance costs. Results from the usability evaluations showed the NextGen One Portal UI having greater efficiency, learnability, memorability, usability and overall user experience than the current Advanced Resistive Exercise Device (ARED) UI used by astronauts on ISS. Specifically, the design of the One-Portal UI as an app interface similar to those found on the Apple and Google's App Store, assisted many of the participants in grasping the concepts of the interface with minimum training. Although the NextGen One-Portal UI was shown to be an overall better interface, observations by the test facilitators noted specific exercise tasks appeared to have a significant impact on the NextGen One-Portal UI efficiency. Future updates to

  14. Hand-held optical imager (Gen-2): improved instrumentation and target detectability

    PubMed Central

    Gonzalez, Jean; DeCerce, Joseph; Erickson, Sarah J.; Martinez, Sergio L.; Nunez, Annie; Roman, Manuela; Traub, Barbara; Flores, Cecilia A.; Roberts, Seigbeh M.; Hernandez, Estrella; Aguirre, Wenceslao; Kiszonas, Richard

    2012-01-01

    Abstract. Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact (∼30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact (∼86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging. PMID:23224163

  15. Distributed Generation Market Demand Model (dGen): Documentation

    SciTech Connect

    Sigrin, Benjamin; Gleason, Michael; Preus, Robert

    The Distributed Generation Market Demand model (dGen) is a geospatially rich, bottom-up, market-penetration model that simulates the potential adoption of distributed energy resources (DERs) for residential, commercial, and industrial entities in the continental United States through 2050. The National Renewable Energy Laboratory (NREL) developed dGen to analyze the key factors that will affect future market demand for distributed solar, wind, storage, and other DER technologies in the United States. The new model builds off, extends, and replaces NREL's SolarDS model (Denholm et al. 2009a), which simulates the market penetration of distributed PV only. Unlike the SolarDS model, dGen can modelmore » various DER technologies under one platform--it currently can simulate the adoption of distributed solar (the dSolar module) and distributed wind (the dWind module) and link with the ReEDS capacity expansion model (Appendix C). The underlying algorithms and datasets in dGen, which improve the representation of customer decision making as well as the spatial resolution of analyses (Figure ES-1), also are improvements over SolarDS.« less

  16. Recommendations and Requirements for GenCade Simluations

    DTIC Science & Technology

    2014-08-01

    sand transport model, GenCade. It is considered as a companion report to the first report in the GenCade series, Frey et al. (2012a), and provides...of output in *.slo (data extend both downward and to the right). .................. 31 Figure 20. Example of output for transport rates...shoreline (in red) and the transport rate at the beginning of the simulation (in blue). The initial shoreline position is shown in black. a

  17. Farewell to the Chairman - Marine Gen. Peter Pace

    Science.gov Websites

    oath of office from Marine Gen. Peter Pace, who retired after more than 40 years active duty military wife Lynne after giving the general his retirement certificate. Defense Dept. photo by Cherie A solutions, Marine Gen. Peter Pace said here today as he retired from the Marine Corps after more than 40

  18. 77 FR 54648 - Seventh Meeting: RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ...' license/State-issued ID Card Number and State of Issuance Company Phone number contact Non-U.S. Citizens... can be used for NextGen Metrics Data Sources for Measuring NextGen Fuel Impact A discussion of a preliminary report on a critical data source to track and analyze the impact of NextGen Non-Technical Barriers...

  19. From AWE-GEN to AWE-GEN-2d: a high spatial and temporal resolution weather generator

    NASA Astrophysics Data System (ADS)

    Peleg, Nadav; Fatichi, Simone; Paschalis, Athanasios; Molnar, Peter; Burlando, Paolo

    2016-04-01

    A new weather generator, AWE-GEN-2d (Advanced WEather GENerator for 2-Dimension grid) is developed following the philosophy of combining physical and stochastic approaches to simulate meteorological variables at high spatial and temporal resolution (e.g. 2 km x 2 km and 5 min for precipitation and cloud cover and 100 m x 100 m and 1 h for other variables variable (temperature, solar radiation, vapor pressure, atmospheric pressure and near-surface wind). The model is suitable to investigate the impacts of climate variability, temporal and spatial resolutions of forcing on hydrological, ecological, agricultural and geomorphological impacts studies. Using appropriate parameterization the model can be used in the context of climate change. Here we present the model technical structure of AWE-GEN-2d, which is a substantial evolution of four preceding models (i) the hourly-point scale Advanced WEather GENerator (AWE-GEN) presented by Fatichi et al. (2011, Adv. Water Resour.) (ii) the Space-Time Realizations of Areal Precipitation (STREAP) model introduced by Paschalis et al. (2013, Water Resour. Res.), (iii) the High-Resolution Synoptically conditioned Weather Generator developed by Peleg and Morin (2014, Water Resour. Res.), and (iv) the Wind-field Interpolation by Non Divergent Schemes presented by Burlando et al. (2007, Boundary-Layer Meteorol.). The AWE-GEN-2d is relatively parsimonious in terms of computational demand and allows generating many stochastic realizations of current and projected climates in an efficient way. An example of model application and testing is presented with reference to a case study in the Wallis region, a complex orography terrain in the Swiss Alps.

  20. 75 FR 56654 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA NextGen Advisory Committee (NAC) SUMMARY: The FAA published a Notice in the Federal Register on September 3, 2010 (75-FR-54221...

  1. A Comparison of the Single-sided (Gen II) and Double-sided (Gen I) Combat Arms Earplugs (CAE): Acoustic Properties, Human Performance, and User Acceptance

    DTIC Science & Technology

    2012-12-01

    results of steady-state and impulse noise attenuation objective and real-ear measurements; localization and speech intelligibility human performance... Intelligibility 12 6.1 Method...12 Figure 8. Speech intelligibility testing of Gen I CAE and Gen II CAE

  2. Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells.

    PubMed

    Yang, Zhao; Li, Chong; Fan, Zusen; Liu, Hongjie; Zhang, Xiaolong; Cai, Zhiming; Xu, Liqin; Luo, Jian; Huang, Yi; He, Luyun; Liu, Chunxiao; Wu, Song

    2017-01-01

    Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis. Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  3. GenSSI 2.0: multi-experiment structural identifiability analysis of SBML models.

    PubMed

    Ligon, Thomas S; Fröhlich, Fabian; Chis, Oana T; Banga, Julio R; Balsa-Canto, Eva; Hasenauer, Jan

    2018-04-15

    Mathematical modeling using ordinary differential equations is used in systems biology to improve the understanding of dynamic biological processes. The parameters of ordinary differential equation models are usually estimated from experimental data. To analyze a priori the uniqueness of the solution of the estimation problem, structural identifiability analysis methods have been developed. We introduce GenSSI 2.0, an advancement of the software toolbox GenSSI (Generating Series for testing Structural Identifiability). GenSSI 2.0 is the first toolbox for structural identifiability analysis to implement Systems Biology Markup Language import, state/parameter transformations and multi-experiment structural identifiability analysis. In addition, GenSSI 2.0 supports a range of MATLAB versions and is computationally more efficient than its previous version, enabling the analysis of more complex models. GenSSI 2.0 is an open-source MATLAB toolbox and available at https://github.com/genssi-developer/GenSSI. thomas.ligon@physik.uni-muenchen.de or jan.hasenauer@helmholtz-muenchen.de. Supplementary data are available at Bioinformatics online.

  4. 25 Years of GenBank

    MedlinePlus

    ... this page please turn Javascript on. Unique DNA database has helped advance scientific discoveries worldwide Since its origin 25 years ago, the database of nucleic acid sequences known as GenBank has ...

  5. Optimal time travel in the Gödel universe

    NASA Astrophysics Data System (ADS)

    Natário, José

    2012-04-01

    Using the theory of optimal rocket trajectories in general relativity, recently developed in Henriques and Natário (2011), we present a candidate for the minimum total integrated acceleration closed timelike curve in the Gödel universe, and give evidence for its minimality. The total integrated acceleration of this curve is lower than Malament's conjectured value (Malament 1984), as was already implicit in the work of Manchak (Gen. Relativ. Gravit. 51-60, 2011); however, Malament's conjecture does seem to hold for periodic closed timelike curves.

  6. 75 FR 54221 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA NextGen Advisory Committee (NAC... (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held September 23, 2010, from 8:30 a.m. to 11:30 a.m...

  7. DOE/NNSA perspective safeguard by design: GEN III/III+ light water reactors and beyond

    SciTech Connect

    Pan, Paul Y

    2010-12-10

    An overview of key issues relevant to safeguards by design (SBD) for GEN III/IV nuclear reactors is provided. Lessons learned from construction of typical GEN III+ water reactors with respect to SBD are highlighted. Details of SBD for safeguards guidance development for GEN III/III+ light water reactors are developed and reported. This paper also identifies technical challenges to extend SBD including proliferation resistance methodologies to other GEN III/III+ reactors (except HWRs) and GEN IV reactors because of their immaturity in designs.

  8. Towards an International Culture: Gen Y Students and SNS?

    ERIC Educational Resources Information Center

    Lichy, Jessica

    2012-01-01

    This article reports the findings of a small-scale investigation into the Internet user behaviour of generation Y (Gen Y) students, with particular reference to social networking sites. The study adds to the literature on cross-cultural Internet user behaviour with specific reference to Gen Y and social networking. It compares how a cohort of…

  9. Introducing AstroGen: the Astronomy Genealogy Project

    NASA Astrophysics Data System (ADS)

    Tenn, Joseph S.

    2016-12-01

    The Astronomy Genealogy Project (AstroGen), a project of the Historical Astronomy Division of the American Astronomical Society (AAS), will soon appear on the AAS website. Ultimately, it will list the world's astronomers with their highest degrees, theses for those who wrote them, academic advisors (supervisors), universities, and links to the astronomers or their obituaries, their theses when online, and more. At present the AstroGen team is working on those who earned doctorates with astronomy-related theses. We show what can be learned already, with just ten countries essentially completed.

  10. An electronic flight bag for NextGen avionics

    NASA Astrophysics Data System (ADS)

    Zelazo, D. Eyton

    2012-06-01

    The introduction of the Next Generation Air Transportation System (NextGen) initiative by the Federal Aviation Administration (FAA) will impose new requirements for cockpit avionics. A similar program is also taking place in Europe by the European Organisation for the Safety of Air Navigation (Eurocontrol) called the Single European Sky Air Traffic Management Research (SESAR) initiative. NextGen will require aircraft to utilize Automatic Dependent Surveillance-Broadcast (ADS-B) in/out technology, requiring substantial changes to existing cockpit display systems. There are two ways that aircraft operators can upgrade their aircraft in order to utilize ADS-B technology. The first is to replace existing primary flight displays with new displays that are ADS-B compatible. The second, less costly approach is to install an advanced Class 3 Electronic Flight Bag (EFB) system. The installation of Class 3 EFBs in the cockpit will allow aircraft operators to utilize ADS-B technology in a lesser amount of time with a decreased cost of implementation and will provide additional benefits to the operator. This paper describes a Class 3 EFB, the NexisTM Flight-Intelligence System, which has been designed to allow users a direct interface with NextGen avionics sensors while additionally providing the pilot with all the necessary information to meet NextGen requirements.

  11. Safety Assurance in NextGen

    NASA Technical Reports Server (NTRS)

    HarrisonFleming, Cody; Spencer, Melissa; Leveson, Nancy; Wilkinson, Chris

    2012-01-01

    The generation of minimum operational, safety, performance, and interoperability requirements is an important aspect of safely integrating new NextGen components into the Communication Navigation Surveillance and Air Traffic Management (CNS/ATM) system. These requirements are used as part of the implementation and approval processes. In addition, they provide guidance to determine the levels of design assurance and performance that are needed for each element of the new NextGen procedures, including aircraft, operator, and Air Navigation and Service Provider. Using the enhanced Airborne Traffic Situational Awareness for InTrail Procedure (ATSA-ITP) as an example, this report describes some limitations of the current process used for generating safety requirements and levels of required design assurance. An alternative process is described, as well as the argument for why the alternative can generate more comprehensive requirements and greater safety assurance than the current approach.

  12. Characterization of Photofrin photobleaching for singlet oxygen dose estimation during photodynamic therapy of MLL cells in vitro

    NASA Astrophysics Data System (ADS)

    Dysart, Jonathan S.; Patterson, Michael S.

    2005-06-01

    A singlet oxygen dose model is developed for PDT with Photofrin. The model is based on photosensitizer photobleaching kinetics, and incorporates both singlet oxygen and non-singlet oxygen mediated bleaching mechanisms. To test our model, in vitro experiments were performed in which MatLyLu (MLL) cells were incubated in Photofrin and then irradiated with 532 nm light. Photofrin fluorescence was monitored during treatment and, at selected fluence levels, cell viability was determined using a colony formation assay. Cell survival correlated well to calculated singlet oxygen dose, independent of initial Photofrin concentration or oxygenation. About 2 × 108 molecules of singlet oxygen per cell were required to reduce the surviving fraction by 1/e. Analysis of the photobleaching kinetics suggests that the lifetime of singlet oxygen in cells is 0.048 ± 0.005 µs. The generation of fluorescent photoproducts was not a result of singlet oxygen reactions exclusively, and therefore did not yield additional information to aid in quantifying singlet oxygen dose.

  13. TrafficGen Architecture Document

    DTIC Science & Technology

    2016-01-01

    sequence diagram ....................................................5 Fig. 5 TrafficGen traffic flows viewed in SDT3D...Scripts contain commands to have the network node listen on specific ports and flows describing the start time, stop time, and specific traffic ...arranged vertically and time presented horizontally. Individual traffic flows are represented by horizontal bars indicating the start time, stop time

  14. A Virtual Reality Framework to Optimize Design, Operation and Refueling of GEN-IV Reactors.

    SciTech Connect

    Rizwan-uddin; Nick Karancevic; Stefano Markidis

    2008-04-23

    many GEN-IV candidate designs are currently under investigation. Technical issues related to material, safety and economics are being addressed at research laboratories, industry and in academia. After safety, economic feasibility is likely to be the most important crterion in the success of GEN-IV design(s). Lessons learned from the designers and operators of GEN-II (and GEN-III) reactors must play a vital role in achieving both safety and economic feasibility goals.

  15. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov.

    PubMed

    Scholz, Christian F P; Kilian, Mogens

    2016-11-01

    The genus Propionibacterium in the family Propionibacteriaceaeconsists of species of various habitats, including mature cheese, cattle rumen and human skin. Traditionally, these species have been grouped as either classical or cutaneous propionibacteria based on characteristic phenotypes and source of isolation. To re-evaluate the taxonomy of the family and to elucidate the interspecies relatedness we compared 162 public whole-genome sequences of strains representing species of the family Propionibacteriaceae. We found substantial discrepancies between the phylogenetic signals of 16S rRNA gene sequence analysis and our high-resolution core-genome analysis. To accommodate these discrepancies, and to address the long-standing issue of the taxonomically problematic Propionibacterium propionicum, we propose three novel genera, Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov., and an amended description of the genus Propionibacterium. Furthermore, our genome-based analyses support the amounting evidence that the subdivision of Propionibacterium freudenreichii into subspecies is not warranted. Our proposals are supported by phylogenetic analyses, DNA G+C content, peptidoglycan composition and patterns of the gene losses and acquisitions in the cutaneous propionibacteria during their adaptation to the human host.

  16. High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group.

    PubMed

    Ho, Phoenix A; Alonzo, Todd A; Gerbing, Robert B; Pollard, Jessica A; Hirsch, Betsy; Raimondi, Susana C; Cooper, Todd; Gamis, Alan S; Meshinchi, Soheil

    2013-09-01

    Ectopic viral integration site-1 (EVI1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia (AML), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI1(high) , defined as expression in excess of normal controls, in paediatric AML. EVI1 mRNA expression was measured via quantitative real-time polymerase chain reaction in diagnostic specimens obtained from 206 patients. Expression levels were correlated with clinical features and outcome. EVI1(high) was present in 58/206 (28%) patients. MLL rearrangements occurred in 40% of EVI1(high) patients as opposed to 12% of the EVI1(low/absent) patients (P < 0·001). No abnormalities of 3q26 were found in EVI1(high) patients by conventional cytogenetic analysis, nor were cryptic 3q26 abnormalities detected in a subset of patients screened by next-generation sequencing. French-American-British class M7 was enriched in the EVI1(high) group, accounting for 24% of these patients. EVI1(high) patients had significantly lower 5-year overall survival from study entry (51% vs. 68%, P = 0·015). However, in multivariate analysis including other established prognostic markers, EVI1 expression did not retain independent prognostic significance. EVI1 expression is currently being studied in a larger cohort of patients enrolled on subsequent Children's Oncology Group trials, to determine if EVI1(high) has prognostic value in MLL-rearranged or intermediate-risk subsets. © 2013 John Wiley & Sons Ltd.

  17. Back to the FutureGen?

    SciTech Connect

    Buchsbaum, L.

    2009-04-15

    After years of political wrangling, Democrats may green-light the experimental clean coal power plants. The article relates how the project came to be curtailed, how Senator Dick Durbin managed to protect $134 million in funding for FutureGen in Mattoon, and how once Obama was in office a $2 billion line item to fund a 'near zero emissions power plant(s)' was placed in the Senate version of the Stimulus Bill. The final version of the legislation cut the funding to $1 billion for 'fossil energy research and development'. In December 2008 the FutureGen Alliance and the City of Mattoon spent $6.5more » billion to purchase the plants eventual 440 acre site. A report by the Government Accountability Office (GAO) said that Bush's inaction may have set back clean coal technology in the US by as much as a decade. If additional funding comes through construction of the plant could start in 2010. 1 fig., 1 photo.« less

  18. GenColors: annotation and comparative genomics of prokaryotes made easy.

    PubMed

    Romualdi, Alessandro; Felder, Marius; Rose, Dominic; Gausmann, Ulrike; Schilhabel, Markus; Glöckner, Gernot; Platzer, Matthias; Sühnel, Jürgen

    2007-01-01

    GenColors (gencolors.fli-leibniz.de) is a new web-based software/database system aimed at an improved and accelerated annotation of prokaryotic genomes considering information on related genomes and making extensive use of genome comparison. It offers a seamless integration of data from ongoing sequencing projects and annotated genomic sequences obtained from GenBank. A variety of export/import filters manages an effective data flow from sequence assembly and manipulation programs (e.g., GAP4) to GenColors and back as well as to standard GenBank file(s). The genome comparison tools include best bidirectional hits, gene conservation, syntenies, and gene core sets. Precomputed UniProt matches allow annotation and analysis in an effective manner. In addition to these analysis options, base-specific quality data (coverage and confidence) can also be handled if available. The GenColors system can be used both for annotation purposes in ongoing genome projects and as an analysis tool for finished genomes. GenColors comes in two types, as dedicated genome browsers and as the Jena Prokaryotic Genome Viewer (JPGV). Dedicated genome browsers contain genomic information on a set of related genomes and offer a large number of options for genome comparison. The system has been efficiently used in the genomic sequencing of Borrelia garinii and is currently applied to various ongoing genome projects on Borrelia, Legionella, Escherichia, and Pseudomonas genomes. One of these dedicated browsers, the Spirochetes Genome Browser (sgb.fli-leibniz.de) with Borrelia, Leptospira, and Treponema genomes, is freely accessible. The others will be released after finalization of the corresponding genome projects. JPGV (jpgv.fli-leibniz.de) offers information on almost all finished bacterial genomes, as compared to the dedicated browsers with reduced genome comparison functionality, however. As of January 2006, this viewer includes 632 genomic elements (e.g., chromosomes and plasmids) of 293

  19. CottonGen: a genomics, genetics and breeding database for cotton research

    USDA-ARS?s Scientific Manuscript database

    CottonGen (http://www.cottongen.org) is a curated and integrated web-based relational database providing access to publicly available genomic, genetic and breeding data for cotton. CottonGen supercedes CottonDB and the Cotton Marker Database, with enhanced tools for easier data sharing, mining, vis...

  20. NextGen Home Sperm Banking Kit: Outcomes of Offsite vs Onsite Collection--Preliminary Findings.

    PubMed

    Agarwal, Ashok; Sharma, Reecha; Gupta, Sajal; Sharma, Rakesh

    2015-06-01

    To compare cryosurvival rates between remote collections with NextGen kit (offsite) and onsite collection of semen samples from infertile men and those with cancer. Prefreeze and post-thaw sperm motility, total motile sperm, and percent cryosurvival rates were compared between samples collected from infertile men onsite at the Andrology Center (n = 10) and samples collected from infertile patients at home (offsite; n = 9), which were shipped by NextGen to our laboratory. A second group (n = 17) consisted of 10 semen samples from cancer patients collected onsite, which were compared with 7 semen samples from cancer patients shipped by the NextGen. All semen samples were assessed within 18 hours of collection. In the infertile men, percent cryosurvival rates were similar with NextGen compared with those of onsite collection (53.14 ± 28.9% vs 61.90 ± 20.46%; P = .51). Similarly, in the cancer patients, all 4 parameters were comparable between the onsite and NextGen. Cryosurvival rates were also similar between NextGen compared with those of onsite collection (52.71 ± 20.37% vs 58.90 ± 22.68%; P = .46). Cancer patients can bank sperm as effectively as men banking for infertility reasons using the NextGen kit. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. ORPC RivGen Acoustic Measurements

    DOE Data Explorer

    Brian Polagye

    2016-06-06

    Drifting hydrophone measurements obtained around the Ocean Renewable Power Company RivGen turbine near the village of Igiugig, Alaska in August, 2014. Each data set contains hydrophone voltage (as well as gain and sensitivity), position on the river (LAT, LONG, and proximity to turbine [xt, yt]), drift velocity, and contextual meteorological data.

  2. Extending Validated Human Performance Models to Explore NextGen Concepts

    NASA Technical Reports Server (NTRS)

    Gore, Brian Francis; Hooey, Becky Lee; Mahlstedt, Eric; Foyle, David C.

    2012-01-01

    To meet the expected increases in air traffic demands, NASA and FAA are researching and developing Next Generation Air Transportation System (NextGen) concepts. NextGen will require substantial increases in the data available to pilots on the flight deck (e.g., weather,wake, traffic trajectory predictions, etc.) to support more precise and closely coordinated operations (e.g., self-separation, RNAV/RNP, and closely spaced parallel operations, CSPOs). These NextGen procedures and operations, along with the pilot's roles and responsibilities, must be designed with consideration of the pilot's capabilities and limitations. Failure to do so will leave the pilots, and thus the entire aviation system, vulnerable to error. A validated Man-machine Integration and design Analysis System (MIDAS) v5 model was extended to evaluate anticipated changes to flight deck and controller roles and responsibilities in NextGen approach and Land operations. Compared to conditions when the controllers are responsible for separation on decent to land phase of flight, the output from these model predictions suggest that the flight deck response time to detect the lead aircraft blunder will decrease, pilot scans to the navigation display will increase, and workload will increase.

  3. 76 FR 28973 - Terra-Gen Dixie Valley, LLC; Order on Rehearing and Accepting Tariff Filing, Subject to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    .... Clustering and Effective Date i. Terra-Gen Tariff Provisions 15. Terra-Gen proposes provisions to address clustering of transmission system impact studies, consistent with the guidance provided in the January 14... on how Terra-Gen may cluster studies.\\22\\ Terra-Gen's proposed clustering provisions provide, among...

  4. SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance.

    PubMed

    Cruickshank, V Adam; Sroczynska, Patrycja; Sankar, Aditya; Miyagi, Satoru; Rundsten, Carsten Friis; Johansen, Jens Vilstrup; Helin, Kristian

    2015-01-01

    Alterations in chromatin structure caused by deregulated epigenetic mechanisms collaborate with underlying genetic lesions to promote cancer. SMARCA4/BRG1, a core component of the SWI/SNF ATP-dependent chromatin-remodelling complex, has been implicated by its mutational spectrum as exerting a tumour-suppressor function in many solid tumours; recently however, it has been reported to sustain leukaemogenic transformation in MLL-rearranged leukaemia in mice. Here we further explore the role of SMARCA4 and the two SWI/SNF subunits SMARCD2/BAF60B and DPF2/BAF45D in leukaemia. We observed the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes.

  5. 76 FR 54526 - Fourth Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held September 29, 2011 from 9 a.m. to 4 p.m...

  6. Validation of recent geopotential models in Tierra Del Fuego

    NASA Astrophysics Data System (ADS)

    Gomez, Maria Eugenia; Perdomo, Raul; Del Cogliano, Daniel

    2017-10-01

    This work presents a validation study of global geopotential models (GGM) in the region of Fagnano Lake, located in the southern Andes. This is an excellent area for this type of validation because it is surrounded by the Andes Mountains, and there is no terrestrial gravity or GNSS/levelling data. However, there are mean lake level (MLL) observations, and its surface is assumed to be almost equipotential. Furthermore, in this article, we propose improved geoid solutions through the Residual Terrain Modelling (RTM) approach. Using a global geopotential model, the results achieved allow us to conclude that it is possible to use this technique to extend an existing geoid model to those regions that lack any information (neither gravimetric nor GNSS/levelling observations). As GGMs have evolved, our results have improved progressively. While the validation of EGM2008 with MLL data shows a standard deviation of 35 cm, GOCO05C shows a deviation of 13 cm, similar to the results obtained on land.

  7. SIPSMetGen: It's Not Just For Aircraft Data and ECS Anymore.

    NASA Astrophysics Data System (ADS)

    Schwab, M.

    2015-12-01

    The SIPSMetGen utility, developed for the NASA EOSDIS project, under the EED contract, simplified the creation of file level metadata for the ECS System. The utility has been enhanced for ease of use, efficiency, speed and increased flexibility. The SIPSMetGen utility was originally created as a means of generating file level spatial metadata for Operation IceBridge. The first version created only ODL metadata, specific for ingest into ECS. The core strength of the utility was, and continues to be, its ability to take complex shapes and patterns of data collection point clouds from aircraft flights and simplify them to a relatively simple concave hull geo-polygon. It has been found to be a useful and easy to use tool for creating file level metadata for many other missions, both aircraft and satellite. While the original version was useful it had its limitations. In 2014 Raytheon was tasked to make enhancements to SIPSMetGen, this resulted a new version of SIPSMetGen which can create ISO Compliant XML metadata; provides optimization and streamlining of the algorithm for creating the spatial metadata; a quicker runtime with more consistent results; a utility that can be configured to run multi-threaded on systems with multiple processors. The utility comes with a java based graphical user interface to aid in configuration and running of the utility. The enhanced SIPSMetGen allows more diverse data sets to be archived with file level metadata. The advantage of archiving data with file level metadata is that it makes it easier for data users, and scientists to find relevant data. File level metadata unlocks the power of existing archives and metadata repositories such as ECS and CMR and search and discovery utilities like Reverb and Earth Data Search. Current missions now using SIPSMetGen include: Aquarius, Measures, ARISE, and Nimbus.

  8. 76 FR 3931 - Second Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held February 11, 2011 from 8:30 a.m. to 1 p.m...

  9. 76 FR 22162 - Third Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ... Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held May 19, 2011 from 9:30 a.m. to 2 p.m. ADDRESSES...

  10. Safer Systems: A NextGen Aviation Safety Strategic Goal

    NASA Technical Reports Server (NTRS)

    Darr, Stephen T.; Ricks, Wendell R.; Lemos, Katherine A.

    2008-01-01

    The Joint Planning and Development Office (JPDO), is charged by Congress with developing the concepts and plans for the Next Generation Air Transportation System (NextGen). The National Aviation Safety Strategic Plan (NASSP), developed by the Safety Working Group of the JPDO, focuses on establishing the goals, objectives, and strategies needed to realize the safety objectives of the NextGen Integrated Plan. The three goal areas of the NASSP are Safer Practices, Safer Systems, and Safer Worldwide. Safer Practices emphasizes an integrated, systematic approach to safety risk management through implementation of formalized Safety Management Systems (SMS) that incorporate safety data analysis processes, and the enhancement of methods for ensuring safety is an inherent characteristic of NextGen. Safer Systems emphasizes implementation of safety-enhancing technologies, which will improve safety for human-centered interfaces and enhance the safety of airborne and ground-based systems. Safer Worldwide encourages coordinating the adoption of the safer practices and safer systems technologies, policies and procedures worldwide, such that the maximum level of safety is achieved across air transportation system boundaries. This paper introduces the NASSP and its development, and focuses on the Safer Systems elements of the NASSP, which incorporates three objectives for NextGen systems: 1) provide risk reducing system interfaces, 2) provide safety enhancements for airborne systems, and 3) provide safety enhancements for ground-based systems. The goal of this paper is to expose avionics and air traffic management system developers to NASSP objectives and Safer Systems strategies.

  11. Next-Gen 3: Sequencing, Modeling, and Advanced Biofuels - Final Technical Report

    SciTech Connect

    Zengler, Karsten; Palsson, Bernhard; Lewis, Nathan

    Successful, scalable implementation of biofuels is dependent on the efficient and near complete utilization of diverse biomass sources. One approach is to utilize the large recalcitrant biomass fraction (or any organic waste stream) through the thermochemical conversion of organic compounds to syngas, a mixture of carbon monoxide (CO), carbon dioxide (CO 2), and hydrogen (H 2), which can subsequently be metabolized by acetogenic microorganisms to produce next-gen biofuels. The goal of this proposal was to advance the development of the acetogen Clostridium ljungdahlii as a chassis organism for next-gen biofuel production from cheap, renewable sources and to detail the interconnectivitymore » of metabolism, energy conservation, and regulation of acetogens using next-gen sequencing and next-gen modeling. To achieve this goal we determined optimization of carbon and energy utilization through differential translational efficiency in C. ljungdahlii. Furthermore, we reconstructed a next-generation model of all major cellular processes, such as macromolecular synthesis and transcriptional regulation and deployed this model to predicting proteome allocation, overflow metabolism, and metal requirements in this model acetogen. In addition we explored the evolutionary significance of tRNA operon structure using the next-gen model and determined the optimal operon structure for bioproduction. Our study substantially enhanced the knowledgebaase for chemolithoautotrophs and their potential for advanced biofuel production. It provides next-generation modeling capability, offer innovative tools for genome-scale engineering, and provide novel methods to utilize next-generation models for the design of tunable systems that produce commodity chemicals from inexpensive sources.« less

  12. On the ground spider genera Marjanus gen. n., Lasophorus gen. n. and Turkozelotes Kovblyuk Seyyar, 2009 (Araneae: Gnaphosidae) from Greece.

    PubMed

    Chatzaki, Maria

    2018-03-11

    New taxonomic data on the ground spiders of the family Gnaphosidae from Greece are presented. Two genera are proposed as new to science (Marjanus gen. n. and Lasophorus gen. n.) together with two new species (Lasophorus zakkak sp. n. and Lasophorus zografae sp. n.) and a new combination (Marjanus platnicki comb. nov.). Additionally the genus Turkozelotes Kovblyuk Seyyar, 2009 is here rediagnosed and the female of the type species T. microb Kovblyuk Seyyar, 2009 is described for the first time. The finding of the matching male of Setaphis mccowani Chatzaki Russell-Smith, 2017 suggests the transfer of this species to Turkozelotes and hence the male of T. mccowani comb. nov. is described for the first time. Taxonomic affinities of these genera and species are discussed.

  13. Technology evaluation: C242-DM1, ImmunoGen Inc.

    PubMed

    Smith, S

    2001-04-01

    C242-DM1 is a tumor-activated immunotoxin under development by GlaxoSmithKline plc (formerly SmithKline Beecham plc), under licence from ImmunoGen Inc, as a potential treatment for colon tumor. It consists of a colon cancer-specific humanized antibody, C242, conjugated to the maytansine derivative DM1. In preclinical studies, C242-DM1 caused complete tumor regression in animal models of both human pancreatic and non-small cell lung cancer (NSCLC) at non-toxic doses. C242-DM1 has also been evaluated in an immunoconjugate combination with J-591 (Cornell University). The J591-DM1 immunoconjugate demonstrated effective, antigen-specific delivery of a highly cytotoxic drug to PSMA-positive Pca cells in vitro and in vivo with low systemic toxicity. Results from studies in monkeys showed that C242-DM1 had no significant toxicity or side effects, when administered at doses higher than those that were previously shown to completely eradicate human colon tumors in mice [271420]. ImmunoGen acquired the right to evaluate, and an option to license, technology related to maytansines from Takeda. In February 1999, ImmunoGen and SmithKline Beecham signed a US $45 million development and commercialization agreement for C242-DM1 [313493]. In August 1997, Immunogen received an SBIR grant to advance development of huC242-DM1 [258356]. EP-00425235, held by ImmunoGen, covers conjugated forms of ansamitocin (maytansine) derivatives. Takeda holds several patents for the production of ansamitocin and its analogs, the first one being JP-53124692.

  14. Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia.

    PubMed

    Wang, Rong; Feng, Wenli; Yang, Feifei; Yang, Xiao; Wang, Lina; Chen, Chong; Hu, Yuting; Ren, Qian; Zheng, Guoguang

    2018-02-01

    Macrophage colony-stimulating factor (M-CSF) regulates both malignant cells and microenvironmental cells. Its splicing isoforms show functional heterogeneity. However, their roles on leukemia have not been well established. Here, the expression of total M-CSF in patients with hematopoietic malignancies was analyzed. The roles of M-CSF isoforms on the progression of acute myeloid leukemia (AML) were studied by establishing MLL-AF9-induced mouse AML models with high level membrane-bound M-CSF (mM-CSF) or soluble M-CSF (sM-CSF). Total M-CSF was highly expressed in myeloid leukemia patients. Furthermore, mM-CSF but not sM-CSF prolonged the survival of leukemia mice. While sM-CSF was more potent to promote proliferation and self-renew, mM-CSF was more potent to promote differentiation. Moreover, isoforms had different effects on leukemia-associated macrophages (LAMs) though they both increase monocytes/macrophages by growth-promoting and recruitment effects. In addition, mM-CSF promoted specific phagocytosis of leukemia cells by LAMs. RNA-seq analysis revealed that mM-CSF enhanced phagocytosis-associated genes and activated oxidative phosphorylation and metabolism pathway. These results highlight heterogeneous effects of M-CSF isoforms on AML progression and the mechanisms of mM-CSF, that is, intrinsically promoting AML cell differentiation and extrinsically enhancing infiltration of macrophages and phagocytosis by macrophages, which may provide potential clues for clinical diagnosis and therapy. © 2017 Australasian Society for Immunology Inc.

  15. Environmental Information for the U.S. Next Generation Air Transportation System (NextGen)

    NASA Astrophysics Data System (ADS)

    Murray, J.; Miner, C.; Pace, D.; Minnis, P.; Mecikalski, J.; Feltz, W.; Johnson, D.; Iskendarian, H.; Haynes, J.

    2009-09-01

    It is estimated that weather is responsible for approximately 70% of all air traffic delays and cancellations in the United States. Annually, this produces an overall economic loss of nearly 40B. The FAA and NASA have determined that weather impacts and other environmental constraints on the U.S. National Airspace System (NAS) will increase to the point of system unsustainability unless the NAS is radically transformed. A Next Generation Air Transportation System (NextGen) is planned to accommodate the anticipated demand for increased system capacity and the super-density operations that this transformation will entail. The heart of the environmental information component that is being developed for NextGen will be a 4-dimensional data cube which will include a single authoritative source comprising probabilistic weather information for NextGen Air Traffic Management (ATM) systems. Aviation weather constraints and safety hazards typically comprise meso-scale, storm-scale and microscale observables that can significantly impact both terminal and enroute aviation operations. With these operational impacts in mind, functional and performance requirements for the NextGen weather system were established which require significant improvements in observation and forecasting capabilities. This will include satellite observations from geostationary and/or polar-orbiting hyperspectral sounders, multi-spectral imagers, lightning mappers, space weather monitors and other environmental observing systems. It will also require improved in situ and remotely sensed observations from ground-based and airborne systems. These observations will be used to better understand and to develop forecasting applications for convective weather, in-flight icing, turbulence, ceilings and visibility, volcanic ash, space weather and the environmental impacts of aviation. Cutting-edge collaborative research efforts and results from NASA, NOAA and the FAA which address these phenomena are summarized

  16. The GenABEL Project for statistical genomics.

    PubMed

    Karssen, Lennart C; van Duijn, Cornelia M; Aulchenko, Yurii S

    2016-01-01

    Development of free/libre open source software is usually done by a community of people with an interest in the tool. For scientific software, however, this is less often the case. Most scientific software is written by only a few authors, often a student working on a thesis. Once the paper describing the tool has been published, the tool is no longer developed further and is left to its own device. Here we describe the broad, multidisciplinary community we formed around a set of tools for statistical genomics. The GenABEL project for statistical omics actively promotes open interdisciplinary development of statistical methodology and its implementation in efficient and user-friendly software under an open source licence. The software tools developed withing the project collectively make up the GenABEL suite, which currently consists of eleven tools. The open framework of the project actively encourages involvement of the community in all stages, from formulation of methodological ideas to application of software to specific data sets. A web forum is used to channel user questions and discussions, further promoting the use of the GenABEL suite. Developer discussions take place on a dedicated mailing list, and development is further supported by robust development practices including use of public version control, code review and continuous integration. Use of this open science model attracts contributions from users and developers outside the "core team", facilitating agile statistical omics methodology development and fast dissemination.

  17. The GenABEL Project for statistical genomics

    PubMed Central

    Karssen, Lennart C.; van Duijn, Cornelia M.; Aulchenko, Yurii S.

    2016-01-01

    Development of free/libre open source software is usually done by a community of people with an interest in the tool. For scientific software, however, this is less often the case. Most scientific software is written by only a few authors, often a student working on a thesis. Once the paper describing the tool has been published, the tool is no longer developed further and is left to its own device. Here we describe the broad, multidisciplinary community we formed around a set of tools for statistical genomics. The GenABEL project for statistical omics actively promotes open interdisciplinary development of statistical methodology and its implementation in efficient and user-friendly software under an open source licence. The software tools developed withing the project collectively make up the GenABEL suite, which currently consists of eleven tools. The open framework of the project actively encourages involvement of the community in all stages, from formulation of methodological ideas to application of software to specific data sets. A web forum is used to channel user questions and discussions, further promoting the use of the GenABEL suite. Developer discussions take place on a dedicated mailing list, and development is further supported by robust development practices including use of public version control, code review and continuous integration. Use of this open science model attracts contributions from users and developers outside the “core team”, facilitating agile statistical omics methodology development and fast dissemination. PMID:27347381

  18. PatGen--a consolidated resource for searching genetic patent sequences.

    PubMed

    Rouse, Richard J D; Castagnetto, Jesus; Niedner, Roland H

    2005-04-15

    Compared to the wealth of online resources covering genomic, proteomic and derived data the Bioinformatics community is rather underserved when it comes to patent information related to biological sequences. The current online resources are either incomplete or rather expensive. This paper describes, PatGen, an integrated database containing data from bioinformatic and patent resources. This effort addresses the inconsistency of publicly available genetic patent data coverage by providing access to a consolidated dataset. PatGen can be searched at http://www.patgendb.com rjdrouse@patentinformatics.com.

  19. GeoBoost: accelerating research involving the geospatial metadata of virus GenBank records.

    PubMed

    Tahsin, Tasnia; Weissenbacher, Davy; O'Connor, Karen; Magge, Arjun; Scotch, Matthew; Gonzalez-Hernandez, Graciela

    2018-05-01

    GeoBoost is a command-line software package developed to address sparse or incomplete metadata in GenBank sequence records that relate to the location of the infected host (LOIH) of viruses. Given a set of GenBank accession numbers corresponding to virus GenBank records, GeoBoost extracts, integrates and normalizes geographic information reflecting the LOIH of the viruses using integrated information from GenBank metadata and related full-text publications. In addition, to facilitate probabilistic geospatial modeling, GeoBoost assigns probability scores for each possible LOIH. Binaries and resources required for running GeoBoost are packed into a single zipped file and freely available for download at https://tinyurl.com/geoboost. A video tutorial is included to help users quickly and easily install and run the software. The software is implemented in Java 1.8, and supported on MS Windows and Linux platforms. gragon@upenn.edu. Supplementary data are available at Bioinformatics online.

  20. SimGen: A General Simulation Method for Large Systems.

    PubMed

    Taylor, William R

    2017-02-03

    SimGen is a stand-alone computer program that reads a script of commands to represent complex macromolecules, including proteins and nucleic acids, in a structural hierarchy that can then be viewed using an integral graphical viewer or animated through a high-level application programming interface in C++. Structural levels in the hierarchy range from α-carbon or phosphate backbones through secondary structure to domains, molecules, and multimers with each level represented in an identical data structure that can be manipulated using the application programming interface. Unlike most coarse-grained simulation approaches, the higher-level objects represented in SimGen can be soft, allowing the lower-level objects that they contain to interact directly. The default motion simulated by SimGen is a Brownian-like diffusion that can be set to occur across all levels of representation in the hierarchy. Links can also be defined between objects, which, when combined with large high-level random movements, result in an effective search strategy for constraint satisfaction, including structure prediction from predicted pairwise distances. The implementation of SimGen makes use of the hierarchic data structure to avoid unnecessary calculation, especially for collision detection, allowing it to be simultaneously run and viewed on a laptop computer while simulating large systems of over 20,000 objects. It has been used previously to model complex molecular interactions including the motion of a myosin-V dimer "walking" on an actin fibre, RNA stem-loop packing, and the simulation of cell motion and aggregation. Several extensions to this original functionality are described. Copyright © 2016 The Francis Crick Institute. Published by Elsevier Ltd.. All rights reserved.

  1. Testing the potential significance of different scion/rootstock genotype combinations on the ecology of old cultivated olive trees in the southeast Mediterranean area.

    PubMed

    Barazani, Oz; Waitz, Yoni; Tugendhaft, Yizhar; Dorman, Michael; Dag, Arnon; Hamidat, Mohammed; Hijawi, Thameen; Kerem, Zohar; Westberg, Erik; Kadereit, Joachim W

    2017-02-06

    A previous multi-locus lineage (MLL) analysis of SSR-microsatellite data of old olive trees in the southeast Mediterranean area had shown the predominance of the Souri cultivar (MLL1) among grafted trees. The MLL analysis had also identified an MLL (MLL7) that was more common among rootstocks than other MLLs. We here present a comparison of the MLL combinations MLL1 (scion)/MLL7 (rootstock) and MLL1/MLL1 in order to investigate the possible influence of rootstock on scion phenotype. A linear regression analysis demonstrated that the abundance of MLL1/MLL7 trees decreases and of MLL1/MLL1 trees increases along a gradient of increasing aridity. Hypothesizing that grafting on MLL7 provides an advantage under certain conditions, Akaike information criterion (AIC) model selection procedure was used to assess the influence of different environmental conditions on phenotypic characteristics of the fruits and oil of the two MLL combinations. The most parsimonious models indicated differential influences of environmental conditions on parameters of olive oil quality in trees belonging to the MLL1/MLL7 and MLL1/MLL1 combinations, but a similar influence on fruit characteristics and oil content. These results suggest that in certain environments grafting of the local Souri cultivar on MLL7 rootstocks and the MLL1/MLL1 combination result in improved oil quality. The decreasing number of MLL1/MLL7 trees along an aridity gradient suggests that use of this genotype combination in arid sites was not favoured because of sensitivity of MLL7 to drought. Our results thus suggest that MLL1/MLL7 and MLL1/MLL1 combinations were selected by growers in traditional rain-fed cultivation under Mediterranean climate conditions in the southeast Mediterranean area.

  2. Paleoserranus lakamhae gen. et sp. nov., a Paleocene seabass (Perciformes: Serranidae) from Palenque, Chiapas, southeastern Mexico

    NASA Astrophysics Data System (ADS)

    Cantalice, Kleyton M.; Alvarado-Ortega, Jesús; Alaniz-Galvan, Abril

    2018-04-01

    Paleoserranus lakamhae gen. et sp. nov. is here described based on well-preserved fossils from the Paleocene marine sediments of the Tenejapa-Lacandón geological unit, belonging to both Division del Norte and Belisario Domínguez quarries, near Palenque, Chiapas, southeastern Mexico. This species exhibits distinctive characters of the order Perciformes, such as the presence of spines in the dorsal, pelvic, and anal fins, as well as the pelvic and pectoral girdles in contact between them. This fish also has neither procurrent spur nor posterior uroneural, characters that support its place within the family Serranidae. It also has a distinctive combination of characters, including a serrated lacrimal and a toothed ectopterygoid, never recorded before among serranids. Additionally, this fossil fish shares some characters with different species nested within the subfamilies Serraninae, Anthiinae, and Ephinephelinae; these include a predorsal formula of 0/0/0 + 2/1 + 1/1; a preopercle with its ventral edge sinuous and showing a strong antrorse spine; its dorsal fin consists of nine spines and eight to ten soft rays; 13 rays in its pectoral fin; and its rounded caudal fin structured with formula I+8-7+I. Paleoserranus lakamhae gen. et sp. nov. is a Serranidae incertae sedis because it does not fit into any subgroup; however, this Paleocene fish is the earliest fossil record of the family Serranidae. The place of occurrence of this new fossil record suggests that the origin and of the seabasses took place in the Caribbean region of North America.

  3. Initial Investigation of Operational Concept Elements for NASA's NextGen-Airportal Project Research

    NASA Technical Reports Server (NTRS)

    Lohr, Gary; Lee, Jonathan; Poage, James L.; Tobias, Leonard

    2009-01-01

    The NextGen-Airportal Project is organized into three research focus areas: Safe and Efficient Surface Operations, Coordinated Arrival/Departure Operations Management, and Airportal Transition and Integration Management. The content in this document was derived from an examination of constraints and problems at airports for accommodating future increases in air traffic, and from an examination of capabilities envisioned for NextGen. The concepts are organized around categories of constraints and problems and therefore do not precisely match, but generally reflect, the research focus areas. The concepts provide a framework for defining and coordinating research activities that are, and will be, conducted by the NextGen-Airportal Project. The concepts will help the research activities function as an integrated set focused on future needs for airport operations and will aid aligning the research activities with NextGen key capabilities. The concepts are presented as concept elements with more detailed sub-elements under each concept element. For each concept element, the following topics are discussed: constraints and problems being addressed, benefit descriptions, required technology and infrastructure, and an initial list of potential research topics. Concept content will be updated and more detail added as the research progresses. The concepts are focused on enhancing airportal capacity and efficiency in a timeframe 20 to 25 years in the future, which is similar to NextGen's timeframe.

  4. Advanced Vehicle Concepts and Implications for NextGen

    NASA Technical Reports Server (NTRS)

    Blake, Matt; Smith, Jim; Wright, Ken; Mediavilla Ricky; Kirby, Michelle; Pfaender, Holger; Clarke, John-Paul; Volovoi, Vitali; Dorbian, Christopher; Ashok, Akshay; hide

    2010-01-01

    This report presents the results of a major NASA study of advanced vehicle concepts and their implications for the Next Generation Air Transportation System (NextGen). Comprising the efforts of dozens of researchers at multiple institutions, the analyses presented here cover a broad range of topics including business-case development, vehicle design, avionics, procedure design, delay, safety, environmental impacts, and metrics. The study focuses on the following five new vehicle types: Cruise-efficient short takeoff and landing (CESTOL) vehicles Large commercial tiltrotor aircraft (LCTRs) Unmanned aircraft systems (UAS) Very light jets (VLJs) Supersonic transports (SST). The timeframe of the study spans the years 2025-2040, although some analyses are also presented for a 3X scenario that has roughly three times the number of flights as today. Full implementation of NextGen is assumed.

  5. Safety Sufficiency for NextGen: Assessment of Selected Existing Safety Methods, Tools, Processes, and Regulations

    NASA Technical Reports Server (NTRS)

    Xu, Xidong; Ulrey, Mike L.; Brown, John A.; Mast, James; Lapis, Mary B.

    2013-01-01

    NextGen is a complex socio-technical system and, in many ways, it is expected to be more complex than the current system. It is vital to assess the safety impact of the NextGen elements (technologies, systems, and procedures) in a rigorous and systematic way and to ensure that they do not compromise safety. In this study, the NextGen elements in the form of Operational Improvements (OIs), Enablers, Research Activities, Development Activities, and Policy Issues were identified. The overall hazard situation in NextGen was outlined; a high-level hazard analysis was conducted with respect to multiple elements in a representative NextGen OI known as OI-0349 (Automation Support for Separation Management); and the hazards resulting from the highly dynamic complexity involved in an OI-0349 scenario were illustrated. A selected but representative set of the existing safety methods, tools, processes, and regulations was then reviewed and analyzed regarding whether they are sufficient to assess safety in the elements of that OI and ensure that safety will not be compromised and whether they might incur intolerably high costs.

  6. A high-precision rule-based extraction system for expanding geospatial metadata in GenBank records

    PubMed Central

    Weissenbacher, Davy; Rivera, Robert; Beard, Rachel; Firago, Mari; Wallstrom, Garrick; Scotch, Matthew; Gonzalez, Graciela

    2016-01-01

    Objective The metadata reflecting the location of the infected host (LOIH) of virus sequences in GenBank often lacks specificity. This work seeks to enhance this metadata by extracting more specific geographic information from related full-text articles and mapping them to their latitude/longitudes using knowledge derived from external geographical databases. Materials and Methods We developed a rule-based information extraction framework for linking GenBank records to the latitude/longitudes of the LOIH. Our system first extracts existing geospatial metadata from GenBank records and attempts to improve it by seeking additional, relevant geographic information from text and tables in related full-text PubMed Central articles. The final extracted locations of the records, based on data assimilated from these sources, are then disambiguated and mapped to their respective geo-coordinates. We evaluated our approach on a manually annotated dataset comprising of 5728 GenBank records for the influenza A virus. Results We found the precision, recall, and f-measure of our system for linking GenBank records to the latitude/longitudes of their LOIH to be 0.832, 0.967, and 0.894, respectively. Discussion Our system had a high level of accuracy for linking GenBank records to the geo-coordinates of the LOIH. However, it can be further improved by expanding our database of geospatial data, incorporating spell correction, and enhancing the rules used for extraction. Conclusion Our system performs reasonably well for linking GenBank records for the influenza A virus to the geo-coordinates of their LOIH based on record metadata and information extracted from related full-text articles. PMID:26911818

  7. JPDO Portfolio Analysis of NextGen

    DTIC Science & Technology

    2009-09-01

    runways. C. Metrics The JPDO Interagency Portfolio & Systems Analysis ( IPSA ) division continues to coordinate, develop, and refine the metrics and...targets associated with the NextGen initiatives with the partner agencies & stakeholder communities. IPSA has formulated a set of top-level metrics as...metrics are calculated from system performance measures that constitute outputs of the American Institute of Aeronautics and Astronautics 8 IPSA

  8. Description of Teunomyces gen. nov. for the Candida kruisii clade, Suhomyces gen. nov. for the Candida tanzawaensis clade and Suhomyces kilbournensis sp. nov.

    PubMed

    Kurtzman, Cletus P; Robnett, Christie J; Blackwell, Meredith

    2016-08-01

    DNA sequence analysis has shown that species of the Candida kruisii clade and species of the C. tanzawaensis clade represent phylogenetically circumscribed genera, which are described as Teunomyces gen. nov., type species T kruisii, and Suhomyces gen. nov., type species S tanzawaensis Many of the species are distributed worldwide and they are often isolated from fungus-feeding insects and their habitats. Included is the description of S. kilbournensis (type strain NRRL Y-17864, CBS 14276), a species found almost exclusively on maize kernels (Zea mays) in IL, USA. Published by Oxford University Press on behalf of FEMS 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  9. VitisGen on the road: mapping the way to the next generation of grapes

    USDA-ARS?s Scientific Manuscript database

    The USDA-NIFA VitisGen project (Award No. 2011-51181-30635) aims to optimize grape cultivar improvement through the integration of grape breeding, cutting edge genomics technology, precision phenotyping, socioeconomic research, and extension. VitisGen is a five-year project involving 25 co-PIs at 11...

  10. Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS

    ClinicalTrials.gov

    2017-07-20

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Untreated Adult Acute Myeloid Leukemia

  11. A high-precision rule-based extraction system for expanding geospatial metadata in GenBank records.

    PubMed

    Tahsin, Tasnia; Weissenbacher, Davy; Rivera, Robert; Beard, Rachel; Firago, Mari; Wallstrom, Garrick; Scotch, Matthew; Gonzalez, Graciela

    2016-09-01

    The metadata reflecting the location of the infected host (LOIH) of virus sequences in GenBank often lacks specificity. This work seeks to enhance this metadata by extracting more specific geographic information from related full-text articles and mapping them to their latitude/longitudes using knowledge derived from external geographical databases. We developed a rule-based information extraction framework for linking GenBank records to the latitude/longitudes of the LOIH. Our system first extracts existing geospatial metadata from GenBank records and attempts to improve it by seeking additional, relevant geographic information from text and tables in related full-text PubMed Central articles. The final extracted locations of the records, based on data assimilated from these sources, are then disambiguated and mapped to their respective geo-coordinates. We evaluated our approach on a manually annotated dataset comprising of 5728 GenBank records for the influenza A virus. We found the precision, recall, and f-measure of our system for linking GenBank records to the latitude/longitudes of their LOIH to be 0.832, 0.967, and 0.894, respectively. Our system had a high level of accuracy for linking GenBank records to the geo-coordinates of the LOIH. However, it can be further improved by expanding our database of geospatial data, incorporating spell correction, and enhancing the rules used for extraction. Our system performs reasonably well for linking GenBank records for the influenza A virus to the geo-coordinates of their LOIH based on record metadata and information extracted from related full-text articles. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. TidGen Power System Commercialization Project

    SciTech Connect

    Sauer, Christopher R.; McEntee, Jarlath

    2013-12-30

    ORPC Maine, LLC, a wholly-owned subsidiary of Ocean Renewable Power Company, LLC (collectively ORPC), submits this Final Technical Report for the TidGen® Power System Commercialization Project (Project), partially funded by the U.S. Department of Energy (DE-EE0003647). The Project was built and operated in compliance with the Federal Energy Regulatory Commission (FERC) pilot project license (P-12711) and other permits and approvals needed for the Project. This report documents the methodologies, activities and results of the various phases of the Project, including design, engineering, procurement, assembly, installation, operation, licensing, environmental monitoring, retrieval, maintenance and repair. The Project represents a significant achievement formore » the renewable energy portfolio of the U.S. in general, and for the U.S. marine hydrokinetic (MHK) industry in particular. The stated Project goal was to advance, demonstrate and accelerate deployment and commercialization of ORPC’s tidal-current based hydrokinetic power generation system, including the energy extraction and conversion technology, associated power electronics, and interconnection equipment capable of reliably delivering electricity to the domestic power grid. ORPC achieved this goal by designing, building and operating the TidGen® Power System in 2012 and becoming the first federally licensed hydrokinetic tidal energy project to deliver electricity to a power grid under a power purchase agreement in North America. Located in Cobscook Bay between Eastport and Lubec, Maine, the TidGen® Power System was connected to the Bangor Hydro Electric utility grid at an on-shore station in North Lubec on September 13, 2012. ORPC obtained a FERC pilot project license for the Project on February 12, 2012 and the first Maine Department of Environmental Protection General Permit issued for a tidal energy project on January 31, 2012. In addition, ORPC entered into a 20-year agreement with Bangor Hydro

  13. Transduction of Photoreceptors With Equine Infectious Anemia Virus Lentiviral Vectors: Safety and Biodistribution of StarGen for Stargardt Disease

    PubMed Central

    Binley, Katie; Widdowson, Peter; Loader, Julie; Kelleher, Michelle; Iqball, Sharifah; Ferrige, Georgina; de Belin, Jackie; Carlucci, Marie; Angell-Manning, Diana; Hurst, Felicity; Ellis, Scott; Miskin, James; Fernandes, Alcides; Wong, Paul; Allikmets, Rando; Bergstrom, Christopher; Aaberg, Thomas; Yan, Jiong; Kong, Jian; Gouras, Peter; Prefontaine, Annick; Vezina, Mark; Bussieres, Martin; Naylor, Stuart; Mitrophanous, Kyriacos A.

    2013-01-01

    Purpose. StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. Methods. Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. Results. Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. Conclusions. In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration. PMID:23620430

  14. InGen Inconsistencies: The "Dinosaurs" Of Jurassic Park May Not Be What The Corporation Claims

    NASA Astrophysics Data System (ADS)

    Haupt, R. J.; Traer, M. M.

    2017-12-01

    InGen has made and continues to make dubious claims about proprietary technology developed to clone non-avian dinosaurs for exhibition within their "Jurassic Park." Notably, there are several inconsistencies between their claims for how their technology works and what has been observed within the park. Here we investigate several of these inconsistencies in the hopes that it will push for increased transparency between corporations and academia. First, we highlight a disconnect between supposedly Jurassic amber used for dinosaur DNA extraction and the overwhelming presence of Late Cretaceous dinosaurs within the park. Further, InGen's mining operations only publicly operate in Jurassic-aged formations of the Dominican Republic, which clashes with the presence of Velociraptor and Gallimimus, known only from Mongolia. Second, the park contains seemingly full-grown adult specimens despite InGen's claims that they first successfully cloned a prehistoric animal in 1984, though there is no publicly available information as to what animal this was. That the park was nearly ready to open by 1993 precludes the presence of fully mature dinosaurs and suggests that InGen might be misrepresenting their technologies. Third, we must point out that fossil DNA denatures to the point of uselessness within thousands, not millions, of years. Additionally, the use of anuran DNA to fill in gaps from fossil dinosaurian DNA is a dubious choice given that more closely related organisms are available. Either there is an unexplained reason for this choice, or little attention has been paid to dinosaurian phylogeny by InGen geneticists. Finally, rumors of a secret InGen project to produce a dinosaur not currently known to paleontologists suggests one of two things: they were able to find DNA from a dinosaur previously unknown in the fossil record, which is highly plausible if their techniques are valid, or that InGen is able to artificially manipulate DNA to a degree far beyond what other

  15. On the new monotypic wolf spider genus Ovia gen. nov. (Araneae: Lycosidae, Lycosinae).

    PubMed

    Sankaran, Pradeep M; Malamel, Jobi J; Sebastian, Pothalil A

    2017-01-17

    A new monotypic wolf spider genus, Ovia gen. nov. is proposed to accommodate a misplaced species: Pardosa procurva Yu & Song, 1988. Ovia procurva comb. nov. is redescribed, illustrated and designated as the type species for the genus. The subfamily placement of the new genus is discussed and it is considered as a member of Lycosinae Sundevall, 1833 and possibly closely related to Alopecosa Simon, 1885. The presence of an apical process (spur) on the median apophysis is proposed as the putative synapomorphy of Ovia gen. nov. The possible sister-taxon relationship of Ovia gen. nov. with Alopecosa is discussed and evidence on the occurrence of sexual dimorphism and mating plug within the genus are presented. Ovia gen. nov. is assumed to be of Holarctic origin, from which it has migrated to the Indomalayan region. Additionally, a current distribution map for the genus is provided.

  16. iGen: An automated generator of simplified models with provable error bounds.

    NASA Astrophysics Data System (ADS)

    Tang, D.; Dobbie, S.

    2009-04-01

    Climate models employ various simplifying assumptions and parameterisations in order to increase execution speed. However, in order to draw conclusions about the Earths climate from the results of a climate simulation it is necessary to have information about the error that these assumptions and parameterisations introduce. A novel computer program, called iGen, is being developed which automatically generates fast, simplified models by analysing the source code of a slower, high resolution model. The resulting simplified models have provable bounds on error compared to the high resolution model and execute at speeds that are typically orders of magnitude faster. iGen's input is a definition of the prognostic variables of the simplified model, a set of bounds on acceptable error and the source code of a model that captures the behaviour of interest. In the case of an atmospheric model, for example, this would be a global cloud resolving model with very high resolution. Although such a model would execute far too slowly to be used directly in a climate model, iGen never executes it. Instead, it converts the code of the resolving model into a mathematical expression which is then symbolically manipulated and approximated to form a simplified expression. This expression is then converted back into a computer program and output as a simplified model. iGen also derives and reports formal bounds on the error of the simplified model compared to the resolving model. These error bounds are always maintained below the user-specified acceptable error. Results will be presented illustrating the success of iGen's analysis of a number of example models. These extremely encouraging results have lead on to work which is currently underway to analyse a cloud resolving model and so produce an efficient parameterisation of moist convection with formally bounded error.

  17. Teleport Generation 3 (Teleport Gen 3)

    DTIC Science & Technology

    2016-03-01

    Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA - Information...144A) reported since the previous MAIS Annual Report to Congress. The program recently achieved a FDD from the MDA on February 13, 2015. Teleport Gen 3...February 13, 2015 granting approval of the FDD . Acronyms and Abbreviations MLGC - MUOS to Legacy UHF SATCOM Gateway Component MOT&E - Multiservice

  18. Targeted NextGen Capabilities for 2025

    DTIC Science & Technology

    2011-11-01

    increased arrival capacity to single runways by reducing longitudinal wake separation standards for Instrument Flight Rules ( IFR ) operations under certain...b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Targeted NextGen Capabilities...The examples cited are not intended to cover every aircraft and every flight. In some instances, the available capabilities for 2025 will not be

  19. GenExp: an interactive web-based genomic DAS client with client-side data rendering.

    PubMed

    Gel Moreno, Bernat; Messeguer Peypoch, Xavier

    2011-01-01

    The Distributed Annotation System (DAS) offers a standard protocol for sharing and integrating annotations on biological sequences. There are more than 1000 DAS sources available and the number is steadily increasing. Clients are an essential part of the DAS system and integrate data from several independent sources in order to create a useful representation to the user. While web-based DAS clients exist, most of them do not have direct interaction capabilities such as dragging and zooming with the mouse. Here we present GenExp, a web based and fully interactive visual DAS client. GenExp is a genome oriented DAS client capable of creating informative representations of genomic data zooming out from base level to complete chromosomes. It proposes a novel approach to genomic data rendering and uses the latest HTML5 web technologies to create the data representation inside the client browser. Thanks to client-side rendering most position changes do not need a network request to the server and so responses to zooming and panning are almost immediate. In GenExp it is possible to explore the genome intuitively moving it with the mouse just like geographical map applications. Additionally, in GenExp it is possible to have more than one data viewer at the same time and to save the current state of the application to revisit it later on. GenExp is a new interactive web-based client for DAS and addresses some of the short-comings of the existing clients. It uses client-side data rendering techniques resulting in easier genome browsing and exploration. GenExp is open source under the GPL license and it is freely available at http://gralggen.lsi.upc.edu/recerca/genexp.

  20. GenExp: An Interactive Web-Based Genomic DAS Client with Client-Side Data Rendering

    PubMed Central

    Gel Moreno, Bernat; Messeguer Peypoch, Xavier

    2011-01-01

    Background The Distributed Annotation System (DAS) offers a standard protocol for sharing and integrating annotations on biological sequences. There are more than 1000 DAS sources available and the number is steadily increasing. Clients are an essential part of the DAS system and integrate data from several independent sources in order to create a useful representation to the user. While web-based DAS clients exist, most of them do not have direct interaction capabilities such as dragging and zooming with the mouse. Results Here we present GenExp, a web based and fully interactive visual DAS client. GenExp is a genome oriented DAS client capable of creating informative representations of genomic data zooming out from base level to complete chromosomes. It proposes a novel approach to genomic data rendering and uses the latest HTML5 web technologies to create the data representation inside the client browser. Thanks to client-side rendering most position changes do not need a network request to the server and so responses to zooming and panning are almost immediate. In GenExp it is possible to explore the genome intuitively moving it with the mouse just like geographical map applications. Additionally, in GenExp it is possible to have more than one data viewer at the same time and to save the current state of the application to revisit it later on. Conclusions GenExp is a new interactive web-based client for DAS and addresses some of the short-comings of the existing clients. It uses client-side data rendering techniques resulting in easier genome browsing and exploration. GenExp is open source under the GPL license and it is freely available at http://gralggen.lsi.upc.edu/recerca/genexp. PMID:21750706

  1. Human-Automation Cooperation for Separation Assurance in Future NextGen Environments

    NASA Technical Reports Server (NTRS)

    Mercer, Joey; Homola, Jeffrey; Cabrall, Christopher; Martin, Lynne; Morey, Susan; Gomez, Ashley; Prevot, Thomas

    2014-01-01

    A 2012 Human-In-The-Loop air traffic control simulation investigated a gradual paradigm-shift in the allocation of functions between operators and automation. Air traffic controllers staffed five adjacent high-altitude en route sectors, and during the course of a two-week experiment, worked traffic under different function-allocation approaches aligned with four increasingly mature NextGen operational environments. These NextGen time-frames ranged from near current-day operations to nearly fully-automated control, in which the ground systems automation was responsible for detecting conflicts, issuing strategic and tactical resolutions, and alerting the controller to exceptional circumstances. Results indicate that overall performance was best in the most automated NextGen environment. Safe operations were achieved in this environment for twice todays peak airspace capacity, while being rated by the controllers as highly acceptable. However, results show that sector operations were not always safe; separation violations did in fact occur. This paper will describe in detail the simulation conducted, as well discuss important results and their implications.

  2. Characterization and design of the FutureGen 2.0 carbon storage site

    SciTech Connect

    Gilmore, Tyler; Bonneville, Alain; Sullivan, Charlotte

    2016-10-01

    The objective of the FutureGen 2.0 Project was to demonstrate, at the commercial scale, the technical feasibility of implementing carbon capture and storage (CCS) in a deep saline formation in Illinois, USA. Over approximately 5 years, the FutureGen Alliance conducted a detailed site-selection process and identified a site for carbon sequestration storage in Morgan County, Illinois. The storage site was fully characterized, including the collection of seismic data and the drilling and characterization of a stratigraphic borehole. The characterization data provided critical input for developing a site-specific conceptual model and subsequent numerical modeling simulations. The modeling simulations, coupled with themore » upstream designs of the pipeline and power plant supported the development of a detailed 90 percent design that included the injection wells and associated control and monitoring infrastructure. Collectively, all these data were used by the FutureGen Alliance to develop the required documentation to support the applications for four underground injection control (UIC) permits (one for each proposed well). In August 2014, the U.S. Environmental Protection Agency issued four, first-of-their-kind, Class VI UIC permits for carbon sequestration in the United States to the FutureGen Alliance. The information and data generated under this project have been made publically available through reports and publications, including this journal and others.« less

  3. GenGIS 2: Geospatial Analysis of Traditional and Genetic Biodiversity, with New Gradient Algorithms and an Extensible Plugin Framework

    PubMed Central

    Parks, Donovan H.; Mankowski, Timothy; Zangooei, Somayyeh; Porter, Michael S.; Armanini, David G.; Baird, Donald J.; Langille, Morgan G. I.; Beiko, Robert G.

    2013-01-01

    GenGIS is free and open source software designed to integrate biodiversity data with a digital map and information about geography and habitat. While originally developed with microbial community analyses and phylogeography in mind, GenGIS has been applied to a wide range of datasets. A key feature of GenGIS is the ability to test geographic axes that can correspond to routes of migration or gradients that influence community similarity. Here we introduce GenGIS version 2, which extends the linear gradient tests introduced in the first version to allow comprehensive testing of all possible linear geographic axes. GenGIS v2 also includes a new plugin framework that supports the development and use of graphically driven analysis packages: initial plugins include implementations of linear regression and the Mantel test, calculations of alpha-diversity (e.g., Shannon Index) for all samples, and geographic visualizations of dissimilarity matrices. We have also implemented a recently published method for biomonitoring reference condition analysis (RCA), which compares observed species richness and diversity to predicted values to determine whether a given site has been impacted. The newest version of GenGIS supports vector data in addition to raster files. We demonstrate the new features of GenGIS by performing a full gradient analysis of an Australian kangaroo apple data set, by using plugins and embedded statistical commands to analyze human microbiome sample data, and by applying RCA to a set of samples from Atlantic Canada. GenGIS release versions, tutorials and documentation are freely available at http://kiwi.cs.dal.ca/GenGIS, and source code is available at https://github.com/beiko-lab/gengis. PMID:23922841

  4. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2018-06-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  5. Structures and stability of metal-doped GenM (n = 9, 10) clusters

    NASA Astrophysics Data System (ADS)

    Qin, Wei; Lu, Wen-Cai; Xia, Lin-Hua; Zhao, Li-Zhen; Zang, Qing-Jun; Wang, C. Z.; Ho, K. M.

    2015-06-01

    The lowest-energy structures of neutral and cationic GenM (n = 9, 10; M = Si, Li, Mg, Al, Fe, Mn, Pb, Au, Ag, Yb, Pm and Dy) clusters were studied by genetic algorithm (GA) and first-principles calculations. The calculation results show that doping of the metal atoms and Si into Ge9 and Ge10 clusters is energetically favorable. Most of the metal-doped Ge cluster structures can be viewed as adding or substituting metal atom on the surface of the corresponding ground-state Gen clusters. However, the neutral and cationic FeGe9,10,MnGe9,10 and Ge10Al are cage-like with the metal atom encapsulated inside. Such cage-like transition metal doped Gen clusters are shown to have higher adsorption energy and thermal stability. Our calculation results suggest that Ge9,10Fe and Ge9Si would be used as building blocks in cluster-assembled nanomaterials because of their high stabilities.

  6. GEN1 from a thermophilic fungus is functionally closely similar to non-eukaryotic junction-resolving enzymes.

    PubMed

    Freeman, Alasdair D J; Liu, Yijin; Déclais, Anne-Cécile; Gartner, Anton; Lilley, David M J

    2014-12-12

    Processing of Holliday junctions is essential in recombination. We have identified the gene for the junction-resolving enzyme GEN1 from the thermophilic fungus Chaetomium thermophilum and expressed the N-terminal 487-amino-acid section. The protein is a nuclease that is highly selective for four-way DNA junctions, cleaving 1nt 3' to the point of strand exchange on two strands symmetrically disposed about a diagonal axis. CtGEN1 binds to DNA junctions as a discrete homodimer with nanomolar affinity. Analysis of the kinetics of cruciform cleavage shows that cleavage of the second strand occurs an order of magnitude faster than the first cleavage so as to generate a productive resolution event. All these properties are closely similar to those described for bacterial, phage and mitochondrial junction-resolving enzymes. CtGEN1 is also similar in properties to the human enzyme but lacks the problems with aggregation that currently prevent detailed analysis of the latter protein. CtGEN1 is thus an excellent enzyme with which to engage in biophysical and structural analysis of eukaryotic GEN1. Copyright © 2014. Published by Elsevier Ltd.

  7. GenColors-based comparative genome databases for small eukaryotic genomes.

    PubMed

    Felder, Marius; Romualdi, Alessandro; Petzold, Andreas; Platzer, Matthias; Sühnel, Jürgen; Glöckner, Gernot

    2013-01-01

    Many sequence data repositories can give a quick and easily accessible overview on genomes and their annotations. Less widespread is the possibility to compare related genomes with each other in a common database environment. We have previously described the GenColors database system (http://gencolors.fli-leibniz.de) and its applications to a number of bacterial genomes such as Borrelia, Legionella, Leptospira and Treponema. This system has an emphasis on genome comparison. It combines data from related genomes and provides the user with an extensive set of visualization and analysis tools. Eukaryote genomes are normally larger than prokaryote genomes and thus pose additional challenges for such a system. We have, therefore, adapted GenColors to also handle larger datasets of small eukaryotic genomes and to display eukaryotic gene structures. Further recent developments include whole genome views, genome list options and, for bacterial genome browsers, the display of horizontal gene transfer predictions. Two new GenColors-based databases for two fungal species (http://fgb.fli-leibniz.de) and for four social amoebas (http://sacgb.fli-leibniz.de) were set up. Both new resources open up a single entry point for related genomes for the amoebozoa and fungal research communities and other interested users. Comparative genomics approaches are greatly facilitated by these resources.

  8. How Does Mentoring Contribute to Gen Y Employees’ Intention to Stay? An Indian Perspective

    PubMed Central

    Naim, Mohammad Faraz; Lenka, Usha

    2017-01-01

    The present study is aimed at investigating the impact of mentoring on intention to stay of Gen Y employees working in Indian IT industry. Also, the mediating roles of perceived organization support and affective commitment are examined. Primary data were collected from a sample of 314 Gen Y employees (born between 1980-2000) from IT industry in Delhi, NCR India. Data analysis was carried out using AMOS and SPSS to test sequential mediation. Findings reveal that mentoring has a direct influence on intention to stay of Gen Y employees and perceived organization support and affective commitment sequentially mediate the relationship between the two. This study contributes to the literature on mentoring, perceived organization support, affective commitment, and intention to stay. PMID:28580029

  9. Reclassification of rhizosphere bacteria including strains causing corky root of lettuce and proposal of Rhizorhapis suberifaciens gen. nov., comb. nov., Sphingobium mellinum sp. nov., Sphingobium xanthum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov.

    PubMed

    Francis, Isolde M; Jochimsen, Kenneth N; De Vos, Paul; van Bruggen, Ariena H C

    2014-04-01

    The genus Rhizorhapis gen. nov. (to replace the illegitimate genus name Rhizomonas) is proposed for strains of Gram-negative bacteria causing corky root of lettuce, a widespread and important lettuce disease worldwide. Only one species of the genus Rhizomonas was described, Rhizomonas suberifaciens, which was subsequently reclassified as Sphingomonas suberifaciens based on 16S rRNA gene sequences and the presence of sphingoglycolipid in the cell envelope. However, the genus Sphingomonas is so diverse that further reclassification was deemed necessary. Twenty new Rhizorhapis gen. nov.- and Sphingomonas-like isolates were obtained from lettuce or sow thistle roots, or from soil using lettuce seedlings as bait. These and previously reported isolates were characterized in a polyphasic study including 16S rRNA gene sequencing, DNA-DNA hybridization, DNA G+C content, whole-cell fatty acid composition, morphology, substrate oxidation, temperature and pH sensitivity, and pathogenicity to lettuce. The isolates causing lettuce corky root belonged to the genera Rhizorhapis gen. nov., Sphingobium, Sphingopyxis and Rhizorhabdus gen. nov. More specifically, we propose to reclassify Rhizomonas suberifaciens as Rhizorhapis suberifaciens gen. nov., comb. nov. (type strain, CA1(T) = LMG 17323(T) = ATCC 49355(T)), and also propose the novel species Sphingobium xanthum sp. nov., Sphingobium mellinum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov. with the type strains NL9(T) ( = LMG 12560(T) = ATCC 51296(T)), WI4(T) ( = LMG 11032(T) = ATCC 51292(T)) and SP1(T) ( = LMG 12581(T) = ATCC 51289(T)), respectively. Several strains isolated from lettuce roots belonged to the genus Sphingomonas, but none of them were pathogenic.

  10. Identification and Characterization of Key Human Performance Issues and Research in the Next Generation Air Transportation System (NextGen)

    NASA Technical Reports Server (NTRS)

    Lee, Paul U.; Sheridan, Tom; Poage, james L.; Martin, Lynne Hazel; Jobe, Kimberly K.

    2010-01-01

    This report identifies key human-performance-related issues associated with Next Generation Air Transportation System (NextGen) research in the NASA NextGen-Airspace Project. Four Research Focus Areas (RFAs) in the NextGen-Airspace Project - namely Separation Assurance (SA), Airspace Super Density Operations (ASDO), Traffic Flow Management (TFM), and Dynamic Airspace Configuration (DAC) - were examined closely. In the course of the research, it was determined that the identified human performance issues needed to be analyzed in the context of NextGen operations rather than through basic human factors research. The main gaps in human factors research in NextGen were found in the need for accurate identification of key human-systems related issues within the context of specific NextGen concepts and better design of the operational requirements for those concepts. By focusing on human-system related issues for individual concepts, key human performance issues for the four RFAs were identified and described in this report. In addition, mixed equipage airspace with components of two RFAs were characterized to illustrate potential human performance issues that arise from the integration of multiple concepts.

  11. Integrated Design and Production Reference Integration with ArchGenXML V1.00

    SciTech Connect

    Barter, R H

    2004-07-20

    ArchGenXML is a tool that allows easy creation of Zope products through the use of Archetypes. The Integrated Design and Production Reference (IDPR) should be highly configurable in order to meet the needs of a diverse engineering community. Ease of configuration is key to the success of IDPR. The purpose of this paper is to describe a method of using a UML diagram editor to configure IDPR through ArchGenXML and Archetypes.

  12. 78 FR 8108 - NextGen Solutions Vendors Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... Commerce is developing a web-based NextGen Solutions Vendors Guide intended to be used by foreign air... being listed on the Vendors Guide Web site should submit their company's name, Web site address, contact... to aviation system upgrades) Example: Engineering Services More information on the four ICAO ASBU...

  13. Generalized background error covariance matrix model (GEN_BE v2.0)

    NASA Astrophysics Data System (ADS)

    Descombes, G.; Auligné, T.; Vandenberghe, F.; Barker, D. M.; Barré, J.

    2015-03-01

    The specification of state background error statistics is a key component of data assimilation since it affects the impact observations will have on the analysis. In the variational data assimilation approach, applied in geophysical sciences, the dimensions of the background error covariance matrix (B) are usually too large to be explicitly determined and B needs to be modeled. Recent efforts to include new variables in the analysis such as cloud parameters and chemical species have required the development of the code to GENerate the Background Errors (GEN_BE) version 2.0 for the Weather Research and Forecasting (WRF) community model. GEN_BE allows for a simpler, flexible, robust, and community-oriented framework that gathers methods used by some meteorological operational centers and researchers. We present the advantages of this new design for the data assimilation community by performing benchmarks of different modeling of B and showing some of the new features in data assimilation test cases. As data assimilation for clouds remains a challenge, we present a multivariate approach that includes hydrometeors in the control variables and new correlated errors. In addition, the GEN_BE v2.0 code is employed to diagnose error parameter statistics for chemical species, which shows that it is a tool flexible enough to implement new control variables. While the generation of the background errors statistics code was first developed for atmospheric research, the new version (GEN_BE v2.0) can be easily applied to other domains of science and chosen to diagnose and model B. Initially developed for variational data assimilation, the model of the B matrix may be useful for variational ensemble hybrid methods as well.

  14. Measuring GE^n at High Momentum Transfer

    NASA Astrophysics Data System (ADS)

    Feuerbach, Robert

    2006-11-01

    A precision measurement of the electric form-factor of the neutron, GE^n, at Q^2 up to 3.5 GeV^2 was recently completed in Hall A at the Thomas Jefferson National Accelerator Facility(Jefferson Lab). The ratio of the electric to magnetic form-factors of the neutron, GE^n/GM^n, was measured through the beam-target asymmetry A of electrons quasi-elastically scattered off neutrons in the reaction ^3He(e,e' n). The experiment took advantage of recent developments of the electron beam and target, as well as two detectors new to Jefferson Lab. The measurement used the accelerator's 100% duty-cycle high-polarization (typically 84%) electron beam and a new, hybrid optically-pumped polarized ^3He target which achieved in-beam polarizations in excess of 50%. A medium acceptance (80msr) open-geometry magnetic spectrometer (BigBite) detected the scattered electron, while a newly contructed neutron detector observed the released neutron. An overview of the experiment and the experimental motivation will be discussed, in particular the large range of predictions from modern calculations for GE^n at this relatively high Q^2. Finally, the analysis progress and preliminary results will be presented.

  15. MitoGen: A Framework for Generating 3D Synthetic Time-Lapse Sequences of Cell Populations in Fluorescence Microscopy.

    PubMed

    Svoboda, David; Ulman, Vladimir

    2017-01-01

    The proper analysis of biological microscopy images is an important and complex task. Therefore, it requires verification of all steps involved in the process, including image segmentation and tracking algorithms. It is generally better to verify algorithms with computer-generated ground truth datasets, which, compared to manually annotated data, nowadays have reached high quality and can be produced in large quantities even for 3D time-lapse image sequences. Here, we propose a novel framework, called MitoGen, which is capable of generating ground truth datasets with fully 3D time-lapse sequences of synthetic fluorescence-stained cell populations. MitoGen shows biologically justified cell motility, shape and texture changes as well as cell divisions. Standard fluorescence microscopy phenomena such as photobleaching, blur with real point spread function (PSF), and several types of noise, are simulated to obtain realistic images. The MitoGen framework is scalable in both space and time. MitoGen generates visually plausible data that shows good agreement with real data in terms of image descriptors and mean square displacement (MSD) trajectory analysis. Additionally, it is also shown in this paper that four publicly available segmentation and tracking algorithms exhibit similar performance on both real and MitoGen-generated data. The implementation of MitoGen is freely available.

  16. ORPC RivGen controller performance raw data - Igiugig 2015

    DOE Data Explorer

    McEntee, Jarlath

    2015-12-18

    Contains raw data for operations of Ocean Renewable Power Company (ORPC) RivGen Power System in Igiugig 2015 in Matlab data file format. Two data files capture the data and timestamps for data, including power in, voltage, rotation rate, and velocity.

  17. Complete cDNAs from Brachymyrmex patagonicus (Hymenoptera: Formicidae). --GenBank accession numbers: GU582126-GU582140.

    USDA-ARS?s Scientific Manuscript database

    15 new gene sequences were identified from workers of Brachymyrmex patagonicus, and submitted to the National Center for Biotechnology Information GenBank. GenBank accession numbers are GU582126-GU582140. This information will provide scientists with genetic tools to study the development and the p...

  18. Complete cDNAs from Solenopsis invicta (Hymenoptera: Formicidae). --GenBank accession numbers: HM130684-HM130685.

    USDA-ARS?s Scientific Manuscript database

    2 new gene sequences were identified from workers of Solenopsis invicta, and submitted to the National Center for Biotechnology Information GenBank. GenBank accession numbers are HM130684-HM130685. This information will provide scientists with genetic tools to study the populations of this ant....

  19. Haneen Shalabi receives The Children’s Cancer Foundation Next Gen Award | Center for Cancer Research

    Cancer.gov

    Haneen Shalabi, D.O., a Physician in the Pediatric Oncology Branch, received the 2017 Next Gen Award from the Children’s Cancer Foundation, Inc (CCF). As the highest award CCF presents to individual researchers, the Next Gen Award recognizes young investigators who are committed to pursuing a long-term career in pediatric oncology research. Read more... 

  20. PanCoreGen - Profiling, detecting, annotating protein-coding genes in microbial genomes.

    PubMed

    Paul, Sandip; Bhardwaj, Archana; Bag, Sumit K; Sokurenko, Evgeni V; Chattopadhyay, Sujay

    2015-12-01

    A large amount of genomic data, especially from multiple isolates of a single species, has opened new vistas for microbial genomics analysis. Analyzing the pan-genome (i.e. the sum of genetic repertoire) of microbial species is crucial in understanding the dynamics of molecular evolution, where virulence evolution is of major interest. Here we present PanCoreGen - a standalone application for pan- and core-genomic profiling of microbial protein-coding genes. PanCoreGen overcomes key limitations of the existing pan-genomic analysis tools, and develops an integrated annotation-structure for a species-specific pan-genomic profile. It provides important new features for annotating draft genomes/contigs and detecting unidentified genes in annotated genomes. It also generates user-defined group-specific datasets within the pan-genome. Interestingly, analyzing an example-set of Salmonella genomes, we detect potential footprints of adaptive convergence of horizontally transferred genes in two human-restricted pathogenic serovars - Typhi and Paratyphi A. Overall, PanCoreGen represents a state-of-the-art tool for microbial phylogenomics and pathogenomics study. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Complete cDNAs from Nylanderia sp. nr. pubens (Hymenoptera: Formicidae). GenBank GU980916-GU980928.

    USDA-ARS?s Scientific Manuscript database

    13 new gene sequences were identified from workers of Rasberry crazy ant, Nylanderia sp.nr. pubens, and submitted to the National Center for Biotechnology Information GenBank. GenBank accession numbers are GU980916-GU980928. This information will provide scientists with genetic tools to study the p...

  2. GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research--an update.

    PubMed

    Peakall, Rod; Smouse, Peter E

    2012-10-01

    GenAlEx: Genetic Analysis in Excel is a cross-platform package for population genetic analyses that runs within Microsoft Excel. GenAlEx offers analysis of diploid codominant, haploid and binary genetic loci and DNA sequences. Both frequency-based (F-statistics, heterozygosity, HWE, population assignment, relatedness) and distance-based (AMOVA, PCoA, Mantel tests, multivariate spatial autocorrelation) analyses are provided. New features include calculation of new estimators of population structure: G'(ST), G''(ST), Jost's D(est) and F'(ST) through AMOVA, Shannon Information analysis, linkage disequilibrium analysis for biallelic data and novel heterogeneity tests for spatial autocorrelation analysis. Export to more than 30 other data formats is provided. Teaching tutorials and expanded step-by-step output options are included. The comprehensive guide has been fully revised. GenAlEx is written in VBA and provided as a Microsoft Excel Add-in (compatible with Excel 2003, 2007, 2010 on PC; Excel 2004, 2011 on Macintosh). GenAlEx, and supporting documentation and tutorials are freely available at: http://biology.anu.edu.au/GenAlEx. rod.peakall@anu.edu.au.

  3. GWAS in a Box: Statistical and Visual Analytics of Structured Associations via GenAMap

    PubMed Central

    Xing, Eric P.; Curtis, Ross E.; Schoenherr, Georg; Lee, Seunghak; Yin, Junming; Puniyani, Kriti; Wu, Wei; Kinnaird, Peter

    2014-01-01

    With the continuous improvement in genotyping and molecular phenotyping technology and the decreasing typing cost, it is expected that in a few years, more and more clinical studies of complex diseases will recruit thousands of individuals for pan-omic genetic association analyses. Hence, there is a great need for algorithms and software tools that could scale up to the whole omic level, integrate different omic data, leverage rich structure information, and be easily accessible to non-technical users. We present GenAMap, an interactive analytics software platform that 1) automates the execution of principled machine learning methods that detect genome- and phenome-wide associations among genotypes, gene expression data, and clinical or other macroscopic traits, and 2) provides new visualization tools specifically designed to aid in the exploration of association mapping results. Algorithmically, GenAMap is based on a new paradigm for GWAS and PheWAS analysis, termed structured association mapping, which leverages various structures in the omic data. We demonstrate the function of GenAMap via a case study of the Brem and Kruglyak yeast dataset, and then apply it on a comprehensive eQTL analysis of the NIH heterogeneous stock mice dataset and report some interesting findings. GenAMap is available from http://sailing.cs.cmu.edu/genamap. PMID:24905018

  4. Discourses in Conflict: The Relationship between Gen Y Pre-Service Teachers, Digital Technologies and Lifelong Learning

    ERIC Educational Resources Information Center

    Donnison, Sharn

    2009-01-01

    This paper analyses Gen Y pre-service primary school teachers' conceptualisations of lifelong learning. It is situated within a context of improving the provision and delivery of pre-service teacher education. This paper argues that Gen Y's understanding of lifelong learning has been influenced by their engagements with digital technologies and…

  5. Transfer of Pseudomonas flectens Johnson 1956 to Phaseolibacter gen. nov., in the family Enterobacteriaceae, as Phaseolibacter flectens gen. nov., comb. nov.

    PubMed

    Halpern, Malka; Fridman, Svetlana; Aizenberg-Gershtein, Yana; Izhaki, Ido

    2013-01-01

    Pseudomonas flectens Johnson 1956, a plant-pathogenic bacterium on the pods of the French bean, is no longer considered to be a member of the genus Pseudomonas sensu stricto. A polyphasic approach that included examination of phenotypic properties and phylogenetic analyses based on 16S rRNA, rpoB and atpD gene sequences supported the transfer of Pseudomonas flectens Johnson 1956 to a new genus in the family Enterobacteriaceae as Phaseolibacter flectens gen. nov., comb. nov. Two strains of Phaseolibacter flectens were studied (ATCC 12775(T) and LMG 2186); the strains shared 99.8 % sequence similarity in their 16S rRNA genes and the housekeeping gene sequences were identical. Strains of Phaseolibacter flectens shared 96.6 % or less 16S rRNA gene sequence similarity with members of different genera in the family Enterobacteriaceae and only 84.7 % sequence similarity with Pseudomonas aeruginosa LMG 1242(T), demonstrating that they are not related to the genus Pseudomonas. As Phaseolibacter flectens formed an independent phyletic lineage in all of the phylogenetic analyses, it could not be affiliated to any of the recognized genera within the family Enterobacteriaceae and therefore was assigned to a new genus. Cells were Gram-negative, straight rods, motile by means of one or two polar flagella, fermentative, facultative anaerobes, oxidase-negative and catalase-positive. Growth occurred in the presence of 0-60 % sucrose. The DNA G+C content of the type strain was 44.3 mol%. On the basis of phenotypic properties and phylogenetic distinctiveness, Pseudomonas flectens Johnson 1956 is transferred to the novel genus Phaseolibacter gen. nov. as Phaseolibacter flectens gen. nov., comb. nov. The type strain of Phaseolibacter flectens is ATCC 12775(T) = CFBP 3281(T) = ICMP 745(T) = LMG 2187(T) = NCPPB 539(T).

  6. Dedicated Caravan Sites for French Gens du Voyage: Public Health Policy or Construction of Health and Environmental Inequalities?

    PubMed

    Foisneau, Lise

    2017-12-01

    In France, gens du voyage ("people who travel" or "travellers") is a term used by the government to categorize various itinerant populations, the majority of which are diverse Romani groups. People categorized as gens du voyage are legally required to reside in particular locations called "dedicated caravan sites." Parliamentary debates about these dedicated caravan sites have clarified that one of the objectives of such sites is to help fulfill the gens du voyage 's right to health. However, there is a significant gap between the officially stated goals of such sites and the reality of life within them. This paper draws on research finding that the conditions in most dedicated caravan sites do not conform with the rights of gens du voyage to acceptable sanitary conditions and other underlying determinants of health.

  7. Targeted amplicon sequencing (TAS): a scalable next-gen approach to multilocus, multitaxa phylogenetics.

    PubMed

    Bybee, Seth M; Bracken-Grissom, Heather; Haynes, Benjamin D; Hermansen, Russell A; Byers, Robert L; Clement, Mark J; Udall, Joshua A; Wilcox, Edward R; Crandall, Keith A

    2011-01-01

    Next-gen sequencing technologies have revolutionized data collection in genetic studies and advanced genome biology to novel frontiers. However, to date, next-gen technologies have been used principally for whole genome sequencing and transcriptome sequencing. Yet many questions in population genetics and systematics rely on sequencing specific genes of known function or diversity levels. Here, we describe a targeted amplicon sequencing (TAS) approach capitalizing on next-gen capacity to sequence large numbers of targeted gene regions from a large number of samples. Our TAS approach is easily scalable, simple in execution, neither time-nor labor-intensive, relatively inexpensive, and can be applied to a broad diversity of organisms and/or genes. Our TAS approach includes a bioinformatic application, BarcodeCrucher, to take raw next-gen sequence reads and perform quality control checks and convert the data into FASTA format organized by gene and sample, ready for phylogenetic analyses. We demonstrate our approach by sequencing targeted genes of known phylogenetic utility to estimate a phylogeny for the Pancrustacea. We generated data from 44 taxa using 68 different 10-bp multiplexing identifiers. The overall quality of data produced was robust and was informative for phylogeny estimation. The potential for this method to produce copious amounts of data from a single 454 plate (e.g., 325 taxa for 24 loci) significantly reduces sequencing expenses incurred from traditional Sanger sequencing. We further discuss the advantages and disadvantages of this method, while offering suggestions to enhance the approach.

  8. Targeted Amplicon Sequencing (TAS): A Scalable Next-Gen Approach to Multilocus, Multitaxa Phylogenetics

    PubMed Central

    Bybee, Seth M.; Bracken-Grissom, Heather; Haynes, Benjamin D.; Hermansen, Russell A.; Byers, Robert L.; Clement, Mark J.; Udall, Joshua A.; Wilcox, Edward R.; Crandall, Keith A.

    2011-01-01

    Next-gen sequencing technologies have revolutionized data collection in genetic studies and advanced genome biology to novel frontiers. However, to date, next-gen technologies have been used principally for whole genome sequencing and transcriptome sequencing. Yet many questions in population genetics and systematics rely on sequencing specific genes of known function or diversity levels. Here, we describe a targeted amplicon sequencing (TAS) approach capitalizing on next-gen capacity to sequence large numbers of targeted gene regions from a large number of samples. Our TAS approach is easily scalable, simple in execution, neither time-nor labor-intensive, relatively inexpensive, and can be applied to a broad diversity of organisms and/or genes. Our TAS approach includes a bioinformatic application, BarcodeCrucher, to take raw next-gen sequence reads and perform quality control checks and convert the data into FASTA format organized by gene and sample, ready for phylogenetic analyses. We demonstrate our approach by sequencing targeted genes of known phylogenetic utility to estimate a phylogeny for the Pancrustacea. We generated data from 44 taxa using 68 different 10-bp multiplexing identifiers. The overall quality of data produced was robust and was informative for phylogeny estimation. The potential for this method to produce copious amounts of data from a single 454 plate (e.g., 325 taxa for 24 loci) significantly reduces sequencing expenses incurred from traditional Sanger sequencing. We further discuss the advantages and disadvantages of this method, while offering suggestions to enhance the approach. PMID:22002916

  9. NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

    PubMed

    Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

    2017-09-21

    High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

  10. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-05-03

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  11. Description of a new genus, Galgoria gen. nov. (Hemiptera: Cicadidae: Cicadinae: Leptopsaltriini: Leptopsaltriina).

    PubMed

    Lee, Young June

    2016-05-10

    A new cicada genus, Galgoria gen. nov., is described with Tanna herzbergi Schmidt, 1932 (from southern China) as its type species, which is placed in the subtribe Leptopsaltriina Moulton, 1923 of the tribe Leptopsaltriini Moulton, 1923 in the subfamily Cicadinae Latreille, 1802 (Hemiptera: Cicadidae). Tanna herzbergi Schmidt, 1932 is transferred from Tanna Distant, 1905 to Galgoria gen. nov. to become Galgoria herzbergi (Schmidt, 1932) comb. nov. Tanna apicalis Chen, 1940 syn. nov. and Tanna pseudocalis Lei & Chou, 1997 syn. nov. are synonymized here with Galgoria herzbergi (Schmidt, 1932) comb. nov.

  12. Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells.

    PubMed

    Tao, Lei; Wei, Libing; Liu, Yishi; Ding, Yang; Liu, Xiuting; Zhang, Xin; Wang, Xiaoping; Yao, Yuyuan; Lu, Jinrong; Wang, Qing; Hu, Rong

    2017-02-01

    We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally, in vivo studies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion, the results showed that Gen-27 had significant anticancer effects against human breast cancer and it may potentially be used as a novel anticancer agent for the treatment of breast cancer. Copyright © 2016. Published by Elsevier Inc.

  13. 78 FR 77670 - AlphaGen Power LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER14-630-000] AlphaGen Power LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding, of AlphaGen Power...

  14. Complete cDNAs from Nylanderia cf. pubens (Hymenoptera: Formicidae). --GenBank accession numbers: JF815100-JF815104

    USDA-ARS?s Scientific Manuscript database

    5 new gene sequences were identified from workers of Caribbean crazy ant, Nylanderia cf. pubens, and submitted to the National Center for Biotechnology Information GenBank. GenBank accession numbers are JF815100-JF815104. This information will provide scientists with genetic tools to study the popu...

  15. Dual-track CCS stakeholder engagement: Lessons learned from FutureGen in Illinois

    USGS Publications Warehouse

    Hund, G.; Greenberg, S.E.

    2011-01-01

    FutureGen, as originally planned, was to be the world's first coal-fueled, near-zero emissions power plant with fully integrated, 90% carbon capture and storage (CCS). From conception through siting and design, it enjoyed strong support from multiple stakeholder groups, which benefited the overall project. Understanding the stakeholder engagement process for this project provides valuable insights into the design of stakeholder programs for future CCS projects. FutureGen is one of few projects worldwide that used open competition for siting both the power plant and storage reservoir. Most site proposals were coordinated by State governments. It was unique in this and other respects relative to the site selection method used on other DOE-supported projects. At the time of site selection, FutureGen was the largest proposed facility designed to combine an integrated gasification combined cycle (IGCC) coal-fueled power plant with a CCS system. Stakeholder engagement by states and the industry consortium responsible for siting, designing, building, and operating the facility took place simultaneously and on parallel tracks. On one track were states spearheading state-wide site assessments to identify candidate sites that they wanted to propose for consideration. On the other track was a public-private partnership between an industry consortium of thirteen coal companies and electric utilities that comprised the FutureGen Alliance (Alliance) and the U.S. Department of Energy (DOE). The partnership was based on a cooperative agreement signed by both parties, which assigned the lead for siting to the Alliance. This paper describes the stakeholder engagement strategies used on both of these tracks and provides examples from the engagement process using the Illinois semi-finalist sites. ?? 2011 Published by Elsevier Ltd.

  16. Next Gen NEAR: Near Earth Asteroid Human Robotic Precursor Mission Concept

    NASA Technical Reports Server (NTRS)

    Rivkin, Andrew S.; Kirby, Karen; Cheng, Andrew F.; Gold, Robert; Kelly, Daniel; Reed, Cheryl; Abell, Paul; Garvin, James; Landis, Rob

    2012-01-01

    Asteroids have long held the attention of the planetary science community. In particular, asteroids that evolve into orbits near that of Earth, called near-Earth objects (NEO), are of high interest as potential targets for exploration due to the relative ease (in terms of delta V) to reach them. NASA's Flexible Path calls for missions and experiments to be conducted as intermediate steps towards the eventual goal of human exploration of Mars; piloted missions to NEOs are such example. A human NEO mission is a valuable exploratory step beyond the Earth-Moon system enhancing capabilities that surpass our current experience, while also developing infrastructure for future mars exploration capabilities. To prepare for a human rendezvous with an NEO, NASA is interested in pursuing a responsible program of robotic NEO precursor missions. Next Gen NEAR is such a mission, building on the NEAR Shoemaker mission experience at the JHU/APL Space Department, to provide an affordable, low risk solution with quick data return. Next Gen NEAR proposes to make measurements needed for human exploration to asteroids: to demonstrate proximity operations, to quantify hazards for human exploration and to characterize an environment at a near-Earth asteroid representative of those that may be future human destinations. The Johns Hopkins University Applied Physics Laboratory has demonstrated exploration-driven mission feasibility by developing a versatile spacecraft design concept using conventional technologies that satisfies a set of science, exploration and mission objectives defined by a concept development team in the summer of 2010. We will describe the mission concept and spacecraft architecture in detail. Configuration options were compared with the mission goals and objectives in order to select the spacecraft design concept that provides the lowest cost, lowest implementation risk, simplest operation and the most benefit for the mission implementation. The Next Gen NEAR

  17. GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research—an update

    PubMed Central

    Peakall, Rod; Smouse, Peter E.

    2012-01-01

    Summary: GenAlEx: Genetic Analysis in Excel is a cross-platform package for population genetic analyses that runs within Microsoft Excel. GenAlEx offers analysis of diploid codominant, haploid and binary genetic loci and DNA sequences. Both frequency-based (F-statistics, heterozygosity, HWE, population assignment, relatedness) and distance-based (AMOVA, PCoA, Mantel tests, multivariate spatial autocorrelation) analyses are provided. New features include calculation of new estimators of population structure: G′ST, G′′ST, Jost’s Dest and F′ST through AMOVA, Shannon Information analysis, linkage disequilibrium analysis for biallelic data and novel heterogeneity tests for spatial autocorrelation analysis. Export to more than 30 other data formats is provided. Teaching tutorials and expanded step-by-step output options are included. The comprehensive guide has been fully revised. Availability and implementation: GenAlEx is written in VBA and provided as a Microsoft Excel Add-in (compatible with Excel 2003, 2007, 2010 on PC; Excel 2004, 2011 on Macintosh). GenAlEx, and supporting documentation and tutorials are freely available at: http://biology.anu.edu.au/GenAlEx. Contact: rod.peakall@anu.edu.au PMID:22820204

  18. Data-Link and Surface Map Traffic Intent Displays for NextGen 4DT and Equivalent Visual Surface Operations

    NASA Technical Reports Server (NTRS)

    Shelton, Kevin J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Jones, Deise R.; Allamandola, Angela S.; Bailey, Randall E.

    2009-01-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a consortium of industry, academia and government agencies have proposed a revolutionary new concept for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the concept of "net-centric" operations whereby each aircraft and air services provider shares information to allow real-time adaptability to ever-changing factors such as weather, traffic, flight trajectories, and security. Data-link is likely to be the primary source of communication in NextGen. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen.

  19. GenIce: Hydrogen-Disordered Ice Generator.

    PubMed

    Matsumoto, Masakazu; Yagasaki, Takuma; Tanaka, Hideki

    2018-01-05

    GenIce is an efficient and user-friendly tool to generate hydrogen-disordered ice structures. It makes ice and clathrate hydrate structures in various file formats. More than 100 kinds of structures are preset. Users can install their own crystal structures, guest molecules, and file formats as plugins. The algorithm certifies that the generated structures are completely randomized hydrogen-disordered networks obeying the ice rule with zero net polarization. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

  20. Paramagnetic-to-nonmagnetic transition in antiperovskite nitride Cr3GeN studied by 14N-NMR and µSR

    NASA Astrophysics Data System (ADS)

    Takao, K.; Liu, Z.; Uji, K.; Waki, T.; Tabata, Y.; Watanabe, I.; Nakamura, H.

    2017-06-01

    The antiperovskite-related nitride Cr3GeN forms a tetragonal structure with the space group P\\bar{4}{2}1m at room temperature. It shows a tetragonal (P\\bar{4}{2}1m) to tetragonal (I4/mcm) structural transition with a large hysteresis at 300-400 K. The magnetic susceptibility of Cr3GeN shows Curie-Weiss type temperature dependence at high temperature, but is almost temperature-independent below room temperature. We carried out µSR and 14N-NMR microscopy measurements to reveal the magnetic ground state of Cr3GeN. Gradual muon spin relaxation, which is nearly temperature-independent below room temperature, was observed, indicating that Cr3GeN is magnetically inactive. In the 14N-NMR measurement, a quadrupole-split spectrum was obtained at around 14 K = 0. The temperature dependence of 14(1/T1) satisfies the Korringa relation. These experimental results indicate that the ground state of Cr3GeN is Pauli paramagnetic, without antiferromagnetic long-range order.

  1. Case study of read-across predictions using a Generalized Read-Across (GenRA) Approach (10th World Congress)

    EPA Science Inventory

    We developed the Generalized Read-Across (GenRA) approach to facilitate automated, algorithmic read across predictions. GenRA uses in vitro bioactivity data in conjunction with chemical information to predict up to 574 different apical outcomes from repeat-dose toxicity studies. ...

  2. NextGen Weather Plan, Version 1.1

    DTIC Science & Technology

    2009-09-17

    values of weather parameters at a station or over an area. In this paper, we often refer to aeronautical climatology, which is the application of the data...Joint Planning and Development Office NEXTGEN Weather Plan Version 1.1 Version 1.1 i September 17, 2009 Report Documentation Page Form...COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE NextGen Weather Plan 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  3. pGenN, a gene normalization tool for plant genes and proteins in scientific literature.

    PubMed

    Ding, Ruoyao; Arighi, Cecilia N; Lee, Jung-Youn; Wu, Cathy H; Vijay-Shanker, K

    2015-01-01

    Automatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines. In this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases. We evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/).

  4. Complexity analysis of the Next Gen Air Traffic Management System: trajectory based operations.

    PubMed

    Lyons, Rhonda

    2012-01-01

    According to Federal Aviation Administration traffic predictions currently our Air Traffic Management (ATM) system is operating at 150 percent capacity; forecasting that within the next two decades, the traffic with increase to a staggering 250 percent [17]. This will require a major redesign of our system. Today's ATM system is complex. It is designed to safely, economically, and efficiently provide air traffic services through the cost-effective provision of facilities and seamless services in collaboration with multiple agents however, contrary the vision, the system is loosely integrated and is suffering tremendously from antiquated equipment and saturated airways. The new Next Generation (Next Gen) ATM system is designed to transform the current system into an agile, robust and responsive set of operations that are designed to safely manage the growing needs of the projected increasingly complex, diverse set of air transportation system users and massive projected worldwide traffic rates. This new revolutionary technology-centric system is dynamically complex and is much more sophisticated than it's soon to be predecessor. ATM system failures could yield large scale catastrophic consequences as it is a safety critical system. This work will attempt to describe complexity and the complex nature of the NextGen ATM system and Trajectory Based Operational. Complex human factors interactions within Next Gen will be analyzed using a proposed dual experimental approach designed to identify hazards, gaps and elicit emergent hazards that would not be visible if conducted in isolation. Suggestions will be made along with a proposal for future human factors research in the TBO safety critical Next Gen environment.

  5. Geophysical Monitoring Methods Evaluation for the FutureGen 2.0 Project

    DOE PAGES

    Strickland, Chris E.; USA, Richland Washington; Vermeul, Vince R.; ...

    2014-12-31

    A comprehensive monitoring program will be needed in order to assess the effectiveness of carbon sequestration at the FutureGen 2.0 carbon capture and storage (CCS) field-site. Geophysical monitoring methods are sensitive to subsurface changes that result from injection of CO 2 and will be used for: (1) tracking the spatial extent of the free phase CO 2 plume, (2) monitoring advancement of the pressure front, (3) identifying or mapping areas where induced seismicity occurs, and (4) identifying and mapping regions of increased risk for brine or CO 2 leakage from the reservoir. Site-specific suitability and cost effectiveness were evaluated formore » a number of geophysical monitoring methods including: passive seismic monitoring, reflection seismic imaging, integrated surface deformation, time-lapse gravity, pulsed neutron capture logging, cross-borehole seismic, electrical resistivity tomography, magnetotellurics and controlled source electromagnetics. The results of this evaluation indicate that CO 2 injection monitoring using reflection seismic methods would likely be difficult at the FutureGen 2.0 site. Electrical methods also exhibited low sensitivity to the expected CO 2 saturation changes and would be affected by metallic infrastructure at the field site. Passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture monitoring were selected for implementation as part of the FutureGen 2.0 storage site monitoring program.« less

  6. Geophysical Monitoring Methods Evaluation for the FutureGen 2.0 Project

    SciTech Connect

    Strickland, Chris E.; USA, Richland Washington; Vermeul, Vince R.

    A comprehensive monitoring program will be needed in order to assess the effectiveness of carbon sequestration at the FutureGen 2.0 carbon capture and storage (CCS) field-site. Geophysical monitoring methods are sensitive to subsurface changes that result from injection of CO 2 and will be used for: (1) tracking the spatial extent of the free phase CO 2 plume, (2) monitoring advancement of the pressure front, (3) identifying or mapping areas where induced seismicity occurs, and (4) identifying and mapping regions of increased risk for brine or CO 2 leakage from the reservoir. Site-specific suitability and cost effectiveness were evaluated formore » a number of geophysical monitoring methods including: passive seismic monitoring, reflection seismic imaging, integrated surface deformation, time-lapse gravity, pulsed neutron capture logging, cross-borehole seismic, electrical resistivity tomography, magnetotellurics and controlled source electromagnetics. The results of this evaluation indicate that CO 2 injection monitoring using reflection seismic methods would likely be difficult at the FutureGen 2.0 site. Electrical methods also exhibited low sensitivity to the expected CO 2 saturation changes and would be affected by metallic infrastructure at the field site. Passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture monitoring were selected for implementation as part of the FutureGen 2.0 storage site monitoring program.« less

  7. 75 FR 5780 - Green Borders Geothermal, LLC, Complainant, v. Terra-Gen Dixie Valley, LLC, Respondent; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL10-36-000] Green Borders Geothermal, LLC, Complainant, v. Terra-Gen Dixie Valley, LLC, Respondent; Notice of Complaint January 28, 2010. Take notice that on January 25, 2010, Green Borders Geothermal, LLC (Green Borders) filed a formal complaint against Terra-Gen Dixie Valle...

  8. Description of two smallest field crickets from South America, Laureopsis nauta Jaiswara gen. nov., sp. nov. and Perugryllus estiron Jaiswara gen. nov., sp. nov. (Orthoptera, Grylloidea, Gryllidae, Gryllinae).

    PubMed

    Jaiswara, Ranjana; Desutter-Grandcolas, Laure

    2017-11-20

    Gryllinae are one of the most diverse and widely distributed cricket groups. However, in South America they are known only from 10 genera. We update this list by describing two new genera and species of field crickets i.e. Laureopsis nauta Jaiswara gen. nov., sp. nov. and Perugryllus estiron Jaiswara gen. nov., sp. nov. from Peru.

  9. The GenDev Curriculum Development Workshop.

    PubMed

    D'cunha, J

    1997-01-01

    This article describes the second Curriculum Development Workshop held in May 1997 at the Asian Institute of Technology (AIT) in Bangkok, Thailand. The workshop aimed to review critically and restructure the Gender and Development Studies (GenDev) curriculum and to assess AIT's role in training gender experts for the region. Participants included 22 people from 16 countries in Asia, Europe, and the US who were teaching graduate students about gender issues and who were activists with nongovernmental organizations working on gender issues. It was determined that the following were required courses: Culture, Knowledge and Gender Relations; Gender, Technology, and Development; Principles of Gender Research and Methodology in Science and Technology; and Gender Analysis and Field Methods. Other suggested core courses included: Gender and Natural Resource Management; Enterprise Management, Technology, and Gender; Gender and Agrarian Reform; Urbanization: A Gender Perspective; Gender-Responsive Development Planning; and Gender and Economic Change: Past and Present Concerns. Participants distinguished between GenDev courses offered to anyone attending AIT and training courses designed to produce gender experts in the region. The aim of training courses for AIT graduate students was to sensitize potential managers, technologists, and others on gender issues and to create awareness of the importance of including gender perspectives within decision-making, policy formation, and implementation. Training courses to produce gender experts should be directed to those with a prior background in gender studies and include gender analysis in field methods. Participants agreed that there should be an independent and autonomous field of gender and development studies. Participants made six recommendations for such a field of study.

  10. Supplementation of OmniGen-AF alters the metabolic response to a glucose tolerance test in beef heifers

    USDA-ARS?s Scientific Manuscript database

    This study was designed to determine whether feeding OmniGen-AF to feedlot heifers would alter metabolic profiles in response to a glucose tolerance test. Heifer calves (n=184; 216±1 kg) were allocated into 2 treatment diets: 1) Control, fed a standard receiving ration, and 2) OmniGen-AF (OG), fed t...

  11. Evaluation of Mixed-Mode Data-Link Communications for NextGen 4DT and Equivalent Visual Surface Operations

    NASA Technical Reports Server (NTRS)

    Prinzel, Lawrence J., III; Shelton, Kevin J.; Jones, Denise R.; Allamandola, Angela S.; Arthur, Jarvis, J., III; Bailey, Randall E.

    2010-01-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a revolutionary new concept has been proposed for U.S. aviation operations, termed the Next Generation Air Transportation System or NextGen. Many key capabilities are being identified to enable NextGen, including the use of data-link communications. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen. The paper describes simulation research examining data-link communications during 4DT and equivalent visual surface operations.

  12. 77 FR 2342 - Fifth Meeting: RTCA, Next Gen Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ... University, Florida NextGen Test Bed, 557 Innovation Way, Daytona Beach, FL 32114. FOR FURTHER INFORMATION... Capabilities to Identified Metroplexes--a recommendation derived from a mapping of integrated capabilities to... specific capabilities. Lunch Break Review and Approve Recommendations for Submission to FAA DataComm...

  13. NextGen flight deck data comm: auxiliary synthetic speech - phase I

    DOT National Transportation Integrated Search

    2012-10-22

    Data Comma digital, text-based controller-pilot communication systemis critical to many NextGen improvements. With Data Comm, communication becomes a visual task. Although Data Comm brings many advantages, interacting with a visual display may ...

  14. Chemopreventive activity of GEN-27, a genistein derivative, in colitis-associated cancer is mediated by p65-CDX2-β-catenin axis

    PubMed Central

    Wang, Hong; Fan, Huimin; Li, Yan; Wang, Jianing; Zhang, Xu; Lu, Jinrong; Ji, Hui; Hu, Rong

    2016-01-01

    Nonresolving inflammation in the intestine predisposes individuals to colitis-associated colorectal cancer (CAC), which leads to high morbidity and mortality. Here we show that genistein-27 (GEN-27), a derivative of genistein, inhibited proliferation of human colorectal cancer cells through inhibiting β-catenin activity. Our results showed that GEN-27 increased expressions of adenomatous polyposis coli (APC) and axis inhibition protein 2 (AXIN2), and reduced β-catenin nuclear localization, which resulted from the inhibition of NF-κB/p65 nuclear localization and up-regulation of caudal-related homeobox transcription factor 2 (CDX2). Furthermore, GEN-27 decreased binding of p65 to the silencer region of CDX2 and increased binding of CDX2 to the promoter regions of APC and AXIN2, thus inhibiting the activation of β-catenin induced by TNF-α. Importantly, GEN-27 protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and tumor volume. Histopathology, immunohistochemistry and flow cytometry revealed that dietary GEN-27 significantly decreased secretion of proinflammatory cytokines and macrophage infiltration. Moreover, GEN-27 inhibited AOM/DSS-induced p65 and β-catenin nuclear translocation, while promoted the expression of CDX2, APC, and AXIN2. Taken together, our findings demonstrate that the anti-proliferation effect of GEN-27 in vitro and the prevention of CAC in vivo is mediated by p65-CDX2-β-catenin axis via inhibiting β-catenin target genes. Our results imply that GEN-27 could be a promising candidate for the chemoprevention of CAC. PMID:26910375

  15. Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-06-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia

  16. CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-07-31

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia

  17. Tools for Designing, Evaluating, and Certifying NextGen Technologies and Procedures: Automation Roles and Responsibilities

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    2011-01-01

    Barbara Kanki from NASA Ames Research Center will discuss research that focuses on the collaborations between pilots, air traffic controllers and dispatchers that will change in NextGen systems as automation increases and roles and responsibilities change. The approach taken by this NASA Ames team is to build a collaborative systems assessment template (CSAT) based on detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, policies, procedures and documented practices as augmented by field observations and interviews. The CSAT is developed to aid the assessment of key human factors and performance tradeoffs that result from considering different collaborative arrangements under NextGen system changes. In theory, the CSAT product may be applied to any NextGen application (such as Trajectory Based Operations) with specified ground and aircraft capabilities.

  18. Non contiguous-finished genome sequence and description of Senegalemassilia anaerobia gen. nov., sp. nov.

    PubMed Central

    Lagier, Jean-Christophe; Elkarkouri, Khalid; Rivet, Romain; Couderc, Carine; Raoult, Didier; Fournier, Pierre-Edouard

    2013-01-01

    Senegalemassilia anaerobia strain JC110T sp.nov. is the type strain of Senegalemassilia anaerobia gen. nov., sp. nov., the type species of a new genus within the Coriobacteriaceae family, Senegalemassilia gen. nov. This strain, whose genome is described here, was isolated from the fecal flora of a healthy Senegalese patient. S. anaerobia is a Gram-positive anaerobic coccobacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,383,131 bp long genome contains 1,932 protein-coding and 58 RNA genes. PMID:24019984

  19. An evaluation of the accuracy of the ORange (Gen II) by comparing it to the IOLMaster in the prediction of postoperative refraction.

    PubMed

    Chen, Ming

    2012-01-01

    The aim of this study was to evaluate the accuracy of ORange(®) Gen II (WaveTec Vision, Aliso Viejo, CA). The Surgical Suites, Honolulu, HI. The prospective 28 consecutive cataract surgical cases were selected from 85 cataract surgical cases between December 16, 2010 and February 24, 2011. With the same intraocular lens implantation, the predicted spherical equivalent refraction from IOLMaster(®) (Carl Zeiss AG, Oberkochen, Germany) and ORange Gen II were statistically compared and verified with 1-month postoperative manifest refraction. The data were put into IBM SPSS 19 (SPSS Inc, Chicago, IL) for analysis of variance. Pearson's correlation coefficient was also calculated to evaluate the correlation between the IOLMaster, ORange Gen II, and 1-month postoperative manifest refraction. There were no statistically significant differences in the mean spherical equivalent refraction from the IOLMaster, ORange Gen II, and 1-month postoperative manifest refraction (IOLMaster -0.40 diopters, P = 0.07; ORange Gen II -0.43 diopters, P = 0.16; 1-month refraction -0.41 diopters, P = 0.07). Pearson's correlation study demonstrated that all three were positively correlated (P < 0.05), with the strongest correlation between the ORange Gen II and 1-month postoperative manifest refraction (r = +0.6, P < 0.01). The ORange Gen II can be considered as an alternative method for intraocular lens selection for cataract patients.

  20. Coal-Gen attendees hear there's no magic bullet

    SciTech Connect

    NONE

    2007-09-15

    Those attending COAL-GEN 2007 in August heard that there is no magic bullet for meeting the energy and infrastructure needs facing the USA. The article reports on the conference which addressed topics including development of supercritical circulating fluidized bed coal unit; IGCC projects, the importance of including carbon capture and sequestration, and the need to attract and train personnel to work in the power industry. 3 photos.

  1. Design Experimentation with Multiple Perspectives: The GenScope Assessment Project.

    ERIC Educational Resources Information Center

    Hickey, Daniel T.; Kruger, Ann Cale; Frederick, Laura D.; Schafer, Nancy Jo; Zuiker, Steven

    The GenScope Assessment Project is studying assessment in the context of a month-long computer-supported learning environment for introductory genetics. Across three annual iterations with multiple teachers, project researchers manipulated the materials, incentives, and contexts in which students were invited to use formative feedback on…

  2. NextGen Flight Deck Data Comm : Auxiliary Synthetic Speech Phase II

    DOT National Transportation Integrated Search

    2015-07-01

    Data Comma text-based controller-pilot communication systemis expected to yield several NextGen safety and efficiency benefits. With Data Comm, communication becomes a visual task, and may potentially increase head-down time on the flight deck ...

  3. pGenN, a Gene Normalization Tool for Plant Genes and Proteins in Scientific Literature

    PubMed Central

    Ding, Ruoyao; Arighi, Cecilia N.; Lee, Jung-Youn; Wu, Cathy H.; Vijay-Shanker, K.

    2015-01-01

    Background Automatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines. Methods In this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases. Results We evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/). PMID:26258475

  4. Effect of application timing on efficacy of site preparation treatments using Chopper® GEN2™

    Treesearch

    A.W. Ezell; J.L. Yeiser; D.K. Lauer; H.E. Quicke

    2013-01-01

    Chopper® GEN2™ is a new imazapyr product for use in forestry site preparation. A single treatment (32 ounces of Chopper® GEN2™ per acre) was applied at three timings on three sites (Louisiana, Mississippi, and Virginia) to test the effect of application timing on treatment efficacy. Hardwood control was excellent for all applications. Pine growth varied by site, but...

  5. Enhanced and Synthetic Vision for Terminal Maneuvering Area NextGen Operations

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Bailey, Randall E.; Ellis, Kyle K. E.; Norman, R. Michael; Williams, Steven P.; Arthur, Jarvis J., III; Shelton, Kevin J.; Prinzel, Lawrence J., III

    2011-01-01

    Synthetic Vision Systems and Enhanced Flight Vision System (SVS/EFVS) technologies have the potential to provide additional margins of safety for aircrew performance and enable operational improvements for low visibility operations in the terminal area environment with equivalent efficiency as visual operations. To meet this potential, research is needed for effective technology development and implementation of regulatory and design guidance to support introduction and use of SVS/EFVS advanced cockpit vision technologies in Next Generation Air Transportation System (NextGen) operations. A fixed-base pilot-in-the-loop simulation test was conducted at NASA Langley Research Center that evaluated the use of SVS/EFVS in NextGen low visibility ground (taxi) operations and approach/landing operations. Twelve crews flew approach and landing operations in a simulated NextGen Chicago O Hare environment. Various scenarios tested the potential for EFVS for operations in visibility as low as 1000 ft runway visibility range (RVR) and SVS to enable lower decision heights (DH) than can currently be flown today. Expanding the EFVS visual segment from DH to the runway in visibilities as low as 1000 RVR appears to be viable as touchdown performance was excellent without any workload penalties noted for the EFVS concept tested. A lower DH to 150 ft and/or possibly reduced visibility minima by virtue of SVS equipage appears to be viable when implemented on a Head-Up Display, but the landing data suggests further study for head-down implementations.

  6. NextGen flight deck Data Comm : auxiliary synthetic speech phase I

    DOT National Transportation Integrated Search

    2012-12-31

    Data Comma text-based controller-pilot communication systemis critical to many NextGen improvements. With Data Comm, communication becomes a visual task. Interacting with a visual Data Comm display may yield an unsafe increase in head-down time...

  7. Batwanema gen. n. and Chokwenema gen. n. (Oxyurida, Hystrignathidae), new nematode genera as parasites of Passalidae (Coleoptera) from the Democratic Republic of Congo

    PubMed Central

    Morffe, Jans; García, Nayla

    2013-01-01

    Abstract Two new genera and species parasitizing passalid beetles from the Democratic Republic of Congo are described. Batwanema congo gen. n. et sp. n. is characterized by having females with the cervical cuticle armed with scale-like projections, arranged initially in rows of eight elements that gradually divide and form pointed spines toward the end of the spiny region, two cephalic annuli, clavate procorpus and genital tract monodelphic-prodelphic. Two Malagasian species of Artigasia Christie, 1934 were placed in this genus as B. latum (Van Waerebeke, 1973) comb. n. and B. annulatum (Van Waerebeke, 1973) comb. n. Chokwenema lepidophorum gen. n. et sp. n. is characterized by having females with the cervical cuticle armed with scale-like projections, arranged initially in rows of eight elements (similar to Batwanema) that divide gradually, forming spines; a single cephalic annule cone-like, truncated, moderately inflated; procorpus sub-cylindrical and genital tract didelphic-amphidelphic. PMID:24363593

  8. Considerations of Alloy 617 Application in the Gen IV Nuclear Reactor Systems - Part II: Metallurgical Property Challenges

    SciTech Connect

    Ren, Weiju

    2010-01-01

    Alloy 617 is currently considered as a leading candidate material for high temperature components in the Gen IV Nuclear Reactor Systems. Because of the unprecedented severe working conditions beyond its commercial service experience required by the Gen IV systems, the alloy faces various challenges in both mechanical and metallurgical properties. Following a previous paper discussing the mechanical property challenges, this paper is focused on the challenges and issues in metallurgical properties of the alloy for the intended nuclear application. Considerations are given in details about its metallurgical stability and aging evolution, aging effects on mechanical properties, potential Co hazard, andmore » internal oxidation. Some research and development activities are suggested with discussions on viability to satisfy the Gen IV Nuclear Reactor System needs.« less

  9. Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

    PubMed Central

    JENABIAN, Niloofar; HAGHANIFAR, Sina; MABOUDI, Avideh; BIJANI, Ali

    2013-01-01

    Objective Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. Material and Methods In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were recorded before the first and re-entry surgery (six months later): vertical clinical attachment level (VCAL), gingival index (GI), plaque index (PI), horizontal probing depth (HPD), vertical probing depth (VPD), gingival recession (GR), furcation vertical component (FVC), furcation to alveolar crest (FAC), fornix to base of defect (FBD), and furcation horizontal component (FHC) were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant. Results Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups. Conclusion The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone material

  10. MicroGen: a MIAME compliant web system for microarray experiment information and workflow management.

    PubMed

    Burgarella, Sarah; Cattaneo, Dario; Pinciroli, Francesco; Masseroli, Marco

    2005-12-01

    Improvements of bio-nano-technologies and biomolecular techniques have led to increasing production of high-throughput experimental data. Spotted cDNA microarray is one of the most diffuse technologies, used in single research laboratories and in biotechnology service facilities. Although they are routinely performed, spotted microarray experiments are complex procedures entailing several experimental steps and actors with different technical skills and roles. During an experiment, involved actors, who can also be located in a distance, need to access and share specific experiment information according to their roles. Furthermore, complete information describing all experimental steps must be orderly collected to allow subsequent correct interpretation of experimental results. We developed MicroGen, a web system for managing information and workflow in the production pipeline of spotted microarray experiments. It is constituted of a core multi-database system able to store all data completely characterizing different spotted microarray experiments according to the Minimum Information About Microarray Experiments (MIAME) standard, and of an intuitive and user-friendly web interface able to support the collaborative work required among multidisciplinary actors and roles involved in spotted microarray experiment production. MicroGen supports six types of user roles: the researcher who designs and requests the experiment, the spotting operator, the hybridisation operator, the image processing operator, the system administrator, and the generic public user who can access the unrestricted part of the system to get information about MicroGen services. MicroGen represents a MIAME compliant information system that enables managing workflow and supporting collaborative work in spotted microarray experiment production.

  11. Surface Map Traffic Intent Displays and Net-Centric Data-link Communications for NextGen

    NASA Technical Reports Server (NTRS)

    Shelton, Kevin J.; Prinzel, Lawrence J., III; Jones, Denise R.; Allamandola, Angela S.; Arthur, Jarvis J., III; Bailey, Randall E.

    2009-01-01

    By 2025, U.S. air traffic is predicted to increase three fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a revolutionary new concept has been proposed for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the use of data-link communications. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen. The paper describes simulation research, conducted at National Aeronautics and Space Administration (NASA) Langley Research Center, examining data-link communications and traffic intent data during envisioned four-dimensional trajectory (4DT)-based and equivalent visual (EV) surface operations. Overall, the results suggest that controller pilot data-link communications (CPDLC) with the use of mandatory pilot read-back of all clearances significantly enhanced situation awareness for 4DT and EV surface operations. The depiction of graphical traffic state and intent information on the surface map display further enhanced off-nominal detection and pilot qualitative reports of safety and awareness.

  12. Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor.

    PubMed

    Kumagai, Takeshi; Aratsu, Yusuke; Sugawara, Ryosuke; Sasaki, Takamitsu; Miyairi, Shinichi; Nagata, Kiyoshi

    2016-04-01

    Ban-Lan-Gen is the common name for the dried roots of indigo plants, including Polygonum tinctorium, Isatis indigotica, Isatis tinctoria, and Strobilanthes cusia. Ban-Lan-Gen is frequently used as an anti-inflammatory and an anti-viral for the treatment of hepatitis, influenza, and various types of inflammation. One of the cytochrome P450 (CYP) enzymes, CYP3A4, is responsible for the metabolism of a wide variety of xenobiotics, including an estimated 60% of all clinically used drugs. In this study, we investigated the effect of Ban-Lan-Gen on the transcriptional activation of the CYP3A4 gene. Ban-Lan-Gen extract increased CYP3A4 gene reporter activity in a dose-dependent manner. Indirubin, one of the biologically active ingredients in the Ban-Lan-Gen, also dose-dependently increased CYP3A4 gene reporter activity. Expression of short hairpin RNA for the human pregnane X receptor (hPXR-shRNA) inhibited CYP3A4 gene reporter activity, and overexpression of human PXR increased indirubin- and rifampicin-induced CYP3A4 gene reporter activity. Furthermore, indirubin induced CYP3A4 mRNA expression in HepG2 cells. Taken together, these results indicate that indirubin, a component of Ban-Lan-Gen, activated CYP3A4 gene transcription through the activation of the human PXR. Copyright © 2016. Published by Elsevier Ltd.

  13. NPDES Permit for NRG Energy (Formerly GenOn Potomac River Generating Station)

    EPA Pesticide Factsheets

    Under National Pollutant Discharge Elimination System permit number DC0022004, NRG Energy (Formerly GenOn Potomac River Generating Station) is authorized to discharge from a facility into receiving waters named Potomac River.

  14. Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine.

    PubMed

    Chen, Xiaoyi; Clark, Jason; Wunderlich, Mark; Fan, Cuiqing; Davis, Ashley; Chen, Song; Guan, Jun-Lin; Mulloy, James C; Kumar, Ashish; Zheng, Yi

    2017-05-04

    Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact of autophagy on acute myeloid leukemia (AML) maintenance and the validity of autophagy as a viable target in AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 AML (MA9-AML) cells have high autophagy flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish autophagy initiation, or via Atg5-disruption to prevent phagophore (the autophagosome precursor) membrane elongation, does not affect the growth or survival of MA9-AML cells, either in vitro or in vivo. Mechanistically, neither Atg5 nor Rb1cc1 disruption impairs endolysosome formation or survival signaling pathways. The autophagy inhibitor chloroquine shows autophagy-independent anti-leukemic effects in vitro but has no efficacy in vivo likely due to limited achievable drug efficacy in blood. Further, vesicular exocytosis appears to mediate chloroquine resistance in AML cells, and exocytotic inhibition significantly enhances the anti-leukemic effect of chloroquine. Thus, chloroquine can induce leukemia cell death in vitro in an autophagy-independent manner but with inadequate efficacy in vivo, and vesicular exocytosis is a possible mechanism of chloroquine resistance in MA9-AML. This study also reveals that autophagy-specific targeting is unlikely to benefit MA9-AML therapy.

  15. genRE: A Method to Extend Gridded Precipitation Climatology Data Sets in Near Real-Time for Hydrological Forecasting Purposes

    NASA Astrophysics Data System (ADS)

    van Osnabrugge, B.; Weerts, A. H.; Uijlenhoet, R.

    2017-11-01

    To enable operational flood forecasting and drought monitoring, reliable and consistent methods for precipitation interpolation are needed. Such methods need to deal with the deficiencies of sparse operational real-time data compared to quality-controlled offline data sources used in historical analyses. In particular, often only a fraction of the measurement network reports in near real-time. For this purpose, we present an interpolation method, generalized REGNIE (genRE), which makes use of climatological monthly background grids derived from existing gridded precipitation climatology data sets. We show how genRE can be used to mimic and extend climatological precipitation data sets in near real-time using (sparse) real-time measurement networks in the Rhine basin upstream of the Netherlands (approximately 160,000 km2). In the process, we create a 1.2 × 1.2 km transnational gridded hourly precipitation data set for the Rhine basin. Precipitation gauge data are collected, spatially interpolated for the period 1996-2015 with genRE and inverse-distance squared weighting (IDW), and then evaluated on the yearly and daily time scale against the HYRAS and EOBS climatological data sets. Hourly fields are compared qualitatively with RADOLAN radar-based precipitation estimates. Two sources of uncertainty are evaluated: station density and the impact of different background grids (HYRAS versus EOBS). The results show that the genRE method successfully mimics climatological precipitation data sets (HYRAS/EOBS) over daily, monthly, and yearly time frames. We conclude that genRE is a good interpolation method of choice for real-time operational use. genRE has the largest added value over IDW for cases with a low real-time station density and a high-resolution background grid.

  16. BioNetFit: a fitting tool compatible with BioNetGen, NFsim and distributed computing environments

    DOE PAGES

    Thomas, Brandon R.; Chylek, Lily A.; Colvin, Joshua; ...

    2015-11-09

    Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here in this paper, we present BioNetFit, a general-purpose fitting tool that is compatible with BioNetGen and NFsim. BioNetFit is designed to take advantage of distributed computing resources. This feature facilitates fitting (i.e. optimization of parameter values for consistency with data) when simulations are computationally expensive.

  17. Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-04-02

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  18. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. The Generic Spacecraft Analyst Assistant (GenSAA): A tool for automating spacecraft monitoring with expert systems

    NASA Technical Reports Server (NTRS)

    Hughes, Peter M.; Luczak, Edward C.

    1991-01-01

    Flight Operations Analysts (FOAs) in the Payload Operations Control Center (POCC) are responsible for monitoring a satellite's health and safety. As satellites become more complex and data rates increase, FOAs are quickly approaching a level of information saturation. The FOAs in the spacecraft control center for the COBE (Cosmic Background Explorer) satellite are currently using a fault isolation expert system named the Communications Link Expert Assistance Resource (CLEAR), to assist in isolating and correcting communications link faults. Due to the success of CLEAR and several other systems in the control center domain, many other monitoring and fault isolation expert systems will likely be developed to support control center operations during the early 1990s. To facilitate the development of these systems, a project was initiated to develop a domain specific tool, named the Generic Spacecraft Analyst Assistant (GenSAA). GenSAA will enable spacecraft analysts to easily build simple real-time expert systems that perform spacecraft monitoring and fault isolation functions. Lessons learned during the development of several expert systems at Goddard, thereby establishing the foundation of GenSAA's objectives and offering insights in how problems may be avoided in future project, are described. This is followed by a description of the capabilities, architecture, and usage of GenSAA along with a discussion of its application to future NASA missions.

  20. 78 FR 28940 - Ninth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    .... Huerta FAA NextGen Performance SnapShots Featured PBN Implementation Location Data Sources for Measuring... by the Business Case and Performance Metrics Work Group Recommendation for Implementing Categorical Exclusion Contained in FAA Modernization Act of 2012 Recommendation developed by CatEx2 Task Group for...

  1. A New Parent Generation: Meet Mr. and Mrs. Gen X

    ERIC Educational Resources Information Center

    Howe, Neil

    2010-01-01

    Slowly but surely, Generation Xers have been taking over from Baby Boomers as the majority of parents in elementary and secondary education. Gen-X parents and Boomer parents belong to two neighboring generations, each possessing its own location in history and its own peer personality. They are similar in some respects, but clearly different in…

  2. The Plant Genome Integrative Explorer Resource: PlantGenIE.org.

    PubMed

    Sundell, David; Mannapperuma, Chanaka; Netotea, Sergiu; Delhomme, Nicolas; Lin, Yao-Cheng; Sjödin, Andreas; Van de Peer, Yves; Jansson, Stefan; Hvidsten, Torgeir R; Street, Nathaniel R

    2015-12-01

    Accessing and exploring large-scale genomics data sets remains a significant challenge to researchers without specialist bioinformatics training. We present the integrated PlantGenIE.org platform for exploration of Populus, conifer and Arabidopsis genomics data, which includes expression networks and associated visualization tools. Standard features of a model organism database are provided, including genome browsers, gene list annotation, Blast homology searches and gene information pages. Community annotation updating is supported via integration of WebApollo. We have produced an RNA-sequencing (RNA-Seq) expression atlas for Populus tremula and have integrated these data within the expression tools. An updated version of the ComPlEx resource for performing comparative plant expression analyses of gene coexpression network conservation between species has also been integrated. The PlantGenIE.org platform provides intuitive access to large-scale and genome-wide genomics data from model forest tree species, facilitating both community contributions to annotation improvement and tools supporting use of the included data resources to inform biological insight. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  3. GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

    PubMed

    Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

    2015-01-01

    Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. 78 FR 5860 - Eighth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ...] Preliminary report to identify and mitigate barriers to implementing PBN. Issues associated with Implementing RNAV/RNP [cir] An open discussion by the Committee of Non-technical barriers of PBN procedures... NextGen. Cat Ex 2 Task Group [cir] Preliminary report on the recommendation for implementing new...

  5. Meet Mr. and Mrs. Gen X: A New Parent Generation

    ERIC Educational Resources Information Center

    Howe, Neil

    2010-01-01

    Slowly but surely, Generation Xers have been taking over from Baby Boomers as the majority of parents in elementary and secondary education. In the early 1990s, Gen Xers began joining parent-teacher associations in the nation's elementary schools. Around 2005, they became the majority of middle school parents. By the fall of 2008, they took over…

  6. Paragnomoxyala gen. nov. (Xyalidae, Monhysterida, Nematoda) from the East China Sea.

    PubMed

    Jiang, Weijun; Huang, Yong

    2015-11-05

    A new genus, Paragnomoxyala gen. nov., and a new species, Paragnomoxyala breviseta sp. nov. are described from the East China Sea. Paragnomoxyala gen. nov. is characterized by having large funnel-shaped buccal cavity with cuticularized walls and extended anteriorly; lips very high; striated cuticle; four cephalic setae, absence of outer labial setae; circular amphidial fovea; straight spicules and absence of gubernaculum; tail conico-cylindrical with three terminal setae; female monodelphic with an anterior outstretched ovary. It differs from similar genera by having a large buccal cavity unique in Xyalidae, straight spicules, lacking gubernaculum, and conico-cylindrical tail with terminal setae. Paragnomoxyala breviseta sp. nov. is characterized by having a large funnel-shaped buccal cavity, with cuticularized walls and extended anteriorly, 1.6-1.8 hd long and 63-79% cbd wide; four cephalic setae 3-4 µm long; circular amphids 6-9 µm in diameter; spicules straight but slightly bent at both ends; absence of gubernaculum and precloacal supplement.

  7. Wilsonosiphonia gen. nov. (Rhodomelaceae, Rhodophyta) based on molecular and morpho-anatomical characters.

    PubMed

    Bustamante, Danilo E; Won, Boo Yeon; Miller, Kathy Ann; Cho, Tae Oh

    2017-04-01

    Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot-shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts. © 2017 Phycological Society of America.

  8. FY13 Annual Report: PHEV Advanced Series Gen-set Development/Demonstration Activity

    SciTech Connect

    Chambon, Paul H.

    2013-12-01

    The objective of this project is to integrate ORNL advancements in vehicle technologies to properly design, and size a gen-set for various vehicle applications and then simulate multiple advanced series hybrid (HEV/PHEV) vehicles with the genset models.

  9. 75 FR 1052 - Terra-Gen Dixie Valley, LLC; TGP Dixie Development Company, LLC; New York Canyon, LLC; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-08

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL10-29-000] Terra-Gen Dixie Valley, LLC; TGP Dixie Development Company, LLC; New York Canyon, LLC; Notice of Filing December 30, 2009. Take notice that on December 24, 2009, Terra-Gen Dixie Valley, LLC, TGP Dixie Development Company, LLC and New York Canyon, LLC (``Petitioner...

  10. Overview of NASA's Next Generation Air Transportation System (NextGen) Research

    NASA Technical Reports Server (NTRS)

    Swenson, Harry N.

    2009-01-01

    This slide presentation is an overview of the research for the Next Generation Air Transportation System (NextGen). Included is a review of the current air transportation system and the challenges of air transportation research. Also included is a review of the current research highlights and significant accomplishments.

  11. Titanogryllus n. gen., the largest Gryllinae cricket from the Neotropical Region with three new species from the Brazilian Atlantic Forest (Orthoptera, Grylloidea, Gryllidae).

    PubMed

    Jaiswara, Ranjana; Souza-Dias, Pedro G B; De Campos, Lucas Denadai; RedÜ, Darlan R; De Mello, Francisco de A G; Desutter-Grandcolas, Laure

    2018-03-29

    Titanogryllus, a new genus and three new species T. salgado n. gen. n. sp., T. oxossi n. gen. n. sp., and T. oxente n. gen. n. sp. from subfamily Gryllinae (Grylloidea, Gryllidae) are described from the Brazilian Atlantic Forest. This genus is characterized by its very large size, and establishes a new record for the largest known cricket from Neotropical Region. The new taxa are characterized by their external morphology and male and female genitalia.

  12. Generalized Background Error covariance matrix model (GEN_BE v2.0)

    NASA Astrophysics Data System (ADS)

    Descombes, G.; Auligné, T.; Vandenberghe, F.; Barker, D. M.

    2014-07-01

    The specification of state background error statistics is a key component of data assimilation since it affects the impact observations will have on the analysis. In the variational data assimilation approach, applied in geophysical sciences, the dimensions of the background error covariance matrix (B) are usually too large to be explicitly determined and B needs to be modeled. Recent efforts to include new variables in the analysis such as cloud parameters and chemical species have required the development of the code to GENerate the Background Errors (GEN_BE) version 2.0 for the Weather Research and Forecasting (WRF) community model to allow for a simpler, flexible, robust, and community-oriented framework that gathers methods used by meteorological operational centers and researchers. We present the advantages of this new design for the data assimilation community by performing benchmarks and showing some of the new features on data assimilation test cases. As data assimilation for clouds remains a challenge, we present a multivariate approach that includes hydrometeors in the control variables and new correlated errors. In addition, the GEN_BE v2.0 code is employed to diagnose error parameter statistics for chemical species, which shows that it is a tool flexible enough to involve new control variables. While the generation of the background errors statistics code has been first developed for atmospheric research, the new version (GEN_BE v2.0) can be easily extended to other domains of science and be chosen as a testbed for diagnostic and new modeling of B. Initially developed for variational data assimilation, the model of the B matrix may be useful for variational ensemble hybrid methods as well.

  13. Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy.

    PubMed

    Wang, Lu; Zhao, Zibo; Ozark, Patrick A; Fantini, Damiano; Marshall, Stacy A; Rendleman, Emily J; Cozzolino, Kira A; Louis, Nundia; He, Xingyao; Morgan, Marc A; Takahashi, Yoh-Hei; Collings, Clayton K; Smith, Edwin R; Ntziachristos, Panagiotis; Savas, Jeffrey N; Zou, Lihua; Hashizume, Rintaro; Meeks, Joshua J; Shilatifard, Ali

    2018-06-01

    The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1. Cancer-associated mutations in the sequence encoding the MLL3 PHD repeats disrupt the interaction between MLL3 and BAP1 and correlate with poor patient survival. Cancer cells that had PHD-associated MLL3 mutations or lacked BAP1 showed reduced recruitment of MLL3 and the H3K27 demethylase KDM6A (also known as UTX) to gene enhancers. As a result, inhibition of the H3K27 methyltransferase activity of the Polycomb repressive complex 2 (PRC2) in tumor cells harboring BAP1 or MLL3 mutations restored normal gene expression patterns and impaired cell proliferation in vivo. This study provides mechanistic insight into the oncogenic effects of PHD-associated mutations in MLL3 and suggests that restoration of a balanced state of Polycomb-COMPASS activity may have therapeutic efficacy in tumors that bear mutations in the genes encoding these epigenetic factors.

  14. Considerations of Alloy 617 Application in the Gen IV Nuclear Reactor Systems - Part I: Mechanical Property Challenges

    SciTech Connect

    Ren, Weiju

    2010-01-01

    Alloy 617 is currently considered as a leading candidate material for high temperature components in the Gen IV Nuclear Reactor Systems. Because of the unprecedented severe working conditions beyond its commercial service experience required by the Gen IV systems, the alloy faces various challenges in both mechanical and metallurgical properties. This paper, as Part I of the discussion, is focused on the challenges and issues in the mechanical properties of Alloy 617 for the intended nuclear application. Considerations are given in details in its mechanical property data scatter, low creep strength in the desired high temperature range, lack of longtermmore » creep curves, high loading rate dependency, and preponderant tertiary creep. Some research and development activities are suggested with discussions on their viability to satisfy the Gen IV Nuclear Reactor System needs in near future and in the long run.« less

  15. Fetchamium prolixispinosum gen. et comb. nov. (division Dinoflagellata)

    NASA Astrophysics Data System (ADS)

    Pearce, Martin A.; Williams, Graham L.

    2018-01-01

    Oligosphaeridium is a gonyaulacacean dinocyst lacking cingular processes and possessing a distinctive process centred on the antapical plate indicating a sexiform hyposomal tabulation. However, specimens referable to the description of Oligosphaeridium prolixispinosum Davey and Williams, 1966, although lacking cingular processes, are clearly not sexiform. As an additional complication, the holotype of Oligosphaeridium prolixispinosum possesses cingular processes. In this brief contribution, we describe the new genus Fetchamium to accommodate the new transfer Fetchamium prolixispinosum gen. et comb. nov. and provide a discussion and emended diagnosis of the species.

  16. A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

  17. Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-05-04

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Plant MetGenMAP: an integrative analysis system for plant systems biology

    USDA-ARS?s Scientific Manuscript database

    We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

  19. Developing a Nuclear Grade of Alloy 617 for Gen IV Nuclear Energy Systems

    SciTech Connect

    Ren, Weiju; Swindeman, Robert W; Santella, Michael L

    2010-01-01

    Alloy 617, an attractive material not particularly developed for nuclear use, is now being considered as a leading candidate alloy by several countries for applications in the Gen IV Nuclear Energy Systems. An extensive review of its existing data suggests that it would be beneficial to refine the alloy s specification to a nuclear grade for the intended Gen IV systems. In this paper, rationale for developing a nuclear grade of the alloy is first discussed through an analysis on existing data from various countries. Then initial experiments for refining the alloy specification are described. Preliminary results have suggested themore » feasibility of the refinement approach, as well as the possibility for achieving a desirable nuclear grade. Based on the results, further research activities are recommended.« less

  20. Complete Mitochondrial Genomes of the Cherskii's Sculpin Cottus czerskii and Siberian Taimen Hucho taimen Reveal GenBank Entry Errors: Incorrect Species Identification and Recombinant Mitochondrial Genome.

    PubMed

    Balakirev, Evgeniy S; Saveliev, Pavel A; Ayala, Francisco J

    2017-01-01

    The complete mitochondrial (mt) genome is sequenced in 2 individuals of the Cherskii's sculpin Cottus czerskii . A surprisingly high level of sequence divergence (10.3%) has been detected between the 2 genomes of C czerskii studied here and the GenBank mt genome of C czerskii (KJ956027). At the same time, a surprisingly low level of divergence (1.4%) has been detected between the GenBank C czerskii (KJ956027) and the Amur sculpin Cottus szanaga (KX762049, KX762050). We argue that the observed discrepancies are due to incorrect taxonomic identification so that the GenBank accession number KJ956027 represents actually the mt genome of C szanaga erroneously identified as C czerskii . Our results are of consequence concerning the GenBank database quality, highlighting the potential negative consequences of entry errors, which once they are introduced tend to be propagated among databases and subsequent publications. We illustrate the premise with the data on recombinant mt genome of the Siberian taimen Hucho taimen (NCBI Reference Sequence Database NC_016426.1; GenBank accession number HQ897271.1), bearing 2 introgressed fragments (≈0.9 kb [kilobase]) from 2 lenok subspecies, Brachymystax lenok and Brachymystax lenok tsinlingensis , submitted to GenBank on June 12, 2011. Since the time of submission, the H taimen recombinant mt genome leading to incorrect phylogenetic inferences was propagated in multiple subsequent publications despite the fact that nonrecombinant H taimen genomes were also available (submitted to GenBank on August 2, 2014; KJ711549, KJ711550). Other examples of recombinant sequences persisting in GenBank are also considered. A GenBank Entry Error Depositary is urgently needed to monitor and avoid a progressive accumulation of wrong biological information.

  1. The GenTechnique Project: Developing an Open Environment for Learning Molecular Genetics.

    ERIC Educational Resources Information Center

    Calza, R. E.; Meade, J. T.

    1998-01-01

    The GenTechnique project at Washington State University uses a networked learning environment for molecular genetics learning. The project is developing courseware featuring animation, hyper-link controls, and interactive self-assessment exercises focusing on fundamental concepts. The first pilot course featured a Web-based module on DNA…

  2. Working with Gen Y Teachers: Dealing with a Changing Teacher Workforce

    ERIC Educational Resources Information Center

    Williamson, Ronald; Meyer-Looze, Catherine

    2010-01-01

    A significant change is coming to American classrooms. As Baby Boomer teachers retire and are replaced by members of Generation Y (born between 1977 and 1995) there is growing evidence that they come from a far different set of experiences, experiences that will shape their lives and their careers (Coggins, 2008). Members of Gen Y share several…

  3. Birth characteristics, maternal reproductive history, and the risk of infant leukemia: a report from the Children's Oncology Group.

    PubMed

    Spector, Logan G; Davies, Stella M; Robison, Leslie L; Hilden, Joanne M; Roesler, Michelle; Ross, Julie A

    2007-01-01

    Leukemias with MLL gene rearrangements predominate in infants (<1 year of age), but not in older children, and may have a distinct etiology. High birth weight, higher birth order, and prior fetal loss have, with varying consistency, been associated with infant leukemia, but no studies have reported results with respect to MLL status. Here, we report for the first time such an analysis. During 1999 to 2003, mothers of 240 incident cases (113 MLL(+), 80 MLL(-), and 47 indeterminate) and 255 random digit dialed controls completed a telephone interview. Odds ratios and 95% confidence intervals for quartile of birth weight, birth order, gestational age, maternal age at delivery, prior fetal loss, pre-pregnancy body mass index, and weight gain during pregnancy were obtained using unconditional logistic regression; P for linear trend was obtained by modeling continuous variables. There was a borderline significant linear trend of increasing birth weight with MLL(+) (P = 0.06), but not MLL(-) (P = 0.93), infant leukemia. Increasing birth order showed a significant inverse linear trend, independent of birth weight, with MLL(+) (P = 0.01), but not MLL(-) (P = 0.18), infant leukemia. Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies.

  4. Complete Mitochondrial Genomes of the Cherskii’s Sculpin Cottus czerskii and Siberian Taimen Hucho taimen Reveal GenBank Entry Errors: Incorrect Species Identification and Recombinant Mitochondrial Genome

    PubMed Central

    Balakirev, Evgeniy S; Saveliev, Pavel A; Ayala, Francisco J

    2017-01-01

    The complete mitochondrial (mt) genome is sequenced in 2 individuals of the Cherskii’s sculpin Cottus czerskii. A surprisingly high level of sequence divergence (10.3%) has been detected between the 2 genomes of C czerskii studied here and the GenBank mt genome of C czerskii (KJ956027). At the same time, a surprisingly low level of divergence (1.4%) has been detected between the GenBank C czerskii (KJ956027) and the Amur sculpin Cottus szanaga (KX762049, KX762050). We argue that the observed discrepancies are due to incorrect taxonomic identification so that the GenBank accession number KJ956027 represents actually the mt genome of C szanaga erroneously identified as C czerskii. Our results are of consequence concerning the GenBank database quality, highlighting the potential negative consequences of entry errors, which once they are introduced tend to be propagated among databases and subsequent publications. We illustrate the premise with the data on recombinant mt genome of the Siberian taimen Hucho taimen (NCBI Reference Sequence Database NC_016426.1; GenBank accession number HQ897271.1), bearing 2 introgressed fragments (≈0.9 kb [kilobase]) from 2 lenok subspecies, Brachymystax lenok and Brachymystax lenok tsinlingensis, submitted to GenBank on June 12, 2011. Since the time of submission, the H taimen recombinant mt genome leading to incorrect phylogenetic inferences was propagated in multiple subsequent publications despite the fact that nonrecombinant H taimen genomes were also available (submitted to GenBank on August 2, 2014; KJ711549, KJ711550). Other examples of recombinant sequences persisting in GenBank are also considered. A GenBank Entry Error Depositary is urgently needed to monitor and avoid a progressive accumulation of wrong biological information. PMID:28890653

  5. [Diagnostic and Treatment Strategies in Morel-Lavallee Lesions in the Spinal Column and Pelvis].

    PubMed

    Becker, Christopher A; Kammerlander, Christian; Greiner, Axel; Sommer, Fabian; Linhart, Christoph; Böcker, Wolfgang; Rubenbauer, Bianka; Weidert, Simon

    2018-04-12

    The Morel-Lavallée lesion is one of the concomitant soft tissue lesions of pelvic fractures. Its role in spine fractures and its treatment in combination with osteosynthesis of pelvic or spine fractures have not yet been determined. The aim of this study was to analyse the best diagnostic and treatment options of both spine and pelvic fractures combined with Morel-Lavallée lesions (MLL). An analysis of the literature was performed via PubMed and Medline. This revealed a total of 197 studies and case reports. After analysing the literature, 19 studies/case reports met our inclusion criteria. There are several diagnostic options for MLL, including ultrasound, computed tomography or MRI. In spinal and pelvic lesions, ultrasound is capable of detecting MLL. Some authors tend to perform open debridement of the MLL, whereas others recommend percutanous treatment. Open debridement and vacuum-assisted closure are recommended in late diagnosed MLL, where primary suture of the soft tissue is impossible. Fracture fixation should be performed simultaneously to treatment of the MLL. Broad-spectrum cephalosporins combined with an aminoglycoside or piperacilline/tazobactam should be initiated. Radical debridement and drainage are recommended, especially when MLL is diagnosed late. Repeated ultrasound examinations should be performed of the surrounding soft tissue of the fracture. When MLL is diagnosed within 2 days, percutanous fracture and MLL treatment should be performed. After more than 2 days, both fracture and MLL should be treated with open debridement, open fracture fixation and primary suture if possible. Georg Thieme Verlag KG Stuttgart · New York.

  6. NextGen Future Safety Assessment Game

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Gheorghe, Adian; Jones, Sharon Monica

    2010-01-01

    The successful implementation of the next generation infrastructure systems requires solid understanding of their technical, social, political and economic aspects along with their interactions. The lack of historical data that relate to the long-term planning of complex systems introduces unique challenges for decision makers and involved stakeholders which in turn result in unsustainable systems. Also, the need to understand the infrastructure at the societal level and capture the interaction between multiple stakeholders becomes important. This paper proposes a methodology in order to develop a holistic approach aiming to provide an alternative subject-matter expert (SME) elicitation and data collection method for future sociotechnical systems. The methodology is adapted to Next Generation Air Transportation System (NextGen) decision making environment in order to demonstrate the benefits of this holistic approach.

  7. NextGen Future Safety Assessment Game

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Gheorghe, Adrian; Jones, Sharon Monica

    2011-01-01

    The successful implementation of the next generation infrastructure systems requires solid understanding of their technical, social, political and economic aspects along with their interactions. The lack of historical data that relate to the long-term planning of complex systems introduces unique challenges for decision makers and involved stakeholders which in turn result in unsustainable systems. Also, the need to understand the infrastructure at the societal level and capture the interaction between multiple stakeholders becomes important. This paper proposes a methodology in order to develop a holistic approach aiming to provide an alternative subject-matter expert (SME) elicitation and data collection method for future sociotechnical systems. The methodology is adapted to Next Generation Air Transportation System (NextGen) decision making environment in order to demonstrate the benefits of this holistic approach.

  8. Face and construct validation of a next generation virtual reality (Gen2-VR) surgical simulator.

    PubMed

    Sankaranarayanan, Ganesh; Li, Baichun; Manser, Kelly; Jones, Stephanie B; Jones, Daniel B; Schwaitzberg, Steven; Cao, Caroline G L; De, Suvranu

    2016-03-01

    Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills laboratory that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR) system to train surgeons in these environments. This study was to establish face and construct validity of our system. The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: Case I: traditional VR; Case II: Gen2-VR with no distractions and Case III: Gen2-VR with distractions and interruptions. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 s and tools malfunctioned for 15 s at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study. Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon signed-rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.0001), (Case I, Case III, p < 0.0001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean 4.18) and tool malfunction (median 4.56) significantly hindered their performance. The results showed that Gen2-VR simulator has both face and construct validity and that it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology.

  9. Face and Construct Validation of a Next Generation Virtual Reality (Gen2-VR©) Surgical Simulator

    PubMed Central

    Sankaranarayanan, Ganesh; Li, Baichun; Manser, Kelly; Jones, Stephanie B.; Jones, Daniel B.; Schwaitzberg, Steven; Cao, Caroline G. L.; De, Suvranu

    2015-01-01

    Introduction Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills lab that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR©) system to train surgeons in these environments. This study was to establish face and construct validity of our system. Methods and Procedures The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: CASE I: traditional VR; CASE II: Gen2-VR© with no distractions and CASE III: Gen2-VR© with distractions and interruptions.. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 seconds and tools malfunctioned for 15 seconds at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study. Results Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon Signed Rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.001), (Case I, Case III, p < 0.001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean= 4.18) and tool malfunction (median = 4.56) significantly hindered their performance. Conclusion The results showed that Gen2-VR© simulator has both face and construct validity and it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology. PMID:26092010

  10. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2018-05-24

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Transitioning Resolution Responsibility between the Controller and Automation Team in Simulated NextGen Separation Assurance

    NASA Technical Reports Server (NTRS)

    Cabrall, C.; Gomez, A.; Homola, J.; Hunt, S..; Martin, L.; Merccer, J.; Prevott, T.

    2013-01-01

    As part of an ongoing research effort on separation assurance and functional allocation in NextGen, a controller- in-the-loop study with ground-based automation was conducted at NASA Ames' Airspace Operations Laboratory in August 2012 to investigate the potential impact of introducing self-separating aircraft in progressively advanced NextGen timeframes. From this larger study, the current exploratory analysis of controller-automation interaction styles focuses on the last and most far-term time frame. Measurements were recorded that firstly verified the continued operational validity of this iteration of the ground-based functional allocation automation concept in forecast traffic densities up to 2x that of current day high altitude en-route sectors. Additionally, with greater levels of fully automated conflict detection and resolution as well as the introduction of intervention functionality, objective and subjective analyses showed a range of passive to active controller- automation interaction styles between the participants. Not only did the controllers work with the automation to meet their safety and capacity goals in the simulated future NextGen timeframe, they did so in different ways and with different attitudes of trust/use of the automation. Taken as a whole, the results showed that the prototyped controller-automation functional allocation framework was very flexible and successful overall.

  12. ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs

    NASA Astrophysics Data System (ADS)

    Cleves, Ann E.; Jain, Ajay N.

    2017-05-01

    We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.

  13. GEN IV reactors: Where we are, where we should go

    SciTech Connect

    Locatelli, G.; Mancini, M.; Todeschini, N.

    2012-07-01

    GEN IV power plants represent the mid-long term option of the nuclear sector. International literature proposes many papers and reports dealing with these reactors, but there is an evident difference of type and shape of information making impossible each kind of detailed comparison. Moreover, authors are often strongly involved in some particular design; this creates many difficulties in their super-partes position. Therefore it is necessary to put order in the most relevant information to understand strengths and weaknesses of each design and derive an overview useful for technicians and policy makers. This paper presents the state-of the art for GENmore » IV nuclear reactors providing a comprehensive literature review of the different designs with a relate taxonomy. It presents the more relevant references, data, advantages, disadvantages and barriers to the adoptions. In order to promote an efficient and wide adoption of GEN IV reactors the paper provides the pre-conditions that must be accomplished, enabling factors promoting the implementation and barriers limiting the extent and intensity of its implementation. It concludes outlying the state of the art of the most important R and D areas and the future achievements that must be accomplished for a wide adoption of these technologies. (authors)« less

  14. Modeling and Evaluating Pilot Performance in NextGen: Review of and Recommendations Regarding Pilot Modeling Efforts, Architectures, and Validation Studies

    NASA Technical Reports Server (NTRS)

    Wickens, Christopher; Sebok, Angelia; Keller, John; Peters, Steve; Small, Ronald; Hutchins, Shaun; Algarin, Liana; Gore, Brian Francis; Hooey, Becky Lee; Foyle, David C.

    2013-01-01

    NextGen operations are associated with a variety of changes to the national airspace system (NAS) including changes to the allocation of roles and responsibilities among operators and automation, the use of new technologies and automation, additional information presented on the flight deck, and the entire concept of operations (ConOps). In the transition to NextGen airspace, aviation and air operations designers need to consider the implications of design or system changes on human performance and the potential for error. To ensure continued safety of the NAS, it will be necessary for researchers to evaluate design concepts and potential NextGen scenarios well before implementation. One approach for such evaluations is through human performance modeling. Human performance models (HPMs) provide effective tools for predicting and evaluating operator performance in systems. HPMs offer significant advantages over empirical, human-in-the-loop testing in that (1) they allow detailed analyses of systems that have not yet been built, (2) they offer great flexibility for extensive data collection, (3) they do not require experimental participants, and thus can offer cost and time savings. HPMs differ in their ability to predict performance and safety with NextGen procedures, equipment and ConOps. Models also vary in terms of how they approach human performance (e.g., some focus on cognitive processing, others focus on discrete tasks performed by a human, while others consider perceptual processes), and in terms of their associated validation efforts. The objectives of this research effort were to support the Federal Aviation Administration (FAA) in identifying HPMs that are appropriate for predicting pilot performance in NextGen operations, to provide guidance on how to evaluate the quality of different models, and to identify gaps in pilot performance modeling research, that could guide future research opportunities. This research effort is intended to help the FAA

  15. Control control control: a reassessment and comparison of GenBank and chromatogram mtDNA sequence variation in Baltic grey seals (Halichoerus grypus).

    PubMed

    Fietz, Katharina; Graves, Jeff A; Olsen, Morten Tange

    2013-01-01

    Genetic data can provide a powerful tool for those interested in the biology, management and conservation of wildlife, but also lead to erroneous conclusions if appropriate controls are not taken at all steps of the analytical process. This particularly applies to data deposited in public repositories such as GenBank, whose utility relies heavily on the assumption of high data quality. Here we report on an in-depth reassessment and comparison of GenBank and chromatogram mtDNA sequence data generated in a previous study of Baltic grey seals. By re-editing the original chromatogram data we found that approximately 40% of the grey seal mtDNA haplotype sequences posted in GenBank contained errors. The re-analysis of the edited chromatogram data yielded overall similar results and conclusions as the original study. However, a significantly different outcome was observed when using the uncorrected dataset based on the GenBank haplotypes. We therefore suggest disregarding the existing GenBank data and instead using the correct haplotypes reported here. Our study serves as an illustrative example reiterating the importance of quality control through every step of a research project, from data generation to interpretation and submission to an online repository. Errors conducted in any step may lead to biased results and conclusions, and could impact management decisions.

  16. Control Control Control: A Reassessment and Comparison of GenBank and Chromatogram mtDNA Sequence Variation in Baltic Grey Seals (Halichoerus grypus)

    PubMed Central

    Fietz, Katharina; Graves, Jeff A.; Olsen, Morten Tange

    2013-01-01

    Genetic data can provide a powerful tool for those interested in the biology, management and conservation of wildlife, but also lead to erroneous conclusions if appropriate controls are not taken at all steps of the analytical process. This particularly applies to data deposited in public repositories such as GenBank, whose utility relies heavily on the assumption of high data quality. Here we report on an in-depth reassessment and comparison of GenBank and chromatogram mtDNA sequence data generated in a previous study of Baltic grey seals. By re-editing the original chromatogram data we found that approximately 40% of the grey seal mtDNA haplotype sequences posted in GenBank contained errors. The re-analysis of the edited chromatogram data yielded overall similar results and conclusions as the original study. However, a significantly different outcome was observed when using the uncorrected dataset based on the GenBank haplotypes. We therefore suggest disregarding the existing GenBank data and instead using the correct haplotypes reported here. Our study serves as an illustrative example reiterating the importance of quality control through every step of a research project, from data generation to interpretation and submission to an online repository. Errors conducted in any step may lead to biased results and conclusions, and could impact management decisions. PMID:23977362

  17. Traffic Generator (TrafficGen) Version 1.4.2: Users Guide

    DTIC Science & Technology

    2016-06-01

    events, the user has to enter them manually . We will research and implement a way to better define and organize the multicast addresses so they can be...the network with Transmission Control Protocol and User Datagram Protocol Internet Protocol traffic. Each node generating network traffic in an...TrafficGen Graphical User Interface (GUI) 3 3.1 Anatomy of the User Interface 3 3.2 Scenario Configuration and MGEN Files 4 4. Working with

  18. Geochemical Monitoring Considerations for the FutureGen 2.0 Project

    DOE PAGES

    Amonette, James E.; Johnson, Timothy A.; Spencer, Clayton F.; ...

    2014-12-31

    Geochemical monitoring is an essential component of a suite of monitoring technologies designed to evaluate CO2 mass balance and detect possible loss of containment at the FutureGen 2.0 geologic sequestration site near Jacksonville, IL. This presentation gives an overview of the potential geochemical approaches and tracer technologies that were considered, and describes the evaluation process by which the most cost-effective and robust of these were selected for implementation

  19. Flight Deck Technologies to Enable NextGen Low Visibility Surface Operations

    NASA Technical Reports Server (NTRS)

    Prinzel, Lawrence (Lance) J., III; Arthur, Jarvis (Trey) J.; Kramer, Lynda J.; Norman, Robert M.; Bailey, Randall E.; Jones, Denise R.; Karwac, Jerry R., Jr.; Shelton, Kevin J.; Ellis, Kyle K. E.

    2013-01-01

    Many key capabilities are being identified to enable Next Generation Air Transportation System (NextGen), including the concept of Equivalent Visual Operations (EVO) . replicating the capacity and safety of today.s visual flight rules (VFR) in all-weather conditions. NASA is striving to develop the technologies and knowledge to enable EVO and to extend EVO towards a Better-Than-Visual operational concept. This operational concept envisions an .equivalent visual. paradigm where an electronic means provides sufficient visual references of the external world and other required flight references on flight deck displays that enable Visual Flight Rules (VFR)-like operational tempos while maintaining and improving safety of VFR while using VFR-like procedures in all-weather conditions. The Langley Research Center (LaRC) has recently completed preliminary research on flight deck technologies for low visibility surface operations. The work assessed the potential of enhanced vision and airport moving map displays to achieve equivalent levels of safety and performance to existing low visibility operational requirements. The work has the potential to better enable NextGen by perhaps providing an operational credit for conducting safe low visibility surface operations by use of the flight deck technologies.

  20. Reflexión bioética sobre el uso de organismos genéticamente modificados

    PubMed Central

    Yunta, Eduardo Rodríguez

    2011-01-01

    El presente artículo reflexiona desde los 4 principios de la bioética el uso comercial de organismos genéticamente modificados. Se cuestiona fundamentalmente la falta de transferencia de tecnología entre el mundo desarrollado y en desarrollo y el que el presente sistema de patentamiento de organismos vivos modificados fomenta intereses comerciales y no da debida importancia al desarrollo sostenible de la agricultura y ganadería en los países en desarrollo, donde más se necesita. Se reflexiona sobre la importancia que tiene evaluar los riesgos antes de introducirse en el mercado organismos genéticamente modificados y la necesidad de regulación en los países. PMID:21927675

  1. Evolutionary Trends of Perkinsozoa (Alveolata) Characters Based on Observations of Two New Genera of Parasitoids of dinoflagellates, Dinovorax gen. nov. and Snorkelia gen. nov.

    PubMed Central

    Reñé, Albert; Alacid, Elisabet; Ferrera, Isabel; Garcés, Esther

    2017-01-01

    Parasites are one of the ecologically most relevant groups of marine food webs, but their taxonomic and biological complexity hampers the assessment of their diversity and evolutionary trends. Moreover, the within-host processes that govern parasitoid infection, development and reproduction are often unknown. In this study, we describe a new species of a perkinsozoan endoparasitoid that infects the toxic dinoflagellate Dinophysis sacculus, by including observations of its morphology, ultrastructure, life-cycle development and phylogeny. The SSU rDNA sequence and main morphological features were also obtained for a second parasitoid species infecting the bloom-forming dinoflagellate Levanderina fissa. Phylogenetic analyses including the sequences obtained show that all known Perkinsozoa species infecting dinoflagellates cluster together. However, sequences of Parvilucifera prorocentri and those obtained in this study cluster at the base of the clade, while the rest of Parvilucifera representatives form a separated highly-supported cluster. These results, together with differing morphological characters like the formation of a germ-tube, the presence of trichocysts, or the heterochromatin presence in zoospores nucleus justify the erection of Dinovorax pyriformis gen. nov. et sp. nov., and Snorkelia prorocentri gen. nov. et comb. nov. (=Parvilucifera prorocentri). The morphological features and phylogenetic position of these parasitoids represent ancestral characters for the Perkinsozoa phylum, and also for Dinozoa clade, allowing the inference of the evolutionary framework of these Alveolata members. PMID:28970818

  2. Description of Alloprevotella rava gen. nov., sp. nov., isolated from the human oral cavity, and reclassification of Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov.

    PubMed

    Downes, Julia; Dewhirst, Floyd E; Tanner, Anne C R; Wade, William G

    2013-04-01

    Five strains of anaerobic, gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group. Phylogenetic analysis of full-length 16S rRNA gene sequences showed that these strains represented a novel group within the family Prevotellaceae, and the most closely related species was Prevotella tannerae. P. tannerae and the novel taxon are deeply branched from the genus Prevotella, with sequence identities to the type strain of the type species of Prevotella, Prevotella melaninogenica, of 82.2 and 85.6 %, respectively. The novel genus Alloprevotella gen. nov. is proposed to accommodate the novel species Alloprevotella rava gen. nov., sp. nov. and the previously named Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov. The type species is Alloprevotella tannerae. The type strain of Alloprevotella rava is 81/4-12(T) ( = DSM 22548(T)  = CCUG 58091(T)) and the type strain of Alloprevotella tannerae is ATCC 51259(T)  = CCUG 34292(T)  = CIP 104476(T)  = NCTC 13073(T). Alloprevotella rava is weakly to moderately saccharolytic and produces moderate amounts of acetic acid and major amounts of succinic acid as end products of fermentation. Strains are sensitive to 20 % bile and hydrolyse gelatin. The principal cellular long-chain fatty acids are anteiso-C15 : 0, iso-C15 : 0, C16 : 0, iso-C17 : 0 and iso-C17 : 0 3-OH. The G+C content of the DNA of the type strain is 47 mol%.

  3. Structural and magnetic properties of FeGen-/0 (n = 3-12) clusters: Mass-selected anion photoelectron spectroscopy and density functional theory calculations

    NASA Astrophysics Data System (ADS)

    Deng, Xiao-Jiao; Kong, Xiang-Yu; Liang, Xiaoqing; Yang, Bin; Xu, Hong-Guang; Xu, Xi-Ling; Feng, Gang; Zheng, Wei-Jun

    2017-12-01

    The structural, electronic, and magnetic properties of FeGen-/0 (n = 3-12) clusters were investigated by using anion photoelectron spectroscopy in combination with density functional theory calculations. For both anionic and neutral FeGen (n = 3-12) clusters with n ≤ 7, the dominant structures are exohedral. The FeGe8-/0 clusters have half-encapsulated boat-shaped structures, and the opening of the boat-shaped structure is gradually covered by the additional Ge atoms to form Gen cage from n = 9 to 11. The structures of FeGe10-/0 can be viewed as two Ge atoms symmetrically capping the opening of the boat-shaped structure of FeGe8, and those of FeGe12-/0 are distorted hexagonal prisms with the Fe atom at the center. Natural population analysis shows that there is an electron transfer from the Ge atoms to the Fe atom at n = 8-12. The total magnetic moment of FeGen-/0 and local magnetic moment of the Fe atom have not been quenched.

  4. Tadaridanema delicatus (Schwartz, 1927) n. gen., n. comb. (Trichostrongylina: Molineidae) parasite of Molossidae bats.

    PubMed

    Falcón-Ordaz, Jorge; Guzmán-Cornejo, Carmen; García-Prieto, Luis; Gardner, Scott Lyell

    2006-10-01

    On the basis of the revision of the type material of Anoplostrongylus delicatus Schwartz, 1927, and new specimens collected from Tadarida brasiliensis mexicana (Saussure, 1860) in 4 arid localities from Mexico, we describe a new genus (Tadaridanema n. gen.), to which A. delicatus is transferred (as Tadaridanema delicatus (Schwartz, 1927) n. gen., n. comb.). This new genus differs from all other genera included in Anoplostrongylinae by having ray 2 larger than ray 3. In addition, T. delicatus can be differentiated from the type species of Anoplostrongylus (Anoplostrongylus paradoxus (Travassos, 1918)) because it possess vestibular branches equal in length, cephalic inflation divided into 2 regions, and synlophe with many small ridges at the midbody level, whereas in T. delicatus, vestibular branches are equal in size, cephalic inflation is simple in structure, and the synlophe has only 2 well-developed dorsal cuticular ridges.

  5. Parametric Modeling of the Safety Effects of NextGen Terminal Maneuvering Area Conflict Scenarios

    NASA Technical Reports Server (NTRS)

    Rogers, William H.; Waldron, Timothy P.; Stroiney, Steven R.

    2011-01-01

    The goal of this work was to analytically identify and quantify the issues, challenges, technical hurdles, and pilot-vehicle interface issues associated with conflict detection and resolution (CD&R)in emerging operational concepts for a NextGen terminal aneuvering area, including surface operations. To this end, the work entailed analytical and trade studies focused on modeling the achievable safety benefits of different CD&R strategies and concepts in the current and future airport environment. In addition, crew-vehicle interface and pilot performance enhancements and potential issues were analyzed based on review of envisioned NextGen operations, expected equipage advances, and human factors expertise. The results of perturbation analysis, which quantify the high-level performance impact of changes to key parameters such as median response time and surveillance position error, show that the analytical model developed could be useful in making technology investment decisions.

  6. Endosporoideus gen. nov., a mitosporic fungus on Phoenix hanceana.

    PubMed

    Ho, Wai Hong; Yanna; Hyde, Kevin D; Goh, Teik Khiang

    2005-01-01

    Endosporoideus pedicellata gen. et sp, nov. is described and illustrated from decaying petioles of Phoenix hanceana collected from grassland in Tai Mo Shan, Hong Kong. The genus is unique in producing solitary, phragmosporous conidia. The conidia comprise a brown to dark brown inner-wall layer and thick, hyaline outer-wall layer and are produced holoblastically from determinate conidiogenous cells on micronematous, mononematous conidiophores. Cells of conidia may disarticulate at the septa. Representative steps in conidiogenesis of E. pedicellata are illustrated with light micrographs, and details of the conidiogenous events are interpreted schematically.

  7. Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

    ClinicalTrials.gov

    2017-02-16

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Fanconi Anemia; Previously Treated Myelodysplastic Syndromes

  8. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    ClinicalTrials.gov

    2018-04-26

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-04

    Acute Myeloid Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following; Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  10. AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-03-12

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    ClinicalTrials.gov

    2018-03-15

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  12. GEN-27, a Newly Synthetic Isoflavonoid, Inhibits the Proliferation of Colon Cancer Cells in Inflammation Microenvironment by Suppressing NF-κB Pathway

    PubMed Central

    Wang, Yajing; Lu, Ping; Zhang, Weifeng; Du, Qianming; Tang, Jingjing; Wang, Hong; Lu, Jinrong; Hu, Rong

    2016-01-01

    Nonresolving inflammation is one of the consistent features of the tumor microenvironment in the intestine and plays a critical role in the initiation and development of colon cancer. Here we reported the inhibitory effects of GEN-27, a new derivative of genistein, on the inflammation-related colon cancer cell proliferation and delineated the mechanism of its action. The results indicated that GEN-27 inhibited the proliferation of human colon tumor HCT116 cells stimulated by culture supernatants of LPS-induced human monocytes THP-1 cells and significantly decreased LPS-induced secretion of proinflammatory cytokines interleukin-6 and interleukin-1β in THP-1 cells. The HCT116 cell proliferation elicited by THP-1-conditioned medium could be blocked by the interleukin-1 receptor antagonist (IL-1RA). Further mechanistic study revealed that GEN-27 remarkably inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β in both HCT116 and THP-1 cells. In addition, GEN-27 markedly suppressed the HCT116 cell proliferation stimulated by IL-1β treatment, which was dependent on the inhibition of NF-κB/p65 nuclear localization, as verified by p65 overexpression and BAY 11-7082, an NF-κB inhibitor. Taken together, our findings established that GEN-27 modulated NF-κB signaling pathway involved in inflammation-induced cancer cells proliferation and therefore could be a potential chemopreventive agent against inflammation-associated colon cancer. PMID:27057094

  13. A rapid UPLC method for simultaneous determination of eleven components in 'Ge-Gen-Qin-Lian' decoction.

    PubMed

    An, Rui; You, Lisha; Zhang, Yizhu; Wang, Xinhong; Ma, Yuemin

    2014-10-01

    'Ge-Gen-Qin-Lian' Decoction derived from 'Shang-Han-Lun' compiled by Zhang Zhongjing. It is widely used in the treatment of acute gastroenteritis, bacillary dysentery, virus diarrhea. This paper describes a sensitive and specific assay for the determination of the 11-marker compounds using ultra performance liquid chromatography (UPLC). To develop an UPLC method for simultaneous determination of 11 bioactive compounds in 'Ge-Gen-Qin-Lian' preparations. The chromatography analysis was performed on an Agilent Proshell 120 EC-C18 column (4.6 × 50 mm, 2.7 μm) at 30°C with a gradient elution of methanol, 0.5% formic acid and 0.5% ammonium acetate at a flow rate 1.0 ml/min and UV detected at 270 nm. All calibration curves showed good linear regression (r ≥ 0.9993) within tested ranges. Limits of detection (LOD) and limits of quantification (LOQ) fell in the range between 0.0691-1.04 μg/ml and 0.23-3.43 μg/ml, respectively. The mean recovery of each herbal medicine ranged from 96.60 to 102.11%. The method was validated for repeatability, precision, stability, accuracy, and selectivity. The validated method was successfully applied to simultaneous analysis of these active components in 'Ge-Gen-Qin-Lian' decoction.

  14. GenSo-EWS: a novel neural-fuzzy based early warning system for predicting bank failures.

    PubMed

    Tung, W L; Quek, C; Cheng, P

    2004-05-01

    Bank failure prediction is an important issue for the regulators of the banking industries. The collapse and failure of a bank could trigger an adverse financial repercussion and generate negative impacts such as a massive bail out cost for the failing bank and loss of confidence from the investors and depositors. Very often, bank failures are due to financial distress. Hence, it is desirable to have an early warning system (EWS) that identifies potential bank failure or high-risk banks through the traits of financial distress. Various traditional statistical models have been employed to study bank failures [J Finance 1 (1975) 21; J Banking Finance 1 (1977) 249; J Banking Finance 10 (1986) 511; J Banking Finance 19 (1995) 1073]. However, these models do not have the capability to identify the characteristics of financial distress and thus function as black boxes. This paper proposes the use of a new neural fuzzy system [Foundations of neuro-fuzzy systems, 1997], namely the Generic Self-organising Fuzzy Neural Network (GenSoFNN) [IEEE Trans Neural Networks 13 (2002c) 1075] based on the compositional rule of inference (CRI) [Commun ACM 37 (1975) 77], as an alternative to predict banking failure. The CRI based GenSoFNN neural fuzzy network, henceforth denoted as GenSoFNN-CRI(S), functions as an EWS and is able to identify the inherent traits of financial distress based on financial covariates (features) derived from publicly available financial statements. The interaction between the selected features is captured in the form of highly intuitive IF-THEN fuzzy rules. Such easily comprehensible rules provide insights into the possible characteristics of financial distress and form the knowledge base for a highly desired EWS that aids bank regulation. The performance of the GenSoFNN-CRI(S) network is subsequently benchmarked against that of the Cox's proportional hazards model [J Banking Finance 10 (1986) 511; J Banking Finance 19 (1995) 1073], the multi

  15. Gen IV Materials Handbook Beta Release for Structural and Functional Evaluation

    SciTech Connect

    Ren, Weiju; Luttrell, Claire

    2006-09-12

    Development of the Gen IV Materials Handbook is briefly summarized up to date. Current status of the Handbook website construction is described. The developed Handbook components and access control of the beta version are discussed for the present evaluation release. Detailed instructions and examples are given to provide guidance for evaluators to browse the constructed parts and use all the currently developed functionalities of the Handbook in evaluation.

  16. Military Standard Generators Prototype Modifications. Volume 3. 60 kW DoD Generator Set

    DTIC Science & Technology

    1988-03-31

    14 JAN ., 17 :35: ’w. 6843 GEN S DS-00 273 . .. •- -,- - 32. 351 3 DE,-.. F Z EX ,-UST 2 895. 93 DEL;. F C REL!:7T 3 988.34 DEC-. F C 4 EXH-4AUST 4...33. 351 DEG. F C 20 GEN. FRAME TOP 11. 64 DEG. F C 2:1 GEN. FRAME BTTM 82. 15± DEG. F C 21 GEN. FRAME BTTM 113. i6 DEG. F C 2,. GEN. EXCITER 32. 992...DEG. F C 21 GEli . FRAME BTTM ±88.15 DEG. F S2 -EN. EXCITER 12. 49 DEG. F C 22 S-EN. EXCITER 185. 5 DEG. F 27 G2N. ’OLT. REG. 95. 459 DEG. F C 23 GEN

  17. Small Cell Lung Cancer Exhibits Frequent Inactivating Mutations in the Histone Methyltransferase KMT2D/MLL2: CALGB 151111 (Alliance)

    PubMed Central

    Augert, Arnaud; Zhang, Qing; Bates, Breanna; Cui, Min; Wang, Xiaofei; Wildey, Gary; Dowlati, Afshin; MacPherson, David

    2017-01-01

    Introduction SCLC is a lethal neuroendocrine tumor type that is highly prone to metastasis. There is an urgency to understand the mutated genes that promote SCLC, as there are no approved targeted therapies yet available. SCLC is rarely resected, limiting the number of samples available for genomic analyses of somatic mutations. Methods To identify potential driver mutations in human SCLC we sequenced the whole exomes of 18 primary SCLCs and seven cell lines along with matched normal controls. We extended these data by resequencing a panel of genes across 40 primary SCLCs and 48 cell lines. Results We report frequent mutations in the lysine methyltransferase 2D gene (KMT2D) (also known as MLL2), a key regulator of transcriptional enhancer function. KMT2D exhibited truncating nonsense/frameshift/splice site mutations in 8% of SCLC tumors and 17% of SCLC cell lines. We found that KMT2D mutation in human SCLC cell lines was associated with reduced lysine methyltransferase 2D protein levels and reduced monomethylation of histone H3 lysine 4, a mark associated with transcriptional enhancers. We also found mutations in other genes associated with transcriptional enhancer control, including CREB binding protein gene (CREBBP), E1A binding protein p300 gene (EP300), and chromodomain helicase DNA binding protein 7 gene (CHD7), and we report mutations in additional chromatin remodeling genes such as polybromo 1 gene (PBRM1). Conclusions These data indicate that KMT2D is one of the major mutated genes in SCLC, and they point to perturbation of transcriptional enhancer control as potentially contributing to SCLC. PMID:28007623

  18. CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma.

    PubMed

    Dahlin, Anna M; Hollegaard, Mads V; Wibom, Carl; Andersson, Ulrika; Hougaard, David M; Deltour, Isabelle; Hjalmars, Ulf; Melin, Beatrice

    2015-10-01

    Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P(combined) < 0.05). The findings were however not statistically significant following correction for multiple testing by the very stringent Bonferroni method. The results do not support our hypothesis that common germline genetic variants in the ten studied genes are associated with the risk of developing medulloblastoma.

  19. Implementing genetic education in primary care: the Gen-Equip programme.

    PubMed

    Paneque, Milena; Cornel, Martina C; Curtisova, Vaclava; Houwink, Elisa; Jackson, Leigh; Kent, Alastair; Lunt, Peter; Macek, Milan; Stefansdottir, Vigdis; Turchetti, Daniela; Skirton, Heather

    2017-04-01

    Genetics and genomics are increasingly relevant to primary healthcare but training is unavailable to many practitioners. Education that can be accessed by practitioners without cost or travel is essential. The Gen-Equip project was formed to provide effective education in genetics for primary healthcare in Europe and so improve patient care. Partners include patient representatives and specialists in genetics and primary care from six countries. Here, we report the progress and challenges involved in creating a European online educational program in genetics.

  20. Gen 2.0 Mixer/Ejector Nozzle Test at LSAF June 1995 to July 1996

    NASA Technical Reports Server (NTRS)

    Arney, L. D.; Sandquist, D. L.; Forsyth, D. W.; Lidstone, G. L.; Long-Davis, Mary Jo (Technical Monitor)

    2005-01-01

    Testing of the HSCT Generation 2.0 nozzle model hardware was conducted at the Boeing Low Speed Aeroacoustic Facility, LSAF. Concurrent measurements of noise and thrust were made at critical takeoff design conditions for a variety of mixer/ejector model hardware. Design variables such as suppressor area ratio, mixer area ratio, liner type and thickness, ejector length, lobe penetration, and mixer chute shape were tested. Parallel testing was conducted at G.E.'s Cell 41 acoustic free jet facility to augment the LSAF test. The results from the Gen 2.0 testing are being used to help shape the current nozzle baseline configuration and guide the efforts in the upcoming Generation 2.5 and 3.0 nozzle tests. The Gen 2.0 results have been included in the total airplane system studies conducted at MDC and Boeing to provide updated noise and thrust performance estimates.

  1. Description of Alloprevotella rava gen. nov., sp. nov., isolated from the human oral cavity, and reclassification of Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov.

    PubMed Central

    Downes, Julia; Dewhirst, Floyd E.; Tanner, Anne C. R.

    2013-01-01

    Five strains of anaerobic, Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group. Phylogenetic analysis of full-length 16S rRNA gene sequences showed that these strains represented a novel group within the family Prevotellaceae, and the most closely related species was Prevotella tannerae. P. tannerae and the novel taxon are deeply branched from the genus Prevotella, with sequence identities to the type strain of the type species of Prevotella, Prevotella melaninogenica, of 82.2 and 85.6 %, respectively. The novel genus Alloprevotella gen. nov. is proposed to accommodate the novel species Alloprevotella rava gen. nov., sp. nov. and the previously named Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov. The type species is Alloprevotella tannerae. The type strain of Alloprevotella rava is 81/4-12T ( = DSM 22548T  = CCUG 58091T) and the type strain of Alloprevotella tannerae is ATCC 51259T  = CCUG 34292T  = CIP 104476T  = NCTC 13073T. Alloprevotella rava is weakly to moderately saccharolytic and produces moderate amounts of acetic acid and major amounts of succinic acid as end products of fermentation. Strains are sensitive to 20 % bile and hydrolyse gelatin. The principal cellular long-chain fatty acids are anteiso-C15 : 0, iso-C15 : 0, C16 : 0, iso-C17 : 0 and iso-C17 : 0 3-OH. The G+C content of the DNA of the type strain is 47 mol%. PMID:22753527

  2. Sandsitermes gen. nov., a new nasute termite genus from South America (Isoptera, Termitidae, Nasutitermitinae).

    PubMed

    Cuezzo, Carolina; Cancello, Eliana M; Carrijo, Tiago F

    2017-01-20

    We establish herein a new genus of Neotropical termites of the subfamily Nasutitermitinae, Sandsitermes gen. nov.. The new genus accommodates a previously described species, Nasutitermes robustus (Holmgren), and is diagnosed by worker characters, including the mandibles, the gut-coiling configuration in situ, and the pattern of cushions and spines of the enteric valve. We characterized and illustrated the imago for the first time and redescribe the soldier and worker castes of Sandsitermes robustus gen. et comb. nov. from syntypes and other samples from eastern Peru. We support our taxonomic decision, presenting morphological differences between the gut pattern and enteric valve of S. robustus and 13 neotropical Nasutitermes species studied for this report, and discuss possible relationships with other neotropical nasute termites.

  3. Didelphostrongylus hayesi gen. et sp. n. (Metastrogyloidea: Filaroididae) from the opossum, Didelphis marsupialis.

    PubMed

    Prestwood, A K

    1976-04-01

    Didelphostrongylus hayesi gen. et sp. n. from the opossum, Didelphis marsupialis, is distinguished from other genera of the Angoistrongylinae by the structure of the dorsal and lateral rays, complex gubernaculum, and ovoviviparity. Third-stage larvae developed in Mesodon perigraptus and Triodopsis albolabris. The prepatent period was 22 days in experimentally infected opossums.

  4. Roles of SLX1–SLX4, MUS81–EME1, and GEN1 in avoiding genome instability and mitotic catastrophe

    PubMed Central

    Sarbajna, Shriparna; Davies, Derek; West, Stephen C.

    2014-01-01

    The resolution of recombination intermediates containing Holliday junctions (HJs) is critical for genome maintenance and proper chromosome segregation. Three pathways for HJ processing exist in human cells and involve the following enzymes/complexes: BLM–TopoIIIα–RMI1–RMI2 (BTR complex), SLX1–SLX4–MUS81–EME1 (SLX–MUS complex), and GEN1. Cycling cells preferentially use the BTR complex for the removal of double HJs in S phase, with SLX–MUS and GEN1 acting at temporally distinct phases of the cell cycle. Cells lacking SLX–MUS and GEN1 exhibit chromosome missegregation, micronucleus formation, and elevated levels of 53BP1-positive G1 nuclear bodies, suggesting that defects in chromosome segregation lead to the transmission of extensive DNA damage to daughter cells. In addition, however, we found that the effects of SLX4, MUS81, and GEN1 depletion extend beyond mitosis, since genome instability is observed throughout all phases of the cell cycle. This is exemplified in the form of impaired replication fork movement and S-phase progression, endogenous checkpoint activation, chromosome segmentation, and multinucleation. In contrast to SLX4, SLX1, the nuclease subunit of the SLX1–SLX4 structure-selective nuclease, plays no role in the replication-related phenotypes associated with SLX4/MUS81 and GEN1 depletion. These observations demonstrate that the SLX1–SLX4 nuclease and the SLX4 scaffold play divergent roles in the maintenance of genome integrity in human cells. PMID:24831703

  5. WallGen, software to construct layered cellulose-hemicellulose networks and predict their small deformation mechanics.

    PubMed

    Kha, Hung; Tuble, Sigrid C; Kalyanasundaram, Shankar; Williamson, Richard E

    2010-02-01

    We understand few details about how the arrangement and interactions of cell wall polymers produce the mechanical properties of primary cell walls. Consequently, we cannot quantitatively assess if proposed wall structures are mechanically reasonable or assess the effectiveness of proposed mechanisms to change mechanical properties. As a step to remedying this, we developed WallGen, a Fortran program (available on request) building virtual cellulose-hemicellulose networks by stochastic self-assembly whose mechanical properties can be predicted by finite element analysis. The thousands of mechanical elements in the virtual wall are intended to have one-to-one spatial and mechanical correspondence with their real wall counterparts of cellulose microfibrils and hemicellulose chains. User-defined inputs set the properties of the two polymer types (elastic moduli, dimensions of microfibrils and hemicellulose chains, hemicellulose molecular weight) and their population properties (microfibril alignment and volume fraction, polymer weight percentages in the network). This allows exploration of the mechanical consequences of variations in nanostructure that might occur in vivo and provides estimates of how uncertainties regarding certain inputs will affect WallGen's mechanical predictions. We summarize WallGen's operation and the choice of values for user-defined inputs and show that predicted values for the elastic moduli of multinet walls subject to small displacements overlap measured values. "Design of experiment" methods provide systematic exploration of how changed input values affect mechanical properties and suggest that changing microfibril orientation and/or the number of hemicellulose cross-bridges could change wall mechanical anisotropy.

  6. GenProBiS: web server for mapping of sequence variants to protein binding sites.

    PubMed

    Konc, Janez; Skrlj, Blaz; Erzen, Nika; Kunej, Tanja; Janezic, Dusanka

    2017-07-03

    Discovery of potentially deleterious sequence variants is important and has wide implications for research and generation of new hypotheses in human and veterinary medicine, and drug discovery. The GenProBiS web server maps sequence variants to protein structures from the Protein Data Bank (PDB), and further to protein-protein, protein-nucleic acid, protein-compound, and protein-metal ion binding sites. The concept of a protein-compound binding site is understood in the broadest sense, which includes glycosylation and other post-translational modification sites. Binding sites were defined by local structural comparisons of whole protein structures using the Protein Binding Sites (ProBiS) algorithm and transposition of ligands from the similar binding sites found to the query protein using the ProBiS-ligands approach with new improvements introduced in GenProBiS. Binding site surfaces were generated as three-dimensional grids encompassing the space occupied by predicted ligands. The server allows intuitive visual exploration of comprehensively mapped variants, such as human somatic mis-sense mutations related to cancer and non-synonymous single nucleotide polymorphisms from 21 species, within the predicted binding sites regions for about 80 000 PDB protein structures using fast WebGL graphics. The GenProBiS web server is open and free to all users at http://genprobis.insilab.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

    ClinicalTrials.gov

    2017-09-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

  8. Mucocele-Like Lesions of the Breast: Clinical Outcome and Histological Analysis of 102 Cases

    PubMed Central

    Meares, Annie L.; Frank, Ryan D.; Degnim, Amy C.; Vierkant, Robert A.; Frost, Marlene H.; Hartmann, Lynn C.; Winham, Stacey J.; Visscher, Daniel W.

    2016-01-01

    Mucocele-like lesions (MLL) of the breast are characterized by cystic architecture with stromal mucin and frequent atypia, but it is unknown whether they convey long term breast cancer risk. We evaluated 102MLL that were derived from a single institution benign breast disease (BBD) cohort of 13412 women who underwent biopsy from 1967–2001.MLL were histologically characterized by type of lining epithelium, architecture of the lesion, associated atypical hyperplasia (AH) and for incidence of breast cancer (14.8 years median follow-up). A relatively large proportion of MLL (42%) were diagnosed in women >55 years of age AH was significantly more frequent in MML patient compared to the cohort overall (27% vs 5%, p<0.001). Breast cancer has developed in 13 patients with MLL.. This frequency is only slightly higher than population expected rates overall (Standardized incidence ratio (SIR) 2.28, 95% CI 1.21–3.91), and not significantly different from women in the cohort with (non atypical) proliferative breast lesions. Younger women (<45) with MLL had a non-significant increase in risk of cancer compared to the general population (SIR 5.16, 95% CI 1.41–13.23). We conclude MLL is an uncommon breast lesion that is often associated with co-existing AH. However, in women over age 45, MLL do not convey additional risk of breast cancer beyond that associated with the presence of proliferative disease. PMID:26826407

  9. Toxicity and physiological effects of neem pesticides applied to rice on the Nilaparvata lugens Stål, the brown planthopper.

    PubMed

    Senthil-Nathan, Sengottayan; Choi, Man-Young; Paik, Chae-Hoon; Seo, Hong-Yul; Kalaivani, Kandaswamy

    2009-09-01

    The effects of two different neem products (Parker Oil and Neema) on mortality, food consumption and survival of the brown planthopper, Nilaparvata lugens Stål (BPH) (Homoptera: Delphacidae) were investigated. The LC(50) (3.45 ml/L for nymph and 4.42 ml/L for adult in Parker Oil treatment; 4.18 ml/L for nymph and 5.63 ml/L for adult in Neema treatment) and LC(90) (8.72 ml/L for nymph and 11.1 ml/L for adult in Parker Oil treatment; 9.84 ml/L for nymph and 13.07 ml/L for adult in Neema treatment) were identified by probit analysis. The LC(90) (equal to recommended dose) was applied in the rice field. The effective concentration of both Parker Oil and Neema took more than 48 h to kill 80% of the N. lugens. Fourth instar nymph and adult female N. lugens were caged on rice plants and exposed to a series (both LC(50) and LC(90)) of neem concentrations. Nymph and adult female N. lugens that were chronically exposed to neem pesticides showed immediate mortality after application in laboratory experiment. The quantity of food ingested and assimilated by N. lugens on neem-treated rice plants was significantly less than on control rice plants. The results clearly indicate the neem-based pesticide (Parker Oil and Neema), containing low lethal concentration, can be used effectively to inhibit the growth and survival of N. lugens.

  10. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.

    PubMed

    Santos, Margarida A; Faryabi, Robert B; Ergen, Aysegul V; Day, Amanda M; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J; Ito, Keisuke; Ge, Kai; Aplan, Peter D; Armstrong, Scott A; Nussenzweig, André

    2014-10-02

    Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.

  11. Modeling Off-Nominal Recovery in NextGen Terminal-Area Operations

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2011-01-01

    Robust schedule-based arrival management requires efficient recovery from off-nominal situations. This paper presents research on modeling off-nominal situations and plans for recovering from them using TRAC, a route/airspace design, fast-time simulation, and analysis tool for studying NextGen trajectory-based operations. The paper provides an overview of a schedule-based arrival-management concept and supporting controller tools, then describes TRAC implementations of methods for constructing off-nominal scenarios, generating trajectory options to meet scheduling constraints, and automatically producing recovery plans.

  12. A Measurement of GE^n at High Momentum Transfer in Hall A

    NASA Astrophysics Data System (ADS)

    Feuerbach, Robert J.; Wojtsekhowski, Bogdan

    2006-10-01

    A precision measurement of the electric form-factor of the neutron, GE^n, at Q^2 up to 3.5 GeV^2 was recently completed in Hall A at the Thomas Jefferson National Accelerator Facility(Jefferson Lab). The ratio GE^n/GM^n was measured through the beam-target asymmetry A of electrons quasi-elastically scattered off neutrons in the reaction ^3He(e,e' n). The experiment took advantage of recent developments of the electron beam and target, as well as two detectors new to Jefferson Lab. The measurement used the accelerator's 100% duty-cycle high-polarization (typically 84%) electron beam and a new, hybrid optically-pumped polarized ^3He target which achieved polarizations above 50%. A medium acceptance (80msr) open-geometry magnetic spectrometer (BigBite) detected the scattered electron, while a new neutron detector was constructed to observe the released neutron. An overview of the experiment and the experimental motivation will be discussed, in particular the large range of predictions from modern calculations for GE^n at this relatively high Q^2. Finally, the analysis progress and preliminary results will be presented.

  13. Hardware and Software Design of FPGA-based PCIe Gen3 interface for APEnet+ network interconnect system

    NASA Astrophysics Data System (ADS)

    Ammendola, R.; Biagioni, A.; Frezza, O.; Lo Cicero, F.; Lonardo, A.; Martinelli, M.; Paolucci, P. S.; Pastorelli, E.; Rossetti, D.; Simula, F.; Tosoratto, L.; Vicini, P.

    2015-12-01

    In the attempt to develop an interconnection architecture optimized for hybrid HPC systems dedicated to scientific computing, we designed APEnet+, a point-to-point, low-latency and high-performance network controller supporting 6 fully bidirectional off-board links over a 3D torus topology. The first release of APEnet+ (named V4) was a board based on a 40 nm Altera FPGA, integrating 6 channels at 34 Gbps of raw bandwidth per direction and a PCIe Gen2 x8 host interface. It has been the first-of-its-kind device to implement an RDMA protocol to directly read/write data from/to Fermi and Kepler NVIDIA GPUs using NVIDIA peer-to-peer and GPUDirect RDMA protocols, obtaining real zero-copy GPU-to-GPU transfers over the network. The latest generation of APEnet+ systems (now named V5) implements a PCIe Gen3 x8 host interface on a 28 nm Altera Stratix V FPGA, with multi-standard fast transceivers (up to 14.4 Gbps) and an increased amount of configurable internal resources and hardware IP cores to support main interconnection standard protocols. Herein we present the APEnet+ V5 architecture, the status of its hardware and its system software design. Both its Linux Device Driver and the low-level libraries have been redeveloped to support the PCIe Gen3 protocol, introducing optimizations and solutions based on hardware/software co-design.

  14. Internal combustion engine report: Spark ignited ICE GenSet optimization and novel concept development

    SciTech Connect

    Keller, J.; Blarigan, P. Van

    1998-08-01

    In this manuscript the authors report on two projects each of which the goal is to produce cost effective hydrogen utilization technologies. These projects are: (1) the development of an electrical generation system using a conventional four-stroke spark-ignited internal combustion engine generator combination (SI-GenSet) optimized for maximum efficiency and minimum emissions, and (2) the development of a novel internal combustion engine concept. The SI-GenSet will be optimized to run on either hydrogen or hydrogen-blends. The novel concept seeks to develop an engine that optimizes the Otto cycle in a free piston configuration while minimizing all emissions. To this end themore » authors are developing a rapid combustion homogeneous charge compression ignition (HCCI) engine using a linear alternator for both power take-off and engine control. Targeted applications include stationary electrical power generation, stationary shaft power generation, hybrid vehicles, and nearly any other application now being accomplished with internal combustion engines.« less

  15. Evaluation of Delcath Systems' Generation 2 (GEN 2) melphalan hemofiltration system in a porcine model of percutaneous hepatic perfusion.

    PubMed

    Moeslein, Fred M; McAndrew, Elizabeth G; Appling, William M; Hryniewich, Nicole E; Jarvis, Kevin D; Markos, Steven M; Sheets, Timothy P; Uzgare, Rajneesh P; Johnston, Daniel S

    2014-06-01

    A new melphalan hemoperfusion filter (GEN 2) was evaluated in a simulated-use porcine model of percutaneous hepatic perfusion (PHP). The current study evaluated melphalan filtration efficiency, the transfilter pressure gradient, and the removal of specific blood products. A porcine PHP procedure using the GEN 2 filter was performed under Good Laboratory Practice conditions to model the 60-min clinical PHP procedure. The mean filter efficiency for removing melphalan in six filters was 99.0 ± 0.4 %. The transfilter pressure gradient across the filter averaged 20.9 mmHg for the 60-min procedure. Many blood components, including albumin and platelets, decreased on average from 3.55 to 2.02 g/dL and from 342 to 177 × 10.e3/μL, respectively, during the procedure. The increased melphalan extraction efficiency of the new filter is expected to decrease systemic melphalan exposure. In addition, the low transfilter pressure gradient resulted in low resistance to blood flow in the GEN 2 filter, and the changes to blood components are expected to be clinically manageable.

  16. search GenBank: interactive orchestration and ad-hoc choreography of Web services in the exploration of the biomedical resources of the National Center For Biotechnology Information

    PubMed Central

    2013-01-01

    Background Due to the growing number of biomedical entries in data repositories of the National Center for Biotechnology Information (NCBI), it is difficult to collect, manage and process all of these entries in one place by third-party software developers without significant investment in hardware and software infrastructure, its maintenance and administration. Web services allow development of software applications that integrate in one place the functionality and processing logic of distributed software components, without integrating the components themselves and without integrating the resources to which they have access. This is achieved by appropriate orchestration or choreography of available Web services and their shared functions. After the successful application of Web services in the business sector, this technology can now be used to build composite software tools that are oriented towards biomedical data processing. Results We have developed a new tool for efficient and dynamic data exploration in GenBank and other NCBI databases. A dedicated search GenBank system makes use of NCBI Web services and a package of Entrez Programming Utilities (eUtils) in order to provide extended searching capabilities in NCBI data repositories. In search GenBank users can use one of the three exploration paths: simple data searching based on the specified user’s query, advanced data searching based on the specified user’s query, and advanced data exploration with the use of macros. search GenBank orchestrates calls of particular tools available through the NCBI Web service providing requested functionality, while users interactively browse selected records in search GenBank and traverse between NCBI databases using available links. On the other hand, by building macros in the advanced data exploration mode, users create choreographies of eUtils calls, which can lead to the automatic discovery of related data in the specified databases. Conclusions search Gen

  17. search GenBank: interactive orchestration and ad-hoc choreography of Web services in the exploration of the biomedical resources of the National Center For Biotechnology Information.

    PubMed

    Mrozek, Dariusz; Małysiak-Mrozek, Bożena; Siążnik, Artur

    2013-03-01

    Due to the growing number of biomedical entries in data repositories of the National Center for Biotechnology Information (NCBI), it is difficult to collect, manage and process all of these entries in one place by third-party software developers without significant investment in hardware and software infrastructure, its maintenance and administration. Web services allow development of software applications that integrate in one place the functionality and processing logic of distributed software components, without integrating the components themselves and without integrating the resources to which they have access. This is achieved by appropriate orchestration or choreography of available Web services and their shared functions. After the successful application of Web services in the business sector, this technology can now be used to build composite software tools that are oriented towards biomedical data processing. We have developed a new tool for efficient and dynamic data exploration in GenBank and other NCBI databases. A dedicated search GenBank system makes use of NCBI Web services and a package of Entrez Programming Utilities (eUtils) in order to provide extended searching capabilities in NCBI data repositories. In search GenBank users can use one of the three exploration paths: simple data searching based on the specified user's query, advanced data searching based on the specified user's query, and advanced data exploration with the use of macros. search GenBank orchestrates calls of particular tools available through the NCBI Web service providing requested functionality, while users interactively browse selected records in search GenBank and traverse between NCBI databases using available links. On the other hand, by building macros in the advanced data exploration mode, users create choreographies of eUtils calls, which can lead to the automatic discovery of related data in the specified databases. search GenBank extends standard capabilities of the

  18. Proposal of Ancylothrix gen. nov., a new genus of Phormidiaceae (Cyanobacteria, Oscillatoriales) based on a polyphasic approach.

    PubMed

    Martins, Mariellen Dornelles; Rigonato, Janaina; Taboga, Sebastião Roberto; Branco, Luis Henrique Zanini

    2016-06-01

    During a study about the diversity of Phormidioideae (Phormidiaceae, Oscillatoriales) in Brazil, seven strains from southern and southeastern regions were isolated in monospecifc cultures and submitted to polyphasic evaluation (morphological, ecological, cytological and molecular studies). The populations studied were found to be morphologically similar to Kamptonema (filaments narrowed and bent at the end) and cytologically different (thylakoids' arrangement - radial distribution in Brazilian strains and parietal distribution in Kamptonema). The original habitats were very diverse among the Brazilian strains (freshwater, wet soil and barks of trees). Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains were placed together in a very distinctive and highly supported clade. Thus, the set of characteristics of the strains resulted in the recognition of the new genus Ancylothrix Martins et Branco gen. nov. with two species [Ancylothrix rivularis gen. nov., sp. nov. (type species) and Ancylothrix terrestris sp. nov.], distinguishable by differences in genetic and ecological characteristics and described under the provisions of the International Code of Nomenclature for algae, fungi and plants. Secondary structures of D1-D1', box-B and V3 regions were conserved in A. rivularis gen. nov. sp. nov. and more variable in A. terrestris sp. nov.

  19. Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia.

    PubMed

    Gao, Yanan; Gao, Juan; Li, Minghao; Zheng, Yawei; Wang, Yajie; Zhang, Hongyan; Wang, Weili; Chu, Yajing; Wang, Xiaomin; Xu, Mingjiang; Cheng, Tao; Ju, Zhenyu; Yuan, Weiping

    2016-04-12

    The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment. The expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model. We observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 (Δ/Δ) AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 (Δ/Δ) AML cells. Our data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.

  20. GBParsy: a GenBank flatfile parser library with high speed.

    PubMed

    Lee, Tae-Ho; Kim, Yeon-Ki; Nahm, Baek Hie

    2008-07-25

    GenBank flatfile (GBF) format is one of the most popular sequence file formats because of its detailed sequence features and ease of readability. To use the data in the file by a computer, a parsing process is required and is performed according to a given grammar for the sequence and the description in a GBF. Currently, several parser libraries for the GBF have been developed. However, with the accumulation of DNA sequence information from eukaryotic chromosomes, parsing a eukaryotic genome sequence with these libraries inevitably takes a long time, due to the large GBF file and its correspondingly large genomic nucleotide sequence and related feature information. Thus, there is significant need to develop a parsing program with high speed and efficient use of system memory. We developed a library, GBParsy, which was C language-based and parses GBF files. The parsing speed was maximized by using content-specified functions in place of regular expressions that are flexible but slow. In addition, we optimized an algorithm related to memory usage so that it also increased parsing performance and efficiency of memory usage. GBParsy is at least 5-100x faster than current parsers in benchmark tests. GBParsy is estimated to extract annotated information from almost 100 Mb of a GenBank flatfile for chromosomal sequence information within a second. Thus, it should be used for a variety of applications such as on-time visualization of a genome at a web site.

  1. Structural materials for Gen-IV nuclear reactors: Challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Murty, K. L.; Charit, I.

    2008-12-01

    Generation-IV reactor design concepts envisioned thus far cater toward a common goal of providing safer, longer lasting, proliferation-resistant and economically viable nuclear power plants. The foremost consideration in the successful development and deployment of Gen-IV reactor systems is the performance and reliability issues involving structural materials for both in-core and out-of-core applications. The structural materials need to endure much higher temperatures, higher neutron doses and extremely corrosive environment, which are beyond the experience of the current nuclear power plants. Materials under active consideration for use in different reactor components include various ferritic/martensitic steels, austenitic stainless steels, nickel-base superalloys, ceramics, composites, etc. This paper presents a summary of various Gen-IV reactor concepts, with emphasis on the structural materials issues depending on the specific application areas. This paper also discusses the challenges involved in using the existing materials under both service and off-normal conditions. Tasks become increasingly complex due to the operation of various fundamental phenomena like radiation-induced segregation, radiation-enhanced diffusion, precipitation, interactions between impurity elements and radiation-produced defects, swelling, helium generation and so forth. Further, high temperature capability (e.g. creep properties) of these materials is a critical, performance-limiting factor. It is demonstrated that novel alloy and microstructural design approaches coupled with new materials processing and fabrication techniques may mitigate the challenges, and the optimum system performance may be achieved under much demanding conditions.

  2. Accuracy evaluation of ClimGen weather generator and daily to hourly disaggregation methods in tropical conditions

    NASA Astrophysics Data System (ADS)

    Safeeq, Mohammad; Fares, Ali

    2011-12-01

    Daily and sub-daily weather data are often required for hydrological and environmental modeling. Various weather generator programs have been used to generate synthetic climate data where observed climate data are limited. In this study, a weather data generator, ClimGen, was evaluated for generating information on daily precipitation, temperature, and wind speed at four tropical watersheds located in Hawai`i, USA. We also evaluated different daily to sub-daily weather data disaggregation methods for precipitation, air temperature, dew point temperature, and wind speed at Mākaha watershed. The hydrologic significance values of the different disaggregation methods were evaluated using Distributed Hydrology Soil Vegetation Model. MuDRain and diurnal method performed well over uniform distribution in disaggregating daily precipitation. However, the diurnal method is more consistent if accurate estimates of hourly precipitation intensities are desired. All of the air temperature disaggregation methods performed reasonably well, but goodness-of-fit statistics were slightly better for sine curve model with 2 h lag. Cosine model performed better than random model in disaggregating daily wind speed. The largest differences in annual water balance were related to wind speed followed by precipitation and dew point temperature. Simulated hourly streamflow, evapotranspiration, and groundwater recharge were less sensitive to the method of disaggregating daily air temperature. ClimGen performed well in generating the minimum and maximum temperature and wind speed. However, for precipitation, it clearly underestimated the number of extreme rainfall events with an intensity of >100 mm/day in all four locations. ClimGen was unable to replicate the distribution of observed precipitation at three locations (Honolulu, Kahului, and Hilo). ClimGen was able to reproduce the distributions of observed minimum temperature at Kahului and wind speed at Kahului and Hilo. Although the weather

  3. BioNetFit: a fitting tool compatible with BioNetGen, NFsim and distributed computing environments

    PubMed Central

    Thomas, Brandon R.; Chylek, Lily A.; Colvin, Joshua; Sirimulla, Suman; Clayton, Andrew H.A.; Hlavacek, William S.; Posner, Richard G.

    2016-01-01

    Summary: Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here, we present BioNetFit, a general-purpose fitting tool that is compatible with BioNetGen and NFsim. BioNetFit is designed to take advantage of distributed computing resources. This feature facilitates fitting (i.e. optimization of parameter values for consistency with data) when simulations are computationally expensive. Availability and implementation: BioNetFit can be used on stand-alone Mac, Windows/Cygwin, and Linux platforms and on Linux-based clusters running SLURM, Torque/PBS, or SGE. The BioNetFit source code (Perl) is freely available (http://bionetfit.nau.edu). Supplementary information: Supplementary data are available at Bioinformatics online. Contact: bionetgen.help@gmail.com PMID:26556387

  4. ORFer--retrieval of protein sequences and open reading frames from GenBank and storage into relational databases or text files.

    PubMed

    Büssow, Konrad; Hoffmann, Steve; Sievert, Volker

    2002-12-19

    Functional genomics involves the parallel experimentation with large sets of proteins. This requires management of large sets of open reading frames as a prerequisite of the cloning and recombinant expression of these proteins. A Java program was developed for retrieval of protein and nucleic acid sequences and annotations from NCBI GenBank, using the XML sequence format. Annotations retrieved by ORFer include sequence name, organism and also the completeness of the sequence. The program has a graphical user interface, although it can be used in a non-interactive mode. For protein sequences, the program also extracts the open reading frame sequence, if available, and checks its correct translation. ORFer accepts user input in the form of single or lists of GenBank GI identifiers or accession numbers. It can be used to extract complete sets of open reading frames and protein sequences from any kind of GenBank sequence entry, including complete genomes or chromosomes. Sequences are either stored with their features in a relational database or can be exported as text files in Fasta or tabulator delimited format. The ORFer program is freely available at http://www.proteinstrukturfabrik.de/orfer. The ORFer program allows for fast retrieval of DNA sequences, protein sequences and their open reading frames and sequence annotations from GenBank. Furthermore, storage of sequences and features in a relational database is supported. Such a database can supplement a laboratory information system (LIMS) with appropriate sequence information.

  5. An outlook on the fungal internal transcribed spacer sequences in GenBank and the introduction of a web-based tool for the exploration of fungal diversity.

    PubMed

    Ryberg, Martin; Kristiansson, Erik; Sjökvist, Elisabet; Nilsson, R Henrik

    2009-01-01

    The environmental and distributional data associated with fungal internal transcribed spacer (ITS) sequences in GenBank are investigated and a new web-based tool with which these sequences can be explored is introduced. All fungal ITS sequences in GenBank were classified as either identified to species level or insufficiently identified and compared using BLAST. The results are made available as a biweekly updated web service that can be queried to retrieve all insufficiently identified sequences (IIS) associated with any fungal genus. The most commonly available annotation items in GenBank are isolation source (55%); country of origin (50%); and specific host (38%). The molecular sampling of fungi shows a bias towards North America, Europe, China, and Japan whereas vast geographical areas remain effectively unexplored. Mycorrhizal and parasitic genera are on average associated with more IIS than are saprophytic taxa. Glomus, Alternaria, and Tomentella are the genera represented by the highest number of insufficiently identified ITS sequences in GenBank. The web service presented (http://andromeda.botany.gu.se/emerencia.html#genus_search) offers new means, particularly for mycorrhizal and plant pathogenic fungi, to examine the IIS in GenBank in a taxon-oriented framework and to explore their metadata in an easily accessible and time-efficient manner.

  6. 77 FR 7123 - ArborGen, LLC; Availability of an Environmental Assessment for Controlled Release of a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... Eucalyptus. ArborGen is requesting that trees be allowed to flower at four locations in Alabama, Florida and... have indicated they will not allow these trees to flower at these locations. Permit application 11-052...

  7. Optimal quality (131)I-monoclonal antibodies on high-dose labeling in a large reaction volume and temporarily coating the antibody with IODO-GEN.

    PubMed

    Visser, G W; Klok, R P; Gebbinck, J W; ter Linden, T; van Dongen, G A; Molthoff, C F

    2001-03-01

    A novel, facile procedure for efficient coupling of high doses of (131)I to monoclonal antibodies (MAbs) was developed with minimal chemical and radiation damage. To diminish the radiation and chemical burden during labeling, iodination was performed in a large reaction volume and by temporarily coating the MAb with a minimal amount of IODO-GEN. The MAb was coated by injection of IODO-GEN (dissolved in acetonitrile [MeCN]) into the aqueous MAb solution, and the coating was subsequently removed by addition of ascorbic acid. For chemoprotection before, during, and after PD-10 purification of the (131)I-MAbs, ascorbic acid and human serum albumin were used. The effects of autoradiolysis in the starting (131)I solution were countered by treatment with NaOH and ascorbic acid. For this so-called IODO-GEN-coated MAb method, the sensitive chimeric MAb MOv18 (c-MOv18) and the more robust murine MAbs K928 and E48 were used. The high-dose (131)I-labeled MAbs were characterized for radiochemical purity and MAb integrity by thin-layer chromatography, high-performance liquid chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by phosphor imager quantification. The high-dose (131)I-labeled MAbs were also characterized for immunoreactivity. The radiopharmacokinetics and biodistribution of (131)I-c-MOv18 were analyzed in human tumor-bearing nude mice. For comparison, (131)I-c-MOv18 batches were made using the conventional chloramine-T or IODO-GEN-coated vial method. Conventional high-dose labeling of 5 mg c-MOv18 with 4.4 GBq (131)I resulted in a labeling yield of 60%, a radiochemical purity of 90%, an immunoreactive fraction of 25% (72% being the maximum in the assay used), and the presence of aggregation and degradation products. Using similar amounts of (131)I and MAb in the IODO-GEN-coated MAb method, 85%-89% overall radiochemical yield, at least 99.7% radiochemical purity, and full preservation of MAb integrity and immunoreactivity were

  8. Enhancing the usability and performance of structured association mapping algorithms using automation, parallelization, and visualization in the GenAMap software system

    PubMed Central

    2012-01-01

    Background Structured association mapping is proving to be a powerful strategy to find genetic polymorphisms associated with disease. However, these algorithms are often distributed as command line implementations that require expertise and effort to customize and put into practice. Because of the difficulty required to use these cutting-edge techniques, geneticists often revert to simpler, less powerful methods. Results To make structured association mapping more accessible to geneticists, we have developed an automatic processing system called Auto-SAM. Auto-SAM enables geneticists to run structured association mapping algorithms automatically, using parallelization. Auto-SAM includes algorithms to discover gene-networks and find population structure. Auto-SAM can also run popular association mapping algorithms, in addition to five structured association mapping algorithms. Conclusions Auto-SAM is available through GenAMap, a front-end desktop visualization tool. GenAMap and Auto-SAM are implemented in JAVA; binaries for GenAMap can be downloaded from http://sailing.cs.cmu.edu/genamap. PMID:22471660

  9. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-12-01

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2014-10-23

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. Sexual Inactivity During Young Adulthood Is More Common Among U.S. Millennials and iGen: Age, Period, and Cohort Effects on Having No Sexual Partners After Age 18.

    PubMed

    Twenge, Jean M; Sherman, Ryne A; Wells, Brooke E

    2017-02-01

    Examining age, time period, and cohort/generational changes in sexual experience is key to better understanding sociocultural influences on sexuality and relationships. Americans born in the 1980s and 1990s (commonly known as Millennials and iGen) were more likely to report having no sexual partners as adults compared to GenX'ers born in the 1960s and 1970s in the General Social Survey, a nationally representative sample of American adults (N = 26,707). Among those aged 20-24, more than twice as many Millennials born in the 1990s (15 %) had no sexual partners since age 18 compared to GenX'ers born in the 1960s (6 %). Higher rates of sexual inactivity among Millennials and iGen also appeared in analyses using a generalized hierarchical linear modeling technique known as age-period-cohort analysis to control for age and time period effects among adults of all ages. Americans born early in the 20th century also showed elevated rates of adult sexual inactivity. The shift toward higher rates of sexual inactivity among Millennials and iGen'ers was more pronounced among women and absent among Black Americans and those with a college education. Contrary to popular media conceptions of a "hookup generation" more likely to engage in frequent casual sex, a higher percentage of Americans in recent cohorts, particularly Millennials and iGen'ers born in the 1990s, had no sexual partners after age 18.

  12. [Application of multiplex rt-PCR assay for screening rare or cryptic chromosome translocations in de novo patients with acute myeloid leukemia].

    PubMed

    Chen, Hai-Min; Yuan, Hai-Yang; Fan, Xing; He, Hai-Yan; Chen, Bing; Shi, Jing-Yi; Zhu, Yong-Mei

    2010-10-01

    This study was aimed to investigate the clinical feasibility of using multiplex PT-PCR assay for screening rare/cryptic chromosome translocations in patients with de novo acute myeloid leukemia. For 126 patients with de novo AML-M4/M5 without common chromosome translocations including t(15;17), t(8;21) and t(16;16), 3 parallel multiplex RT-PCR assays were set up to detect 6 mll-related gene rearrangements (mll/af10, mll/af17, mll/ell, mll/af9, mll/af6 and mll/enl) with low detection rate and 4 rare fusion genes (dek/can, tls/erg, aml1/mds (evi1) and npm/mlf1). The results showed that 11 patients with positive result from 126 patients were detected which involved in 5 molecular abnormalities. Among them, 10 cases were AML-M5 (16.67%), 1 cases AML-M4 (1.51%). The marker chromosomes were observed in 2 cases out of 11 cases through conventional karyotyping analysis, the karyotyping analysis in 1 case was not performed because this case had 1 mitotic figure only, no any cytogenetic aberrations were found in other 8 cases through R-band karyotyping analysis. It is concluded that multiplex RT-PCR designed in this study can quickly, effectively and accurately identify the rare/cryptic chromosome translocations and can be used in clinical detection.

  13. A rapid UPLC method for simultaneous determination of eleven components in ‘Ge-Gen-Qin-Lian’ decoction

    PubMed Central

    An, Rui; You, Lisha; Zhang, Yizhu; Wang, Xinhong; Ma, Yuemin

    2014-01-01

    Background: ‘Ge-Gen-Qin-Lian’ Decoction derived from ‘Shang-Han-Lun’ compiled by Zhang Zhongjing. It is widely used in the treatment of acute gastroenteritis, bacillary dysentery, virus diarrhea. This paper describes a sensitive and specific assay for the determination of the 11-marker compounds using ultra performance liquid chromatography (UPLC). Objective: To develop an UPLC method for simultaneous determination of 11 bioactive compounds in ‘Ge-Gen-Qin-Lian’ preparations. Materials and Methods: The chromatography analysis was performed on an Agilent Proshell 120 EC-C18 column (4.6 × 50 mm, 2.7 μm) at 30°C with a gradient elution of methanol, 0.5% formic acid and 0.5% ammonium acetate at a flow rate 1.0 ml/min and UV detected at 270 nm. Results: All calibration curves showed good linear regression (r ≥ 0.9993) within tested ranges. Limits of detection (LOD) and limits of quantification (LOQ) fell in the range between 0.0691-1.04 μg/ml and 0.23–3.43 μg/ml, respectively. The mean recovery of each herbal medicine ranged from 96.60 to 102.11%. Conclusion: The method was validated for repeatability, precision, stability, accuracy, and selectivity. The validated method was successfully applied to simultaneous analysis of these active components in ‘Ge-Gen-Qin-Lian’ decoction. PMID:25422547

  14. DEL phenotype.

    PubMed

    Kwon, Dong H; Sandler, S G; Flegel, Willy A

    2017-09-01

    DEL red blood cells (RBCs) type as D- by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent of African individuals who are D-, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D- recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are transfused as D- annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.

  15. New data on two remarkable Antarctic species Amblydorylaimus isokaryon (Loof, 1975) Andrássy, 1998 and Pararhyssocolpus paradoxus (Loof, 1975), gen. n., comb. n. (Nematoda, Dorylaimida)

    PubMed Central

    Elshishka, Milka; Lazarova, Stela; Radoslavov, Georgi; Hristov, Petar; Peneva, Vlada K.

    2015-01-01

    Abstract The taxonomic position of two antarctic dorylaimid species Amblydorylaimus isokaryon (Loof, 1975) Andrássy, 1998 and Pararhyssocolpus paradoxus (Loof, 1975), gen. n., comb. n. are discussed on the basis of morphological, including SEM study, morphometric, postembryonic and sequence data of 18S rDNA and the D2-D3 expansion fragments of large subunit rDNA. The evolutionary trees inferred from 18S sequences show insufficient resolution to determine the assignment of the two species to particular families, moreover Pararhyssocolpus paradoxus gen. n., comb. n. (=Rhyssocolpus paradoxus) previously regarded as a member of Nordiidae or Qudsianematidae, showed distant relationship both to Rhyssocolpus vinciguerrae and Eudorylaimus spp. The phylogram inferred from 28S sequences revealed that Amblydorylaimus isokaryon is a member of a well-supported group comprised of several Aporcelaimellus spp., while, no close relationships could be revealed for the Pararhyssocolpus paradoxus gen. n., comb. n. to any nematode genus. On the basis of molecular data and morphological characteristics, some taxonomic changes are proposed. Amblydorylaimus isokaryon is transferred from family Qudsianematidae to family Aporcelaimidae, and a new monotypic genus Pararhyssocolpus gen. n. is proposed, attributed to Pararhyssocolpidae fam. n. The diagnosis of the new family is provided together with emended diagnosis of the genera Amblydorylaimus and Pararhyssocolpus gen. n. Data concerning distribution of these endemic genera in the Antarctic region are also given. PMID:26257550

  16. 2nd Gen FeCrAl ODS Alloy Development For Accident-Tolerant Fuel Cladding

    SciTech Connect

    Dryepondt, Sebastien N.; Massey, Caleb P.; Edmondson, Philip D.

    Extensive research at ORNL aims at developing advanced low-Cr high strength FeCrAl alloys for accident tolerant fuel cladding. One task focuses on the fabrication of new low Cr oxide dispersion strengthened (ODS) FeCrAl alloys. The first Fe-12Cr-5Al+Y 2O 3 (+ ZrO 2 or TiO 2) ODS alloys exhibited excellent tensile strength up to 800 C and good oxidation resistance in steam up to 1400 C, but very limited plastic deformation at temperature ranging from room to 800 C. To improve alloy ductility, several fabrication parameters were considered. New Fe-10-12Cr-6Al gas-atomized powders containing 0.15 to 0.5wt% Zr were procured and ballmore » milled for 10h, 20h or 40h with Y2O3. The resulting powder was then extruded at temperature ranging from 900 to 1050 C. Decreasing the ball milling time or increasing the extrusion temperature changed the alloy grain size leading to lower strength but enhanced ductility. Small variations of the Cr, Zr, O and N content did not seem to significantly impact the alloy tensile properties, and, overall, the 2nd gen ODS FeCrAl alloys showed significantly better ductility than the 1st gen alloys. Tube fabrication needed for fuel cladding will require cold or warm working associated with softening heat treatments, work was therefore initiated to assess the effect of these fabrications steps on the alloy microstructure and properties. This report has been submitted as fulfillment of milestone M3FT 16OR020202091 titled, Report on 2nd Gen FeCrAl ODS Alloy Development for the Department of Energy Office of Nuclear Energy, Advanced Fuel Campaign of the Fuel Cycle R&D program.« less

  17. When Opportunity Only Knocks Once: Lessons From Gen Petraeus In Iraq And Afghanistan

    DTIC Science & Technology

    2016-03-01

    Afghanistan because of the unfavorable contextual elements including the lack of both popular and political support at home and abroad, the tribal...decades-long, war ravaged land in Afghanistan. Different contextual environments and battlefield elements can stymie a war effort of an otherwise...37th Commandant of the U.S.M.C. GEN David Petraeus’ counterinsurgency (COIN) efforts failed in Afghanistan because of the unfavorable contextual

  18. Balancing Formative and Summative Science Assessment Practices: Year One of the GenScope Assessment Project.

    ERIC Educational Resources Information Center

    Hickey, Daniel T.; Kruger, Ann Cale; Fredrick, Laura D.; Schafer, Nancy Jo; Kindfield, Ann C. H.

    This paper describes the GenScope Assessment Project, a project that is exploring ways of using multimedia computers to teach complex science content, refining sociocultural views of assessment and motivation, and considering different ways of reconciling the differences between these newer views and prior behavioral and cognitive views. The…

  19. Enhanced Vision for All-Weather Operations Under NextGen

    NASA Technical Reports Server (NTRS)

    Bailey, Randall E.; Kramer, Lynda J.; Williams, Steven P.; Bailey, Randall E.; Kramer, Lynda J.; Williams, Steven P.

    2010-01-01

    Recent research in Synthetic/Enhanced Vision technology is analyzed with respect to existing Category II/III performance and certification guidance. The goal is to start the development of performance-based vision systems technology requirements to support future all-weather operations and the NextGen goal of Equivalent Visual Operations. This work shows that existing criteria to operate in Category III weather and visibility are not directly applicable since, unlike today, the primary reference for maneuvering the airplane is based on what the pilot sees visually through the "vision system." New criteria are consequently needed. Several possible criteria are discussed, but more importantly, the factors associated with landing system performance using automatic and manual landings are delineated.

  20. Enhanced Flight Vision Systems and Synthetic Vision Systems for NextGen Approach and Landing Operations

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Bailey, Randall E.; Ellis, Kyle K. E.; Williams, Steven P.; Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Shelton, Kevin J.

    2013-01-01

    Synthetic Vision Systems and Enhanced Flight Vision System (SVS/EFVS) technologies have the potential to provide additional margins of safety for aircrew performance and enable operational improvements for low visibility operations in the terminal area environment with equivalent efficiency as visual operations. To meet this potential, research is needed for effective technology development and implementation of regulatory standards and design guidance to support introduction and use of SVS/EFVS advanced cockpit vision technologies in Next Generation Air Transportation System (NextGen) operations. A fixed-base pilot-in-the-loop simulation test was conducted at NASA Langley Research Center that evaluated the use of SVS/EFVS in NextGen low visibility approach and landing operations. Twelve crews flew approach and landing operations in a simulated NextGen Chicago O'Hare environment. Various scenarios tested the potential for using EFVS to conduct approach, landing, and roll-out operations in visibility as low as 1000 feet runway visual range (RVR). Also, SVS was tested to evaluate the potential for lowering decision heights (DH) on certain instrument approach procedures below what can be flown today. Expanding the portion of the visual segment in which EFVS can be used in lieu of natural vision from 100 feet above the touchdown zone elevation to touchdown and rollout in visibilities as low as 1000 feet RVR appears to be viable as touchdown performance was acceptable without any apparent workload penalties. A lower DH of 150 feet and/or possibly reduced visibility minima using SVS appears to be viable when implemented on a Head-Up Display, but the landing data suggests further study for head-down implementations.

  1. 78 FR 56263 - HydroGen Corp., QueryObject Systems Corp., Security Intelligence Technologies, Inc., Skins, Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] HydroGen Corp., QueryObject Systems Corp., Security Intelligence Technologies, Inc., Skins, Inc., SLM Holdings, Inc., Spring Creek Healthcare Systems... securities of Security Intelligence Technologies, Inc. because it has not filed any periodic reports since...

  2. BioNetFit: a fitting tool compatible with BioNetGen, NFsim and distributed computing environments.

    PubMed

    Thomas, Brandon R; Chylek, Lily A; Colvin, Joshua; Sirimulla, Suman; Clayton, Andrew H A; Hlavacek, William S; Posner, Richard G

    2016-03-01

    Rule-based models are analyzed with specialized simulators, such as those provided by the BioNetGen and NFsim open-source software packages. Here, we present BioNetFit, a general-purpose fitting tool that is compatible with BioNetGen and NFsim. BioNetFit is designed to take advantage of distributed computing resources. This feature facilitates fitting (i.e. optimization of parameter values for consistency with data) when simulations are computationally expensive. BioNetFit can be used on stand-alone Mac, Windows/Cygwin, and Linux platforms and on Linux-based clusters running SLURM, Torque/PBS, or SGE. The BioNetFit source code (Perl) is freely available (http://bionetfit.nau.edu). Supplementary data are available at Bioinformatics online. bionetgen.help@gmail.com. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Effects of Petrol Exposure on Glucose, Liver and Muscle glycogen levels in the Common African toad Bufo regularis.

    PubMed

    Isehunwa, G O; Yusuf, I O; Alada, A Ar

    2017-03-06

    This study investigated the effects of exposure to petrol on blood glucose, liver and muscle glycogen levels in the common African toad Bufo regularis. A total of 126 adult toads of either sex weighing between 70-100g were used for this study. The experiment was divided into three phases. The phase 1 experiment the acute toxicity test consisted of animals divided into six groups of 10 toads per group and were exposed to water (H2O), H2O + Tween 80, 2ml/l, 3ml/l, 5ml/l, and 10ml/l of petrol respectively for 96 hours using the static renewal bioassay system. In the Phase 2 experiment, the animals were exposed to H2O, H2O + Tween 80, 0.14ml/l, 0.3ml/l, 0.6ml/l, and 1.13ml/l of petrol respectively for 3 days; while in phase 3 experiment they were exposed to petrol solutions for 14 days. After the various exposures, the blood glucose, liver and muscle glycogen contents were determined using standard methods. The results of the study showed that the median lethal concentration of petrol (96 hours LC50) was 4.5ml/l and sub-lethal concentration of petrol caused mortality of animals. Exposure to petrol solutions for 3 days had no significant effect on blood glucose level of the animals but caused significant decrease in the liver and muscle glycogen levels at high concentrations. In the animals exposed to petrol solutions for 14 days, there was a significant increase in glucose levels and significant reduction in liver and muscle glycogen levels at high concentrations when compared with the control. The results show that sub-lethal concentrations of petrol can cause mortality of animals, hyperglycemia and reduction in liver and muscle glycogen levels. The effects of petrol exposure on carbohydrate metabolism depend on the concentration and duration of exposure.

  4. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-02-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  5. Vorinostat and Decitabine in Treating Patients With Relapsed, Refractory, or Poor-Prognosis Hematologic Cancer or Other Diseases

    ClinicalTrials.gov

    2013-01-04

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  6. Evolution of AF6-RAS association and its implications in mixed-lineage leukemia

    SciTech Connect

    Smith, Matthew J.; Ottoni, Elizabeth; Ishiyama, Noboru

    Elucidation of activation mechanisms governing protein fusions is essential for therapeutic development. MLL undergoes rearrangement with numerous partners, including a recurrent translocation fusing the epigenetic regulator to a cytoplasmic RAS effector, AF6/afadin. We show here that AF6 employs a non-canonical, evolutionarily conserved α-helix to bind RAS, unique to AF6 and the classical RASSF effectors. Further, all patients with MLL-AF6 translocations express fusion proteins missing only this helix from AF6, resulting in exposure of hydrophobic residues that induce dimerization. We provide evidence that oligomerization is the dominant mechanism driving oncogenesis from rare MLL translocation partners and employ our mechanistic understanding ofmore » MLL-AF6 to examine how dimers induce leukemia. Proteomic data resolve association of dimerized MLL with gene expression modulators, and inhibiting dimerization disrupts formation of these complexes while completely abrogating leukemogenesis in mice. Oncogenic gene translocations are thus selected under pressure from protein structure/function, underscoring the complex nature of chromosomal rearrangements.« less

  7. Baltileuctra gen. nov., a new genus of Leuctridae (Insecta: Plecoptera) in Baltic amber.

    PubMed

    Chen, Zhi-Teng

    2018-04-10

    A new genus and species of the stonefly family Leuctridae, Baltileuctra foraminis gen. et sp. nov., is described and illustrated based on a well-preserved male specimen from the Eocene Baltic amber. The new genus possesses typical characters of Leuctridae but has diagnostic characters of the thoracic sclerites and terminalia. The relationship between the new genus and other leuctrids is briefly discussed.

  8. Description of Loffienema dhanoriensis gen. n., sp. n. (Nematoda: Rhabditidae) from Jammu and Kashmir State, India

    USDA-ARS?s Scientific Manuscript database

    A new genus, Loffienema dhanoriensis gen. n., sp. n. is described and illustrated from soil mixed with mature compost of Biodiversity Park, Baba Ghulam Shah Badshah (BGSB) University, Rajouri, Jammu and Kashmir, India. It is characterized by medium-sized body, slightly offset labial region, weakly d...

  9. Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study.

    PubMed

    Aguilar, Frank G; Selvaraj, Senthil; Martinez, Eva E; Katz, Daniel H; Beussink, Lauren; Kim, Kwang-Youn A; Ping, Jie; Rasmussen-Torvik, Laura; Goyal, Amita; Sha, Jin; Irvin, Marguerite R; Arnett, Donna K; Shah, Sanjiv J

    2016-03-01

    Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results. In the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter-/intra-observer agreement was calculated. Accuracy was evaluated in: (1) a separate second study (N = 50) comparing prospective digital strain versus post hoc analog-to-digital strain, and (2) in a third study (N = 95) comparing prospectively obtained TDI e' velocities with post hoc STE e' velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data. Of the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intra-observer agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post hoc STE to prospective digital STE for strain analysis. STE-derived e' velocities correlated with, but systematically underestimated, TDI e' velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted β = -2.4 [95% CI -3.6, -1.2]% per 1-SD increase in fasting glucose; P < 0.001). Archeological echocardiography, the digitization and speckle tracking analysis of archival echocardiograms, is feasible and generates indices of cardiac mechanics similar to contemporary studies. © 2015

  10. Archeological Echocardiography: Digitization and Speckle-Tracking Analysis of Archival Echocardiograms in the HyperGEN Study

    PubMed Central

    Aguilar, Frank G.; Selvaraj, Senthil; Martinez, Eva E.; Katz, Daniel H.; Beussink, Lauren; Kim, Kwang-Youn A.; Ping, Jie; Rasmussen-Torvik, Laura; Goyal, Amita; Sha, Jin; Irvin, Marguerite R.; Arnett, Donna K.; Shah, Sanjiv J.

    2015-01-01

    Background Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle-tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results. Methods In the NHLBI HyperGEN study (N=2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter/intraobserver agreement was calculated. Accuracy was evaluated in (1) a separate second study (N=50) comparing prospective digital strain vs. post-hoc analog-to-digital strain; and (2) in a third study (N=95) comparing prospectively-obtained TDI e′ velocities with post-hoc STE e′ velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data. Results Of the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intraobserver agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post-hoc STE to prospective digital STE for strain analysis. STE-derived e′ velocities correlated with, but systematically underestimated, TDI e′ velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted β =−2.4 [95% CI −3.6,−1.2]% per 1-SD increase in fasting glucose; P<0.001). Conclusions Archeological echocardiography, the digitization and speckle-tracking analysis of archival echocardiograms, is feasible and generates parameters of cardiac mechanics

  11. [Study on the hypoglycemic activity of different extracts of wild Psidium guajava leaves in Panzhihua Area].

    PubMed

    Wang, Bo; Liu, Heng-Chuan; Ju, Chang-Yan

    2005-11-01

    To illuminate the role of water-soluble, 650 ml/L edible alcohol and 950 ml/L edible alcohol-soluble extracts of wild Psidium guajava leaves in Panzhihua Area in decreasing blood glucose. High-level blood glucose models were made by use of male Kunming mice given intraperitoneal injection of glucose, subcutaneous injection of adrenaline and intraperitoneal injection of streptozotocin (STZ), respectively. Blood glucose concentration was measured after oral administration (gastrogavage) of the soluble extracts of Psidium guajava leaves, respectively. Body weight and organ morphology were observed, and organ index was obtained. The All available indexes were statistically analyzed in comparing the study groups and control group. three extracts resisted the rise of blood glucose level induced by exogenous glucose and adrenaline to various degrees. The extracts of water, 650 ml/L alcohol and 950 ml/L alcohol significantly decreased the blood glucose level in STZ-induced diabetic mice by 36.3%, 33.5% and 31.3% respectively. Furthermore, among three extracts, water-soluble extract showed little influence on the growth of mice. The water-soluble, 650 ml/L edible alcohol and 950 ml/L edible alcohol-soluble extracts of wild Psidium guajava leaves in Panzhihua area may have different hypoglycemic potential.

  12. Gen-2 hand-held optical imager towards cancer imaging: reflectance and transillumination phantom studies.

    PubMed

    Gonzalez, Jean; Roman, Manuela; Hall, Michael; Godavarty, Anuradha

    2012-01-01

    Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1-5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies.

  13. FutureGen 2.0 Oxy-combustion Large Scale Test – Final Report

    SciTech Connect

    Kenison, LaVesta; Flanigan, Thomas; Hagerty, Gregg

    The primary objectives of the FutureGen 2.0 CO 2 Oxy-Combustion Large Scale Test Project were to site, permit, design, construct, and commission, an oxy-combustion boiler, gas quality control system, air separation unit, and CO 2 compression and purification unit, together with the necessary supporting and interconnection utilities. The project was to demonstrate at commercial scale (168MWe gross) the capability to cleanly produce electricity through coal combustion at a retrofitted, existing coal-fired power plant; thereby, resulting in near-zeroemissions of all commonly regulated air emissions, as well as 90% CO 2 capture in steady-state operations. The project was to be fully integratedmore » in terms of project management, capacity, capabilities, technical scope, cost, and schedule with the companion FutureGen 2.0 CO 2 Pipeline and Storage Project, a separate but complementary project whose objective was to safely transport, permanently store and monitor the CO 2 captured by the Oxy-combustion Power Plant Project. The FutureGen 2.0 Oxy-Combustion Large Scale Test Project successfully achieved all technical objectives inclusive of front-end-engineering and design, and advanced design required to accurately estimate and contract for the construction, commissioning, and start-up of a commercial-scale "ready to build" power plant using oxy-combustion technology, including full integration with the companion CO 2 Pipeline and Storage project. Ultimately the project did not proceed to construction due to insufficient time to complete necessary EPC contract negotiations and commercial financing prior to expiration of federal co-funding, which triggered a DOE decision to closeout its participation in the project. Through the work that was completed, valuable technical, commercial, and programmatic lessons were learned. This project has significantly advanced the development of near-zero emission technology and will be helpful to plotting the course of, and

  14. The Three Wars of Lt. Gen. George E. Stratemeyer. His Korean War Diary

    DTIC Science & Technology

    1999-01-01

    Powers (SCAP), he exercised command over all occupation forces and, in essence , ruled Japan; as Commander-in-Chief, Far East Command (CINCFE), he exercised... essence , he was attempting to make national policy himself and was giving the Chinese an ultimatum that the war would be extended to their mainland...LT. GEN. GEORGE E. STRATEMEYER : HIS KOREAN WAR DIARY 45. The Sykes report was, in essence , General Stratemeyer’s diary entries for those dates with

  15. Gen Y Recruitment: Understanding Graduate Intentions to Join an Organisation Using the Theory of Planned Behaviour

    ERIC Educational Resources Information Center

    Warmerdam, Amanda; Lewis, Ioni; Banks, Tamara

    2015-01-01

    Purpose: Using the Theory of Planned Behaviour (TPB) framework, the purpose of this paper is to explore whether the standard TPB constructs explained variance in Generation Y (Gen Y) individuals' intentions to join their ideal organisation. Design/methodology/approach: A mixed methods approach was used featuring qualitative and quantitative…

  16. GIDL: a rule based expert system for GenBank Intelligent Data Loading into the Molecular Biodiversity database

    PubMed Central

    2012-01-01

    Background In the scientific biodiversity community, it is increasingly perceived the need to build a bridge between molecular and traditional biodiversity studies. We believe that the information technology could have a preeminent role in integrating the information generated by these studies with the large amount of molecular data we can find in bioinformatics public databases. This work is primarily aimed at building a bioinformatic infrastructure for the integration of public and private biodiversity data through the development of GIDL, an Intelligent Data Loader coupled with the Molecular Biodiversity Database. The system presented here organizes in an ontological way and locally stores the sequence and annotation data contained in the GenBank primary database. Methods The GIDL architecture consists of a relational database and of an intelligent data loader software. The relational database schema is designed to manage biodiversity information (Molecular Biodiversity Database) and it is organized in four areas: MolecularData, Experiment, Collection and Taxonomy. The MolecularData area is inspired to an established standard in Generic Model Organism Databases, the Chado relational schema. The peculiarity of Chado, and also its strength, is the adoption of an ontological schema which makes use of the Sequence Ontology. The Intelligent Data Loader (IDL) component of GIDL is an Extract, Transform and Load software able to parse data, to discover hidden information in the GenBank entries and to populate the Molecular Biodiversity Database. The IDL is composed by three main modules: the Parser, able to parse GenBank flat files; the Reasoner, which automatically builds CLIPS facts mapping the biological knowledge expressed by the Sequence Ontology; the DBFiller, which translates the CLIPS facts into ordered SQL statements used to populate the database. In GIDL Semantic Web technologies have been adopted due to their advantages in data representation, integration and

  17. Tziminema unachi n. gen., n. sp. (Nematoda: Strongylidae: Strongylinae) parasite of Baird's tapir Tapirus bairdii from Mexico.

    PubMed

    Güiris-Andrade, D M; Oceguera-Figueroa, A; Osorio-Sarabia, D; Pérez-Escobar, M E; Nieto-López, M G; Rojas-Hernández, N M; García-Prieto, L

    2017-11-20

    A new genus and species of nematode, Tziminema unachi n. gen., n. sp. is described from the caecum and colon of Baird's tapir Tapirus bairdii (Gill, 1865), found dead in the Reserva de la Biósfera El Triunfo, Chiapas State, in the Neotropical realm of Mexico. Tziminema n. gen. differs from the other nine genera included in the Strongylinae by two main characteristics: having 7-9 posteriorly directed tooth-like structures at the anterior end of the buccal capsule, and the external surface of the buccal capsule being heavily striated. Phylogenetic analyses of the DNA sequences of the mitochondrial cytochrome c oxidase and nuclear DNA, including a partial sequence of the internal transcribed spacer 1, 5.8S and a partial sequence of the internal transcribed spacer 2 of the new taxon, confirmed its inclusion in Strongylinae and its rank as a new genus.

  18. The New Digital Scholar: Exploring and Enriching the Research and Writing Practices of NextGen Students

    ERIC Educational Resources Information Center

    McClure, Randall, Ed.; Purdy, James P., Ed.

    2013-01-01

    "The New Digital Scholar" presents innovative thinking and groundbreaking research on the challenges NextGen students face with research-writing projects. Reminding readers of the history of the academic research paper and the scope of the recent information explosion, editors McClure and Purdy open a discussion long silent in academic…

  19. A new genus and species of isanthid sea anemone (Cnidaria: Anthozoa: Actiniaria) from Chilean Patagonia, Anthoparactis fossii n. gen. et sp

    NASA Astrophysics Data System (ADS)

    Häussermann, Verena; Rodríguez, Estefanía

    2014-09-01

    We describe a new genus and species of sea anemone from Chilean Patagonia. Anthoparactis fossii n. gen. et sp. adds another acontiate genus and species to the family Isanthidae Carlgren, 1938. Anthoparactis n. gen. differs from the other isanthid genera in having the same number of mesenteries distally and proximally, acontia with basitrichs only, and a column with verrucae distally. Anthoparactis fossii n. sp. differs from the most similar species, Isoparactis fionae Lauretta et al., 2013, in the number of cycles of mesenteries and tentacles, structures of the column, colour pattern of the oral disc, cnidae, and geographical distribution. Isanthidae now includes seven genera and 11 species.

  20. A new sensitive automated assay for procalcitonin detection: LIAISON® BRAHMS PCT® II GEN.

    PubMed

    Fortunato, Antonio

    2016-12-01

    To assess the performance of LIAISON ® BRAHMS PCT ® II GEN (DiaSorin, Saluggia, Italy) in procalcitonin (PCT) determination by comparing it to the assay reference method B·R·A·H·M·S PCT KRYPTOR (Thermo Fisher Scientific Clinical Diagnostics, Hennigsdorf, Germany) and assessing its ability to discriminate between healthy subjects and patients with suspected infection. Diagnostic performance was evaluated on: a) 193 selected samples covering the assay range, whose procalcitonin levels were already evaluated with the B·R·A·H·M·S PCT ® KRYPTOR; b) prospective samples: 150 apparently healthy specimens obtained from a blood bank, 161 hospitalized patients (not with specific pathologies), 243 apparently healthy children. The comparison of LIAISON ® BRAHMS PCT ® II GEN to the reference method B·R·A·H·M·S PCT KRYPTOR yielded high correlation coefficients: slope of Deming fit equal to 1.04 (95% CI: 0.99-1.09) with an intercept equal to 0.05 (95% CI: -0.09 to 0.19) and a high concordance (98.4% (95% CI: 95.5-99.7%)) at the 0.5 ng/mL cut-off. Moreover, the results obtained using prospective samples showed: (i) no samples with PCT concentration >0.5 ng/mL (cut-off) for the apparently healthy adults (highest value=0.033 ng/mL, 95th percentile and 97.5th percentile <0.02 ng/mL); (ii) 2 samples >0.5 ng/mL for hospitalized patients (highest value=0.715 ng/mL, 95th percentile: 0.054 ng/mL; 97.5th percentile: 0.088 ng/mL); (iii) 3 samples >0.5 ng/mL for the healthy children population (highest value=0.713 ng/mL, 95th percentile: 0.155 ng/mL; 97.5th percentile: 0.275 ng/mL). The fully automated LIAISON ® BRAHMS PCT ® II GEN agrees well with the reference method and is suitable for early diagnosis of sepsis, severe bacterial infection and guiding antibiotic therapy.

  1. Can a Morel-Lavallée lesion be misdiagnosed as a mass like lesion?

    PubMed

    Lee, Yoon Jae; Kim, Jun Hyeok; Kim, Ji Young; Han, Hyun Ho

    2017-12-01

    The Morel-Lavallée lesion (MLL) is a post-traumatic closed soft tissue degloving injury. Common complaints of MLL patients are a haematoma or fluid collection on the trunk or the lower extremity. However, the authors introduce unique cases of MLL that present an atypical appearance. The fluid collection was not apparent, and the capsule formation was not detected on preoperative image study. The main complaint of patients was the uncomfortable mass-like lesion that was regarded as a simple benign lump. The purpose of this case study is to introduce the atypical cases of MLL and to help other physicians make accurate diagnosis based on trial and error of our cases. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  2. 77 FR 56839 - GenOn Marsh Landing, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER12-2545-000] GenOn Marsh Landing, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket... Landing, LLC's application for market-based rate authority, with an accompanying rate schedule, noting...

  3. Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.

    PubMed

    Toro, Carlos A; Wright, Hollis; Aylwin, Carlos F; Ojeda, Sergio R; Lomniczi, Alejandro

    2018-01-04

    Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members of the Trithorax group (TrxG) of modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components of an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes the chromatin configuration at the promoters of Kiss1 and Tac3, two genes required for puberty to occur, from repressive to permissive. Concomitantly, MLL3 institutes a chromatin structure that changes the functional status of a Kiss1 enhancer from poised to active. RNAi-mediated, ARC-specific Mll1 knockdown reduced Kiss1 and Tac3 expression, whereas CRISPR-Cas9-directed epigenome silencing of the Kiss1 enhancer selectively reduced Kiss1 activity. Both interventions delay puberty and disrupt reproductive cyclicity. Our results demonstrate that an epigenetic switch from transcriptional repression to activation is crucial to the regulatory mechanism controlling the timing of mammalian puberty.

  4. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

    Rowley, Janet D.; Diaz, Manuel O.

    2000-01-01

    Disclosed is a series of nucleic acid probes for use in diagnosing and monitoring certain types of leukemia using, e.g., Southern and Northern blot analyses and fluorescence in situ hybridization (FISH). These probes detect rearrangements, such as translocations involving chromosome band 11q23 with other chromosomes bands, including 4q21, 6q27, 9p22, 19p13.3, in both dividing leukemic cells and interphase nuclei. The breakpoints in all such translocations are clustered within an 8.3 kb BamHI genomic region of the MLL gene. A novel 0.7 kb BamH1 cDNA fragment derived from this gene detects rearrangements on Southern blot analysis with a single BamHI restriction digest in all patients with the common 11q23 translocations and in patients with other 11q23 anomalies. Northern blot analyses are presented demonstrating that the MLL gene has multiple transcripts and that transcript size differentiates leukemic cells from normal cells. Also disclosed are MLL fusion proteins, MLL protein domains and anti-MLL antibodies.

  5. An Antarctic hypotrichous ciliate, Parasterkiella thompsoni (Foissner) nov. gen., nov. comb., recorded in Argentinean peat-bogs: morphology, morphogenesis, and molecular phylogeny.

    PubMed

    Küppers, Gabriela Cristina; Paiva, Thiago da Silva; Borges, Bárbara do Nascimento; Harada, Maria Lúcia; Garraza, Gabriela González; Mataloni, Gabriela

    2011-05-01

    The ciliate Parasterkiella thompsoni (Foissner, 1996) nov. gen., nov. comb. was originally described from Antarctica. In the present study, we report the morphology, morphogenesis during cell division, and molecular phylogeny inferred from the 18S-rDNA sequence of a population isolated from the Rancho Hambre peat bog, Tierra del Fuego Province (Argentina). The study is based on live and protargol-impregnated specimens. Molecular phylogeny was inferred from trees constructed by means of the maximum parsimony, neighbor joining, and Bayesian analyses. The interphase morphology matches the original description of the species. During the cell division, stomatogenesis begins with the de novo proliferation of two fields of basal bodies, each one left of the postoral ventral cirri and of transverse cirri, which later unify. Primordia IV-VI of the proter develop from disaggregation of cirrus IV/3, while primordium IV of the opisthe develops from cirrus IV/2 and primordia V and VI from cirrus V/4. Dorsal morphogenesis occurs in the Urosomoida pattern-that is, the fragmentation of kinety 3 is lacking. Three macronuclear nodules are generated before cytokinesis. Phylogenetic analyses consistently placed P. thompsoni within the stylonychines. New data on the morphogenesis of the dorsal ciliature justifies the transference of Sterkiella thompsoni to a new genus Parasterkiella. Copyright © 2011 Elsevier GmbH. All rights reserved.

  6. A gilled mushroom, Gerontomyces lepidotus gen. et sp. nov. (Basidiomycota: Agaricales), in Baltic amber.

    PubMed

    Poinar, George

    2016-09-01

    A densely scaled small mushroom in Baltic amber is described as Gerontomyces lepidotus gen. et sp. nov. and is characterized by a convex pileus 1.0 mm in diameter, distant to subdistant lamellae with smooth margins and a centrally inserted cylindrical, solid stipe. Its taxonomic placement is uncertain. This is the first mushroom described from Baltic amber. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  7. Curvas de fusión de regiones genómicas específicas: una herramienta prometedora para el diagnóstico y tipificación de las especies causantes de la leishmaniasis cutánea en Colombia.

    PubMed

    Marin, Johana; Urrea, Daniel; Muskus, Carlos; Echeverry, María Clara; Mejía, Ana María; Triana, Omar

    2017-12-01

    Introducción. La leishmaniasis cutánea es una enfermedad causada por parásitos del género Leishmania que tiene gran incidencia en Colombia. El diagnóstico y la identificación de la especie infecciosa son factores críticos en el momento de escoger e iniciar el tratamiento. Actualmente, los métodos de diagnóstico y tipificación requieren procedimientos complejos, por lo que es necesario validar nuevos marcadores moleculares y métodos que simplifiquen el proceso.Objetivo. Desarrollar una herramienta basada en la reacción en cadena de la polimerasa (PCR) con curvas de fusión (High Resolution Melting; PCR-HRM) para el diagnóstico y tipificación de las tres especies de Leishmania de importancia epidemiológica en casos de leishmaniasis cutánea en Colombia.Materiales y métodos. Los genomas de Leishmania panamensis, L. braziliensis y L. guyanensis se compararon mediante métodos bioinformáticos. Las regiones específicas de especie identificadas se validaron mediante PCR. Para los marcadores seleccionados se diseñó una PCR-HRM y se estimaron algunos parámetros de validez y seguridad usando aislamientos de pacientes colombianos caracterizados previamente mediante PCR y análisis de polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism - RFLP; PCR-RFLP) del gen hsp70.Resultados. El análisis genómico comparativo mostró 24 regiones específicas de especie. Sin embargo, la validación mediante PCR solo identificó un marcador específico para cada especie de Leishmania. Los otros marcadores mostraron amplificación cruzada. El límite de detección para los tres marcadores seleccionados fue de un parásito, mientras que la sensibilidad, la especificidad, el valor predictivo positivo y el negativo fueron de 91,4, 100, 100 y 75 %, respectivamente.Conclusiones. Las tres regiones seleccionadas pueden emplearse como marcadores moleculares en el diagnóstico y tipificación de las especies causantes de la

  8. Challenges and Opportunities in Gen3 Embedded Cooling with High-Quality Microgap Flow

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Avram; Robinson, Franklin L.; Deisenroth, David C.

    2018-01-01

    Gen3, Embedded Cooling, promises to revolutionize thermal management of advanced microelectronic systems by eliminating the sequential conductive and interfacial thermal resistances which dominate the present 'remote cooling' paradigm. Single-phase interchip microfluidic flow with high thermal conductivity chips and substrates has been used successfully to cool single transistors dissipating more than 40kW/sq cm, but efficient heat removal from transistor arrays, larger chips, and chip stacks operating at these prodigious heat fluxes would require the use of high vapor fraction (quality), two-phase cooling in intra- and inter-chip microgap channels. The motivation, as well as the challenges and opportunities associated with evaporative embedded cooling in realistic form factors, is the focus of this paper. The paper will begin with a brief review of the history of thermal packaging, reflecting the 70-year 'inward migration' of cooling technology from the computer-room, to the rack, and then to the single chip and multichip module with 'remote' or attached air- and liquid-cooled coldplates. Discussion of the limitations of this approach and recent results from single-phase embedded cooling will follow. This will set the stage for discussion of the development challenges associated with application of this Gen3 thermal management paradigm to commercial semiconductor hardware, including dealing with the effects of channel length, orientation, and manifold-driven centrifugal acceleration on the governing behavior.

  9. Glucocorticoid sensitisation in Mixed Lineage Leukaemia-rearranged acute lymphoblastic leukaemia by the pan-BCL-2 family inhibitors gossypol and AT-101.

    PubMed

    Spijkers-Hagelstein, Jill A P; Schneider, Pauline; Pinhanços, Sandra Mimoso; Garrido Castro, Patricia; Pieters, Rob; Stam, Ronald W

    2014-06-01

    Resistance to glucocorticoids (GCs) remains a major problem in the treatment of infants with acute lymphoblastic leukaemia (ALL) carrying Mixed Lineage Leukaemia (MLL) translocations. Despite intensive research, the mechanism(s) underlying GC resistance remain poorly understood. Recent studies suggested an important role for the pro-survival BCL-2 family member MCL1 in GC resistance in MLL-rearranged ALL. We exposed GC-resistant MLL-rearranged SEMK2 cells to potent MCL1-inhibiting agents, including gossypol, AT-101, rapamycin, SU9516 and obatoclax (GX15-070) and determined GC sensitisation using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays. Using Western blotting we analysed the protein expression of most BCL-2 family members in MLL-rearranged SEMK2 cells after treatment with potent MCL-1 inhibiting agents. Only gossypol and its synthetic analogue AT-101 induced GC sensitivity in MLL-rearranged ALL cells. Remarkably, the GC-sensitising effects of gossypol and AT-101 appeared not to be mediated by down-regulation MCL1 or other anti-apoptotic BCL-2 family members, but rather involved up-regulation of multiple pro-apoptotic BCL-2 family members, in particular that of BIM and BID. In conclusion, gossypol and AT-101 induce GC sensitivity in MLL-rearranged ALL cells, most likely mediated by the activation of BID and BIM without the necessity to down-regulate anti-apoptotic BCL-2 family members like MCL1. Hence, co-administration of either gossypol or AT-101 during GC treatment of GC-resistant MLL-rearranged ALL patients may overcome GC resistance and improve prognosis in this high-risk childhood leukaemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Selection, proliferation and differentiation of bone marrow-derived liver stem cells with a culture system containing cholestatic serum in vitro.

    PubMed

    Cai, Yun-Feng; Zhen, Zuo-Jun; Min, Jun; Fang, Tian-Ling; Chu, Zhong-Hua; Chen, Ji-Sheng

    2004-11-15

    To explore the feasibility of direct separation, selective proliferation and differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro. Whole bone marrow cells of rats cultured in routine medium were replaced with conditioning selection media containing 20 mL/L, 50 mL/L, 70 mL/L, and 100 mL/L cholestatic sera, respectively, after they attached to the plates. The optimal concentration of cholestatic serum was determined according to the outcome of the selected cultures. Then the selected BDLSC were induced to proliferate and differentiate with the addition of hepatocyte growth factor (HGF). The morphology and phenotypic markers of BDLSC were characterized using immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. Bone marrow cells formed fibroblast-like but not hepatocyte-like colonies in the presence of 20 mL/L cholestatic serum. In 70 mL/L cholestatic serum, BDLSC colonies could be selected but could not maintain good growth status. In 100 mL/L cholestatic serum, all of the bone marrow cells were unable to survive. A 50 mL/L cholestatic serum was the optimal concentration for the selection of BDLSC at which BDLSC could survive while the other populations of the bone marrow cells could not. The selected BDLSC proliferated and differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU) then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors (HNF-1alpha and HNF-3beta). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. The selected medium containing cholestatic serum can select BDLSC from whole bone marrow cells. It

  11. Comparison of the CT OligoGen kit with cobas 4800 assay for detection of Chlamydia trachomatis.

    PubMed

    Parra-Sánchez, Manuel; Marcuello-López, Ana; García-Rey, Silvia; Zakariya-Yousef, Ismail; Sivianes-Valdecantos, Nieves; Sierra-Atienza, Celestina; Bernal-Martínez, Samuel; Pueyo-Rodrígez, Isabel; Martín-Mazuelos, Estrella; Palomares-Folía, José Carlos

    2015-12-01

    A prospective study was designed to assess the performance of the new CT OligoGen kit and the cobas 4800 assay for detection of Chlamydia trachomatis. A set of samples that included urine samples (n=212), endocervical (n=167), rectal (n=53), pharyngeal (n=7) and urethral swabs (n=3). The samples were sent from a regional sexually transmitted diseases (STD) clinic in Seville, Spain, and were collected from 261 men and 181 women. Discordant results were re-analyzed and clinical data and other tests were reviewed in order to resolve them. Sensitivity, specificity, positive predicative value (PPV), negative predictive value (NPV) and kappa value for C. trachomatis detection using the CT OligoGen kit were 98.5%, 100%, 100%, 95.4% and 0.97, respectively. This new kit had a high sensitivity, specificity, PPV and NPV for C. trachomatis, therefore the performance profile confirms the usefulness and reliable results of this new assay. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Fontibacillus aquaticus gen. nov., sp. nov., isolated from a warm spring.

    PubMed

    Saha, P; Krishnamurthi, S; Bhattacharya, A; Sharma, R; Chakrabarti, T

    2010-02-01

    A novel facultatively anaerobic strain, designated GPTSA 19(T), was isolated from a warm spring and characterized using a polyphasic approach. The strain behaved as Gram-negative in the Gram staining procedure but showed a Gram-positive reaction in the aminopeptidase test. The novel strain was a mesophilic rod with ellipsoidal endospores. On the basis of 16S rRNA gene sequence analysis, the strain showed closest similarity (96.0 %) with Paenibacillus motobuensis MC10(T). The gene sequence similarity of the novel strain with other species of the genus Paenibacillus was <95.8 %. The novel strain also had PAEN 515F and 682F signature sequence stretches in the 16S rRNA gene that are usually found in most species of the genus Paenibacillus. The strain possessed anteiso-C(15 : 0) as the major fatty acid and MK-7 as the predominant menaquinone. Polar lipids included diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), six unknown phospholipids (PLs), one aminophospholipid (PN), three glycolipids (GLs), two aminolipids (ALs), one aminophosphoglycolipid (APGL) and three unknown lipids (ULs). The polar lipid profile of the novel strain, especially as regards ALs, GLs and PLs, distinguished it from the recognized type species of the genus Paenibacillus, Paenibacillus polymyxa, as well as from its closest relative P. motobuensis. Based on phenotypic and chemotaxonomic characteristics and analysis of the 16S rRNA gene sequence, the new strain merits the rank of a novel genus for which the name Fontibacillus gen. nov. is proposed. The type species of the new genus is Fontibacillus aquaticus gen. nov., sp. nov. with the type strain GPTSA 19(T) (=MTCC 7155(T)=DSM 17643(T)).

  13. Mercury: Next-gen Data Analysis and Annotation Pipeline (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    Sexton, David

    2018-01-22

    David Sexton (Baylor) gives a talk titled "Mercury: Next-gen Data Analysis and Annotation Pipeline" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  14. Mercury: Next-gen Data Analysis and Annotation Pipeline (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    SciTech Connect

    Sexton, David

    2012-06-01

    David Sexton (Baylor) gives a talk titled "Mercury: Next-gen Data Analysis and Annotation Pipeline" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  15. Parapedobacter koreensis gen. nov., sp. nov.

    PubMed

    Kim, Myung Kyum; Na, Ju-Ryun; Cho, Dong Ha; Soung, Nak-Kyun; Yang, Deok-Chun

    2007-06-01

    Strain Jip14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from dried rice straw and characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain Jip14(T) belongs to the family Sphingobacteriaceae, and the highest degree of sequence similarity was determined to be to Pedobacter saltans DSM 12145(T) (88.5 %), Pedobacter africanus DSM 12126(T) (87.6 %), Pedobacter heparinus DSM 2366(T) (87.1 %) and Pedobacter caeni LMG 22862(T) (86.9 %). Chemotaxonomic data revealed that strain Jip14(T) possesses menaquinone MK-7 and the predominant fatty acids C(15 : 0) iso, C(16 : 0), C(16 : 0) 10-methyl, C(17 : 0) iso 3-OH and summed feature 3 (C(15 : 0) iso 2-OH/C(16 : 1)omega7c). The results of physiological and biochemical tests clearly demonstrated that strain Jip14(T) represents a distinct species. Based on these data, Jip14(T) should be classified within a novel genus and species, for which the name Parapedobacter koreensis gen. nov., sp. nov. is proposed. The type strain of Parapedobacter koreensis is Jip14(T) (=KCTC 12643(T)=LMG 23493(T)).

  16. Australasian sequestrate fungi 18: Solioccasus polychromus gen. & sp. nov., a richly colored, tropical to subtropical, hypogeous fungus

    Treesearch

    J. M. Trappe; M. A. Castellano; R. E. Halling; T. W. Osmundson; M. Binder; N. Fechner; N. Malajczuk

    2013-01-01

    Solioccasus polychromus gen. & sp. nov., the most brightly colored hypogeous fungus known, is described from Papua New Guinea and tropical northern Australia south into subtropical forests along the Queensland coast and coastal mountains to near Brisbane. Phylogenetic analysis of molecular data places it as a sister genus to Bothia...

  17. A Phocus on Phenotyping: opportunities and challenges in local and centralized trait evaluation from the VitisGen experience

    USDA-ARS?s Scientific Manuscript database

    The integration of relevant genetic resources, robust phenotypes, and cutting-edge genotypic data is a challenge that individual scientists rarely overcome successfully. In the USDA-NIFA VitisGen project ( www.vitisgen.org ) for grapevine cultivar improvement, our research team has pursued a shared ...

  18. YouGenMap: a web platform for dynamic multi-comparative mapping and visualization of genetic maps

    Treesearch

    Keith Batesole; Kokulapalan Wimalanathan; Lin Liu; Fan Zhang; Craig S. Echt; Chun Liang

    2014-01-01

    Comparative genetic maps are used in examination of genome organization, detection of conserved gene order, and exploration of marker order variations. YouGenMap is an open-source web tool that offers dynamic comparative mapping capability of users' own genetic mapping between 2 or more map sets. Users' genetic map data and optional gene annotations are...

  19. Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-02-13

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  20. Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    ClinicalTrials.gov

    2017-10-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. viGEN: An Open Source Pipeline for the Detection and Quantification of Viral RNA in Human Tumors.

    PubMed

    Bhuvaneshwar, Krithika; Song, Lei; Madhavan, Subha; Gusev, Yuriy

    2018-01-01

    An estimated 17% of cancers worldwide are associated with infectious causes. The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples. We present an open source bioinformatics pipeline viGEN, which allows for not only the detection and quantification of viral RNA, but also variants in the viral transcripts. The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. The fourth module calls variants in these viruses. To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package. In this paper, we applied the viGEN pipeline to two case studies. We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort. In the second case study, we performed an in-depth analysis on a small focused study of TCGA liver cancer patients. In the latter cohort, we performed viral-gene quantification, viral-variant extraction and survival analysis. This allowed us to find differentially expressed viral-transcripts and viral-variants between the groups of patients, and connect them to clinical outcome. From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients. We compared the viGEN pipeline with two metagenomics tools and demonstrate similar sensitivity/specificity. We were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset. The results

  2. Meeting Air Transportation Demand in 2025 by Using Larger Aircraft and Alternative Routing to Complement NextGen Operational Improvements

    NASA Technical Reports Server (NTRS)

    Smith, Jeremy C.; Guerreiro, Nelson M.; Viken, Jeffrey K.; Dollyhigh, Samuel M.; Fenbert, James W.

    2010-01-01

    A study was performed that investigates the use of larger aircraft and alternative routing to complement the capacity benefits expected from the Next Generation Air Transportation System (NextGen) in 2025. National Airspace System (NAS) delays for the 2025 demand projected by the Transportation Systems Analysis Models (TSAM) were assessed using NASA s Airspace Concept Evaluation System (ACES). The shift in demand from commercial airline to automobile and from one airline route to another was investigated by adding the route delays determined from the ACES simulation to the travel times used in the TSAM and re-generating new flight scenarios. The ACES simulation results from this study determined that NextGen Operational Improvements alone do not provide sufficient airport capacity to meet the projected demand for passenger air travel in 2025 without significant system delays. Using larger aircraft with more seats on high-demand routes and introducing new direct routes, where demand warrants, significantly reduces delays, complementing NextGen improvements. Another significant finding of this study is that the adaptive behavior of passengers to avoid congested airline-routes is an important factor when projecting demand for transportation systems. Passengers will choose an alternative mode of transportation or alternative airline routes to avoid congested routes, thereby reducing delays to acceptable levels for the 2025 scenario; the penalty being that alternative routes and the option to drive increases overall trip time by 0.4% and may be less convenient than the first-choice route.

  3. Modulation of the metabolic response to an endotoxin challenge in Brahman heifers through OmniGen-AF supplementation

    USDA-ARS?s Scientific Manuscript database

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the metabolic response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton, TX, were separated into 2...

  4. Acrocarpospora gen. nov., a new genus of the order Actinomycetales.

    PubMed

    Tamura, T; Suzuki, S; Hatano, K

    2000-05-01

    The taxonomic position of two actinomycete strains isolated from soil was studied. The isolates contained glutamic acid, alanine and meso-diaminopimelic acid as cell-wall amino acids and menaquinone MK-9(H4) and madurose in the whole-cell hydrolysate. Phylogenetic analysis revealed that the isolates belonged to the family Streptosporangiaceae, but not to any known genus, and formed a monophyletic cluster with Streptosporangium corrugatum. On the basis of morphological characteristics, phylogenetic analysis and DNA-DNA hybridization, the name Acrocarpospora gen. nov. is proposed for a new genus containing the isolates and Streptosporangium corrugatum, and Acrocarpospora pleiomorpha sp. nov. R-31T (= IFO 16267T), Acrocarpospora macrocephala sp. nov. R-55T (=IFO 16266T) and Acrocarpospora corrugata comb. nov. IFO 13972T are described.

  5. Optimized Gen-II FeCrAl cladding production in large quantity for campaign testing

    SciTech Connect

    Yamamoto, Yukinori; Sun, Zhiqian; Pint, Bruce A.

    2016-06-03

    There are two major objectives in this report; (1) to optimize microstructure control of ATF FeCrAl alloys during tube drawing processes, and (2) to provide an update on the progress of ATF FeCrAl tube production via commercial manufacturers. Experimental efforts have been made to optimize the process parameters balancing the tube fabricability, especially for tube drawing processes, and microstructure control of the final tube products. Lab-scale sheet materials of Gen II FeCrAl alloys (Mo-containing and Nb-containing FeCrAl alloys) were used in the study, combined with a stepwise warm-rolling process and intermediate annealing, aiming to simulate the tube drawing process inmore » a commercial tube manufacturer. The intermediate annealing at 650ºC for 1h was suggested for the tube-drawing process of Mo-containing FeCrAl alloys because it successfully softened the material by recovering the work hardening introduced through the rolling step, without inducing grain coarsening due to recrystallization. The final tube product is expected to have stabilized deformed microstructure providing the improved tensile properties with sufficient ductility. Optimization efforts on Nb-containing FeCrAl alloys focused on the effect of alloying additions and annealing conditions on the stability of deformed microstructure. Relationships between the second-phase precipitates (Fe 2Nb-Laves phase) and microstructure stability are discussed. FeCrAl tube production through commercial tube manufacturers is currently in progress. Three different manufacturers, Century Tubes, Inc. (CTI), Rhenium Alloys, Inc. (RAI), and Superior Tube Company, Inc. (STC), are providing capabilities for cold-drawing, warm-drawing, and HPTR cold-pilgering, respectively. The first two companies are currently working on large quantity tube production (expected 250 ft length) of Gen I model FeCrAl alloy (B136Y3, at CTI) and Gen II (C35M4, at RAI), with the process parameters obtained from the experimental

  6. Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae: Heterocotylinae) from the gills of a captive onefin electric ray, Narke capensis (Narkidae) at Two Oceans Aquarium, Cape Town, South Africa.

    PubMed

    Vaughan, David B; Chisholm, Leslie A; Hansen, Haakon

    2016-09-01

    Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae) is described from the gills of a captive female onefin electric ray, Narke capensis, collected for exhibition at Two Oceans Aquarium in Cape Town, South Africa. Electrocotyle n. gen. is most similar to the heterocotyline genera Heterocotyle and Potamotrygonocotyle but could not be accommodated easily in either of these groups. The new genus is characterised by a haptor with one central and eight peripheral loculi, four unsclerotised structures on the dorsal surface of the haptor, a single unsclerotised non-sinous ridge on the ventral surface of the haptoral septa, large hamuli with a long handle and reduced guard, a vagina with sclerotised walls, and tetrahedral eggs. Molecular phylogenetic analyses based on 28S sequences strongly support the separate genus status of Electrocotyle n. gen and thus support our morphological conclusion. The Heterocotylinae is amended to accommodate the new genus, and the new species is fully described and illustrated herein. This is the first record of a monocotylid from the Narkidae. Electrocotyle whittingtoni n. gen. n. sp. is considered potentially pathogenic given its negative impact on the health of its captive host kept in the quarantine facility at Two Oceans Aquarium.

  7. New Australian stiletto flies: revision of Manestella Metz and description of Medomega gen. n. (Diptera, Therevidae, Agapophytinae)

    PubMed Central

    Winterton, Shaun L.; Lambkin, Christine L.

    2012-01-01

    Abstract The previously monotypic genus Manestella Metz, 2003 is revised with a single species, Manestella tristriata (Mann, 1933), redescribed and an additional 14 new species described: Manestella caesia sp. n., Manestella campestris sp. n., Manestella canities sp. n., Manestella cooloola sp. n., Manestella fumosa sp. n., Manestella incompleta sp. n., Manestella nubis sp. n., Manestella obscura sp. n., Manestella ocellaris sp. n., Manestella persona sp. n., Manestella poecilothorax sp. n., Manestella umbrapennis sp. n., Manestella vasta sp. n. and Manestella vespera sp. n. The putative sister genus to Manestella, Medomega gen. n., is described containing six new species: Medomega averyi sp. n., Medomega bailmeup sp. n., Medomega chlamydos sp. n., Medomega danielsi sp. n., Medomega gigasathe sp. n., and Medomega nebrias sp. n. Complete taxonomic descriptions were generated from a character matrix developed in Lucid Builder from which natural language descriptions (NLD) were parsed. Images of all species of Manestella and Medomega gen. n. are included, along with dichotomous keys to species. PMID:23226714

  8. A Network Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Ge-Gen-Qin-Lian Decoction for Treatment of Type 2 Diabetes

    PubMed Central

    Li, Huiying; Zhao, Linhua; Zhang, Bo; Jiang, Yuyu; Wang, Xu; Guo, Yun; Liu, Hongxing; Li, Shao; Tong, Xiaolin

    2014-01-01

    Traditional Chinese medicine (TCM) herbal formulae can be valuable therapeutic strategies and drug discovery resources. However, the active ingredients and action mechanisms of most TCM formulae remain unclear. Therefore, the identification of potent ingredients and their actions is a major challenge in TCM research. In this study, we used a network pharmacology approach we previously developed to help determine the potential antidiabetic ingredients from the traditional Ge-Gen-Qin-Lian decoction (GGQLD) formula. We predicted the target profiles of all available GGQLD ingredients to infer the active ingredients by clustering the target profile of ingredients with FDA-approved antidiabetic drugs. We also applied network target analysis to evaluate the links between herbal ingredients and pharmacological actions to help explain the action mechanisms of GGQLD. According to the predicted results, we confirmed that a novel antidiabetic ingredient from Puerariae Lobatae radix (Ge-Gen), 4-Hydroxymephenytoin, increased the insulin secretion in RIN-5F cells and improved insulin resistance in 3T3-L1 adipocytes. The network pharmacology strategy used here provided a powerful means for identifying bioactive ingredients and mechanisms of action for TCM herbal formulae, including Ge-Gen-Qin-Lian decoction. PMID:24527048

  9. Mode-locked laser with pulse interleavers in a monolithic photonic integrated circuit for millimeter wave and terahertz carrier generation.

    PubMed

    Lo, Mu-Chieh; Guzmán, Robinson; Gordón, Carlos; Carpintero, Guillermo

    2017-04-15

    This Letter presents a photonics-based millimeter wave and terahertz frequency synthesizer using a monolithic InP photonic integrated circuit composed of a mode-locked laser (MLL) and two pulse interleaver stages to multiply the repetition rate frequency. The MLL is a multiple colliding pulse MLL producing an 80 GHz repetition rate pulse train. Through two consecutive monolithic pulse interleaver structures, each doubling the repetition rate, we demonstrate the achievement of 160 and 320 GHz. The fabrication was done on a multi-project wafer run of a generic InP photonic technology platform.

  10. A review of Chinese tribe Achilini (Hemiptera: Fulgoromorpha: Achilidae), with descriptions of Paracatonidia webbeda gen. & sp. nov.

    PubMed

    Long, Jian-Kun; Yang, Lin; Chen, Xiang-Sheng

    2015-12-02

    Planthoppers of the tribe Achilini (Hemiptera: Fulgoromorpha: Achilidae) from China, are reviewed. A key to the three genera of Chinese Achilini is given. A new genus and species of the tribe from southwestern China: Paracatonidia webbeda gen. & sp. nov., is described. A new genus and species record for China, Cixidia kasparyani Anufriev, is also given.

  11. Gen Green: Changes in Australian Apprentices' and Trainees' Experience of Skills and Sustainability from 2008 to 2011

    ERIC Educational Resources Information Center

    Sack, Fabian

    2012-01-01

    The Gen Green research in 2008 and 2011 indicates that skills for sustainability public policy and business initiatives are having an impact, but that young skilled Australians' high level of interest in sustainability skills is confounded by a lack of guidance and incentives from employers, the market and educators. The research indicates that,…

  12. Acerca del moho

    EPA Pesticide Factsheets

    El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

  13. Eonandeva gen. nov., a new distinctive genus from Eocene Baltic amber (Diptera: Chironomidae).

    PubMed

    Zakrzewska, Marta; Giłka, Wojciech

    2015-11-20

    A new fossil genus, Eonandeva gen. nov., with two new species: E. helva sp. nov. (type for the genus) and E. latistyla sp. nov., is described from Eocene Baltic amber (~45-40 Ma). Adult males of both new species show the wing venation pattern, shape and chaetotaxy typical for the tribe Tanytarsini. The characters defined as prior apomorphies for the new genus--the gonostylus with a subapical flattened lobe and the stout, strongly elongated superior volsella--separate Eonandeva from the closely related extant genus Nandeva Wiedenbrug, Reiss et Fittkau, 1998.

  14. An update on VitisGen: recent advances in using DNA marker technologies in U.S. grape breeding programs

    USDA-ARS?s Scientific Manuscript database

    The USDA-NIFA VitisGen project involves a multidisciplinary team of 25 co-PIs at 11 institutions aiming to optimize grape cultivar improvement. To this end, an impressive collection of phenotypic data and high-resolution genetic maps has been developed for seventeen F1 families. Here, we will prese...

  15. OmniGen-AF supplementation modulated the physiological and acute phase responses of Brahman heifers to an endotoxin challenge

    USDA-ARS?s Scientific Manuscript database

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the physiological and acute phase responses (APR) of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183±5 kilograms) from the Texas AgriLife Research Center in Overton...

  16. Commissioning and Performance Analysis of WhisperGen Stirling Engine

    NASA Astrophysics Data System (ADS)

    Pradip, Prashant Kaliram

    Stirling engine based cogeneration systems have potential to reduce energy consumption and greenhouse gas emission, due to their high cogeneration efficiency and emission control due to steady external combustion. To date, most studies on this unit have focused on performance based on both experimentation and computer models, and lack experimental data for diversified operating ranges. This thesis starts with the commissioning of a WhisperGen Stirling engine with components and instrumentation to evaluate power and thermal performance of the system. Next, a parametric study on primary engine variables, including air, diesel, and coolant flowrate and temperature were carried out to further understand their effect on engine power and efficiency. Then, this trend was validated with the thermodynamic model developed for the energy analysis of a Stirling cycle. Finally, the energy balance of the Stirling engine was compared without and with heat recovery from the engine block and the combustion chamber exhaust.

  17. Produccion Gaseosa del Cometa Halley: Erupciones Y Fotodisociacion del Radical OH

    NASA Astrophysics Data System (ADS)

    Silva, A. M.; Mirabel, I. F.

    1990-11-01

    RESUMEN:En este trabajo informamos la detecci6n de 20 erupciones en la li'nea de =18cm (1667MHz) del radical OH en el Cometa Halley.Las observaciones incluyen todos los monitoreos existentes y se extienden desde 120 dias antes del perihelio hasta 90 dias despues.Se detectan bruscos crecimientos en el flujo medido,hasta un factor 1O,seguidos por decaimientos lentos asociados con la fotodisociaci6n del OH. Se obtuvieron valores para el tiempo de vida fotoquimico del OH y del H2O basandose en el modelo desarrollado previamente por Silva(1988). Esos tiempos de vida estan de acuerdo con predicciones teoricas y con las observaciones en el Ultravioleta, y los resultados, los que son fuertemente dependientes de la velocidad heliocentrica del Coineta (variando hasta un factor 6), han sido calculados para varios rangos de velocidad entre +28 y -28 km/seg. Key wo'L :

  18. Gen-2 RFID compatible, zero down-time, programmable mechanical strain-monitors and mechanical impact detectors

    NASA Astrophysics Data System (ADS)

    Chakrabartty, Shantanu; Feng, Tao; Aono, Kenji

    2013-04-01

    A key challenge in structural health monitoring (SHM) sensors embedded inside civil structures is that elec- tronics need to operate continuously such that mechanical events of interest can be detected and appropriately analyzed. Continuous operation however requires a continuous source of energy which cannot be guaranteed using conventional energy scavenging techniques. The paper describes a hybrid energy scavenging SHM sensor which experiences zero down-time in monitoring mechanical events of interest. At the core of the proposed sensor is an analog floating-gate storage technology that can be precisely programmed at nano-watt and pico- watt power levels. This facilitates self-powered, non-volatile data logging of the mechanical events of interest by scavenging energy directly from the mechanical events itself. Remote retrieval of the stored data is achieved using a commercial off-the-shelf Gen-2 radio-frequency identification (RFID) reader which periodically reads an electronic product code (EPC) that encapsulates the sensor data. The Gen-2 interface also facilitates in simultaneous remote access to multiple sensors and also facilitates in determining the range and orientation of the sensor. The architecture of the sensor is based on a token-ring topology which enables sensor channels to be dynamically added or deleted through software control.

  19. Yamaguchia toyensis n. sp., n. gen. (Annelida, Clitellata, Lumbriculidae) from profundal lake habitat in Japan

    USGS Publications Warehouse

    Fend, S.V.; Ohtaka, A.

    2004-01-01

    Yamaguchia toyensis n. sp., n. gen. is described from an oligotrophic caldera lake, Lake Toya, Hokkaido, Japan. Although the taxonomic affinities are unknown, the genus differs from all other Lumbriculidae in having the combination of testes and atria in X, a single, prosoporous male funnel per atrium, and spermathecae in XI. Unlike other Japanese lakes that have thus far been surveyed, Lake Toya supports abundant populations of lumbriculids in the profundal benthos.

  20. GenSeq: An updated nomenclature and ranking for genetic sequences from type and non-type sources

    PubMed Central

    Chakrabarty, Prosanta; Warren, Melanie; Page, Lawrence M.; Baldwin, Carole C.

    2013-01-01

    Abstract An improved and expanded nomenclature for genetic sequences is introduced that corresponds with a ranking of the reliability of the taxonomic identification of the source specimens. This nomenclature is an advancement of the “Genetypes” naming system, which some have been reluctant to adopt because of the use of the “type” suffix in the terminology. In the new nomenclature, genetic sequences are labeled “genseq,” followed by a reliability ranking (e.g., 1 if the sequence is from a primary type), followed by the name of the genes from which the sequences were derived (e.g., genseq-1 16S, COI). The numbered suffix provides an indication of the likely reliability of taxonomic identification of the voucher. Included in this ranking system, in descending order of taxonomic reliability, are the following: sequences from primary types – “genseq-1,” secondary types – “genseq-2,” collection-vouchered topotypes – “genseq-3,” collection-vouchered non-types – “genseq-4,” and non-types that lack specimen vouchers but have photo vouchers – “genseq-5.” To demonstrate use of the new nomenclature, we review recently published new-species descriptions in the ichthyological literature that include DNA data and apply the GenSeq nomenclature to sequences referenced in those publications. We encourage authors to adopt the GenSeq nomenclature (note capital “G” and “S” when referring to the nomenclatural program) to provide a searchable tag (e.g., “genseq”; note lowercase “g” and “s” when referring to sequences) for genetic sequences from types and other vouchered specimens. Use of the new nomenclature and ranking system will improve integration of molecular phylogenetics and biological taxonomy and enhance the ability of researchers to assess the reliability of sequence data. We further encourage authors to update sequence information on databases such as GenBank whenever nomenclatural changes are made. PMID:24223486

  1. Investigation of taxa of the family Pasteurellaceae isolated from Syrian and European hamsters and proposal of Mesocricetibacter intestinalis gen. nov., sp. nov. and Cricetibacter osteomyelitidis gen. nov., sp. nov.

    PubMed

    Christensen, H; Nicklas, W; Bisgaard, M

    2014-11-01

    Eleven strains from hamster of Bisgaard taxa 23 and 24, also referred to as Krause's groups 2 and 1, respectively, were investigated by a polyphasic approach including data published previously. Strains showed small, regular and circular colonies with smooth and shiny appearance, typical of members of the family Pasteurellaceae. The strains formed two monophyletic groups based on 16S rRNA gene sequence comparison to other members of the family Pasteurellaceae. Partial rpoB sequencing as well as published data on DNA-DNA hybridization showed high genotypic relationships within both groups. Menaquinone 7 (MK7) was found in strains of both groups as well as an unknown ubiquinone with shorter chain length than previously reported for any other member of the family Pasteurellaceae. A new genus with one species, Mesocricetibacter intestinalis gen. nov., sp. nov., is proposed to accommodate members of taxon 24 of Bisgaard whereas members of taxon 23 of Bisgaard are proposed to represent Cricetibacter osteomyelitidis gen. nov., sp. nov. Major fatty acids of type strains of type species of both genera are C(14:0), C(14:0) 3-OH/iso-C(16:1) I, C(16:1)ω7c and C(16:0). The two genera are clearly separated by phenotype from each other and from existing genera of the family Pasteurellaceae. The type strain of Mesocricetibacter intestinalis is HIM 933/7(T) ( =Kunstyr 246/85(T) =CCUG 28030(T) =DSM 28403(T)) while the type strain of Cricetibacter osteomyelitidis is HIM943/7(T) ( =Kunstyr 507/85(T) =CCUG 36451(T) =DSM 28404(T)). © 2014 IUMS.

  2. Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA.

    PubMed

    Tamori, Akihiro; Yamanishi, Yoshihiro; Kawashima, Shuichi; Kanehisa, Minoru; Enomoto, Masaru; Tanaka, Hiromu; Kubo, Shoji; Shiomi, Susumu; Nishiguchi, Shuhei

    2005-08-15

    Integration of hepatitis B virus (HBV) DNA into the human genome is one of the most important steps in HBV-related carcinogenesis. This study attempted to find the link between HBV DNA, the adjoining cellular sequence, and altered gene expression in hepatocellular carcinoma (HCC) with integrated HBV DNA. We examined 15 cases of HCC infected with HBV by cassette ligation-mediated PCR. The human DNA adjacent to the integrated HBV DNA was sequenced. Protein coding sequences were searched for in the human sequence. In five cases with HBV DNA integration, from which good quality RNA was extracted, gene expression was examined by cDNA microarray analysis. The human DNA sequence successive to integrated HBV DNA was determined in the 15 HCCs. Eight protein-coding regions were involved: ras-responsive element binding protein 1, calmodulin 1, mixed lineage leukemia 2 (MLL2), FLJ333655, LOC220272, LOC255345, LOC220220, and LOC168991. The MLL2 gene was expressed in three cases with HBV DNA integrated into exon 3 of MLL2 and in one case with HBV DNA integrated into intron 3 of MLL2. Gene expression analysis suggested that two HCCs with HBV integrated into MLL2 had similar patterns of gene expression compared with three HCCs with HBV integrated into other loci of human chromosomes. HBV DNA was integrated at random sites of human DNA, and the MLL2 gene was one of the targets for integration. Our results suggest that HBV DNA might modulate human genes near integration sites, followed by integration site-specific expression of such genes during hepatocarcinogenesis.

  3. Mexiare gen. nov., a new Doryctinae genus (Hymenoptera: Braconidae) from Mexico with fused first and second metasomal tergites.

    PubMed

    Belokobylskij, Sergey A; Samaca-Sáenz, Ernesto; Zaldívar-Riverón, Alejandro

    2015-01-27

    A new braconid genus from the subfamily Doryctinae, Mexiare gen. nov. (type species M. toledoi sp. nov.) is described from the state of Morelos in Central Mexico. The described species of this genus is characterised by having immovably fused first and second metasomal tergites, a feature also present in species of two Oriental (Arhaconotus Belokobylskij and Mimipodoryctes Belokobylskij) and one Neotropical (Iare Barbalho et Penteado-Dias) genera. The new genus, however, can be distinguished from the Neotropical Iare by the presence of a semi-oval basal area on the second metasomal tergite, distinctly short submedial (subbasal) cell of hind wing, more than three hamuli, considerably short second radiomedial (submarginal) cell, narrow radial (marginal) cell of fore wing and mostly smooth mesoscutum. A phylogenetic analysis among doryctine genera based on two gene markers (28S and COI) placed Mexiare gen. nov. within a previously recovered major South American clade, though its relationships with other taxa remain unclear. 

  4. Hungatella effluvii gen. nov., sp. nov., an obligately anaerobic bacterium isolated from an effluent treatment plant, and reclassification of Clostridium hathewayi as Hungatella hathewayi gen. nov., comb. nov.

    PubMed

    Kaur, Sukhpreet; Yawar, Mir; Kumar, P Anil; Suresh, K

    2014-03-01

    A Gram-stain-positive, rod-shaped, spore-forming and strictly anaerobic bacterium, designated UB-B.2(T), was isolated from an industrial effluent anaerobic digester sample. It grew optimally at 30 °C and pH 7.0. Comparative analysis of the 16S rRNA gene sequence confirmed that strain UB-B.2(T) was closely related to Clostridium hathewayi DSM 13479(T) (97.84% similarity), a member of rRNA gene cluster XIVa of the genus Clostridium, and formed a coherent cluster with other related members of the Blautia (Clostridium) coccoides rRNA group in phylogenetic analyses. The end products of glucose fermentation by strain UB-B.2(T) were acetate and propionate. The G+C content of the DNA was 51.4 mol%. Although strain UB-B.2(T) showed 97.8% 16S rRNA gene sequence identity to the type strain of C. hathewayi, it exhibited only 38.4% relatedness at the whole-genome level. It also showed differences from its closest phylogenetic relative, C. hathewayi DSM 13479(T), in phenotypic characteristics such as hydrolysis of aesculin, starch and urea and fermentation end products. Both strains showed phenotypic differences from the members of rRNA gene cluster XIVa of the genus Clostridium. Based on these differences, C. hathewayi DSM 13479(T) and strain UB-B.2(T) were identified as representatives of a new genus of the family Clostridiaceae. Thus, we propose the reclassification of Clostridium hathewayi as Hungatella hathewayi gen. nov., comb. nov., the type species of the new genus (type strain DSM 13479(T) = CCUG 43506(T) = MTCC 10951(T)). Strain UB-B.2(T) ( = MTCC 11101(T) = DSM 24995(T)) is assigned to the novel species Hungatella effluvii gen. nov., sp. nov as the type strain.

  5. Seeking consent to genetic and genomic research in a rural Ghanaian setting: A qualitative study of the MalariaGEN experience

    PubMed Central

    2012-01-01

    Background Seeking consent for genetic and genomic research can be challenging, particularly in populations with low literacy levels, and in emergency situations. All of these factors were relevant to the MalariaGEN study of genetic factors influencing immune responses to malaria in northern rural Ghana. This study sought to identify issues arising in practice during the enrolment of paediatric cases with severe malaria and matched healthy controls into the MalariaGEN study. Methods The study used a rapid assessment incorporating multiple qualitative methods including in depth interviews, focus group discussions and observations of consent processes. Differences between verbal information provided during community engagement processes, and consent processes during the enrolment of cases and controls were identified, as well as the factors influencing the tailoring of such information. Results MalariaGEN participants and field staff seeking consent were generally satisfied with their understanding of the project and were familiar with aspects of the study relating to malaria. Some genetic aspects of the study were also well understood. Participants and staff seeking consent were less aware of the methodologies employed during genomic research and their implications, such as the breadth of data generated and the potential for future secondary research. Moreover, trust in and previous experience with the Navrongo Health Research Centre which was conducting the research influenced beliefs about the benefits of participating in the MalariaGEN study and subsequent decision-making about research participation. Conclusions It is important to recognise that some aspects of complex genomic research may be of less interest to and less well understood by research participants and that such gaps in understanding may not be entirely addressed by best practice in the design and conduct of consent processes. In such circumstances consideration needs to be given to additional

  6. Vigilando la Calidad del Agua de los Grandes Rios de la Nacion: El Programa NASQAN del Rio Grande (Rio Bravo del Norte)

    USGS Publications Warehouse

    Lurry, Dee L.; Reutter, David C.; Wells, Frank C.; Rivera, M.C.; Munoz, A.

    1998-01-01

    La Oficina del Estudio Geologico de los Estados Unidos (U.S. Geological Survey, 0 USGS) ha monitoreado la calidad del agua de la cuenca del Rio Grande (Rio Bravo del Norte) desde 1995 como parte de la rediseiiada Red Nacional para Contabilizar la Calidad del Agua de los Rios (National Stream Quality Accounting Network, o NASOAN) (Hooper and others, 1997). EI programa NASOAN fue diseiiado para caracterizar las concentraciones y el transporte de sedimento y constituyentes quimicos seleccionados, encontrados en los grandes rios de los Estados Unidos - incluyendo el Misisipi, el Colorado y el Columbia, ademas del Rio Grande. En estas cuatro cuencas, el USGS opera actualmente (1998) una red de 40 puntos de muestreo pertenecientes a NASOAN, con un enfasis en cuantificar el flujo en masa (la cantidad de material que pasa por la estacion, expresado en toneladas por dial para cada constituyente. Aplicacando un enfoque consistente, basado en la cuantificacion de flujos en la cuenca del Rio Grande, el programa NASOAN esta generando la informacion necesaria para identificar fuentes regionales de diversos contaminantes, incluyendo sustancias qui micas agricolas y trazas elementos en la cuenca. EI efecto de las grandes reservas en el Rio Grande se puede observar segun los flujos de constituyentes discurren a 10 largo del rio. EI analisis de los flujos de constituyentes a escala de la cuenca proveera los medios para evaluar la influencia de la actividad humana sobre las condiciones de calidad del agua del Rio Grande.

  7. Microplastic in beach sediments of the Isle of Rügen (Baltic Sea) - Implementing a novel glass elutriation column.

    PubMed

    Hengstmann, Elena; Tamminga, Matthias; Vom Bruch, Constantin; Fischer, Elke Kerstin

    2018-01-01

    To extent the understanding on microplastics in the marine environment we performed a case study at four beaches on the Isle of Rügen considering abundance and spatial distribution of microplastics in beach sediments. For the analysis, density separation via a glass elutriation column was implemented. In advance, efficiencies were tested for two polymers, being not buoyant in water. Recovery rates of 80% for PET and 72% for PVC particles in sandy samples were achieved. A median abundance of 88.10 (Q 1 =55.01/Q 3 =114.72) microplastic particles per kg dry sediment or 2862.56 (Q 1 =1787.34/Q 3 =3727.28) particles per m 2 was found at the beaches on Rügen. Fibers were more abundant than fragments at all beaches. In this study, no statistically significant differences but only tendencies were determined between the beaches with different exposition and anthropogenic activity as well as for distribution patterns which showed that microplastic fragments accumulate in topographic depressions, similar to macrolitter items. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  9. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-04-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  10. Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-11-06

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  11. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2018-06-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  12. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-25

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  13. Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer

    ClinicalTrials.gov

    2013-01-08

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Relapsing Chronic Myelogenous Leukemia; Thrombocytopenia; Untreated Adult Acute Myeloid Leukemia

  14. Surfactant-enhanced anaerobic acidogenesis of Canna indica L. by rumen cultures.

    PubMed

    Yue, Zheng-Bo; Yu, Han-Qing; Hu, Zhen-Hu; Harada, Hideki; Li, Yu-You

    2008-06-01

    Polyoxyethylene sorbitan monoolate (Tween 80) was used to enhance the anaerobic acidogenesis of Canna indica L. (canna) by rumen culture in this study. Dose of Tween 80 at 1 ml/l enhanced the volatile fatty acids (VFA) production from the acidogenesis of canna compared to the control. However, Tween 80 at higher dosages than 5 ml/l inhibited the rumen microbial activity and reduced the VFA yield. Response surface methodology was successfully used to optimize the VFA yield. A maximum of VFA yield of 0.147 g/g total solids (TS) added was obtained at canna and Tween 80 concentrations of 6.3g TS/l and 2.0 ml/l, respectively. Dosage of Tween 80 at 1-3.75 ml/l reduced the unproductive adsorption of microbes or enzymes on the lignin part in canna and increased microbial activity. A high VFA production was achieved from canna presoaked with Tween 80, suggesting that the structure of canna was disrupted by Tween 80.

  15. Evaluation of the Hologic gen-probe PANTHER, APTIMA Combo 2 assay in a tertiary care teaching hospital.

    PubMed

    Cheng, Annie; Kirby, James E

    2014-03-01

    To evaluate the performance of the Hologic Gen-Probe (San Diego, CA) PANTHER system. The performance of PANTHER was compared with the Hologic Gen-Probe TIGRIS and/or Roche (Indianapolis, IN) COBAS AMPLICOR systems through testing of patient specimens and the spiked-urine matrix. After discrepant resolution, PANTHER demonstrated a 99.3% (95% confidence interval [CI], 96.0%-99.9%) positive and 100% (98.5%-100.0%) negative agreement for Chlamydia trachomatis (CT) and 100% (96.6%-100.0%) positive and 100% (98.6%-100.0%) negative agreement for Neisseria gonorrhoeae (NG) for all male, female, unsexed, and NG-spiked female urine specimens combined. For other specimen types collectively, the PANTHER demonstrated 100% (95% CI, 90.6%-100.0%) positive and 100% (88.3%-100.0%) negative agreement for CT and 90.9% (62.8%-98.4%) positive and 100% (93.5%-100.0%) negative agreement for NG. Analytical sensitivity of the PANTHER in urine matrix was similar to the TIGRIS system. The PANTHER system provides an excellent new addition to options for detecting CT and NG, is appropriate for testing urine samples, and will facilitate high-throughput testing in the clinical laboratory.

  16. Decontamination of a municipal landfill leachate from endocrine disruptors using a combined sorption/bioremoval approach.

    PubMed

    Loffredo, Elisabetta; Castellana, Giancarlo; Senesi, Nicola

    2014-02-01

    Sorption and biodegradation are the main mechanisms for the removal of endocrine disruptor compounds (EDs) from both solid and liquid matrices. There are recent evidences about the capacity of white-rot fungi to decontaminate water systems from phenolic EDs by means of their ligninolytic enzymes. Most of the available studies report the removal of EDs by biodegradation or adsorption separately. This study assessed the simultaneous removal of five EDs—the xenoestrogens bisphenol A (BPA), ethynilestradiol (EE2), and 4-n-nonylphenol (NP), and the herbicide linuron and the insecticide dimethoate—from a municipal landfill leachate (MLL) using a combined sorption/bioremoval approach. The adsorption matrices used were potato dextrose agar alone or added with each of the following adsorbent materials: ground almond shells, a coffee compost, a coconut fiber, and a river sediment. These matrices were either not inoculated or inoculated with the fungus Pleurotus ostreatus and superimposed on the MLL. The residual amount of each ED in the MLL was quantified after 4, 7, 12, and 20 days by HPLC analysis and UV detection. Preliminary experiments showed that (1) all EDs did not degrade significantly in the untreatedMLL for at least 28 days, (2) the mycelial growth of P. ostreatus was largely stimulated by components of the MLL, and (3) the enrichment of potato dextrose agar with any adsorbent material favored the fungal growth for 8 days after inoculation. A prompt relevant disappearance of EDs in the MLL occurred both without and, especially, with fungal activity, with the only exception of the very water soluble dimethoate that was poorly adsorbed and possibly degraded only during the first few days of experiments. An almost complete removal of phenolic EDs, especially EE2 and NP, occurred after 20 days or much earlier and was generally enhanced by the adsorbent materials used. Data obtained indicated that both adsorption and biodegradation mechanisms contribute

  17. Morel-Lavallee lesion.

    PubMed

    Li, Hui; Zhang, Fangjie; Lei, Guanghua

    2014-01-01

    To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity. Familiarization may decrease missed diagnoses and misdiagnoses. It could also help steer the clinician to the proper treatment choice. A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords: Morel-Lavallee lesion, closed degloving injury, concealed degloving injury, Morel-Lavallee effusion, Morel-Lavallee hematoma, posttraumatic pseudocyst, posttraumatic soft tissue cyst. Chinese and English language literatures relevant to the subject were collected. Their references were also reviewed. Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury. It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. Apart from the classic location over the region of the greater trochanter, MLLs have been described in other parts of the body. The natural history of MLL has not yet been established. The lesion may decrease in volume, remain stable, enlarge progressively or show a recurrent pattern. Diagnosis of MLL was often missed or delayed. Ultrasonography, computed tomography, and magnetic resonance imaging have great value in the diagnosis of MLL. Treatment of MLL has included compression, local aspiration, open debridement, and sclerodesis. No standard treatment has been established. A diagnosis of MLL should be suspected when a soft, fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury. Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis. Treatment decisions should base on association with fractures, the condition of the lesion, symptom and desire of the patient.

  18. Gen IV Materials Handbook Functionalities and Operation (4A) Handbook Version 4.0

    SciTech Connect

    Ren, Weiju

    2013-09-01

    This document is prepared for navigation and operation of the Gen IV Materials Handbook, with architecture description and new user access initiation instructions. Development rationale and history of the Handbook is summarized. The major development aspects, architecture, and design principles of the Handbook are briefly introduced to provide an overview of its past evolution and future prospects. Detailed instructions are given with examples for navigating the constructed Handbook components and using the main functionalities. Procedures are provided in a step-by-step fashion for Data Upload Managers to upload reports and data files, as well as for new users to initiate Handbookmore » access.« less

  19. 77 FR 13592 - AER NY-Gen, LLC; Eagle Creek Hydro Power, LLC, Eagle Creek Water Resources, LLC, Eagle Creek Land...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ...; Eagle Creek Hydro Power, LLC, Eagle Creek Water Resources, LLC, Eagle Creek Land Resources, LLC; Notice... 24, 2012, AER NY-Gen, LLC (transferor), Eagle Creek Hydro Power, LLC, Eagle Creek Water Resources.... Cherry, Eagle Creek Hydro Power, LLC, Eagle Creek Water Resources, LLC, and Eagle Creek Land Resources...

  20. ABCB1-Gen-Polymorphismus in einer polnischen Kohorte ist mit Risiko für bullöses Pemphigoid assoziiert.

    PubMed

    Rychlik-Sych, Mariola; Barańska, Małgorzata; Dudarewicz, Michał; Skrętkowicz, Jadwiga; Żebrowska, Agnieszka; Owczarek, Jacek; Waszczykowska, Elżbieta

    2017-05-01

    Polymorphismen im ABCB1-Gen, das für das P-Glykoprotein kodiert, können die intrazelluläre Konzentration von Xenobiotika beeinflussen und so zur Entwicklung von Autoimmunerkrankungen, einschließlich des bullösen Pemphigoids (BP), beitragen. In der vorliegenden Studie sollte untersucht werden, ob in einer polnischen Kohorte die C3435T- und G2677T/A-Polymorphismen im ABCB1-Gen mit dem Risiko für ein BP assoziiert sind. Die Studie umfasste 71 Patienten mit BP und 156 gesunde Probanden. Der C3435T-Polymorphismus wurde mittels PCR-RFLP bestimmt und der G2677T/A-Polymorphismus mittels Allel-spezifischer PCR. Es gab zwar keine Korrelation zwischen dem C3435-Polymorphismus und dem BP-Risiko, aber wir konnten eine derartige Assoziation hinsichtlich des G2677T/A-Polymorphismus nachweisen. Das relative Risiko eines BP war bei Personen mit dem 2677TA-Genotyp um mehr als den Faktor fünf erhöht (OR = 5,52; p = 0,0063) und bei Trägern des 2677TT-Genotyps mehr als verdoppelt (OR = 2,40; p = 0,0076). Mit 2,40 (p = 0,000018) war die OR bei Trägern des 2677T-Allels ebenfalls erhöht. Die höhere Prävalenz des 2677GG-Genotyps und des 2677G-Allels bei der Kontrollgruppe sowie eine OR < 1,0 (0,22 beziehungsweise 0,33) legen eine Schutzfunktion des 2677G-Allels hinsichtlich der Ausbildung eines BP nahe. Die Ergebnisse der vorliegenden Studie zeigen, dass der G2677T/A-Polymorphismus im ABCB1-Gen das Risiko für die Entstehung eines BP beeinflussen könnte. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  1. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

    PubMed Central

    Manchia, Mirko; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Aubry, Jean-Michel; Backlund, Lena; Banzato, Claudio EM.; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Biernacka, Joanna M.; Brichant-Petitjean, Clara; Bui, Elise; Calkin, Cynthia V.; Cheng, Andrew Tai Ann; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Czerski, Piotr M.; Dantas, Clarissa; Zompo, Maria Del; DePaulo, J. Raymond; Detera-Wadleigh, Sevilla D.; Etain, Bruno; Falkai, Peter; Frisén, Louise; Frye, Mark A.; Fullerton, Jan; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs; Hoban, Rebecca; Hou, Liping; Jamain, Stéphane; Kahn, Jean-Pierre; Kassem, Layla; Kato, Tadafumi; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kuo, Po-Hsiu; Kusumi, Ichiro; Laje, Gonzalo; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; López Jaramillo, Carlos A.; Maj, Mario; Malafosse, Alain; Martinsson, Lina; Masui, Takuya; Mitchell, Philip B.; Mondimore, Frank; Monteleone, Palmiero; Nallet, Audrey; Neuner, Maria; Novák, Tomás; O’Donovan, Claire; Ösby, Urban; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Potash, James B.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Richardson, Sara; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Schofield, Peter R.; Schubert, Oliver K.; Schweizer, Barbara; Seemüller, Florian; Grigoroiu-Serbanescu, Maria; Severino, Giovanni; Seymour, Lisa R.; Slaney, Claire; Smoller, Jordan W.; Squassina, Alessio; Stamm, Thomas; Steele, Jo; Stopkova, Pavla; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Wray, Naomi R.; Wright, Adam; Zandi, Peter P.; Zilles, David; Bauer, Michael; Rietschel, Marcella; McMahon, Francis J.

    2013-01-01

    Objective The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. PMID:23840348

  2. Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.

    PubMed

    Giusiano, S; Formisano-Tréziny, C; Benziane, A; Maroc, N; Picard, C; Hermitte, F; Taranger-Charpin, C; Gabert, J

    2010-08-01

    Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets. Today, the challenge is to propose an individual follow-up for each patient even for those with a rare fusion event. In this study, we propose a biochip-based assay integrated in a global strategy for identification of rare FT in AML, after fluorescence in situ hybridization detection, as described by the World Health Organization classification. Using cell lines, we developed and validated a biochip-based assay called the AMLFusionChip that identifies every FT of AML1-ETO, CBFbeta-MYH11 as well as MLL-AF9, MLL-ENL, MLL-AF6, and MLL-AF10. The original design of our AMLFusionChip.v01 enables the identification of these FT wherever the breakpoint on the partner gene may be. In case of biochip negative result, our 3'RACE amplification strategy enables to clone and then sequence the new translocation partner. This AMLFusionChip strategy fits into the concept of personalized medicine for the largest number of patients.

  3. GenLocDip: A Generalized Program to Calculate and Visualize Local Electric Dipole Moments.

    PubMed

    Groß, Lynn; Herrmann, Carmen

    2016-09-30

    Local dipole moments (i.e., dipole moments of atomic or molecular subsystems) are essential for understanding various phenomena in nanoscience, such as solvent effects on the conductance of single molecules in break junctions or the interaction between the tip and the adsorbate in atomic force microscopy. We introduce GenLocDip, a program for calculating and visualizing local dipole moments of molecular subsystems. GenLocDip currently uses the Atoms-In-Molecules (AIM) partitioning scheme and is interfaced to various AIM programs. This enables postprocessing of a variety of electronic structure output formats including cube and wavefunction files, and, in general, output from any other code capable of writing the electron density on a three-dimensional grid. It uses a modified version of Bader's and Laidig's approach for achieving origin-independence of local dipoles by referring to internal reference points which can (but do not need to be) bond critical points (BCPs). Furthermore, the code allows the export of critical points and local dipole moments into a POVray readable input format. It is particularly designed for fragments of large systems, for which no BCPs have been calculated for computational efficiency reasons, because large interfragment distances prevent their identification, or because a local partitioning scheme different from AIM was used. The program requires only minimal user input and is written in the Fortran90 programming language. To demonstrate the capabilities of the program, examples are given for covalently and non-covalently bound systems, in particular molecular adsorbates. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. 75 FR 27332 - AER NY-Gen, LLC; Eagle Creek Hydro Power, LLC; Eagle Creek Water Resources, LLC; Eagle Creek Land...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... 9690-106] AER NY-Gen, LLC; Eagle Creek Hydro Power, LLC; Eagle Creek Water Resources, LLC; Eagle Creek... Power, LLC, Eagle Creek Water Resources, LLC, and Eagle Creek Land Resources, LLC (transferees) filed an.... Paul Ho, Eagle Creek Hydro Power, LLC, Eagle Creek Water Resources, LLC, and Eagle Creek Land Resources...

  5. Cyanomargarita gen. nov. (Nostocales, Cyanobacteria): convergent evolution resulting in a cryptic genus.

    PubMed

    Shalygin, Sergei; Shalygina, Regina; Johansen, Jeffrey R; Pietrasiak, Nicole; Berrendero Gómez, Esther; Bohunická, Markéta; Mareš, Jan; Sheil, Christopher A

    2017-08-01

    Two populations of Rivularia-like cyanobacteria were isolated from ecologically distinct and biogeographically distant sites. One population was from an unpolluted stream in the Kola Peninsula of Russia, whereas the other was from a wet wall in the Grand Staircase-Escalante National Monument, a desert park-land in Utah. Though both were virtually indistinguishable from Rivularia in field and cultured material, they were both phylogenetically distant from Rivularia and the Rivulariaceae based on both 16S rRNA and rbcLX phylogenies. We here name the new cryptic genus Cyanomargarita gen. nov., with type species C. melechinii sp. nov., and additional species C. calcarea sp. nov. We also name a new family for these taxa, the Cyanomargaritaceae. © 2017 Phycological Society of America.

  6. NASA System-Level Design, Analysis and Simulation Tools Research on NextGen

    NASA Technical Reports Server (NTRS)

    Bardina, Jorge

    2011-01-01

    A review of the research accomplished in 2009 in the System-Level Design, Analysis and Simulation Tools (SLDAST) of the NASA's Airspace Systems Program is presented. This research thrust focuses on the integrated system-level assessment of component level innovations, concepts and technologies of the Next Generation Air Traffic System (NextGen) under research in the ASP program to enable the development of revolutionary improvements and modernization of the National Airspace System. The review includes the accomplishments on baseline research and the advancements on design studies and system-level assessment, including the cluster analysis as an annualization standard of the air traffic in the U.S. National Airspace, and the ACES-Air MIDAS integration for human-in-the-loop analyzes within the NAS air traffic simulation.

  7. A Controller-in-the Loop Simulation of Ground-Based Automated Separation Assurance in a NextGen Environment

    NASA Technical Reports Server (NTRS)

    Homola, J.; Prevot, Thomas; Mercer, Joey S.; Brasil, Connie L.; Martin, Lynne Hazel; Cabrall, C.

    2010-01-01

    A controller-in-the-loop simulation was conducted in the Airspace Operations Laboratory (AOL) at the NASA Ames Research Center to investigate the functional allocation aspects associated with ground-based automated separation assurance in a far-term NextGen environment. In this concept, ground-based automation handled the detection and resolution of strategic and tactical conflicts and alerted the controller to deferred situations. The controller was responsible for monitoring the automation and managing situations by exception. This was done in conditions both with and without arrival time constraints across two levels of traffic density. Results showed that although workload increased with an increase in traffic density, it was still manageable in most situations. The number of conflicts increased similarly with a related increase in the issuance of resolution clearances. Although over 99% of conflicts were resolved, operational errors did occur but were tied to local sector complexities. Feedback from the participants revealed that they thought they maintained reasonable situation awareness in this environment, felt that operations were highly acceptable at the lower traffic density level but were less so as it increased, and felt overall that the concept as it was introduced here was a positive step forward to accommodating the more complex environment envisioned as part of NextGen.

  8. A pipeline of programs for collecting and analyzing group II intron retroelement sequences from GenBank

    PubMed Central

    2013-01-01

    Background Accurate and complete identification of mobile elements is a challenging task in the current era of sequencing, given their large numbers and frequent truncations. Group II intron retroelements, which consist of a ribozyme and an intron-encoded protein (IEP), are usually identified in bacterial genomes through their IEP; however, the RNA component that defines the intron boundaries is often difficult to identify because of a lack of strong sequence conservation corresponding to the RNA structure. Compounding the problem of boundary definition is the fact that a majority of group II intron copies in bacteria are truncated. Results Here we present a pipeline of 11 programs that collect and analyze group II intron sequences from GenBank. The pipeline begins with a BLAST search of GenBank using a set of representative group II IEPs as queries. Subsequent steps download the corresponding genomic sequences and flanks, filter out non-group II introns, assign introns to phylogenetic subclasses, filter out incomplete and/or non-functional introns, and assign IEP sequences and RNA boundaries to the full-length introns. In the final step, the redundancy in the data set is reduced by grouping introns into sets of ≥95% identity, with one example sequence chosen to be the representative. Conclusions These programs should be useful for comprehensive identification of group II introns in sequence databases as data continue to rapidly accumulate. PMID:24359548

  9. Radio-Observaciones del OH EN la Coma del Cometa Halley Desde EL Hemisferio Sur

    NASA Astrophysics Data System (ADS)

    Silva, A. M.; Bajaja, E.; Morras, R.; Cersosimo, J. C.; Martin, M. C.; Arnal, E. M.; Poppel, W. G. L.; Colomb, F. R.; Mazzaro, J.; Olalde, J. C.; Boriakoff, V.; Mirabel, I. F.

    1987-05-01

    Se utilizó una antena de 30 metros del Instituto Argentino de Radioastronomía para observaciones diarias Cf ebrero a abril de 1986) de la transición en 1667 MHz ( λ = 18 cm) del OH en la coma del cometa Halley. De las observaciones realizadas se concluye: 1) El número promedio de moléculas de OH en la coma durante 37 días de observación fue de (8.9±3.5)x1034 moléculas, lo que implica una tasa de producción promedio de OH de 1.8x1029 moléculas seg-1 y consecuentemente una pérdida de masa promedio de 17±6 toneladas seg-1 . Este valor está de acuerdo con las mediciones realizadas por las sondas Vega y Giotto. 2) El monitoreo desde el lAR revela la existencia de variaciones bruscas en los flujos de absorción del OH. Estas variaciones son consistentes con los modelos que representan la producción gaseosa a partir de ejecciones y/o desprendimientos discretos de materia congelada del núcleo. 3) Las variaciones en la densidad de flujo son consistentes con las estimaciones de los tiem- pos de vida medios del H2O y del OH en presencia del campo de radiación solar. 4) Se encuentra una correlación entre la intensidad del flujo absorbido y anisotropías en Ia dinamica de la coma.

  10. Decay Heat Removal in GEN IV Gas-Cooled Fast Reactors

    DOE PAGES

    Cheng, Lap-Yan; Wei, Thomas Y. C.

    2009-01-01

    The safety goal of the current designs of advanced high-temperature thermal gas-cooled reactors (HTRs) is that no core meltdown would occur in a depressurization event with a combination of concurrent safety system failures. This study focused on the analysis of passive decay heat removal (DHR) in a GEN IV direct-cycle gas-cooled fast reactor (GFR) which is based on the technology developments of the HTRs. Given the different criteria and design characteristics of the GFR, an approach different from that taken for the HTRs for passive DHR would have to be explored. Different design options based on maintaining core flow weremore » evaluated by performing transient analysis of a depressurization accident using the system code RELAP5-3D. The study also reviewed the conceptual design of autonomous systems for shutdown decay heat removal and recommends that future work in this area should be focused on the potential for Brayton cycle DHRs.« less

  11. Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation.

    PubMed

    Shinsky, Stephen A; Monteith, Kelsey E; Viggiano, Susan; Cosgrove, Michael S

    2015-03-06

    Mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of histone H3 lysine 4 (H3K4) methyltransferases that are required for metazoan development. MLL1 is the best characterized human SET1 family member, which includes MLL1-4 and SETd1A/B. MLL1 assembles with WDR5, RBBP5, ASH2L, DPY-30 (WRAD) to form the MLL1 core complex, which is required for H3K4 dimethylation and transcriptional activation. Because all SET1 family proteins interact with WRAD in vivo, it is hypothesized they are regulated by similar mechanisms. However, recent evidence suggests differences among family members that may reflect unique regulatory inputs in the cell. Missing is an understanding of the intrinsic enzymatic activities of different SET1 family complexes under standard conditions. In this investigation, we reconstituted each human SET1 family core complex and compared subunit assembly and enzymatic activities. We found that in the absence of WRAD, all but one SET domain catalyzes at least weak H3K4 monomethylation. In the presence of WRAD, all SET1 family members showed stimulated monomethyltransferase activity but differed in their di- and trimethylation activities. We found that these differences are correlated with evolutionary lineage, suggesting these enzyme complexes have evolved to accomplish unique tasks within metazoan genomes. To understand the structural basis for these differences, we employed a "phylogenetic scanning mutagenesis" assay and identified a cluster of amino acid substitutions that confer a WRAD-dependent gain-of-function dimethylation activity on complexes assembled with the MLL3 or Drosophila trithorax proteins. These results form the basis for understanding how WRAD differentially regulates SET1 family complexes in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Morel-Lavallee Lesion in the Upper Extremity.

    PubMed

    Cochran, Grant K; Hanna, Kathryn H

    2017-01-01

    Background: The Morel-Lavallee lesion (MLL) is a closed internal degloving injury that results from shearing of the skin and subcutaneous tissue from the underlying fascia. Disruption of the perforating blood vessels and lymphatics results in a lesion filled with serosanguinous fluid and necrotized fat. MLLs are most commonly described in association with pelvic and lower extremity trauma, and there are limited reports of these lesions in other locations. Methods: This case report describes a 58-year-old male referred from his primary care physician with a soft tissue mass in the upper arm. Careful history discovered prior trauma with extensive bruising and MRI revealed a large encapsulated mass consistent with MLL. Results: An open debridement with excision of pseudocapsule was performed. Meticulous closure over a drain was performed and the patient healed without complication or recurrence. Intra-operative cultures were negative and pathology was consistent with MLL. Conclusion: MLL should always be considered in the setting of previous trauma regardless the location. In the chronic setting an open approach with excision of pseudocapsule can have an acceptable result.

  13. Complete pulse characterization of quantum dot mode-locked lasers suitable for optical communication up to 160 Gbit/s.

    PubMed

    Schmeckebier, H; Fiol, G; Meuer, C; Arsenijević, D; Bimberg, D

    2010-02-15

    A complete characterization of pulse shape and phase of a 1.3 microm, monolithic-two-section, quantum-dot mode-locked laser (QD-MLL) at a repetition rate of 40 GHz is presented, based on frequency resolved optical gating. We show that the pulse broadening of the QD-MLL is caused by linear chirp for all values of current and voltage investigated here. The chirp increases with the current at the gain section, whereas larger bias at the absorber section leads to less chirp and therefore to shorter pulses. Pulse broadening is observed at very high bias, likely due to the quantum confined stark effect. Passive- and hybrid-QD-MLL pulses are directly compared. Improved pulse intensity profiles are found for hybrid mode locking. Via linear chirp compensation pulse widths down to 700 fs can be achieved independent of current and bias, resulting in a significantly increased overall mode-locking range of 101 MHz. The suitability of QD-MLL chirp compensated pulse combs for optical communication up to 160 Gbit/s using optical-time-division multiplexing are demonstrated by eye diagrams and autocorrelation measurements.

  14. A rare case of severe third degree friction burns and large Morel-Lavallee lesion of the abdominal wall.

    PubMed

    Brown, Darnell J; Lu, Kuo Jung G; Chang, Kristina; Levin, Jennifer; Schulz, John T; Goverman, Jeremy

    2018-01-01

    Morel-Lavallee lesions (MLLs) are rare internal degloving injuries typically caused by blunt traumatic injuries and most commonly occur around the hips and in association with pelvic or acetabular fractures. MLL is often overlooked in the setting of poly-trauma; therefore, clinicians must maintain a high degree of suspicion and be familiar with the management of such injuries, especially in obese poly-trauma patients. We present a 30-year-old female pedestrian struck by a motor vehicle who sustained multiple long bone fractures, a mesenteric hematoma, and full-thickness abdominal skin friction burn which masked a significant underlying abdominal MLL. The internal degloving caused significant devascularization of the overlying soft tissue and skin which required surgical drainage of hematoma, abdominal wall reconstruction with tangential excision, allografting, negative pressure wound therapy, and ultimately autografting. MLL is a rare, often overlooked, internal degloving injury. Surgeons must maintain a high index of suspicion when dealing with third degree friction burns as they may mask underlying injuries such as MLL, and a delay in diagnosis can lead to increased morbidity.

  15. Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements: a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation.

    PubMed

    Kato, Motohiro; Hasegawa, Daiichiro; Koh, Katsuyoshi; Kato, Keisuke; Takita, Junko; Inagaki, Jiro; Yabe, Hiromasa; Goto, Hiroaki; Adachi, Souichi; Hayakawa, Akira; Takeshita, Yasufumi; Sawada, Akihisa; Atsuta, Yoshiko; Kato, Koji

    2015-02-01

    Allogeneic haematopoietic stem cell transplantation (HSCT) is still considered to play an important role as a consolidation therapy for high-risk infants with acute lymphoblastic leukaemia (ALL). Here, we retrospectively analysed outcomes of HSCT in infants with ALL based on nationwide registry data of the Japan Society for Haematopoietic Cell Transplantation. A total of 132 allogeneic HSCT for infant ALL with KMT2A (MLL) gene rearrangements, which were performed in first complete remission (CR1), were analysed. The 5-year overall survival rate after transplantation was 67·4 ± 4·5%). Although recent HSCT (after 2004) had a trend toward better survival, no statistical correlation was observed between outcomes and each factor, including age at diagnosis, initial leucocyte count, cytogenetics, donor types or conditioning of HSCT. Myeloablative conditioning with total body irradiation did not provide a better survival (60·7 ± 9·2%) over that with busulfan (BU; 67·8 ± 5·7%). Two of the 28 patients treated with irradiation, but none of the 90 BU-treated patients, developed a secondary malignant neoplasm. In conclusion, allogeneic HSCT using BU was a valuable option for infant ALL with KMT2A rearrangements in CR1. © 2014 John Wiley & Sons Ltd.

  16. GenCLiP 2.0: a web server for functional clustering of genes and construction of molecular networks based on free terms.

    PubMed

    Wang, Jia-Hong; Zhao, Ling-Feng; Lin, Pei; Su, Xiao-Rong; Chen, Shi-Jun; Huang, Li-Qiang; Wang, Hua-Feng; Zhang, Hai; Hu, Zhen-Fu; Yao, Kai-Tai; Huang, Zhong-Xi

    2014-09-01

    Identifying biological functions and molecular networks in a gene list and how the genes may relate to various topics is of considerable value to biomedical researchers. Here, we present a web-based text-mining server, GenCLiP 2.0, which can analyze human genes with enriched keywords and molecular interactions. Compared with other similar tools, GenCLiP 2.0 offers two unique features: (i) analysis of gene functions with free terms (i.e. any terms in the literature) generated by literature mining or provided by the user and (ii) accurate identification and integration of comprehensive molecular interactions from Medline abstracts, to construct molecular networks and subnetworks related to the free terms. http://ci.smu.edu.cn. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. GenASiS Basics: Object-oriented utilitarian functionality for large-scale physics simulations

    DOE PAGES

    Cardall, Christian Y.; Budiardja, Reuben D.

    2015-06-11

    Aside from numerical algorithms and problem setup, large-scale physics simulations on distributed-memory supercomputers require more basic utilitarian functionality, such as physical units and constants; display to the screen or standard output device; message passing; I/O to disk; and runtime parameter management and usage statistics. Here we describe and make available Fortran 2003 classes furnishing extensible object-oriented implementations of this sort of rudimentary functionality, along with individual `unit test' programs and larger example problems demonstrating their use. Lastly, these classes compose the Basics division of our developing astrophysics simulation code GenASiS (General Astrophysical Simulation System), but their fundamental nature makes themmore » useful for physics simulations in many fields.« less

  18. Description of Bryantinus gen. n. from Sarawak, and New Distributional Records for Cerochusa cilioceps in Thailand (Coleoptera: Staphylinidae: Pselaphinae)

    PubMed Central

    Yin, Zi-Wei; Li, Li-Zhen

    2014-01-01

    A new genus and species of the subtribe Batrisina from western Sarawak, Bryantinus matangus gen. et sp. n., is described, illustrated, and compared with related taxa. In addition, examination of a small series of batrisine material from Thailand revealed a new country record for Cerochusa cilioceps Yin & Nomura, which was previously known only from the island of Hainan in southern China. PMID:25409318

  19. Espectroscopia del Cometa Halley

    NASA Astrophysics Data System (ADS)

    Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

    1987-05-01

    Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

  20. A new anaerobic fungus (Oontomyces anksri gen. nov., sp. nov.) from the digestive tract of the Indian camel (Camelus dromedarius).

    PubMed

    Dagar, Sumit S; Kumar, Sanjay; Griffith, Gareth W; Edwards, Joan E; Callaghan, Tony M; Singh, Rameshwar; Nagpal, Ashok K; Puniya, Anil K

    2015-08-01

    Two cultures of anaerobic fungi were isolated from the forestomach of an Indian camel (Camelus dromedarius). Phylogenetic analysis using both the internal transcribed spacer (ITS) and large-subunit (LSU) regions of the rRNA locus demonstrated that these isolates were identical and formed a distinct clade within the anaerobic fungi (phylum Neocallimastigomycota). Morphological examination showed that these fungi formed monocentric thalli with filamentous rhizoids and uniflagellate zoospores, broadly similar to members of the genus Piromyces. However, distinctive morphological features were observed, notably the pinching of the cytoplasm in the sporangiophore and the formation of intercalary rhizoidal swellings. Since genetic analyses demonstrated this fungus was only distantly related to Piromyces spp. and closer to the polycentric Anaeromyces clade, we have assigned it to a new genus and species Oontomyces anksri gen. nov., sp. nov. Interrogation of the GenBank database identified several closely related ITS sequences, which were all environmental sequences obtained from camels, raising the possibility that this fungus may be specific to camelids. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  1. AML Therapy With Irradiated Allogeneic Cells

    ClinicalTrials.gov

    2017-02-01

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-01-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2018-05-16

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  5. CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-06-12

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  6. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-07-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-06-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  8. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-05-30

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  9. Production of hydrogen and volatile fatty acid by Enterobacter sp. T4384 using organic waste materials.

    PubMed

    Kim, Byung-Chun; Deshpande, Tushar R; Chun, Jongsik; Yi, Sung Chul; Kim, Hyunook; Um, Youngsoon; Sang, Byoung-In

    2013-02-01

    In a study of hydrogen-producing bacteria, strain T4384 was isolated from rice field samples in the Republic of Korea. The isolate was identified as Enterobacter sp. T4384 by phylogenetic analysis of 16S rRNA and rpoB gene sequences. Enterobacter sp. T4384 grew at a temperature range of 10-45 degrees C and at an initial pH range of 4.5-9.5. Strain T4384 produced hydrogen at 0-6% NaCl by using glucose, fructose, and mannose. In serum bottle cultures using a complete medium, Enterobacter sp. T4384 produced 1,098 ml/l H2, 4.0 g/l ethanol, and 1.0 g/l acetic acid. In a pH-regulated jar fermenter culture with the biogas removed, 2,202 ml/l H2, 6.2 g/l ethanol, and 1.0 g/l acetic acid were produced, and the lag-phase time was 4.8 h. Strain T4384 metabolized the hydrolysate of organic waste for the production of hydrogen and volatile fatty acid. The strain T4384 produced 947 ml/l H2, 3.2 g/l ethanol, and 0.2 g/l acetic acid from 6% (w/v) food waste hydrolysate; 738 ml/l H2, 4.2 g/l ethanol, and 0.8 g/l acetic acid from Miscanthus sinensis hydrolysate; and 805 ml/l H2, 5.0 g/l ethanol, and 0.7 g/l acetic acid from Sorghum bicolor hydrolysate.

  10. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier

    PubMed Central

    Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J.; Ito, Keisuke; Ge, Kai; Aplan, Peter D.; Armstrong, Scott A.; Nussenzweig, André

    2015-01-01

    Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells1. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks2–4, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma5,6, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4−/− MLL–AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL–AF9 blasts, which requires cyclin-dependent kinase inhibitor p21Cip1 (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia. PMID:25079327

  11. Focus of a multilayer Laue lens with an aperture of 102 microns determined by ptychography at beamline 1-BM at the Advanced Photon Source

    NASA Astrophysics Data System (ADS)

    Macrander, Albert; Wojcik, Michael; Maser, Jörg; Bouet, Nathalie; Conley, Raymond

    2017-09-01

    Ptychography was used to determine the focus of a Multilayer-Laue-Lens (MLL) at beamline 1-BM at the Advanced Photon Source (APS). The MLL had a record aperture of 102 microns with 15170 layers. The measurements were made at 12 keV. The focal length was 9.6 mm, and the outer-most zone was 4 nm thick. MLLs with ever larger apertures are under continuous development since ever longer focal lengths, ever larger working distances, and ever increased flux in the focus are desired. A focus size of 25 nm was determined by ptychographic phase retrieval from a gold grating sample with 1 micron lines and spaces over 3.0 microns horizontal distance. The MLL was set to focus in the horizontal plane of the bending magnet beamline. A CCD with 13.0 micron pixel size positioned 1.13 m downstream of the sample was used to collect the transmitted intensity distribution. The beam incident on the MLL covered the whole 102 micron aperture in the horizontal focusing direction and 20 microns in the vertical direction. 160 iterations of the difference map algorithm were sufficient to obtain a reconstructed image of the sample. The present work highlights the utility of a bending magnet source at the APS for performing coherence-based experiments. Use of ptychography at 1-BM on MLL optics opens the way to study diffraction-limited imaging of other hard x-ray optics.

  12. Reclassification of Halothiobacillus hydrothermalis and Halothiobacillus halophilus to Guyparkeria gen. nov. in the Thioalkalibacteraceae fam. nov., with emended descriptions of the genus Halothiobacillus and family Halothiobacillaceae.

    PubMed

    Boden, Rich

    2017-10-01

    The genus Halothiobacillus contains four species of obligate autotrophs with validly published names, of which Halothiobacillus halophilus and Halothiobacillus hydrothermalis are very distant from the type species - on the basis of the 16S rRNA gene, they have 90.7 % and 90.9 % identity to that of the type species, Halothiobacillus neapolitanus. As these values fall below the Yarza cut-off for the rank of genus, and these two species also show no clear affiliation to the closely related genus Thioalkalibacter, a polyphasic study was undertaken to determine if they represent a separate genus. Unlike Halothiobacillus spp. sensu stricto, H. halophilus and H. hydrothermalis are halophilic (rather than halotolerant) and moderately alkaliphilic (rather than neutrophilic) and additionally do not produce tetrathionate as a detectable intermediate of thiosulfate metabolism, indicating some significant metabolic differences. On the basis of these data and of functional gene examination, it is proposed that they be circumscribed as a new genus Guyparkeria gen.nov, for which the type species is Guyparkeria halophila gen. nov., comb. nov. Additionally, Thioalkalibacter and Guyparkeria gen. nov. fall distant from the Halothiobacillaceae so the Thioalkalibacteraceae fam. nov. is proposed, for which Thioalkalibacter is the type genus. Emended descriptions of Halothiobacillus, Halothiobacillus neapolitanus and the Halothiobacillaceae are provided.

  13. Quisarctus yasumurai gen. et sp. nov. (Arthrotardigrada: Halechiniscidae) from a submarine cave, off Iejima, Ryukyu Islands, Japan.

    PubMed

    Fujimoto, Shinta

    2015-04-20

    Quisarctus yasumurai gen. et sp. nov. (Arthrotardigrada: Halechiniscidae) is described from the submarine cave 'Daidokutsu', off Iejima, Okinawa Islands, Ryukyu Islands, Japan. It is characterised by a cylindrical body, long primary clava and shorter lateral cirrus inserted on a common cirrophore, and simple digits of unequal lengths (without folds, peduncles, proximal pads, pretarsi, or wrinkles) that terminate in a sheathed, small, crescent-shaped claw with a minute calcar. Quisarctinae subfam. nov. is erected for this unique new genus.

  14. Rhizonema sequoiae n.gen. n.sp. from Coast Redwood Sequoia sempervirens (D.Don) Endl.

    PubMed Central

    Del Prado Vera, I. Cid; Lownsbery, B. F.; Maggenti, A. R.

    1983-01-01

    Rhizonema sequoiae n.gen, u. sp. is described from the roots of Coast Redwood, Sequoia sempervirens (D. Don) Endl., growing near Lake Lagunitas, Marin County, California. Rhizonema females are annulated over their entire bodies, are wholly embedded in host tissue, and secrete an abundant amount of gel material. Mature females do not form a cyst. The vulva is located on a large posterior terminal cone, and the anus is on the dorsal vulval lip. Esophageal glands of the second-stage larvae fill more than half of the body cavity. Tails of the vermiform males are blunt, and a cloacal tubus is present. PMID:19295834

  15. DESCRIPTION OF VIRIDILOBUS MARINUS (GEN. ET SP. NOV.), A NEW RAPHIDOPHYTE FROM DELAWARE'S INLAND BAYS.

    PubMed

    Demir-Hilton, Elif; Hutchins, David A; Czymmek, Kirk J; Coyne, Kathryn J

    2012-10-01

    Delaware's Inland Bays (DIB), USA, are subject to blooms of potentially harmful raphidophytes, including Heterosigma akashiwo. In 2004, a dense bloom was observed in a low salinity tributary of the DIB. Light microscopy initially suggested that the species was H. akashiwo; however, the cells were smaller than anticipated. 18S rDNA sequences of isolated cultures differed substantially from all raphidophyte sequences in GenBank. Phylogenetic analysis placed it approximately equidistant from Chattonella and Heterosigma with only ~96% sequence homology with either group. Here, we describe this marine raphidophyte as a novel genus and species, Viridilobus marinus (gen. et sp. nov.). We also compared this species with H. akashiwo, because both species are superficially similar with respect to morphology and their ecological niches overlap. V. marinus cells are ovoid to spherical (11.4 × 9.4 μm), and the average number of chloroplasts (4 per cell) is lower than in H. akashiwo (15 per cell). Pigment analysis of V. marinus revealed the presence of fucoxanthin, violaxanthin, and zeaxanthin, which are characteristic of marine raphidophytes within the family Chattonellaceae of the Raphidophyceae. TEM and confocal microscopy, however, revealed diagnostic microscopic and ultrastructural characteristics that distinguish it from other raphidophytes. Chloroplasts were in close association with the nucleus and thylakoids were arranged either parallel or perpendicular to the cell surface. Putative mucocysts were identified, but trichocysts were not observed. These features, along with DNA sequence data, distinguish this species from all other raphidophyte genera within the family Chattonellaceae of the Raphidophyceae. © 2012 Phycological Society of America.

  16. Intertextual Sexual Politics: Illness and Desire in Enrique Gomez Carrillo's "Del amor", "del dolor y del vicio" and Aurora Caceres's "La rosa muerta"

    ERIC Educational Resources Information Center

    LaGreca, Nancy

    2012-01-01

    This study explores the intertextuality between Aurora Caceres's "La rosa muerta" (1914) and the novel "Del amor, del dolor y del vicio" (1898) by her ex-husband, Enrique Gomez Carrillo. Caceres strategically mentions Gomez Carrillo's novel in "La rosa muerta" to invite a reading of her work in dialogue with his. Both narratives follow the sexual…

  17. Pyramidobacter piscolens gen. nov., sp. nov., a member of the phylum 'Synergistetes' isolated from the human oral cavity.

    PubMed

    Downes, Julia; Vartoukian, Sonia R; Dewhirst, Floyd E; Izard, Jacques; Chen, Tsute; Yu, Wen-Han; Sutcliffe, Iain C; Wade, William G

    2009-05-01

    Four strains of anaerobic, Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group distinct from any species with validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA-DNA reassociation data revealed that the strains constituted a novel group within the phylum 'Synergistetes' and were most closely related to Jonquetella anthropi. Two libraries of randomly cloned DNA were prepared from strain W5455(T) and were sequenced to provide a genome survey as a resource for metagenomic studies. A new genus and novel species, Pyramidobacter piscolens gen. nov., sp. nov., is proposed to accommodate these strains. The genus Pyramidobacter comprises strains that are anaerobic, non-motile, asaccharolytic bacilli that produce acetic and isovaleric acids and minor to trace amounts of propionic, isobutyric, succinic and phenylacetic acids as end products of metabolism. P. piscolens gen. nov., sp. nov. produced hydrogen sulphide but was otherwise largely biochemically unreactive. Growth was stimulated by the addition of glycine to broth media. The G+C content of the DNA of the type strain was 59 mol%. The type strain of Pyramidobacter piscolens sp. nov. is W5455(T) (=DSM 21147(T)=CCUG 55836(T)).

  18. Rhizarian 'Novel Clade 10' Revealed as Abundant and Diverse Planktonic and Terrestrial Flagellates, including Aquavolon n. gen.

    PubMed

    Bass, David; Tikhonenkov, Denis Victorovich; Foster, Rachel; Dyal, Patricia; Janouškovec, Jan; Keeling, Patrick J; Gardner, Michelle; Neuhauser, Sigrid; Hartikainen, Hanna; Mylnikov, Alexandre P; Berney, Cédric

    2018-04-15

    Rhizarian 'Novel Clade 10' (NC10) is frequently detected by 18S rRNA gene sequencing studies in freshwater planktonic samples. We describe a new genus and two species of eukaryovorous biflagellate protists, Aquavolon hoantrani n. gen. n. sp. and A. dientrani n. gen. n. sp., which represent the first morphologically characterized members of NC10, here named Aquavolonida ord. nov. The slightly metabolic cells possess naked heterodynamic flagella, whose kinetosomes lie at a right angle to each other and are connected by at least one fibril. Unlike their closest known relative Tremula longifila, they rotate around their longitudinal axis when swimming and only very rarely glide on surfaces. Screening of a wide range of environmental DNA extractions with lineage-specific PCR primers reveals that Aquavolonida consists of a large radiation of protists, which are most diversified in freshwater planktonic habitats and as yet undetected in marine environments. Earlier-branching lineages in Aquavolonida include less frequently detected organisms from soils and freshwater sediments. The 18S rRNA gene phylogeny suggests that Aquavolonida forms a common evolutionary lineage with tremulids and uncharacterized 'Novel Clade 12', which likely represents one of the deepest lineages in the Rhizaria, separate from Cercozoa (Filosa), Endomyxa, and Retaria. © 2018 The Authors Journal of Eukaryotic Microbiology published by Wiley Periodicals, Inc. on behalf of International Society of Protistologists.

  19. Irradiation effects in oxide dispersion strengthened (ODS) Ni-base alloys for Gen. IV nuclear reactors

    NASA Astrophysics Data System (ADS)

    Oono, Naoko; Ukai, Shigeharu; Kondo, Sosuke; Hashitomi, Okinobu; Kimura, Akihiko

    2015-10-01

    Oxide particle dispersion strengthened (ODS) Ni-base alloys are irradiated by using simulation technique (Fe/He dual-ion irradiation) to investigate the reliability to Gen. IV high-temperature reactors. The fine oxide particles with less than 10 nm in average size and approximately 8.0 × 1022 m-3 in number density remained after 101 dpa irradiation. The tiny helium bubbles were inside grains, not at grain-boundaries; it is advantageous effect of oxide particles which trap the helium atoms at the particle-matrix interface. Ni-base ODS alloys demonstrated their great ability to overcome He embrittlement.

  20. Patient characteristics driving clinical utility in psychiatric pharmacogenetics: a reanalysis from the AB-GEN multicentric trial.

    PubMed

    Menchón, J M; Espadaler, J; Tuson, M; Saiz-Ruiz, J; Bobes, J; Vieta, E; Álvarez, E; Pérez, V

    2018-05-04

    Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode.Trial registration ClinicalTrials.gov NCT02529462.

  1. Comparison of the Gen-Probe Aptima HIV-1 and Abbott HIV-1 qualitative assays with the Roche Amplicor HIV-1 DNA assay for early infant diagnosis using dried blood spots.

    PubMed

    Nelson, Julie A E; Hawkins, J Tyler; Schanz, Maria; Mollan, Katie; Miller, Melissa B; Schmitz, John L; Fiscus, Susan A

    2014-08-01

    The current gold standard for infant diagnosis of HIV-1 is the Roche Amplicor Qualitative DNA assay, but it is being phased out. Compare the Abbott qualitative assay and the Gen-Probe Aptima assay to the gold standard Roche DNA assay using dried blood spots (DBS). The Gen-Probe Aptima and Abbott qualitative HIV-1 assays were compared to the Roche DNA assay for early infant diagnosis. Specificity and sensitivity were determined for the three assays using DBS from 50 HIV-exposed uninfected infants and 269 HIV-1 infected adults from North Carolina, respectively. All of the negative and 151 of the positive DBS had valid results on the 3 different assays, and an additional 118 positive DBS had valid results on the Roche DNA and Aptima assays. All three assays were very specific. The Roche DNA assay was the most sensitive (96.7%) over a wide range of HIV PVL, including samples with PVL<400 copies/ml. Restricted to samples with PVL>400 copies/ml, the Gen-Probe Aptima assay had sensitivity (96.5%) comparable to the Roche DNA assay (98.8%). The Abbott Qualitative assay was the least sensitive and only had sensitivity above 95% among samples with PVL over 1000 copies/ml. The Abbott HIV-1 Qualitative assay was not as sensitive as the comparator assays, so it would not be a useful replacement assay, especially for infants taking antiretroviral prophylaxis. The Gen-Probe Aptima assay is an adequate replacement option for infant diagnosis using DBS. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

    PubMed Central

    Burger, Jan A.; Landau, Dan A.; Taylor-Weiner, Amaro; Bozic, Ivana; Zhang, Huidan; Sarosiek, Kristopher; Wang, Lili; Stewart, Chip; Fan, Jean; Hoellenriegel, Julia; Sivina, Mariela; Dubuc, Adrian M.; Fraser, Cameron; Han, Yulong; Li, Shuqiang; Livak, Kenneth J.; Zou, Lihua; Wan, Youzhong; Konoplev, Sergej; Sougnez, Carrie; Brown, Jennifer R.; Abruzzo, Lynne V.; Carter, Scott L.; Keating, Michael J.; Davids, Matthew S.; Wierda, William G.; Cibulskis, Kristian; Zenz, Thorsten; Werner, Lillian; Cin, Paola Dal; Kharchencko, Peter; Neuberg, Donna; Kantarjian, Hagop; Lander, Eric; Gabriel, Stacey; O'Brien, Susan; Letai, Anthony; Weitz, David A.; Nowak, Martin A.; Getz, Gad; Wu, Catherine J.

    2016-01-01

    Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance. PMID:27199251

  3. Evaluation of the Next-Gen Exercise Software Interface in the NEEMO Analog

    NASA Technical Reports Server (NTRS)

    Hanson, Andrea; Kalogera, Kent; Sandor, Aniko; Hardy, Marc; Frank, Andrew; English, Kirk; Williams, Thomas; Perera, Jeevan; Amonette, William

    2017-01-01

    NSBRI (National Space Biomedical Research Institute) funded research grant to develop the 'NextGen' exercise software for the NEEMO (NASA Extreme Environment Mission Operations) analog. Develop a software architecture to integrate instructional, motivational and socialization techniques into a common portal to enhance exercise countermeasures in remote environments. Increase user efficiency and satisfaction, and institute commonality across multiple exercise systems. Utilized GUI (Graphical User Interface) design principals focused on intuitive ease of use to minimize training time and realize early user efficiency. Project requirement to test the software in an analog environment. Top Level Project Aims: 1) Improve the usability of crew interface software to exercise CMS (Crew Management System) through common app-like interfaces. 2) Introduce virtual instructional motion training. 3) Use virtual environment to provide remote socialization with family and friends, improve exercise technique, adherence, motivation and ultimately performance outcomes.

  4. Functional Allocation for Ground-Based Automated Separation Assurance in NextGen

    NASA Technical Reports Server (NTRS)

    Prevot, Thomas; Mercer, Joey; Martin, Lynne; Homola, Jeffrey; Cabrall, Christopher; Brasil, Connie

    2010-01-01

    As part of an ongoing research effort into functional allocation in a NextGen environment, a controller-in-the-loop study on ground-based automated separation assurance was conducted at NASA Ames' Airspace Operations Laboratory in February 2010. Participants included six FAA front line managers, who are currently certified professional controllers and four recently retired controllers. Traffic scenarios were 15 and 30 minutes long where controllers interacted with advanced technologies for ground-based separation assurance, weather avoidance, and arrival metering. The automation managed the separation by resolving conflicts automatically and involved controllers only by exception, e.g., when the automated resolution would have been outside preset limits. Results from data analyses show that workload was low despite high levels of traffic, Operational Errors did occur but were closely tied to local complexity, and safety acceptability ratings varied with traffic levels. Positive feedback was elicited for the overall concept with discussion on the proper allocation of functions and trust in automation.

  5. Effects of washed platelets vs platelet-rich plasma on the proliferation and mineralization of rat dental pulp cells.

    PubMed

    Zhang, L; Xie, Y H; Lin, B R

    2015-08-14

    We examined the effects of washed platelets (WPLTs) and platelet-rich plasma (PRP) on the proliferation and mineralization of rat dental pulp cells. Rat dental pulp cells were separated, cultured, and identified. Medium containing 1, 10, 100, or 500 mL/L PRP or WPLTs was added to 4th generation cells. The MTS method was used to determine cell proliferation. Alizarin red staining was used to observe the formation of mineralized nodules after cell mineralization and induction for 10 and 20 days under different culture conditions, and the areas of the mineralized nodules formed 20 days after induction were computed. The addition of 1, 10, and 100 mL/L WPLTs or PRP significantly promoted rat dental pulp cell proliferation (P < 0.05) whereas 500 mL/L WPLTs or PRP had no significant effect (P > 0.05). Under the same concentrations, no significant differences on cell proliferation were observed between WPLT and PRP treatments (P > 0.05 in all groups). After 10 days mineralization and culture, the 100 and 500 mL/L WPLT and PRP group positive nodule rates were significantly higher than those of the low concentration and the control groups (P < 0.05). After 20 days, the areas of the mineralized nodules formed in the 100 and 500 mL/L WPLT and PRP groups were significantly larger than those in the control group (P < 0.05). These results demonstrate that both WPLTs and PRP are equally able to significantly promote the proliferation and calcification of rat dental pulp cells under a certain range of concentrations.

  6. Augmenting in vitro shoot multiplication by vipul (triacontanol) and adventitious rhizogenesis by rice bran extract in Dendrocalamus strictus.

    PubMed

    Mishra, Y; Rana, P K; Shirin, F; Ansari, S A

    2001-02-01

    Like other bamboo species, Dendrocalamus strictus flowers gregariously after a prolonged intermast period of 48 years and constitutes an ideal material for in vitro clonal propagation. In this study, MS liquid medium containing 0.5, 1.0 and 2.0 mL/L vipul (Godrej Agrovet, Ltd., Sachin, India), a commercial formulation of triacontanol, with or without BA (3.0 mg/L) was tested for in vitro shoot multiplication and 1.0, 2.5 and 5.0 mL/L of 20% (w/v) alcoholic/aqueous rice bran extract (alone or in combination) with NAA (3 mg/L) used for in vitro adventitious rhizogenesis in single node culture derived shoots of Dendrocalamus strictus.. After a multiplication cycle for 4-5 week, vipul (0.5 mL/L) with BA (3.0 mg/L) in the culture medium induced 4.59 fold shoot multiplication rate whereas application of BA and vipul alone had corresponding values of 3.29 and 0.53 fold respectively. Maximum vipul concentration (2 mL/L) with BA (3 mg/L) exhibited shoot multiplication higher than (or equal to) that of BA alone. Maximum in vitro rooting percentage (55.66%) was obtained on half MS medium enriched with alcoholic rice bran extract (2.5 mL/L) and NAA (3 mg/L). This is the first investigation reporting amelioration of in vitro shoot multiplication rate by triacontanol and rooting percentage by rice bran extract in explants from mature bamboo culms. The protocol is economical and rapid for in vitro clonal propagation of Dendrocalamus strictus.

  7. Reclassification of Alcaligenes latus strains IAM 12599T and IAM 12664 and Pseudomonas saccharophila as Azohydromonas lata gen. nov., comb. nov., Azohydromonas australica sp. nov. and Pelomonas saccharophila gen. nov., comb. nov., respectively.

    PubMed

    Xie, Cheng-Hui; Yokota, Akira

    2005-11-01

    The aim of this study was to clarify the taxonomic position of the nitrogen-fixing and hydrogen-oxidizing bacteria Alcaligenes latus strains IAM 12599T, IAM 12664 and IAM 12665 and Pseudomonas saccharophila IAM 14368T. It was found that the type strain of Alcaligenes latus, IAM 12599T, showed 99 x 9 and 96 x 1 % 16S rRNA gene sequence similarity to strains IAM 12665 and IAM 12664, respectively. A comparison using DNA-DNA hybridization suggested that strains IAM 12599T and IAM 12665 belong to a single species (89 x 7 %) and that strain IAM 12664 (35 x 1 %) forms a separate species. The phenotypic characteristics also support the conclusion that these bacteria should be identified as two species of a new genus: Azohydromonas lata gen. nov., comb. nov. (type strain IAM 12599T=DSM 1122T=LMG 3321T=ATCC 29712T; reference strain IAM 12665=DSM 1123=LMG 3325=ATCC 29714) and Azohydromonas australica sp. nov. (type strain IAM 12664T=DSM 1124T=LMG 3324T=ATCC 29713T). Pseudomonas saccharophila IAM 14368T was found to be closely related to the phototrophic bacterium Roseateles depolymerans, with 96 x 8 % 16S rRNA gene sequence similarity, but the two bacteria are quite different with respect to their metabolism and some significant phenotypic characteristics, suggesting that they cannot be included in a single genus. Further studies on their nifH gene sequences, G+C content of the DNA and cellular fatty acid composition confirm that Pseudomonas saccharophila should be reclassified: the name Pelomonas saccharophila gen. nov., comb. nov. is proposed, with the type strain IAM 14368T (=LMG 2256T=ATCC 15946T).

  8. ORPC RivGen Hydrokinetic Turbine Wake Characterization

    SciTech Connect

    Thomson, Jim; Guerra, Maricarmen

    Field measurements of mean flow and turbulence parameters at the Kvichak river prior to and after the deployment of ORPC's RivGen hydrokinetic turbine. Data description and turbine wake analysis are presented in the attached manuscript "Wake measurements from a hydrokinetic river turbine" by Guerra and Thomson (recently submitted to Renewable Energy). There are three data sets: NoTurbine (prior to deployment), Not_Operational_Turbine (turbine underwater, but not operational), and Operational_Turbine. The data has been quality controlled and organized into a three-dimensional grid using a local coordinate system described in the paper. All data sets are in Matlab format (.mat). Variables available inmore » the data sets are: qx: X coordinate matrix (m) qy: Y coordinate matrix (m) z : z coordinate vector (m) lat : grid cell latitude (degrees) lon: grid cell longitude (degrees) U : velocity magnitude (m/s) Ux: x velocity (m/s) Vy: y velocity (m/s) W: vertical velocity (m/s) Pseudo_beam.b_i: pseudo-along beam velocities (i = 1 to 4) (m/s) (structure with raw data within each grid cell) beam5.b5: 5th-beam velocity (m/s) (structure with raw data within each grid cell) tke: turbulent kinetic energy (m2/s2) epsilon: TKE dissipation rate (m2/s3) Reynolds stresses: uu, vv, ww, uw, vw (m2/s2) Variables from the Not Operational Turbine data set are identified with _T Variables from the Operational Turbine data set are identified with _TO« less

  9. Neutron Detection Efficiency Optimization Studies of the Neutron Polarimeter for the C-GEN Electric Form Factor at Jefferson National Laboratory

    NASA Astrophysics Data System (ADS)

    Adzima, Ashley; Tireman, William; C-Gen Collaboration

    The electric form factor is an important quantity to further the understanding of the atom and its constituent parts. The C-GEN collaboration at Jefferson National Laboratory plans to measure this fundamental quantity using recoil polarimetry. An efficient neutron polarimeter is essential for the collection of precise data and involves maximizing the ratio of elastic to inelastic events identified. The determination of the elastic to inelastic ratio of neutron events was simulated using GEANT-4 on 5 cm, 10 cm, and 15 cm thick detectors. Specific requirements were set in place by C-GEN to determine what marks an elastic event. Plots of neutron scattering events versus detector thickness were analyzed, and the ratio of elastic to inelastic events was extracted for each section per vertical slice, as well as an average ratio. The average ratio of elastic to inelastic events were 0.2206, 0.1706, and 0.1507 for the 5 cm, 10 cm, and 15 cm detectors, respectfully. The impact of these ratios on the statistics and costs of altering the polarimeter's original 10 cm detector design will be further discussed. U.S. Department of Education - TRIO McNair Scholars Program.

  10. Ultrastructure and molecular phylogenetic position of a novel phagotrophic stramenopile from low oxygen environments: Rictus lutensis gen. et sp. nov. (Bicosoecida, incertae sedis).

    PubMed

    Yubuki, Naoji; Leander, Brian S; Silberman, Jeffrey D

    2010-04-01

    A novel free free-living phagotrophic flagellate, Rictus lutensis gen. et sp. nov., with two heterodynamic flagella, a permanent cytostome and a cytopharynx was isolated from muddy, low oxygen coastal sediments in Cape Cod, MA, USA. We cultivated and characterized this flagellate with transmission electron microscopy, scanning electron microscopy and molecular phylogenetic analyses inferred from small subunit (SSU) rDNA sequences. These data demonstrated that this organism has the key ultrastructural characters of the Bicosoecida, including similar transitional zones and a similar overall flagellar apparatus consisting of an x fiber and an L-shape microtubular root 2 involved in food capture. Although the molecular phylogenetic analyses were concordant with the ultrastructural data in placing R. lutensis with the bicosoecid clade, the internal position of this relatively divergent sequence within the clade was not resolved. Therefore, we interpret R. lutensis gen. et sp. nov. as a novel bicosoecid incertae sedis. Copyright 2009 Elsevier GmbH. All rights reserved.

  11. A new remarkable subterranean beetle of the Rhodopes: Paralovricia gen. n. beroni sp. n. belonging to Lovriciina new subtribe (Coleoptera, Carabidae, Trechinae, Bembidiini)

    PubMed Central

    Giachino, Pier Mauro; Guéorguiev, Borislav; Vailati, Dante

    2011-01-01

    Abstract Paralovricia gen. n. beroni sp. n., belonging to the new subtribe Lovriciina, is described from two caves in the Western Rhodopes (Bulgaria): Kraypatnata peshtera, near Smilyan Village (Smolyan Municipality) and Snezhanka, near Peshtera Town (Peshtera Municipality). Three currently known genera, Lovricia Pretner, 1979, Neolovricia Lakota, Jalžić & Moravec, 2009 and Paralovricia gen. n. represent a monophyletic unit supported by important synapomorphies that allows to propose the establishment of the new subtribe Lovriciina, characterized by the following characters: last maxillary palpomeres very long and narrow, basal angles of pronotum without seta, elytra without discal setae, elytral umbilicate series of nine pores in which the main pores are the 2nd, 6th and 9th, apical recurrent striole absent and mesotibial apex expanded outward. Its systematic position within the subfamily Trechinae (sensu Lorenz 2005) is discussed and Lovriciina is placed near Anillina. Key to the genera of the subtribe is proposed. Distribution data and zoogeographical hypotheses are discussed. PMID:21998506

  12. Lanfrediella amphicirrus gen. nov. sp. nov. Nematotaeniidae (Cestoda: Cyclophyllidea), a tapeworm parasite of Rhinella marina (Linnaeus, 1758) (Amphibia: Bufonidae).

    PubMed

    Melo, Francisco Tiago de Vasconcelos; Giese, Elane Guerreiro; Furtado, Adriano Penha; Soares, Maurílio José; Gonçalves, Evonnildo Costa; Vallinoto, Antonio Carlos Rosário; Santos, Jeannie Nascimento dos

    2011-09-01

    The family Nematotaeniidae, tapeworms commonly found in the small intestines of amphibians and reptiles, includes 27 recognised species distributed among four genera: Bitegmen Jones, Cylindrotaenia Jewell, Distoichometra Dickey and Nematotaenia Lühe. The taxonomy of these cestodes is poorly defined, due in part to the difficulties of observing many anatomical traits. This study presents and describes a new genus and species of nematotaeniid parasite found in cane toads (Rhinella marina) from eastern Brazilian Amazonia. The cestodes were collected during the necropsy of 20 hosts captured in the urban area of Belém, Pará. The specimens were fixed and processed for light microscopy, scanning electron microscopy (SEM) and three-dimensional (3D) reconstruction. Samples were also collected for molecular analyses. The specimens presented a cylindrical body, two testes and paruterine organs. However, they could not be allocated to any of the four existing nematotaeniid genera due to the presence of two each of dorsal compact medullary testes, cirri, cirrus pouches, genital pores, ovaries and vitelline glands per mature segment. Lanfrediella amphicirrus gen. nov. sp. nov. is the first nematotaeniid studied using Historesin analysis, SEM and 3D reconstruction, and it is the second taxon for which molecular data have been deposited in GenBank.

  13. Lumbar Morel-Lavallée lesion: Case report and review of the literature.

    PubMed

    Zairi, F; Wang, Z; Shedid, D; Boubez, G; Sunna, T

    2016-06-01

    The Morel-Lavallée lesion (MLL) is a rarely reported closed degloving injury, in which shearing forces have lead to break off subcutaneous tissues from the underlying fascia. Lumbar MLL have been rarely reported to date, explaining that patients are frequently misdiagnosed. While patients could be treated conservatively or with non-invasive procedures, delayed diagnosis may require open surgery for its cure. Indeed, untreated lesions can cause pain, infection or growing subcutaneous mass that can be confused with a soft tissue tumor. We report the clinical and radiological features of a 45-year old man with voluminous lumbar MLL initially misdiagnosed. We also reviewed the relevant English literature to summarize the diagnostic tools and the main therapeutic options. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Critical Issues on Materials for Gen-IV Reactors

    SciTech Connect

    Caro, M; Marian, J; Martinez, E

    2009-02-27

    Within the LDRD on 'Critical Issues on Materials for Gen-IV Reactors' basic thermodynamics of the Fe-Cr alloy and accurate atomistic modeling were used to help develop the capability to predict hardening, swelling and embrittlement using the paradigm of Multiscale Materials Modeling. Approaches at atomistic and mesoscale levels were linked to build-up the first steps in an integrated modeling platform that seeks to relate in a near-term effort dislocation dynamics to polycrystal plasticity. The requirements originated in the reactor systems under consideration today for future sources of nuclear energy. These requirements are beyond the present day performance of nuclear materials andmore » calls for the development of new, high temperature, radiation resistant materials. Fe-Cr alloys with 9-12% Cr content are the base matrix of advanced ferritic/martensitic (FM) steels envisaged as fuel cladding and structural components of Gen-IV reactors. Predictive tools are needed to calculate structural and mechanical properties of these steels. This project represents a contribution in that direction. The synergy between the continuous progress of parallel computing and the spectacular advances in the theoretical framework that describes materials have lead to a significant advance in our comprehension of materials properties and their mechanical behavior. We took this progress to our advantage and within this LDRD were able to provide a detailed physical understanding of iron-chromium alloys microstructural behavior. By combining ab-initio simulations, many-body interatomic potential development, and mesoscale dislocation dynamics we were able to describe their microstructure evolution. For the first time in the case of Fe-Cr alloys, atomistic and mesoscale were merged and the first steps taken towards incorporating ordering and precipitation effects into dislocation dynamics (DD) simulations. Molecular dynamics (MD) studies of the transport of self-interstitial, vacancy

  15. Proteinivorax tanatarense gen. nov., sp. nov., an anaerobic, haloalkaliphilic, proteolytic bacterium isolated from a decaying algal bloom, and proposal of Proteinivoraceae fam. nov.

    PubMed

    Kevbrin, Vadim; Boltyanskaya, Yulia; Zhilina, Tatjana; Kolganova, Tatjana; Lavrentjeva, Elena; Kuznetsov, Boris

    2013-09-01

    Two strains of a novel anaerobic, protein- and nucleoside-utilizing bacterium, Z-910(T) and Z-810, were isolated. The strains were spore-forming, mainly nonmotile rods, exhibiting positive Gram reaction with Gram-positive cell wall structure. The strains were mesophilic and haloalkaliphilic. Cultures used proteins and proteinaceous substrates as carbon, nitrogen, and energy sources. Both strains used also ribonucleosides, cellobiose, pyruvate, and glycerol. Ribose and nucleobases did not support growth. The fermentation products from all utilized substrates were identical but varied in content and included straight and branched acids, as well as hydrogen and ammonia. When grown on tryptone, strain Z-910(T) was able to reduce fumarate, dimethyl sulfoxide, thiosulfate, and elemental sulfur. Neither nitrate nor sulfate was reduced. The DNA G + C content of strain Z-910(T) was 32.2 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence similarity revealed that strains Z-910(T) and Z-810 represented a new branch within the order Clostridiales, with 90.2 % similarity to the nearest genus with a validly published name Anaerobranca gottschalkii DSM 13577(T). According to their physiological, chemotaxonomic, and phylogenetic properties, strains Z-910(T) and Z-810 represented a new genus and novel species, for which the name Proteinivorax tanatarense gen. nov., sp. nov. was proposed. Phylogenetic analysis showed that the genera Proteinivorax gen. nov. and Anaerobranca formed a separate cluster within the order Clostridiales. The family Proteinivoraceae fam. nov. comprising the genera Proteinivorax gen. nov. and Anaerobranca was therefore proposed within the order Clostridiales of the phylum Firmicutes with Proteinivorax as a type genus of the new family.

  16. A new basal sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), northwestern Argentina.

    PubMed

    Apaldetti, Cecilia; Martinez, Ricardo N; Alcober, Oscar A; Pol, Diego

    2011-01-01

    Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of

  17. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production—Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management

    PubMed Central

    Barbot, Yann Nicolas; Thomsen, Laurenz; Benz, Roland

    2015-01-01

    Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP) of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix)) originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanation to disintegrate the biomass macrostructure. Acid hydrolysis was successfully triggered with 0.2 M industry-grade HCl at 80 °C for a 2 h period, increasing biomethane recovery by +39%, with a maximum BMP of 121 mL·g−1 volatile solids (VS). To reduce the necessity for input material, HCl was replaced by the acidic waste product flue gas condensate (FGC). Improved performance was achieved by showing an increase in biomethane recovery of +24% and a maximum BMP of 108 mL·g−1 VS. Continuous anaerobic digestion trials of RM were conducted for three hydraulic retention times, showing the feasibility of monodigestion. The biomethane recovery was 60 mL and 65 mL·g−1 VS·d−1 for thermophilic and mesophilic operation, respectively. The quality of biomethanation performance aligned to the composition of the source material which exhibited a low carbon/nitrogen ratio and an increased concentration of sulfur compounds. PMID:26404327

  18. Thermo-Acidic Pretreatment of Beach Macroalgae from Rügen to Optimize Biomethane Production--Double Benefit with Simultaneous Bioenergy Production and Improvement of Local Beach and Waste Management.

    PubMed

    Barbot, Yann Nicolas; Thomsen, Laurenz; Benz, Roland

    2015-09-03

    Eutrophication is a phenomenon which can rapidly generate masses of marine macroalgae, particularly in areas with high nutrient pollution. Washed ashore, this biomass impairs coastal tourism and negatively affects the coastal ecosystem. The present study evaluates the biochemical methane potential (BMP) of a macroalgae mix (Rügen-Mix, RM (RM = Rügen-Mix)) originating from Rügen, Germany. To improve biomethane recovery, thermo-acidic pretreatment was applied to the biomass prior to biomethanation to disintegrate the biomass macrostructure. Acid hydrolysis was successfully triggered with 0.2 M industry-grade HCl at 80 °C for a 2 h period, increasing biomethane recovery by +39%, with a maximum BMP of 121 mL·g(-1) volatile solids (VS). To reduce the necessity for input material, HCl was replaced by the acidic waste product flue gas condensate (FGC). Improved performance was achieved by showing an increase in biomethane recovery of +24% and a maximum BMP of 108 mL·g(-1) VS. Continuous anaerobic digestion trials of RM were conducted for three hydraulic retention times, showing the feasibility of monodigestion. The biomethane recovery was 60 mL and 65 mL·g(-1) VS·d(-1) for thermophilic and mesophilic operation, respectively. The quality of biomethanation performance aligned to the composition of the source material which exhibited a low carbon/nitrogen ratio and an increased concentration of sulfur compounds.

  19. UAS in the NAS Project: Large-Scale Communication Architecture Simulations with NASA GRC Gen5 Radio Model

    NASA Technical Reports Server (NTRS)

    Kubat, Gregory

    2016-01-01

    This report provides a description and performance characterization of the large-scale, Relay architecture, UAS communications simulation capability developed for the NASA GRC, UAS in the NAS Project. The system uses a validated model of the GRC Gen5 CNPC, Flight-Test Radio model. Contained in the report is a description of the simulation system and its model components, recent changes made to the system to improve performance, descriptions and objectives of sample simulations used for test and verification, and a sampling and observations of results and performance data.

  20. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2018-05-24

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia