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Sample records for expanded pebp gene

  1. Characterization and Functional Analysis of PEBP Family Genes in Upland Cotton (Gossypium hirsutum L.)

    PubMed Central

    Wang, Congcong; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Song, Meizhen; Fan, Shuli; Yu, Shuxun

    2016-01-01

    Upland cotton (Gossypium hirsutum L.) is a naturally occurring photoperiod-sensitive perennial plant species. However, sensitivity to the day length was lost during domestication. The phosphatidylethanolamine-binding protein (PEBP) gene family, of which three subclades have been identified in angiosperms, functions to promote and suppress flowering in photoperiod pathway. Recent evidence indicates that PEBP family genes play an important role in generating mobile flowering signals. We isolated homologues of the PEBP gene family in upland cotton and examined their regulation and function. Nine PEBP-like genes were cloned and phylogenetic analysis indicated the genes belonged to four subclades (FT, MFT, TFL1 and PEBP). Cotton PEBP-like genes showed distinct expression patterns in relation to different cotton genotypes, photoperiod responsive and cultivar maturity. The GhFT gene expression of a semi-wild race of upland cotton were strongly induced under short day condition, whereas the GhPEBP2 gene expression was induced under long days. We also elucidated that GhFT but not GhPEBP2 interacted with FD-like bZIP transcription factor GhFD and promote flowering under both long- and short-day conditions. The present result indicated that GhPEBP-like genes may perform different functions. This work corroborates the involvement of PEBP-like genes in photoperiod response and regulation of flowering time in different cotton genotypes, and contributes to an improved understanding of the function of PEBP-like genes in cotton. PMID:27552108

  2. Characterization and Functional Analysis of PEBP Family Genes in Upland Cotton (Gossypium hirsutum L.).

    PubMed

    Zhang, Xiaohong; Wang, Congcong; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Song, Meizhen; Fan, Shuli; Yu, Shuxun

    2016-01-01

    Upland cotton (Gossypium hirsutum L.) is a naturally occurring photoperiod-sensitive perennial plant species. However, sensitivity to the day length was lost during domestication. The phosphatidylethanolamine-binding protein (PEBP) gene family, of which three subclades have been identified in angiosperms, functions to promote and suppress flowering in photoperiod pathway. Recent evidence indicates that PEBP family genes play an important role in generating mobile flowering signals. We isolated homologues of the PEBP gene family in upland cotton and examined their regulation and function. Nine PEBP-like genes were cloned and phylogenetic analysis indicated the genes belonged to four subclades (FT, MFT, TFL1 and PEBP). Cotton PEBP-like genes showed distinct expression patterns in relation to different cotton genotypes, photoperiod responsive and cultivar maturity. The GhFT gene expression of a semi-wild race of upland cotton were strongly induced under short day condition, whereas the GhPEBP2 gene expression was induced under long days. We also elucidated that GhFT but not GhPEBP2 interacted with FD-like bZIP transcription factor GhFD and promote flowering under both long- and short-day conditions. The present result indicated that GhPEBP-like genes may perform different functions. This work corroborates the involvement of PEBP-like genes in photoperiod response and regulation of flowering time in different cotton genotypes, and contributes to an improved understanding of the function of PEBP-like genes in cotton.

  3. Evolution of the PEBP gene family in plants: functional diversification in seed plant evolution.

    PubMed

    Karlgren, Anna; Gyllenstrand, Niclas; Källman, Thomas; Sundström, Jens F; Moore, David; Lascoux, Martin; Lagercrantz, Ulf

    2011-08-01

    The phosphatidyl ethanolamine-binding protein (PEBP) gene family is present in all eukaryote kingdoms, with three subfamilies identified in angiosperms (FLOWERING LOCUS T [FT], MOTHER OF FT AND TFL1 [MFT], and TERMINAL FLOWER1 [TFL1] like). In angiosperms, PEBP genes have been shown to function both as promoters and suppressors of flowering and to control plant architecture. In this study, we focus on previously uncharacterized PEBP genes from gymnosperms. Extensive database searches suggest that gymnosperms possess only two types of PEBP genes, MFT-like and a group that occupies an intermediate phylogenetic position between the FT-like and TFL1-like (FT/TFL1-like). Overexpression of Picea abies PEBP genes in Arabidopsis (Arabidopsis thaliana) suggests that the FT/TFL1-like genes (PaFTL1 and PaFTL2) code for proteins with a TFL1-like function. However, PaFTL1 and PaFTL2 also show highly divergent expression patterns. While the expression of PaFTL2 is correlated with annual growth rhythm and mainly confined to needles and vegetative and reproductive buds, the expression of PaFTL1 is largely restricted to microsporophylls of male cones. The P. abies MFT-like genes (PaMFT1 and PaMFT2) show a predominant expression during embryo development, a pattern that is also found for many MFT-like genes from angiosperms. P. abies PEBP gene expression is primarily detected in tissues undergoing physiological changes related to growth arrest and dormancy. A first duplication event resulting in two families of plant PEBP genes (MFT-like and FT/TFL1-like) seems to coincide with the evolution of seed plants, in which independent control of bud and seed dormancy was required, and the second duplication resulting in the FT-like and TFL1-like clades probably coincided with the evolution of angiosperms.

  4. Evolution of the PEBP Gene Family in Plants: Functional Diversification in Seed Plant Evolution1[W][OA

    PubMed Central

    Karlgren, Anna; Gyllenstrand, Niclas; Källman, Thomas; Sundström, Jens F.; Moore, David; Lascoux, Martin; Lagercrantz, Ulf

    2011-01-01

    The phosphatidyl ethanolamine-binding protein (PEBP) gene family is present in all eukaryote kingdoms, with three subfamilies identified in angiosperms (FLOWERING LOCUS T [FT], MOTHER OF FT AND TFL1 [MFT], and TERMINAL FLOWER1 [TFL1] like). In angiosperms, PEBP genes have been shown to function both as promoters and suppressors of flowering and to control plant architecture. In this study, we focus on previously uncharacterized PEBP genes from gymnosperms. Extensive database searches suggest that gymnosperms possess only two types of PEBP genes, MFT-like and a group that occupies an intermediate phylogenetic position between the FT-like and TFL1-like (FT/TFL1-like). Overexpression of Picea abies PEBP genes in Arabidopsis (Arabidopsis thaliana) suggests that the FT/TFL1-like genes (PaFTL1 and PaFTL2) code for proteins with a TFL1-like function. However, PaFTL1 and PaFTL2 also show highly divergent expression patterns. While the expression of PaFTL2 is correlated with annual growth rhythm and mainly confined to needles and vegetative and reproductive buds, the expression of PaFTL1 is largely restricted to microsporophylls of male cones. The P. abies MFT-like genes (PaMFT1 and PaMFT2) show a predominant expression during embryo development, a pattern that is also found for many MFT-like genes from angiosperms. P. abies PEBP gene expression is primarily detected in tissues undergoing physiological changes related to growth arrest and dormancy. A first duplication event resulting in two families of plant PEBP genes (MFT-like and FT/TFL1-like) seems to coincide with the evolution of seed plants, in which independent control of bud and seed dormancy was required, and the second duplication resulting in the FT-like and TFL1-like clades probably coincided with the evolution of angiosperms. PMID:21642442

  5. Characterization of two PEBP genes, SrFT and SrMFT, in thermogenic skunk cabbage (Symplocarpus renifolius)

    PubMed Central

    Ito-Inaba, Yasuko; Masuko-Suzuki, Hiromi; Maekawa, Haruhiko; Watanabe, Masao; Inaba, Takehito

    2016-01-01

    Floral thermogenesis has been found in dozens of primitive seed plants and the reproductive organs in these plants produce heat during anthesis. Thus, characterization of the molecular mechanisms underlying flowering is required to fully understand the role of thermogenesis, but this aspect of thermogenic plant development is largely unknown. In this study, extensive database searches and cloning experiments suggest that thermogenic skunk cabbage (Symplocarpus renifolius), which is a member of the family Araceae, possesses two genes encoding phosphatidyl ethanolamine-binding proteins (PEBP), FLOWERING LOCUS T (SrFT) and MOTHER OF FT AND TFL1 (SrMFT). Functional analyses of SrFT and SrMFT in Arabidopsis indicate that SrFT promotes flowering, whereas SrMFT does not. In S. renifolius, the stage- and tissue-specific expression of SrFT was more evident than that of SrMFT. SrFT was highly expressed in flowers and leaves and was mainly localized in fibrovascular tissues. In addition, microarray analysis revealed that, within floral tissues, SrFT was co-regulated with the genes associated with cellular respiration and mitochondrial function, including ALTERNATIVE OXIDASE gene proposed to play a major role in floral thermogenesis. Taken together, these data suggest that, among the PEBP genes, SrFT plays a role in flowering and floral development in the thermogenic skunk cabbage. PMID:27389636

  6. Characterization of two PEBP genes, SrFT and SrMFT, in thermogenic skunk cabbage (Symplocarpus renifolius).

    PubMed

    Ito-Inaba, Yasuko; Masuko-Suzuki, Hiromi; Maekawa, Haruhiko; Watanabe, Masao; Inaba, Takehito

    2016-07-08

    Floral thermogenesis has been found in dozens of primitive seed plants and the reproductive organs in these plants produce heat during anthesis. Thus, characterization of the molecular mechanisms underlying flowering is required to fully understand the role of thermogenesis, but this aspect of thermogenic plant development is largely unknown. In this study, extensive database searches and cloning experiments suggest that thermogenic skunk cabbage (Symplocarpus renifolius), which is a member of the family Araceae, possesses two genes encoding phosphatidyl ethanolamine-binding proteins (PEBP), FLOWERING LOCUS T (SrFT) and MOTHER OF FT AND TFL1 (SrMFT). Functional analyses of SrFT and SrMFT in Arabidopsis indicate that SrFT promotes flowering, whereas SrMFT does not. In S. renifolius, the stage- and tissue-specific expression of SrFT was more evident than that of SrMFT. SrFT was highly expressed in flowers and leaves and was mainly localized in fibrovascular tissues. In addition, microarray analysis revealed that, within floral tissues, SrFT was co-regulated with the genes associated with cellular respiration and mitochondrial function, including ALTERNATIVE OXIDASE gene proposed to play a major role in floral thermogenesis. Taken together, these data suggest that, among the PEBP genes, SrFT plays a role in flowering and floral development in the thermogenic skunk cabbage.

  7. Molecular and functional characterization of PEBP genes in barley reveal the diversification of their roles in flowering.

    PubMed

    Kikuchi, Rie; Kawahigashi, Hiroyuki; Ando, Tsuyu; Tonooka, Takuji; Handa, Hirokazu

    2009-03-01

    Five barley (Hordeum vulgare) PEBP (for phosphatidylethanolamine-binding protein) genes were analyzed to clarify their functional roles in flowering using transgenic, expression, and quantitative trait locus analyses. Introduction of HvTFL1 and HvMFT1 into rice (Oryza sativa) plants did not result in any changes in flowering, suggesting that these two genes have functions distinct from flowering. Overexpression of HvFT1, HvFT2, and HvFT3 in rice resulted in early heading, indicating that these FT-like genes can act as promoters of the floral transition. HvFT1 transgenic plants showed the most robust flowering initiation. In barley, HvFT1 was expressed at the time of shoot meristem phase transition. These results suggest that HvFT1 is the key gene responsible for flowering in the barley FT-like gene family. HvFT2 transgenic plants also showed robust flowering initiation, but HvFT2 was expressed only under short-day (SD) conditions during the phase transition, suggesting that its role is limited to specific photoperiodic conditions in barley. Flowering activity in HvFT3 transgenic rice was not as strong and was modulated by the photoperiod. These results suggest that HvFT3 functions in flowering promotion but that its effect is indirect. HvFT3 expression was observed in Morex, a barley cultivar carrying a dominant allele of Ppd-H2, a major quantitative trait locus for flowering under SD conditions, although no expression was detected in Steptoe, a cultivar carrying ppd-H2. HvFT3 was expressed in Morex under both long-day and SD conditions, although its expression was increased under SD conditions. HvFT3 was mapped to chromosome 1HL, the same chromosome that carries Ppd-H2. Genomic sequence analyses revealed that Morex possesses an intact HvFT3 gene, whereas most of this gene has been lost in Steptoe. These data strongly suggest that HvFT3 may be identical to Ppd-H2.

  8. PEBP1 — EDRN Public Portal

    Cancer.gov

    PEBP1 is a cytoplasmic protein that binds ATP, opioids and phosphatidylethanolamine. It has lower affinity for phosphatidylinositol and phosphatidylcholine. PEBP1 is a serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. PEBP1 may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. PEBP1 increases the production of choline acetyltransferase but not acetylcholinesterase and seems to be mediated by a specific receptor.

  9. Molecular and Functional Characterization of PEBP Genes in Barley Reveal the Diversification of Their Roles in Flowering1[W][OA

    PubMed Central

    Kikuchi, Rie; Kawahigashi, Hiroyuki; Ando, Tsuyu; Tonooka, Takuji; Handa, Hirokazu

    2009-01-01

    Five barley (Hordeum vulgare) PEBP (for phosphatidylethanolamine-binding protein) genes were analyzed to clarify their functional roles in flowering using transgenic, expression, and quantitative trait locus analyses. Introduction of HvTFL1 and HvMFT1 into rice (Oryza sativa) plants did not result in any changes in flowering, suggesting that these two genes have functions distinct from flowering. Overexpression of HvFT1, HvFT2, and HvFT3 in rice resulted in early heading, indicating that these FT-like genes can act as promoters of the floral transition. HvFT1 transgenic plants showed the most robust flowering initiation. In barley, HvFT1 was expressed at the time of shoot meristem phase transition. These results suggest that HvFT1 is the key gene responsible for flowering in the barley FT-like gene family. HvFT2 transgenic plants also showed robust flowering initiation, but HvFT2 was expressed only under short-day (SD) conditions during the phase transition, suggesting that its role is limited to specific photoperiodic conditions in barley. Flowering activity in HvFT3 transgenic rice was not as strong and was modulated by the photoperiod. These results suggest that HvFT3 functions in flowering promotion but that its effect is indirect. HvFT3 expression was observed in Morex, a barley cultivar carrying a dominant allele of Ppd-H2, a major quantitative trait locus for flowering under SD conditions, although no expression was detected in Steptoe, a cultivar carrying ppd-H2. HvFT3 was expressed in Morex under both long-day and SD conditions, although its expression was increased under SD conditions. HvFT3 was mapped to chromosome 1HL, the same chromosome that carries Ppd-H2. Genomic sequence analyses revealed that Morex possesses an intact HvFT3 gene, whereas most of this gene has been lost in Steptoe. These data strongly suggest that HvFT3 may be identical to Ppd-H2. PMID:19168644

  10. Role of the PEBP4 protein in the development and metastasis of gastric cancer

    PubMed Central

    Zheng, Xuemin; Hou, Huijing; Li, Ying

    2017-01-01

    Phosphatidylethanolamine-binding protein 4 (PEBP4) has previously been reported to be upregulated in various cancers. However, the physiological functions of PEBP4 in gastric cancer are still unknown. Aiming to clarify the properties and role of PEBP4 in the development and invasion of gastric cancer, we performed several biological assays and a knockdown assay. The expression level of PEBP4 was shown to be significantly upregulated in gastric cancer tissue samples, and knockdown of the expression of PEBP4 induced significant inhibitory effects on cell proliferation, migration and invasiveness. In addition, it was demonstrated that PEBP4 was associated with the development and invasion of gastric cancer cells through activation of the PI3K/Akt signaling pathway. Our findings supported the hypothesis that PEBP4 might be a novel potential drug target for the treatment of gastric cancer. PMID:28193908

  11. An expanded clade of rodent Trim5 genes.

    PubMed

    Tareen, Semih U; Sawyer, Sara L; Malik, Harmit S; Emerman, Michael

    2009-03-15

    Trim5alpha from primates (including humans), cows, and rabbits has been shown to be an active antiviral host gene that acts against a range of retroviruses. Although this suggests that Trim5alpha may be a common antiviral restriction factor among mammals, the status of Trim5 genes in rodents has been unclear. Using genomic and phylogenetic analyses, we describe an expanded paralogous cluster of at least eight Trim5-like genes in mice (including the previously described Trim12 and Trim30 genes), and three Trim5-like genes in rats. Our characterization of the rodent Trim5 locus, and comparison to the Trim5 locus in humans, cows, and rabbits, indicates that Trim5 has undergone independent evolutionary expansions within species. Evolutionary analysis shows that rodent Trim5 genes have evolved under positive selection, suggesting evolutionary conflicts consistent with important antiviral function. Sampling six rodent Trim5 genes failed to reveal antiviral activities against a set of eight retroviral challenges, although we predict that such activities exist.

  12. Filamin A-Bound PEBP2β/CBFβ Is Retained in the Cytoplasm and Prevented from Functioning as a Partner of the Runx1 Transcription Factor

    PubMed Central

    Yoshida, Naomi; Ogata, Takehiro; Tanabe, Kenji; Li, Songhua; Nakazato, Megumi; Kohu, Kazuyoshi; Takafuta, Toshiro; Shapiro, Sandor; Ohta, Yasutaka; Satake, Masanobu; Watanabe, Toshio

    2005-01-01

    The heterodimeric transcription factor PEBP2/CBF is composed of a DNA-binding subunit, called Runx1, and a non-DNA-binding subunit, called PEBP2β/CBFβ. The Runx1 protein is detected exclusively in the nuclei of most cells and tissues, whereas PEBP2β is located in the cytoplasm. We addressed the mechanism by which PEBP2β localizes to the cytoplasm and found that it is associated with filamin A, an actin-binding protein. Filamin A retains PEBP2β in the cytoplasm, thereby hindering its engagement as a Runx1 partner. The interaction with filamin A is mediated by a region within PEBP2β that includes amino acid residues 68 to 93. The deletion of this region or the repression of filamin A enables PEBP2β to translocate to the nucleus. Based on these observations, we propose that PEBP2β has two distinct domains, a newly defined regulatory domain that interacts with filamin A and the previously identified Runx1-binding domain. PMID:15657428

  13. A polyomavirus enhancer-binding protein, PEBP5, responsive to 12-O-tetradecanoylphorbol-13-acetate but distinct from AP-1.

    PubMed Central

    Asano, M; Murakami, Y; Furukawa, K; Yamaguchi-Iwai, Y; Satake, M; Ito, Y

    1990-01-01

    Element I, homologous to the adenovirus type 5 E1A enhancer core, is a 10-bp sequence in the A core of the polyomavirus enhancer and was shown previously to be responsive to 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that element I by itself was capable of activating polyomavirus DNA replication in COP-5 cells which express the polyomavirus large T antigen. A nuclear factor, polyomavirus enhancer-binding protein 5 (PEBP5), which bound to the entire sequence of element I and was responsive to TPA was identified by an in vitro binding assay. Although the binding site of PEBP5 partly overlaps with that of PEBP1 (PEA1), a member of the AP-1 family, PEBP5 appears to be a distinct factor. Since we previously showed that element I alone was able to activate transcription, our present results suggest that PEBP5 is involved in the regulation of both transcription and replication of DNA. The amount of PEBP5 increased after F9 cells were induced to differentiate by retinoic acid. A relatively large amount of PEBP5 was detected in lymphoid and trophoblast cells. Images PMID:2173774

  14. Ligand Binding Study of Human PEBP1/RKIP: Interaction with Nucleotides and Raf-1 Peptides Evidenced by NMR and Mass Spectrometry

    PubMed Central

    Tavel, Laurette; Jaquillard, Lucie; Karsisiotis, Andreas I.; Saab, Fabienne; Jouvensal, Laurence; Brans, Alain; Delmas, Agnès F.; Schoentgen, Françoise; Cadene, Martine; Damblon, Christian

    2012-01-01

    Background Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and Alzheimer's disease. Human PEBP1 has also been shown to inhibit the Raf/MEK/ERK pathway. Numerous reports concern various mammalian PEBP1 binding ligands. However, since PEBP1 proteins from many different species were investigated, drawing general conclusions regarding human PEBP1 binding properties is rather difficult. Moreover, the binding site of Raf-1 on hPEBP1 is still unknown. Methods/Findings In the present study, we investigated human PEBP1 by NMR to determine the binding site of four different ligands: GTP, FMN, and one Raf-1 peptide in tri-phosphorylated and non-phosphorylated forms. The study was carried out by NMR in near physiological conditions, allowing for the identification of the binding site and the determination of the affinity constants KD for different ligands. Native mass spectrometry was used as an alternative method for measuring KD values. Conclusions/Significance Our study demonstrates and/or confirms the binding of hPEBP1 to the four studied ligands. All of them bind to the same region centered on the conserved ligand-binding pocket of hPEBP1. Although the affinities for GTP and FMN decrease as pH, salt concentration and temperature increase from pH 6.5/NaCl 0 mM/20°C to pH 7.5/NaCl 100 mM/30°C, both ligands clearly do bind under conditions similar to what is found in cells regarding pH, salt concentration and temperature. In addition, our work confirms that residues in the vicinity of the pocket rather than those within the pocket seem to be required for interaction with Raf-1. PMID:22558375

  15. Evolution of an expanded mannose receptor gene family.

    PubMed

    Staines, Karen; Hunt, Lawrence G; Young, John R; Butter, Colin

    2014-01-01

    Sequences of peptides from a protein specifically immunoprecipitated by an antibody, KUL01, that recognises chicken macrophages, identified a homologue of the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the genomic environment of the chicken gene revealed an array of five paralogous genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either side of the single MRC1 gene in mammals. Transcripts of all five genes were detected in RNA from a macrophage cell line and other RNAs, whose sequences allowed the precise definition of spliced exons, confirming or correcting existing bioinformatic annotation. The confirmed gene structures were used to locate orthologues of all five genes in the genomes of two other avian species and of the painted turtle, all with intact coding sequences. The lizard genome had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L-B antigen gene resulting from a recent duplication. The Xenopus genome, like that of most mammals, had only a single MRC1-like gene at the corresponding locus. MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative of similar subcellular migration and functions. Cytoplasmic regions of the other three genes were very divergent, possibly indicating the evolution of a new functional repertoire for this family of molecules, which might include novel interactions with pathogens.

  16. An expanded evolutionary role for flower symmetry genes

    PubMed Central

    2009-01-01

    CYCLOIDEA (CYC)-like TCP genes are critical for flower developmental patterning. Exciting recent breakthroughs, including a study by Song et al. published in BMC Evolutionary Biology, demonstrate that CYC-like genes have also had an important role in the evolution of flower form. See research article http://www.biomedcentral.com/1471-2148/9/244. PMID:19895716

  17. Cleavage and polyadenylation: Ending the message expands gene regulation

    PubMed Central

    Neve, Jonathan

    2017-01-01

    ABSTRACT Cleavage and polyadenylation (pA) is a fundamental step that is required for the maturation of primary protein encoding transcripts into functional mRNAs that can be exported from the nucleus and translated in the cytoplasm. 3′end processing is dependent on the assembly of a multiprotein processing complex on the pA signals that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals, resulting in alternative cleavage and polyadenylation (APA), a widespread phenomenon that is important to establish cell state and cell type specific transcriptomes. Here, we review how pA sites are recognized and comprehensively summarize how APA is regulated and creates mRNA isoform profiles that are characteristic for cell types, tissues, cellular states and disease. PMID:28453393

  18. Transcript expression bias of phosphatidylethanolamine binding protein gene in bumblebee, Bombus lantschouensis (Hymenoptera: Apidae).

    PubMed

    Dong, Jie; Han, Lei; Wang, Ye; Huang, Jiaxing; Wu, Jie

    2017-09-05

    The phosphatidylethanolamine-binding protein (PEBP) family is a highly conserved group of proteins found in a wide range of organism. It plays an important role in innate immunity of insects. Little is known on the expression characteristic and function of PEBP in bees. In the current study, we cloned the pebp gene and investigated its expression profiles at different developmental stages and reproductive status from bumblebee, Bombus lantschouensis (Vogt), which is one of the most abundant pollinators for wild plants and crops in Northern China. Two transcripts (PEBPX1 and PEBPX2) of the pebp gene were cloned for the first time. The transcript PEBPX2 lacked a signal peptide sequence compared to PEBPX1. The full-length cDNA of these two PEBP transcripts is 1005bp and 915bp, with an open reading frame of 627bp and 549bp, respectively. Transcript PEBPX2 was one order of magnitude more expressed than transcript PEBPX1 at most of the developmental stages and different reproductive status (egg-laying versus non- egg-laying females). Both of the PEBP transcripts were highly expressed in brown-eyed with light and dark pigmented cuticle pupae stages. Quantitative PCR and Western Blot demonstrated that PEBP was significantly up-regulated in egg-laying females. In summary, we suggest that levels of these two PEBPs could be related to the regulation of reproduction in bumblebees. In addition, both transcripts likely play an important role in the metamorphosis developmental stage of bumblebee pupae. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Loss of responsiveness of an AP1-related factor, PEBP1, to 12-O-tetradecanoylphorbol-13-acetate after transformation of NIH 3T3 cells by the Ha-ras oncogene

    SciTech Connect

    Sataka, Masanobu; Ibaraki, Tamotsu; Yamaguchi, Yuko; Ito, Yoshiaki )

    1989-09-01

    The function of the A element (nucleotides 5107 to 5130) of the polyomavirus enhancer is augmented in NIH 3T3 cells by a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). One of its targets is an AP1 consensus sequence motif recognized by a nuclear factor, PEBP1. In Ha-ras-transformed NIH 3T3 cells, however, A element function was not enhanced by TPA treatment, and at the same time PEBP1 was not detected in the nuclear extract by a mobility shift assay. PEBP1 was not detected in either the extract from NIH 3T3 cells treated in vivo with a protein kinase inhibitor, staurosporine, or the extract from NIH 3T3 cells after treatment in vitro with phosphatase. These results suggest that PEBP1 is required to be properly phosphorylated for DNA binding and that it is underphosphorylated, possibly due to the downregulation of protein kinase C in Ha-ras-transformed cells. In addition, it was observed that PEBP2, which bound to the A element adjacent to PEBP1, was converted to apparently related PEBP3 when conditions favored underphosphorylation.

  20. Atypical Protein Phosphatase 2A Gene Families Do Not Expand via Paleopolyploidization1[OPEN

    PubMed Central

    2017-01-01

    Protein phosphatase 2A (PP2A) presents unique opportunities for analyzing molecular mechanisms of functional divergence between gene family members. The canonical PP2A holoenzyme regulates multiple eukaryotic signaling pathways by dephosphorylating target proteins and contains a catalytic (C) subunit, a structural/scaffolding (A) subunit, and a regulatory (B) subunit. Genes encoding PP2A subunits have expanded into multigene families in both flowering plants and mammals, and the extent to which different isoform functions may overlap is not clearly understood. To gain insight into the diversification of PP2A subunits, we used phylogenetic analyses to reconstruct the evolutionary histories of PP2A gene families in Arabidopsis (Arabidopsis thaliana). Genes encoding PP2A subunits in mammals represent ancient lineages that expanded early in vertebrate evolution, while flowering plant PP2A subunit lineages evolved much more recently. Despite this temporal difference, our data indicate that the expansion of PP2A subunit gene families in both flowering plants and animals was driven by whole-genome duplications followed by nonrandom gene loss. Selection analysis suggests that the expansion of one B subunit gene family (B56/PPP2R5) was driven by functional diversification rather than by the maintenance of gene dosage. We also observed reduced expansion rates in three distinct B subunit subclades. One of these subclades plays a highly conserved role in cell division, while the distribution of a second subclade suggests a specialized function in supporting beneficial microbial associations. Thus, while whole-genome duplications have driven the expansion and diversification of most PP2A gene families, members of functionally specialized subclades quickly revert to singleton status after duplication events. PMID:28034953

  1. Association of CRISP2, CCT8, PEBP1 mRNA abundance in sperm and sire conception rate in Holstein bulls.

    PubMed

    Arangasamy, A; Kasimanickam, V R; DeJarnette, J M; Kasimanickam, R K

    2011-08-01

    The objective was to determine the association of mRNA expression of cystine rich secretary protein 2 (CRISP2), chaperonin containing T-complex protein 1, subunit 8 (CCT8), and phosphatidylethanolamine-binding protein 1 (PEBP1), in sperm of Holstein bulls with Sire Conception Rate (SCR) scores between -4 and +4. These proteins were involved in sperm capacitation and sperm-egg fusion. Samples of sperm obtained on a single day from Holstein bulls (N = 34) in a commercial AI centre were used to evaluate relative mRNA expression of CRISP2, CCT8, and PEBP1. The mRNA abundance of CRISP2 was positively correlated (r = 0.88; P < 0.002), CCT8 was negatively correlated (r = -0.87; P < 0.002), and PEBP1 was positively correlated (r = 0.83; P < 0.006) with SCR-scores. The means of CRISP2 mRNA abundance was greater among positive SCR-score bulls (2.5 to 8 fold), the means of CCT8 mRNA abundance was greater among the negative SCR-score bulls (9.5 to 3.5 fold), and the means of PEBP1 mRNA abundance was greater for the positive SCR-score bulls (5.4 to 7.7 fold). In multivariate regression models predicting SCR-scores, mRNA abundance of CCT8 was significantly associated with SCR-score in all models. In the presence of CRISP2 mRNA abundance in the model, the SCR score's predictability of PEBP1 was insignificant. However, in the absence of CRISP2 mRNA abundance in the model, the SCR-score's predictability of PEBP1 was significant. In multivariate regression models, CRISP2 and CCT8 mRNA expression in sperm accounted for 95% of the variance in Holstein bull's SCR-scores. In conclusion, Holstein bulls with greater CRISP2 and lower CCT8 mRNA expression in sperm had higher probabilities of siring calves.

  2. Multispecies Analysis of Expression Pattern Diversification in the Recently Expanded Insect Ly6 Gene Family

    PubMed Central

    Tanaka, Kohtaro; Hazbun, Alexis; Hijazi, Assia; Vreede, Barbara; Sucena, Élio

    2015-01-01

    Gene families often consist of members with diverse expression domains reflecting their functions in a wide variety of tissues. However, how the expression of individual members, and thus their tissue-specific functions, diversified during the course of gene family expansion is not well understood. In this study, we approached this question through the analysis of the duplication history and transcriptional evolution of a rapidly expanding subfamily of insect Ly6 genes. We analyzed different insect genomes and identified seven Ly6 genes that have originated from a single ancestor through sequential duplication within the higher Diptera. We then determined how the original embryonic expression pattern of the founding gene diversified by characterizing its tissue-specific expression in the beetle Tribolium castaneum, the butterfly Bicyclus anynana, and the mosquito Anopheles stephensi and those of its duplicates in three higher dipteran species, representing various stages of the duplication history (Megaselia abdita, Ceratitis capitata, and Drosophila melanogaster). Our results revealed that frequent neofunctionalization episodes contributed to the increased expression breadth of this subfamily and that these events occurred after duplication and speciation events at comparable frequencies. In addition, at each duplication node, we consistently found asymmetric expression divergence. One paralog inherited most of the tissue-specificities of the founder gene, whereas the other paralog evolved drastically reduced expression domains. Our approach attests to the power of combining a well-established duplication history with a comprehensive coverage of representative species in acquiring unequivocal information about the dynamics of gene expression evolution in gene families. PMID:25743545

  3. Histone deacetylase inhibitors induce leukemia gene expression in cord blood hematopoietic stem cells expanded ex vivo.

    PubMed

    Lam, Yuk Man; Chan, Yuen Fan; Chan, Li Chong; Ng, Ray Kit

    2017-01-01

    Umbilical cord blood is a valuable source of hematopoietic stem cells. While cytokine stimulation can induce ex vivo hematopoietic cell proliferation, attempts have been made to use epigenetic-modifying agents to facilitate stem cell expansion through the modulation of cellular epigenetic status. However, the potential global effect of these modifying agents on epigenome raises concerns about the functional normality of the expanded cells. We studied the ex vivo expansion of cord blood hematopoietic stem and progenitor cells (HSPCs) by histone deacetylase (HDAC) inhibitors, trichostatin A and valproic acid. Treatment with HDAC inhibitors resulted in mild expansion of the total hematopoietic cell number when compared with cytokine stimulated sample. Nevertheless, we observed 20-30-fold expansion of the CD34(+) CD38(-) HSPC population. Strikingly, cord blood cells cultured with HDAC inhibitors exhibited aberrant expression of leukemia-associated genes, including CDKN1C, CEBPα, HOXA9, MN1, and DLK1. Our results thus suggest that the expansion of HSPCs by this approach may provoke a pre-leukemic cell state. We propose that the alteration of epigenome by HDAC inhibitors readily expands cord blood HSPC population through the re-activation of the leukemia gene transcription. The present study provides an assessment of the leukemogenic potential of HSCs expanded ex vivo using HDAC inhibitors for clinical applications.

  4. Ibudilast reverses the decrease in the synaptic signaling protein phosphatidylethanolamine-binding protein 1 (PEBP1) produced by chronic methamphetamine intake in rats.

    PubMed

    Charntikov, Sergios; Pittenger, Steven T; Thapa, Ishwor; Bastola, Dhundy R; Bevins, Rick A; Pendyala, Gurudutt

    2015-07-01

    Chronic methamphetamine intake has been shown to induce a neuroinflammatory state leading to significant changes in brain functioning including behavioral changes. These changes can persist for years after drug use is discontinued and likely contribute to the risk of relapse. A better understanding of inflammation responses associated with methamphetamine intake may help in designing novel and more efficacious treatment strategies. Rats were trained to self-administer methamphetamine or saline on a variable ratio 3 schedule of reinforcement (25 days). This training was followed by 12 days of extinction (i.e., methamphetamine unavailable) during which rats received daily post-session administration of ibudilast (AV411; 2.5 or 7.5mg/kg) or saline. Following extinction, synaptosomes were isolated from the prefrontal cortex (PFC) and the differential pattern of synaptic proteins was assessed using mass spectrometry based proteomics. Treatment with ibudilast allowed for deeper extinction of active lever pressing. Quantitative mass spectrometry based proteomics on the PFC identified one potential hit; the synaptic signaling protein phosphatidylethanolamine-binding protein 1 (PEBP1). While methamphetamine intake was associated with reduced PEBP1 protein levels, treatment with ibudilast reversed this effect. Furthermore, decreased PEBP1 expression was correlated with subsequent activation of Raf-1, MEK, and ERK signaling components of the mitogen-activated protein kinase cascade (MAPK). Raf-1, MEK, and ERK expression levels were also attenuated by ibudilast treatment. PEBP1, given its synaptic localization and its role as a signaling molecule acting via the ERK/MAPK pathway, could be a potential therapeutic target mediating drug-seeking behaviors associated with neuroinflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. PathwaysWeb: a gene pathways API with directional interactions, expanded gene ontology, and versioning.

    PubMed

    Melott, James M; Weinstein, John N; Broom, Bradley M

    2016-01-15

    PathwaysWeb is a resource-based, well-documented web system that provides publicly available information on genes, biological pathways, Gene Ontology (GO) terms, gene-gene interaction networks (importantly, with the directionality of interactions) and links to key-related PubMed documents. The PathwaysWeb API simplifies the construction of applications that need to retrieve and interrelate information across multiple, pathway-related data types from a variety of original data sources. PathwaysBrowser is a companion website that enables users to explore the same integrated pathway data. The PathwaysWeb system facilitates reproducible analyses by providing access to all versions of the integrated datasets. Although its GO subsystem includes data for mouse, PathwaysWeb currently focuses on human data. However, pathways for mouse and many other species can be inferred with a high success rate from human pathways. PathwaysWeb can be accessed via the Internet at http://bioinformatics.mdanderson.org/main/PathwaysWeb:Overview. jmmelott@mdanderson.org Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Expanded functional diversity of shaker K(+) channels in cnidarians is driven by gene expansion.

    PubMed

    Jegla, Timothy; Marlow, Heather Q; Chen, Bihan; Simmons, David K; Jacobo, Sarah M; Martindale, Mark Q

    2012-01-01

    The genome of the cnidarian Nematostella vectensis (starlet sea anemone) provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+) channel gene family: Shaker (Kv1), Shaw (Kv3) and Shal (Kv4). In order to better understand the physiological significance of these voltage-gated K(+) channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+) channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2) family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

  7. Expanded Functional Diversity of Shaker K+ Channels in Cnidarians Is Driven by Gene Expansion

    PubMed Central

    Jegla, Timothy; Marlow, Heather Q.; Chen, Bihan; Simmons, David K.; Jacobo, Sarah M.; Martindale, Mark Q.

    2012-01-01

    The genome of the cnidarian Nematostella vectensis (starlet sea anemone) provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K+ channel gene family: Shaker (Kv1), Shaw (Kv3) and Shal (Kv4). In order to better understand the physiological significance of these voltage-gated K+ channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K+ channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct “silent” or “regulatory” phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2) family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages. PMID:23251506

  8. Positioning the expanded akirin gene family of Atlantic salmon within the transcriptional networks of myogenesis

    SciTech Connect

    Macqueen, Daniel J.; Bower, Neil I.; Johnston, Ian A.

    2010-10-01

    Research highlights: {yields} The expanded akirin gene family of Atlantic salmon was characterised. {yields} akirin paralogues are regulated between mono- and multi-nucleated muscle cells. {yields} akirin paralogues positioned within known genetic networks controlling myogenesis. {yields} Co-expression of akirin paralogues is evident across cell types/during myogenesis. {yields} Selection has likely maintained common regulatory elements among akirin paralogues. -- Abstract: Vertebrate akirin genes usually form a family with one-to-three members that regulate gene expression during the innate immune response, carcinogenesis and myogenesis. We recently established that an expanded family of eight akirin genes is conserved across salmonid fish. Here, we measured mRNA levels of the akirin family of Atlantic salmon (Salmo salar L.) during the differentiation of primary myoblasts cultured from fast-skeletal muscle. Using hierarchical clustering and correlation, the data was positioned into a network of expression profiles including twenty further genes that regulate myogenesis. akirin1(2b) was not significantly regulated during the maturation of the cell culture. akirin2(1a) and 2(1b), along with IGF-II and several igfbps, were most highly expressed in mononuclear cells, then significantly and constitutively downregulated as differentiation proceeded and myotubes formed/matured. Conversely, akirin1(1a), 1(1b), 1(2a), 2(2a) and 2(2b) were expressed at lowest levels when mononuclear cells dominated the culture and highest levels when confluent layers of myotubes were evident. However, akirin1(2a) and 2(2a) were first upregulated earlier than akirin1(1a), 1(1b) and 2(2b), when rates of myoblast proliferation were highest. Interestingly, akirin1(1b), 1(2a), 2(2a) and 2(2b) formed part of a module of co-expressed genes involved in muscle differentiation, including myod1a, myog, mef2a, 14-3-3{beta} and 14-3-3{gamma}. All akirin paralogues were expressed ubiquitously across ten

  9. Expanded natural product diversity revealed by analysis of lanthipeptide-like gene clusters in actinobacteria.

    PubMed

    Zhang, Qi; Doroghazi, James R; Zhao, Xiling; Walker, Mark C; van der Donk, Wilfred A

    2015-07-01

    Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters from Actinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities.

  10. Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

    PubMed Central

    Zhang, Qi; Doroghazi, James R.; Zhao, Xiling; Walker, Mark C.

    2015-01-01

    Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters from Actinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities. PMID:25888176

  11. Covariation in stress and immune gene expression in a range expanding bird.

    PubMed

    Martin, Lynn B; Liebl, Andrea L; Kilvitis, Holly J

    2015-01-15

    The enemy release hypothesis (ERH) posits that hosts encounter fewer infectious parasites when they arrive in new areas, so individuals that adjust their immune defenses most effectively should thrive and even expand the range of that species. An important aspect of vertebrate immune defense is inflammation, as it provides rapid defense against diverse parasites. Glucocorticoids (GCs) are integral to the regulation of inflammation, so here we investigated whether and how covariation in the expression of genes affecting the regulation of inflammation and GCs might have impacted the house sparrow (Passer domesticus) invasion of Kenya. Toll-like receptors 2 and 4 (TLRs) detect microbial threats and instigate inflammatory responses, whereas the glucocorticoid receptor (GR) is integral to resolving inflammation via both local and systemic pathways. As with a previous study on circulating leukocytes, we found that splenic TLR-4 and TLR-2 (the latter marginally non-significant) expression was higher in younger than older populations but only when differences in spleen size were considered; birds at the range edge had larger spleens. In regards to covariation, we found that TLR-2, TLR-4 and GR expression were closely inter-related within individuals, but covariation did not differ among populations. Subsequently, our data suggest that house sparrows are using variants of a common stress-immune regulatory mechanism to expand their Kenyan range.

  12. The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination.

    PubMed

    Laube, Beth L

    2005-09-01

    Aerosolized medications have been used for centuries to treat respiratory diseases. Until recently, inhalation therapy focused primarily on the treatment of asthma and chronic obstructive pulmonary disease, and the pressurized metered-dose inhaler was the delivery device of choice. However, the role of aerosol therapy is clearly expanding beyond that initial focus. This expansion has been driven by the Montreal protocol and the need to eliminate chlorofluorocarbons (CFCs) from traditional metered-dose inhalers, by the need for delivery devices and formulations that can efficiently and reproducibly target the systemic circulation for the delivery of proteins and peptides, and by developments in medicine that have made it possible to consider curing lung diseases with aerosolized gene therapy and preventing epidemics of influenza and measles with aerosolized vaccines. Each of these drivers has contributed to a decade or more of unprecedented research and innovation that has altered how we think about aerosol delivery and has expanded the role of aerosol therapy into the fields of systemic drug delivery, gene therapy, and vaccination. During this decade of innovation, we have witnessed the coming of age of dry powder inhalers, the development of new soft mist inhalers, and improved pressurized metered-dose inhaler delivery as a result of the replacement of CFC propellants with hydrofluoroalkane. The continued expansion of the role of aerosol therapy will probably depend on demonstration of the safety of this route of administration for drugs that have their targets outside the lung and are administered long term (eg, insulin aerosol), on the development of new drugs and drug carriers that can efficiently target hard-to-reach cell populations within the lungs of patients with disease (eg, patients with cystic fibrosis or lung cancer), and on the development of devices that improve aerosol delivery to infants, so that early intervention in disease processes with aerosol

  13. Expanding the view of Clock and cycle gene evolution in Diptera.

    PubMed

    Chahad-Ehlers, S; Arthur, L P; Lima, A L A; Gesto, J S M; Torres, F R; Peixoto, A A; de Brito, R A

    2017-02-24

    We expanded the view of Clock (Clk) and cycle (cyc) gene evolution in Diptera by studying the fruit fly Anastrepha fraterculus (Afra), a Brachycera. Despite the high conservation of clock genes amongst insect groups, striking structural and functional differences of some clocks have appeared throughout evolution. Clk and cyc nucleotide sequences and corresponding proteins were characterized, along with their mRNA expression data, to provide an evolutionary overview in the two major groups of Diptera: Lower Diptera and Higher Brachycera. We found that AfraCYC lacks the BMAL (Brain and muscle ARNT-like) C-terminus region (BCTR) domain and is constitutively expressed, suggesting that AfraCLK has the main transactivation function, which is corroborated by the presence of poly-Q repeats and an oscillatory pattern. Our analysis suggests that the loss of BCTR in CYC is not exclusive of drosophilids, as it also occurs in other Acalyptratae flies such as tephritids and drosophilids, however, but it is also present in some Calyptratae, such as Muscidae, Calliphoridae and Sarcophagidae. This indicates that BCTR is missing from CYC of all higher-level Brachycera and that it was lost during the evolution of Lower Brachycera. Thus, we can infer that CLK protein may play the main role in the CLK\\CYC transcription complex in these flies, like in its Drosophila orthologues.

  14. Genomics of crop wild relatives: expanding the gene pool for crop improvement.

    PubMed

    Brozynska, Marta; Furtado, Agnelo; Henry, Robert J

    2016-04-01

    Plant breeders require access to new genetic diversity to satisfy the demands of a growing human population for more food that can be produced in a variable or changing climate and to deliver the high-quality food with nutritional and health benefits demanded by consumers. The close relatives of domesticated plants, crop wild relatives (CWRs), represent a practical gene pool for use by plant breeders. Genomics of CWR generates data that support the use of CWR to expand the genetic diversity of crop plants. Advances in DNA sequencing technology are enabling the efficient sequencing of CWR and their increased use in crop improvement. As the sequencing of genomes of major crop species is completed, attention has shifted to analysis of the wider gene pool of major crops including CWR. A combination of de novo sequencing and resequencing is required to efficiently explore useful genetic variation in CWR. Analysis of the nuclear genome, transcriptome and maternal (chloroplast and mitochondrial) genome of CWR is facilitating their use in crop improvement. Genome analysis results in discovery of useful alleles in CWR and identification of regions of the genome in which diversity has been lost in domestication bottlenecks. Targeting of high priority CWR for sequencing will maximize the contribution of genome sequencing of CWR. Coordination of global efforts to apply genomics has the potential to accelerate access to and conservation of the biodiversity essential to the sustainability of agriculture and food production. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  15. Expanded IT-15 genes in patients without known family history of Huntington Disease

    SciTech Connect

    Buchanan, J.A.; Klock, R.J.; Kennedu, D.

    1994-09-01

    The NYGH laboratory is funded by the Ontario Ministry of Health to provide DNA-based diagnostic and predictive testing for HD through a network of provincial Genetics centres. To date, samples from 146 apparently independent kindreds were received to test and/or bank for HD. Not all have been assayed for size of the IT-15 gene, but in 19 cases an expansion (> 39 CAG repeats) was found despite lack of known family history. These cases were classified according to the likelihood that they are true {open_quotes}new{close_quotes} full expansions in IT-15. Six were unlikely, due to a lack of information (adoption, history uncertain, or pedigree not provided). Ten cases were considered possible or probable based on a good negative family history with parents who were asymptomatic beyond age 50 but family samples unavailable. For one of those, parents are deceased, but inference of parental alleles from the proband`s sibship suggests a pre-mutation allele of approximately 30 repeats. In 3 cases, a new expansion was considered proven. One was first ascertained by another laboratory and reported elsewhere. For another, the proband`s father has one allele of about 35 repeats. In a third remarkable case, the proband has an expanded allele near 50 repeats and a normal sized allele that matches one maternal allele. The father`s larger allele has 30+/-1 repeats. Paternity was established by concordance of 10 independent polymorphic alleles. Additional family samples may help to assess the allelic stability. This prevalence of new HD cases was unanticipated before discovery of the predisposing gene, but has emerged over the first year of direct diagnostic testing and may foreshadow greater demand for testing as the extended families become aware of their risks. These cases provoke new questions about interpretation of DNA data for patients, raise ethical concerns about informing extended families, and special counselling issues for families to whom HD is a new entity.

  16. Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.

    PubMed

    Mariani, Louise-Laure; Tesson, Christelle; Charles, Perrine; Cazeneuve, Cécile; Hahn, Valérie; Youssov, Katia; Freeman, Leorah; Grabli, David; Roze, Emmanuel; Noël, Sandrine; Peuvion, Jean-Noel; Bachoud-Levi, Anne-Catherine; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra

    2016-09-01

    Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units. However, not all patients with an HD phenotype carry the pathological expansion in HTT, and the positive diagnosis rate is poor. To examine patients with HD phenotypes to determine the frequency of HD phenocopies with typical features of HD but without pathological CAG repeat expansions in HTT in an attempt to improve the positive diagnosis rate. Between January 1, 2004, and April 18, 2011, a total of 226 consecutive index patients with an HD phenotype were referred to specialized clinics of the French National Huntington Disease Reference Centre for Rare Diseases. They underwent detailed clinical examination and follow-up, as well as neuropsychological, biological, imaging, and genetic examinations. Nucleotide expansions in JPH3, ATN1, TBP, and C9ORF72 and mutations in PRNP, as well as acquired conditions commonly causing HD phenocopies, were first screened. The diagnostic rate of HD phenocopies and frequency of other etiologies using deep clinical phenotyping and next generation sequencing. Our goal was to improve the genetic diagnosis of HD phenocopies and to identify new HD related genes. One hundred ninety-eight patients carried a pathological CAG repeat expansion in HTT, whereas 28 patients (12 women and 16 men) did not. Huntington disease phenocopies accounted for 12.4%, and their mean (SD) age at onset was similar to those of the HD-HTT group (47.3 [12.7] years vs 50.3 [16.4] years, P = .29). We first identified 3 patients with abnormal CTG expansions in JPH3, a fourth patient with an antiphospholipid syndrome, and a fifth patient with B12 avitaminosis. A custom-made 63-gene panel was generated based on clinical evolution and exome sequencing. It contained genes responsible for HD phenocopies and other neurodegenerative conditions, as well as candidate genes from exome sequencing in 3 index cases with imaging features of brain

  17. In vitro gene and chromosome characterization of expanded bone marrow mesenchymal stem cells for musculo-skeletal applications.

    PubMed

    Roseti, L; Serra, M; Canella, F; Munno, C; Tosi, A; Zuntini, M; Pandolfi, M; Sangiorgi, L; Biso, P; Pittalis, M C; Bini, C; Pelotti, S; Gasbarrini, A; Boriani, L; Bassi, A; Grigolo, B

    2014-01-01

    A number of studies have shown the role of expanded Bone Marrow-derived Mesenchymal Stem Cells in the repair and regeneration of musculo-skeletal tissues. The current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced-Therapy Medicinal Products to be manufactured in compliance with current Good Manufacturing Practice. Among the characteristics that such cells should display, genomic stability has recently become a major safety concern. The aim of this study is to perform a chromosomal and genetic characterization of Bone Marrow-derived Mesenchymal Stem Cells expanded in compliance with Good Manufacturing Practice for a potential clinical use in orthopaedics. Mesenchymal Stem Cells, isolated from bone marrow, were expanded for six weeks in compliance with current Good Manufacturing Practice. DNA profiling analyses were applied to test cross-contamination absence. Genomic stability was evaluated by means of karyotyping, sequencing of TP53, p21/CDKN1A and MDM2 genes and the expression analysis of c-MYC and H-RAS oncogenes, p21/CDKN1A, TP53, p16/CDKN2A, RB1 and p27/CDKN1B tumor suppressor genes and hTERT gene. The DNA profiling analysis showed a unique genetic profile for each Mesenchymal Stem Cell culture, indicating the absence of cross-contamination. Karyotyping evidentiated some chromosomal abnormalities within the 10% limit set by the Cell Products Working Party review, except for one patient. In all cases, the molecular biology analyses did not revealed DNA point mutations, acquisition or changes in gene expression. hTERT levels were undetectable. Cultured Mesenchymal Stem Cells do not seem to be prone to malignant transformation. In fact, although some chromosomal aberrations were found, molecular biology analyses demonstrated that the expansion phase did not induce the acquisition of de novo genetic changes.

  18. Structure and expression of the Huntington's disease gene: Evidence against simple inactivation due to an expanded CAG repeat

    SciTech Connect

    Ambrose, C.M.; Duyao, M.P.; Barnes, G.; Lin, C.S.; Srinidhi, J. ); Bates, G.P.; Baxendale, S.; Hummerich, H.; Lehrach, H. ); Altherr, M. )

    1994-01-01

    Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expanded, unstable trinucleotide repeat in a novel 4p16.3 gene. To lay the foundation for exploring the pathogenic mechanism in HD, the authors have determined the structure of the disease gene and examined its expression. The HD locus spans 180 kb and consists of 67 exons ranging in size from 48 bp to 341 bp with an average of 138 bp. Scanning of the HD transcript failed to reveal any additional sequence alterations characteristic of HD chromosomes. A codon loss polymorphism in linkage disequilibrium with the disorder revealed that both normal and HD alleles are represented in the mRNA population in HD heterozygotes, indicating that the defect does not eliminate transcription. The gene is ubiquitously expressed as two alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues, suggesting the operation of interacting factors in determining specificity of cell loss. The HD gene was disrupted in a female carrying a balanced translocation with a breakpoint between exons 40 and 41. The absence of any abnormal phenotype in this individual argues against simple inactivation of the gene as the mechanism by which the expanded trinucleotide repeat causes HD. Taken together, these observations suggest that the dominant HD mutation either confers a new property on the mRNA or, more likely, alters an interaction at the protein level.

  19. Identification of genes containing expanded purine repeats in the human genome and their apparent protective role against cancer.

    PubMed

    Singh, Himanshu Narayan; Rajeswari, Moganty R

    2016-01-01

    Purine repeat sequences present in a gene are unique as they have high propensity to form unusual DNA-triple helix structures. Friedreich's ataxia is the only human disease that is well known to be associated with DNA-triplexes formed by purine repeats. The purpose of this study was to recognize the expanded purine repeats (EPRs) in human genome and find their correlation with cancer pathogenesis. We developed "PuRepeatFinder.pl" algorithm to identify non-overlapping EPRs without pyrimidine interruptions in the human genome and customized for searching repeat lengths, n ≥ 200. A total of 1158 EPRs were identified in the genome which followed Wakeby distribution. Two hundred and ninety-six EPRs were found in geneic regions of 282 genes (EPR-genes). Gene clustering of EPR-genes was done based on their cellular function and a large number of EPR-genes were found to be enzymes/enzyme modulators. Meta-analysis of 282 EPR-genes identified only 63 EPR-genes in association with cancer, mostly in breast, lung, and blood cancers. Protein-protein interaction network analysis of all 282 EPR-genes identified proteins including those in cadherins and VEGF. The two observations, that EPRs can induce mutations under malignant conditions and that identification of some EPR-gene products in vital cell signaling-mediated pathways, together suggest the crucial role of EPRs in carcinogenesis. The new link between EPR-genes and their functionally interacting proteins throws a new dimension in the present understanding of cancer pathogenesis and can help in planning therapeutic strategies. Validation of present results using techniques like NGS is required to establish the role of the EPR genes in cancer pathology.

  20. GExplore 1.4: An expanded web interface for queries on Caenorhabditis elegans protein and gene function

    PubMed Central

    Hutter, Harald; Suh, Jinkyo

    2016-01-01

    ABSTRACT Genetic high-throughput experiments often result in hundreds or thousands of genes satisfying certain experimental conditions. Grouping and prioritizing a large number of genes for further analysis can be a time-consuming challenge. In 2009 we developed a web-based user interface, GExplore, to assist with large-scale data-mining related to gene function in Caenorhabditis elegans. The underlying database contained information about Caenorhabditis elegans genes and proteins including domain organization of the proteins, phenotypic descriptions, expression data and Gene Ontology Consortium annotations. These data enable users to quickly obtain an overview of biological and biochemical functions of a large number of genes at once. Since its inception the underlying database has been updated and expanded significantly. Here we describe the current version of GExplore 1.4, documenting the changes since the original release. GExplore 1.4 now contains information about the domain organization of the proteomes of 9 nematode species, can display the location of Caenorhabditis elegans mutations with respect to the domain organization of the proteins, and includes stage-specific RNAseq gene expression data generated by the modENCODE project. The underlying database has been reorganized to facilitate independent updates of the different parts of the database and to allow the addition of novel data sets in the future. The web interface is available under http://genome.sfu.ca/gexplore. PMID:28090394

  1. GExplore 1.4: An expanded web interface for queries on Caenorhabditis elegans protein and gene function.

    PubMed

    Hutter, Harald; Suh, Jinkyo

    2016-01-01

    Genetic high-throughput experiments often result in hundreds or thousands of genes satisfying certain experimental conditions. Grouping and prioritizing a large number of genes for further analysis can be a time-consuming challenge. In 2009 we developed a web-based user interface, GExplore, to assist with large-scale data-mining related to gene function in Caenorhabditis elegans. The underlying database contained information about Caenorhabditis elegans genes and proteins including domain organization of the proteins, phenotypic descriptions, expression data and Gene Ontology Consortium annotations. These data enable users to quickly obtain an overview of biological and biochemical functions of a large number of genes at once. Since its inception the underlying database has been updated and expanded significantly. Here we describe the current version of GExplore 1.4, documenting the changes since the original release. GExplore 1.4 now contains information about the domain organization of the proteomes of 9 nematode species, can display the location of Caenorhabditis elegans mutations with respect to the domain organization of the proteins, and includes stage-specific RNAseq gene expression data generated by the modENCODE project. The underlying database has been reorganized to facilitate independent updates of the different parts of the database and to allow the addition of novel data sets in the future. The web interface is available under http://genome.sfu.ca/gexplore.

  2. Virulence Genes in Expanded-Spectrum-Cephalosporin-Resistant and -Susceptible Escherichia coli Isolates from Treated and Untreated Chickens.

    PubMed

    Baron, S; Delannoy, S; Bougeard, S; Larvor, E; Jouy, E; Balan, O; Fach, P; Kempf, I

    2015-12-14

    This study investigated antimicrobial resistance, screened for the presence of virulence genes involved in intestinal infections, and determined phylogenetic groups of Escherichia coli isolates from untreated poultry and poultry treated with ceftiofur, an expanded-spectrum cephalosporin. Results show that none of the 76 isolates appeared to be Shiga toxin-producing E. coli or enteropathogenic E. coli. All isolates were negative for the major virulence factors/toxins tested (ehxA, cdt, heat-stable enterotoxin [ST], and heat-labile enterotoxin [LT]). The few virulence genes harbored in isolates generally did not correlate with isolate antimicrobial resistance or treatment status. However, some of the virulence genes were significantly associated with certain phylogenetic groups.

  3. geneLAB: Expanding the Impact of NASA's Biological Research in Space

    NASA Technical Reports Server (NTRS)

    Rayl, Nicole; Smith, Jeffrey D.

    2014-01-01

    The geneLAB project is designed to leverage the value of large 'omics' datasets from molecular biology projects conducted on the ISS by making these datasets available, citable, discoverable, interpretable, reusable, and reproducible. geneLAB will create a collaboration space with an integrated set of tools for depositing, accessing, analyzing, and modeling these diverse datasets from spaceflight and related terrestrial studies.

  4. The alleles at the E1 locus impact the expression pattern of two soybean FT-like genes shown to induce flowering in Arabidopsis

    USDA-ARS?s Scientific Manuscript database

    A small gene family of phosphatidyl ethanolamine-binding proteins (PEBP) has been shown to function as key regulators in flowering; inArabidopsis thaliana the FT protein promotes flowering whilst theclosely related TFL1 protein represses flowering. Control of flowering time in soybean [Glycine max ...

  5. The rapid generation of chimerical genes expanding protein diversity in zebrafish.

    PubMed

    Fu, Beide; Chen, Ming; Zou, Ming; Long, Manyuan; He, Shunping

    2010-11-24

    Variation of gene number among species indicates that there is a general process of new gene origination. One of the major mechanism providing raw materials for the origin of new genes is gene duplication. Retroposition, as a special type of gene duplication- the RNA-based duplication, has been found to play an important role in new gene evolution in mammals and plants, but little is known about the process in the teleostei genome. Here we screened the zebrafish genome for identification of retrocopies and new chimerical retrogenes and investigated their origination and evolution. We identified 652 retrocopies, of which 440 are intact retrogenes and 212 are pseudogenes. Retrocopies have long been considered evolutionary dead ends without functional significance due to the presumption that retrocopies lack the regulatory element needed for expression. However, 437 transcribed retrocopies were identified from all of the retrocopies. This discovery combined with the substitution analysis suggested that the majority of all retrocopies are subject to negative selection, indicating that most of the retrocopies may be functional retrogenes. Moreover, we found that 95 chimerical retrogenes had recruited new sequences from neighboring genomic regions that formed de novo splice sites, thus generating new intron-containing chimeric genes. Based on our analysis of 38 pairs of orthologs between Cyprinus carpio and Danio rerio, we found that the synonymous substitution rate of zebrafish genes is 4.13×10⁻⁹ substitution per silent site per year. We also found 10 chimerical retrogenes that were created in the last 10 million years, which is 7.14 times the rate of 0.14 chimerical retrogenes per million years in the primate lineage toward human and 6.25 times the rate of 0.16 chimerical genes per million years in Drosophila. This is among the most rapid rates of generation of chimerical genes, just next to the rice. There is compelling evidence that much of the extensive

  6. IL-17 Induces an Expanded Range of Downstream Genes in Reconstituted Human Epidermis Model

    PubMed Central

    Chiricozzi, Andrea; Nograles, Kristine E.; Johnson-Huang, Leanne M.; Fuentes-Duculan, Judilyn; Cardinale, Irma; Bonifacio, Kathleen M.; Gulati, Nicholas; Mitsui, Hiroshi; Guttman-Yassky, Emma

    2014-01-01

    Background IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro. Methodology/Principal Findings Given the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that C/CAAT-enhancer-binding proteins (C/EBP) -β, the transcription factor regulating IL-17-responsive genes, is expressed preferentially in differentiated keratinocytes. Conclusions/Significance The genes identified in IL-17-treated RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti-IL-17A agent) strongly suppressed the “RHE” genes in psoriasis patients treated in vivo with this IL-17 antagonist. PMID:24587313

  7. Expanding Duplication of Free Fatty Acid Receptor-2 (GPR43) Genes in the Chicken Genome.

    PubMed

    Meslin, Camille; Desert, Colette; Callebaut, Isabelle; Djari, Anis; Klopp, Christophe; Pitel, Frédérique; Leroux, Sophie; Martin, Pascal; Froment, Pascal; Guilbert, Edith; Gondret, Florence; Lagarrigue, Sandrine; Monget, Philippe

    2015-04-24

    Free fatty acid receptors (FFAR) belong to a family of five G-protein coupled receptors that are involved in the regulation of lipid metabolism, so that their loss of function increases the risk of obesity. The aim of this study was to determine the expansion of genes encoding paralogs of FFAR2 in the chicken, considered as a model organism for developmental biology and biomedical research. By estimating the gene copy number using quantitative polymerase chain reaction, genomic DNA resequencing, and RNA sequencing data, we showed the existence of 23 ± 1.5 genes encoding FFAR2 paralogs in the chicken genome. The FFAR2 paralogs shared an identity from 87.2% up to 99%. Extensive gene conversion was responsible for this high degree of sequence similarities between these genes, and this concerned especially the four amino acids known to be critical for ligand binding. Moreover, elevated nonsynonymous/synonymous substitution ratios on some amino acids within or in close-vicinity of the ligand-binding groove suggest that positive selection may have reduced the effective rate of gene conversion in this region, thus contributing to diversify the function of some FFAR2 paralogs. All the FFAR2 paralogs were located on a microchromosome in a same linkage group. FFAR2 genes were expressed in different tissues and cells such as spleen, peripheral blood mononuclear cells, abdominal adipose tissue, intestine, and lung, with the highest rate of expression in testis. Further investigations are needed to determine whether these chicken-specific events along evolution are the consequence of domestication and may play a role in regulating lipid metabolism in this species.

  8. Expanding Duplication of Free Fatty Acid Receptor-2 (GPR43) Genes in the Chicken Genome

    PubMed Central

    Meslin, Camille; Desert, Colette; Callebaut, Isabelle; Djari, Anis; Klopp, Christophe; Pitel, Frédérique; Leroux, Sophie; Martin, Pascal; Froment, Pascal; Guilbert, Edith; Gondret, Florence; Lagarrigue, Sandrine; Monget, Philippe

    2015-01-01

    Free fatty acid receptors (FFAR) belong to a family of five G-protein coupled receptors that are involved in the regulation of lipid metabolism, so that their loss of function increases the risk of obesity. The aim of this study was to determine the expansion of genes encoding paralogs of FFAR2 in the chicken, considered as a model organism for developmental biology and biomedical research. By estimating the gene copy number using quantitative polymerase chain reaction, genomic DNA resequencing, and RNA sequencing data, we showed the existence of 23 ± 1.5 genes encoding FFAR2 paralogs in the chicken genome. The FFAR2 paralogs shared an identity from 87.2% up to 99%. Extensive gene conversion was responsible for this high degree of sequence similarities between these genes, and this concerned especially the four amino acids known to be critical for ligand binding. Moreover, elevated nonsynonymous/synonymous substitution ratios on some amino acids within or in close-vicinity of the ligand-binding groove suggest that positive selection may have reduced the effective rate of gene conversion in this region, thus contributing to diversify the function of some FFAR2 paralogs. All the FFAR2 paralogs were located on a microchromosome in a same linkage group. FFAR2 genes were expressed in different tissues and cells such as spleen, peripheral blood mononuclear cells, abdominal adipose tissue, intestine, and lung, with the highest rate of expression in testis. Further investigations are needed to determine whether these chicken-specific events along evolution are the consequence of domestication and may play a role in regulating lipid metabolism in this species. PMID:25912043

  9. The expanding universe of transposon technologies for gene and cell engineering.

    PubMed

    Ivics, Zoltán; Izsvák, Zsuzsanna

    2010-12-07

    Transposable elements can be viewed as natural DNA transfer vehicles that, similar to integrating viruses, are capable of efficient genomic insertion. The mobility of class II transposable elements (DNA transposons) can be controlled by conditionally providing the transposase component of the transposition reaction. Thus, a DNA of interest (be it a fluorescent marker, a small hairpin (sh)RNA expression cassette, a mutagenic gene trap or a therapeutic gene construct) cloned between the inverted repeat sequences of a transposon-based vector can be used for stable genomic insertion in a regulated and highly efficient manner. This methodological paradigm opened up a number of avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture, the production of germline transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species, and therapy of genetic disorders in humans. Sleeping Beauty (SB) was the first transposon shown to be capable of gene transfer in vertebrate cells, and recent results confirm that SB supports a full spectrum of genetic engineering including transgenesis, insertional mutagenesis, and therapeutic somatic gene transfer both ex vivo and in vivo. The first clinical application of the SB system will help to validate both the safety and efficacy of this approach. In this review, we describe the major transposon systems currently available (with special emphasis on SB), discuss the various parameters and considerations pertinent to their experimental use, and highlight the state of the art in transposon technology in diverse genetic applications.

  10. Surface markers and gene expression to characterize the differentiation of monolayer expanded human articular chondrocytes.

    PubMed

    Hamada, Takashi; Sakai, Tadahiro; Hiraiwa, Hideki; Nakashima, Motoshige; Ono, Yohei; Mitsuyama, Hirohito; Ishiguro, Naoki

    2013-02-01

    Autologous chondrocyte implantation (ACI) is a method of cartilage repair. To improve the quality of regenerated tissue by ACI, it is essential to identify surface marker expression correlated with the differentiation status of monolayer expanded human articular chondrocytes and to define the index for discriminating dedifferentiated cells from monolayer expanded human articular chondrocytes. Normal human articular chondrocytes were cultured in monolayer until passage 4. At each passage, mRNA expression of collagen type I, II, and X and aggrecan was analyzed by real-time quantitative PCR, and the surface marker expression of CD14, CD26, CD44, CD49a, CD49c, CD54, and CD151 was analyzed by fluorescence-activated cell sorting (FACS). The ratios of mRNA levels of collagen type II to I (Col II/Col I) represented the differentiation status of chondrocytes more appropriately during monolayer culture. The surface marker expression of CD44, CD49c, and CD151 was upregulated according to the dedifferentiation status, whereas that of CD14, CD49a, and CD54 was downregulated. The most appropriate combination of the ratio of Col II/Col I was CD54 and CD44. Cell sorting was performed using a magnetic cell sorting system (MACS) according to CD54 and CD44, and real-time quantitative PCR was performed for the cell subpopulations before and after cell sorting. The expression of collagen type II and aggrecan of the chondrocytes after MACS was higher than that before sorting, but not significantly. The mean fluorescence intensity (MFI) ratio of CD54 to CD44 could be an adequate candidate as the index of the differentiation status.

  11. Neonatal Diabetes: An Expanding List of Genes Allows for Improved Diagnosis and Treatment

    PubMed Central

    Naylor, Rochelle N.; Philipson, Louis H.; Bell, Graeme I.

    2011-01-01

    There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (KATP), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. This compelling example of personalized genetic medicine leading to improved glucose regulation and quality of life may—with continued research—be repeated for other forms of neonatal diabetes in the future. PMID:21993633

  12. Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

    PubMed Central

    Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

    2013-01-01

    After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

  13. Identification of a uniquely expanded V1R (ORA) gene family in the Japanese grenadier anchovy (Coilia nasus).

    PubMed

    Zhu, Guoli; Tang, Wenqiao; Wang, Liangjiang; Wang, Cong; Wang, Xiaomei

    A number of studies have suggested that olfaction plays an important role in fish migration. Fish use several distinct families of olfactory receptors to detect environmental odorants, including MORs (main olfactory receptors), V1Rs (vomeronasal type-1 receptors), V2Rs (vomeronasal type-2 receptors), TAARs (trace amine-associated receptors), and FPRs (formyl peptide receptors). The V1Rs have been reported to detect pheromones, and a pheromone hypothesis for the spawning migration of anadromous fish has been proposed. Examining whether Coilia nasus relies on V1R-mediated olfaction for spawning migration is important for understanding the molecular basis of spawning migration behavior. Here, we explored the V1R gene family in anadromous C. nasus. Six V1R genes previously reported in other teleost fish were successfully identified. Interestingly, we detected the largest V1R repertoire in teleost fish from C. nasus and identified a species-specific expansion event of V1R3 gene that has previously been detected as single-copy genes in other teleost fish. The V1R loci were found to be populated with repetitive sequences, especially in the expanded V1R3 genes. Additionally, the divergence of V1R3 genetic structures in different populations of C. nasus indicates the copy number variation (CNV) in V1R3 gene among individuals of C. nasus. Most of the putative C. nasus V1R genes were expressed primarily in the olfactory epithelium, consistent with the role of the gene products as functional olfactory receptors. Significant differences in the expression levels of V1R genes were detected between the anadromous and non-anadromous C. nasus. This study represents a first step in the elucidation of the olfactory communication system of C. nasus at the molecular level. Our results indicate that some V1R genes may be involved in the spawning migration of C. nasus, and the study provides new insights into the spawning migration and genome evolution of C. nasus.

  14. Expanding the environment: gene × school-level SES interaction on reading comprehension.

    PubMed

    Hart, Sara A; Soden, Brooke; Johnson, Wendy; Schatschneider, Christopher; Taylor, Jeanette

    2013-10-01

    Influential work has explored the role of family socioeconomic status (SES) as an environmental moderator of genetic and environmental influences on cognitive outcomes. This work has provided evidence that socioeconomic circumstances differentially impact the heritability of cognitive abilities, generally supporting the bioecological model in that genetic influences are greater at higher levels of family SES. The present work expanded consideration of the environment, using school-level SES as a moderator of reading comprehension. The sample included 577 pairs of twins from the Florida Twin Project on Reading, Behavior and Environment. Reading comprehension was measured by the Florida Comprehensive Achievement Test (FCAT) Reading in third or fourth grade. School-level SES was measured by the mean Free and Reduced Lunch Status (FRLS) of the schoolmates of the twins. The best-fitting univariate G × E moderation model indicated greater genetic influences on reading comprehension when fewer schoolmates qualified for FRLS (i.e., 'higher' school-level SES). There was also an indication of moderation of the shared environment; there were greater shared environmental influences on reading comprehension at higher school-level SES. The results supported the bioecological model; greater genetic variance was found in school environments in which student populations experienced less poverty. In general, 'higher' school-level SES allowed genetic and probably shared environmental variance to contribute as sources of individual differences in reading comprehension outcomes. Poverty suppresses these influences. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

  15. Expanding the environment: Gene × School-Level SES Interaction on Reading Comprehension

    PubMed Central

    Hart, Sara A.; Soden, Brooke; Johnson, Wendy; Schatschneider, Christopher; Taylor, Jeanette

    2013-01-01

    Background Influential work has explored the role of family socioeconomic status (SES) as an environmental moderator of genetic and environmental influences on cognitive outcomes. This work has provided evidence that socioeconomic circumstances differentially impact the heritability of cognitive abilities, generally supporting the bioecological model in that genetic influences are greater at higher levels of family SES. The present work expanded consideration of the environment, using school-level SES as a moderator of reading comprehension. Methods The sample included 577 pairs of twins from the Florida Twin Project on Reading, Behavior and Environment. Reading comprehension was measured by the Florida Comprehensive Achievement Test (FCAT) Reading in third or fourth grade. School-level SES was measured by the mean Free and Reduced Lunch Status (FRLS) of the schoolmates of the twins. Results The best-fitting univariate G × E moderation model indicated greater genetic influences on reading comprehension when fewer schoolmates qualified for FRLS (i.e., “higher” school-level SES). There was also an indication of moderation of the shared environment; there were greater shared environmental influences on reading comprehension at higher school-level SES. Conclusions The results supported the bioecological model; greater genetic variance was found in school environments in which student populations experienced less poverty. In general, “higher” school-level SES allowed genetic and probably shared environmental variance to contribute as sources of individual differences in reading comprehension outcomes. Poverty suppresses these influences. PMID:23725549

  16. Globularity and language-readiness: generating new predictions by expanding the set of genes of interest

    PubMed Central

    Boeckx, Cedric; Benítez-Burraco, Antonio

    2014-01-01

    This study builds on the hypothesis put forth in Boeckx and Benítez-Burraco (2014), according to which the developmental changes expressed at the levels of brain morphology and neural connectivity that resulted in a more globular braincase in our species were crucial to understand the origins of our language-ready brain. Specifically, this paper explores the links between two well-known ‘language-related’ genes like FOXP2 and ROBO1 implicated in vocal learning and the initial set of genes of interest put forth in Boeckx and Benítez-Burraco (2014), with RUNX2 as focal point. Relying on the existing literature, we uncover potential molecular links that could be of interest to future experimental inquiries into the biological foundations of language and the testing of our initial hypothesis. Our discussion could also be relevant for clinical linguistics and for the interpretation of results from paleogenomics. PMID:25505436

  17. Globularity and language-readiness: generating new predictions by expanding the set of genes of interest.

    PubMed

    Boeckx, Cedric; Benítez-Burraco, Antonio

    2014-01-01

    This study builds on the hypothesis put forth in Boeckx and Benítez-Burraco (2014), according to which the developmental changes expressed at the levels of brain morphology and neural connectivity that resulted in a more globular braincase in our species were crucial to understand the origins of our language-ready brain. Specifically, this paper explores the links between two well-known 'language-related' genes like FOXP2 and ROBO1 implicated in vocal learning and the initial set of genes of interest put forth in Boeckx and Benítez-Burraco (2014), with RUNX2 as focal point. Relying on the existing literature, we uncover potential molecular links that could be of interest to future experimental inquiries into the biological foundations of language and the testing of our initial hypothesis. Our discussion could also be relevant for clinical linguistics and for the interpretation of results from paleogenomics.

  18. Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent functional genomics approach.

    PubMed

    Rodd, Z A; Bertsch, B A; Strother, W N; Le-Niculescu, H; Balaraman, Y; Hayden, E; Jerome, R E; Lumeng, L; Nurnberger, J I; Edenberg, H J; McBride, W J; Niculescu, A B

    2007-08-01

    We describe a comprehensive translational approach for identifying candidate genes for alcoholism. The approach relies on the cross-matching of animal model brain gene expression data with human genetic linkage data, as well as human tissue data and biological roles data, an approach termed convergent functional genomics. An analysis of three animal model paradigms, based on inbred alcohol-preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to treatments with alcohol, was used. A comprehensive analysis of microarray gene expression data from five key brain regions (frontal cortex, amygdala, caudate-putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like integration of multiple independent lines of evidence, each by itself lacking sufficient discriminatory power, led to the identification of high probability candidate genes, pathways and mechanisms for alcoholism. These data reveal that alcohol has pleiotropic effects on multiple systems, which may explain the diverse neuropsychiatric and medical pathology in alcoholism. Some of the pathways identified suggest avenues for pharmacotherapy of alcoholism with existing agents, such as angiotensin-converting enzyme (ACE) inhibitors. Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show a marked modulation of alcohol intake. Other pathways are new potential targets for drug development. The emergent overall picture is that physical and physiological robustness may permit alcohol-preferring individuals to withstand the aversive effects of alcohol. In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur.

  19. Expanding our knowledge of conditions associated with the ASXL gene family

    PubMed Central

    2013-01-01

    Genome-wide sequencing has identified de novo truncating mutations in ASXL3 in four patients with intellectual disability, feeding problems and distinctive facial features. Their presentation resembles that of Bohring-Opitz syndrome, which is associated with de novo nonsense mutations in ASXL1. This newly defined phenotype provides an important clinical resource for comparison with future cases in which mutations are found in ASXL3. The phenotypes for patients with mutations in each gene will undoubtedly be further delineated as more patients are reported. PMID:23672984

  20. The expanding roles of the ghrelin-gene derived peptide obestatin in health and disease.

    PubMed

    Seim, Inge; Walpole, Carina; Amorim, Laura; Josh, Peter; Herington, Adrian; Chopin, Lisa

    2011-06-20

    Obestatin is a 23 amino acid, ghrelin gene-derived peptide hormone produced in the stomach and a range of other tissues throughout the body. While it was initially reported that obestatin opposed the actions of ghrelin with regards to appetite and food intake, it is now clear that obestatin is not an endogenous ghrelin antagonist, but it is a multi-functional peptide hormone in its own right. In this review we will discuss the controversies associated with the discovery of obestatin and explore emerging central and peripheral roles of obestatin, which includes adipogenesis, pancreatic homeostasis and cancer.

  1. Identification of Expanded Alleles of the "FMR1" Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study

    ERIC Educational Resources Information Center

    Tassone, Flora; Choudhary, Nimrah S.; Tassone, Federica; Durbin-Johnson, Blythe; Hansen, Robin; Hertz-Picciotto, Irva; Pessah, Isaac

    2013-01-01

    Fragile X syndrome (FXS) is a neuro-developmental disorder characterized by intellectual disabilities and autism spectrum disorders (ASD). Expansion of a CGG trinucleotide repeat (greater than 200 repeats) in the 5'UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies…

  2. Identification of Expanded Alleles of the "FMR1" Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study

    ERIC Educational Resources Information Center

    Tassone, Flora; Choudhary, Nimrah S.; Tassone, Federica; Durbin-Johnson, Blythe; Hansen, Robin; Hertz-Picciotto, Irva; Pessah, Isaac

    2013-01-01

    Fragile X syndrome (FXS) is a neuro-developmental disorder characterized by intellectual disabilities and autism spectrum disorders (ASD). Expansion of a CGG trinucleotide repeat (greater than 200 repeats) in the 5'UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies…

  3. Characterization of the cystatin B gene promoter harboring the dodecamer repeat expanded in progressive myoclonus epilepsy, EPM1.

    PubMed

    Alakurtti, K; Virtaneva, K; Joensuu, T; Palvimo, J J; Lehesjoki, A E

    2000-01-25

    Mutations in the gene encoding cystatin B (CSTB) are responsible for the primary defect in progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1). A novel and unique type of disease-causing mutation, an unstable dodecamer repeat expansion, accounts for the majority of EPM1 patients world-wide. This minisatellite repeat expansion, located in the putative promoter of CSTB 175 bp upstream from the translation initiation codon, appears to downregulate CSTB gene expression in vivo. We report here the characterization of the CSTB promoter using different promoter-luciferase gene constructs. Transient transfections of cultured mammalian cells suggest that the region from -670 to -1 bp from the translation initiation codon functions as the CSTB promoter. Active binding to five Sp1 and four AP1 sites as well as weak binding to an androgen response element (ARE) half site was demonstrated by electrophoretic mobility shift assays. The effect of the minisatellite expansion on the promoter activity was evaluated by comparing the activity of constructs containing wild-type and expanded alleles. An increase in the number of dodecamer units from three to 19 repeats lowered transcription in vitro by 10-fold. Northern analysis of lymphoblastoid RNA from individuals with 'premutation' length dodecamer repeat (12-17 copies) expansions showed decreased levels of CSTB mRNA expression. These data indicate that expansion of the dodecamer repeat located in the proximal promoter of CSTB severely disrupts the function of the promoter and thereby reduces transcription of CSTB.

  4. Expanded insecticide catabolic activity gained by a single nucleotide substitution in a bacterial carbamate hydrolase gene.

    PubMed

    Öztürk, Başak; Ghequire, Maarten; Nguyen, Thi Phi Oanh; De Mot, René; Wattiez, Ruddy; Springael, Dirk

    2016-12-01

    Carbofuran-mineralizing strain Novosphingobium sp. KN65.2 produces the CfdJ enzyme that converts the N-methylcarbamate insecticide to carbofuran phenol. Purified CfdJ shows a remarkably low KM towards carbofuran. Together with the carbaryl hydrolase CehA of Rhizobium sp. strain AC100, CfdJ represents a new protein family with several uncharacterized bacterial members outside the proteobacteria. Although both enzymes differ by only four amino acids, CehA does not recognize carbofuran as a substrate whereas CfdJ also hydrolyzes carbaryl. None of the CfdJ amino acids that differ from CehA were shown to be silent regarding carbofuran hydrolytic activity but one particular amino acid substitution, i.e., L152 to F152, proved crucial. CfdJ is more efficient in degrading methylcarbamate pesticides with an aromatic side chain whereas CehA is more efficient in degrading the oxime carbamate nematicide oxamyl. The presence of common flanking sequences suggest that the cfdJ gene is located on a remnant of the mobile genetic element Tnceh carrying cehA. Our results suggest that these enzymes can be acquired through horizontal gene transfer and can evolve to degrade new carbamate substrates by limited amino acid substitutions. We demonstrate that a carbaryl hydrolase can gain the additional capacity to degrade carbofuran by a single nucleotide transversion. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  5. New ALS-Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis.

    PubMed

    Sabatelli, Mario; Marangi, Giuseppe; Conte, Amelia; Tasca, Giorgio; Zollino, Marcella; Lattante, Serena

    2016-03-01

    Amyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. Clinical heterogeneity is a well-recognized feature of the disease as age of onset, site of onset and the duration of the disease can vary greatly among patients. A number of genes have been identified and associated to familial and sporadic forms of ALS but the majority of cases remains still unexplained. Recent breakthrough discoveries have demonstrated that clinical manifestations associated with ALS-related genes are not circumscribed to motor neurons involvement. In this view, ALS appears to be linked to different conditions over a continuum or spectrum in which overlapping phenotypes may be identified. In this review, we aim to examine the increasing number of spectra, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra. Considering all these neurodegenerative disorders as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases. © 2016 International Society of Neuropathology.

  6. Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy.

    PubMed

    Maini, Ilenia; Iodice, Alessandro; Spagnoli, Carlotta; Salerno, Grazia Gabriella; Bertani, Gianna; Frattini, Daniele; Fusco, Carlo

    2016-05-01

    Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early infancy have not been reported. We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Xp11 neoplasm with melanocytic differentiation of the prostate harbouring the novel NONO-TFE3 gene fusion: report of a unique case expanding the gene fusion spectrum.

    PubMed

    Wang, Xiao-Tong; Xia, Qiu-Yuan; Ni, Hao; Wang, Zi-Yu; Ye, Sheng-Bing; Li, Rui; Wang, Xuan; Lv, Jing-Huan; Shi, Shan-Shan; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Zhou, Xiao-Jun; Rao, Qiu

    2016-09-01

    Recently, an increasing number of TFE3 rearrangement-associated tumours have been reported, such as TFE3 rearrangement-associated perivascular epithelioid cell tumours (PEComas), melanotic Xp11 translocation renal cancers and melanotic Xp11 neoplasms. We have suggested that these tumours belong to a single clinicopathological spectrum. 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm' have been proposed to designate this unique neoplasm. Herein, we describe the first case of an Xp11 neoplasm with melanocytic differentiation to be described in the prostate, bearing the novel NONO-TFE3 gene fusion. This study both adds to the spectrum regarding melanotic Xp11 neoplasms and expands its gene fusion spectrum. Moreover, we discuss the relationship of these rare tumours to neoplasms such as conventional PEComas, alveolar soft part sarcomas, malignant melanomas, clear cell sarcomas and Xp11 translocation renal cancers.

  8. Evolution of high cellulolytic activity in symbiotic Streptomyces through selection of expanded gene content and coordinated gene expression

    DOE PAGES

    Book, Adam J.; Lewin, Gina R.; McDonald, Bradon R.; ...

    2016-06-08

    In this study, the evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil andmore » symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology.« less

  9. Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression.

    PubMed

    Book, Adam J; Lewin, Gina R; McDonald, Bradon R; Takasuka, Taichi E; Wendt-Pienkowski, Evelyn; Doering, Drew T; Suh, Steven; Raffa, Kenneth F; Fox, Brian G; Currie, Cameron R

    2016-06-01

    The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology.

  10. Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression

    PubMed Central

    McDonald, Bradon R.; Takasuka, Taichi E.; Wendt-Pienkowski, Evelyn; Doering, Drew T.; Raffa, Kenneth F.; Fox, Brian G.; Currie, Cameron R.

    2016-01-01

    The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology. PMID:27276034

  11. Multiple source genes of HAmo SINE actively expanded and ongoing retroposition in cyprinid genomes relying on its partner LINE.

    PubMed

    Tong, Chaobo; Gan, Xiaoni; He, Shunping

    2010-04-29

    We recently characterized HAmo SINE and its partner LINE in silver carp and bighead carp based on hybridization capture of repetitive elements from digested genomic DNA in solution using a bead-probe 1. To reveal the distribution and evolutionary history of SINEs and LINEs in cyprinid genomes, we performed a multi-species search for HAmo SINE and its partner LINE using the bead-probe capture and internal-primer-SINE polymerase chain reaction (PCR) techniques. Sixty-seven full-size and 125 internal-SINE sequences (as well as 34 full-size and 9 internal sequences previously reported in bighead carp and silver carp) from 17 species of the family Cyprinidae were aligned as well as 14 new isolated HAmoL2 sequences. Four subfamilies (type I, II, III and IV), which were divided based on diagnostic nucleotides in the tRNA-unrelated region, expanded preferentially within a certain lineage or within the whole family of Cyprinidae as multiple active source genes. The copy numbers of HAmo SINEs were estimated to vary from 104 to 106 in cyprinid genomes by quantitative RT-PCR. Over one hundred type IV members were identified and characterized in the primitive cyprinid Danio rerio genome but only tens of sequences were found to be similar with type I, II and III since the type IV was the oldest subfamily and its members dispersed in almost all investigated cyprinid fishes. For determining the taxonomic distribution of HAmo SINE, inter-primer SINE PCR was conducted in other non-cyprinid fishes, the results shows that HAmo SINE- related sequences may disperse in other families of order Cypriniforms but absent in other orders of bony fishes: Siluriformes, Polypteriformes, Lepidosteiformes, Acipenseriformes and Osteoglossiforms. Depending on HAmo LINE2, multiple source genes (subfamilies) of HAmo SINE actively expanded and underwent retroposition in a certain lineage or within the whole family of Cyprinidae. From this perspective, HAmo SINE should provide useful phylogenetic makers

  12. Thermal expander

    NASA Astrophysics Data System (ADS)

    Huang, Junying; Shen, Xiangying; Jiang, Chaoran; Wu, Zuhui; Huang, Jiping

    2017-08-01

    One type of thermal device, named as thermal expander, is proposed and verified through both simulation and experiment. The thermal expander performs an efficient way to expand a heat flow of line-shape front. Moreover, the thermal expander shows an advantage in rectifying a heat flow from crooked front to line-shape front, which indicates that the thermal expander could act as an efficient point-to-line heat source convertor. We suggest that the thermal expander would be of help to energy saving and emission reduction, especially in thermal circuits and thermal management.

  13. Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis genes.

    PubMed

    Cerro-Herreros, Estefania; Chakraborty, Mouli; Pérez-Alonso, Manuel; Artero, Rubén; Llamusí, Beatriz

    2017-06-06

    Myotonic dystrophies (DM1-2) are neuromuscular genetic disorders caused by the pathological expansion of untranslated microsatellites. DM1 and DM2, are caused by expanded CTG repeats in the 3'UTR of the DMPK gene and CCTG repeats in the first intron of the CNBP gene, respectively. Mutant RNAs containing expanded repeats are retained in the cell nucleus, where they sequester nuclear factors and cause alterations in RNA metabolism. However, for unknown reasons, DM1 is more severe than DM2. To study the differences and similarities in the pathogenesis of DM1 and DM2, we generated model flies by expressing pure expanded CUG ([250]×) or CCUG ([1100]×) repeats, respectively, and compared them with control flies expressing either 20 repeat units or GFP. We observed surprisingly severe muscle reduction and cardiac dysfunction in CCUG-expressing model flies. The muscle and cardiac tissue of both DM1 and DM2 model flies showed DM1-like phenotypes including overexpression of autophagy-related genes, RNA mis-splicing and repeat RNA aggregation in ribonuclear foci along with the Muscleblind protein. These data reveal, for the first time, that expanded non-coding CCUG repeat-RNA has similar in vivo toxicity potential as expanded CUG RNA in muscle and heart tissues and suggests that specific, as yet unknown factors, quench CCUG-repeat toxicity in DM2 patients.

  14. GENE EXPRESSION PROFILING AND EXPANDED IMMUNOHISTOCHEMISTRY TESTS TO GUIDE SELECTION OF CHEMOTHERAPY REGIMENS IN BREAST CANCER MANAGEMENT: A SYSTEMATIC REVIEW.

    PubMed

    Scope, Alison; Essat, Munira; Pandor, Abdullah; Rafia, Rachid; Ward, Sue E; Wyld, Lynda; Cross, Simon; Woods, Helen Buckley

    2017-01-01

    The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint, and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. Searches identified 7,064 citations, of which forty-one citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat, and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomized controlled trial data.

  15. Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

    PubMed

    Denora, Paola S; Schlesinger, David; Casali, Carlo; Kok, Fernando; Tessa, Alessandra; Boukhris, Amir; Azzedine, Hamid; Dotti, Maria Teresa; Bruno, Claudio; Truchetto, Jeremy; Biancheri, Roberta; Fedirko, Estelle; Di Rocco, Maja; Bueno, Clarissa; Malandrini, Alessandro; Battini, Roberta; Sickl, Elisabeth; de Leva, Maria Fulvia; Boespflug-Tanguy, Odile; Silvestri, Gabriella; Simonati, Alessandro; Said, Edith; Ferbert, Andreas; Criscuolo, Chiara; Heinimann, Karl; Modoni, Anna; Weber, Peter; Palmeri, Silvia; Plasilova, Martina; Pauri, Flavia; Cassandrini, Denise; Battisti, Carla; Pini, Antonella; Tosetti, Michela; Hauser, Erwin; Masciullo, Marcella; Di Fabio, Roberto; Piccolo, Francesca; Denis, Elodie; Cioni, Giovanni; Massa, Roberto; Della Giustina, Elvio; Calabrese, Olga; Melone, Marina A B; De Michele, Giuseppe; Federico, Antonio; Bertini, Enrico; Durr, Alexandra; Brockmann, Knut; van der Knaap, Marjo S; Zatz, Mayana; Filla, Alessandro; Brice, Alexis; Stevanin, Giovanni; Santorelli, Filippo M

    2009-03-01

    Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.

  16. Identification of I-7 expands the repertoire of genes for resistance to Fusarium wilt in tomato to three resistance gene classes.

    PubMed

    Gonzalez-Cendales, Yvonne; Catanzariti, Ann-Maree; Baker, Barbara; Mcgrath, Des J; Jones, David A

    2016-04-01

    The tomato I-3 and I-7 genes confer resistance to Fusarium oxysporum f. sp. lycopersici (Fol) race 3 and were introgressed into the cultivated tomato, Solanum lycopersicum, from the wild relative Solanum pennellii. I-3 has been identified previously on chromosome 7 and encodes an S-receptor-like kinase, but little is known about I-7. Molecular markers have been developed for the marker-assisted breeding of I-3, but none are available for I-7. We used an RNA-seq and single nucleotide polymorphism (SNP) analysis approach to map I-7 to a small introgression of S. pennellii DNA (c. 210 kb) on chromosome 8, and identified I-7 as a gene encoding a leucine-rich repeat receptor-like protein (LRR-RLP), thereby expanding the repertoire of resistance protein classes conferring resistance to Fol. Using an eds1 mutant of tomato, we showed that I-7, like many other LRR-RLPs conferring pathogen resistance in tomato, is EDS1 (Enhanced Disease Susceptibility 1) dependent. Using transgenic tomato plants carrying only the I-7 gene for Fol resistance, we found that I-7 also confers resistance to Fol races 1 and 2. Given that Fol race 1 carries Avr1, resistance to Fol race 1 indicates that I-7-mediated resistance, unlike I-2- or I-3-mediated resistance, is not suppressed by Avr1. This suggests that Avr1 is not a general suppressor of Fol resistance in tomato, leading us to hypothesize that Avr1 may be acting against an EDS1-independent pathway for resistance activation. The identification of I-7 has allowed us to develop molecular markers for marker-assisted breeding of both genes currently known to confer Fol race 3 resistance (I-3 and I-7). Given that I-7-mediated resistance is not suppressed by Avr1, I-7 may be a useful addition to I-3 in the tomato breeder's toolbox.

  17. Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

    PubMed Central

    Merritt, Kristen K; Bradley, Kevin M; Hutter, Daniel; Matsuura, Mariko F; Rowold, Diane J

    2014-01-01

    Summary Background: Many synthetic biologists seek to increase the degree of autonomy in the assembly of long DNA (L-DNA) constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide “letters”, the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non-canonical folded structures that compete with Watson–Crick pairing, and other features intrinsic to natural DNA, generally prevent the autonomous assembly of short single-stranded oligonucleotides greater than a dozen or so. Results: We describe a new strategy to autonomously assemble L-DNA constructs from fragments of synthetic single-stranded DNA. This strategy uses an artificially expanded genetic information system (AEGIS) that adds nucleotides to the four (G, A, C, and T) found in standard DNA by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick base-pairing geometry. The added information density allows larger numbers of synthetic fragments to self-assemble without off-target hybridization, hairpin formation, and non-canonical folding interactions. The AEGIS pairs are then converted into standard pairs to produce a fully natural L-DNA product. Here, we report the autonomous assembly of a gene encoding kanamycin resistance using this strategy. Synthetic fragments were built from a six-letter alphabet having two AEGIS components, 5-methyl-2’-deoxyisocytidine and 2’-deoxyisoguanosine (respectively S and B), at their overlapping ends. Gaps in the overlapped assembly were then filled in using DNA polymerases, and the nicks were sealed by ligase. The S:B pairs in the ligated construct were then converted to T:A pairs during PCR amplification. When cloned into a plasmid, the product was shown to make Escherichia coli resistant to kanamycin. A parallel study that attempted to assemble similarly sized genes with

  18. Analysis of the grape MYB R2R3 subfamily reveals expanded wine quality-related clades and conserved gene structure organization across Vitis and Arabidopsis genomes.

    PubMed

    Matus, José Tomás; Aquea, Felipe; Arce-Johnson, Patricio

    2008-07-22

    The MYB superfamily constitutes the most abundant group of transcription factors described in plants. Members control processes such as epidermal cell differentiation, stomatal aperture, flavonoid synthesis, cold and drought tolerance and pathogen resistance. No genome-wide characterization of this family has been conducted in a woody species such as grapevine. In addition, previous analysis of the recently released grape genome sequence suggested expansion events of several gene families involved in wine quality. We describe and classify 108 members of the grape R2R3 MYB gene subfamily in terms of their genomic gene structures and similarity to their putative Arabidopsis thaliana orthologues. Seven gene models were derived and analyzed in terms of gene expression and their DNA binding domain structures. Despite low overall sequence homology in the C-terminus of all proteins, even in those with similar functions across Arabidopsis and Vitis, highly conserved motif sequences and exon lengths were found. The grape epidermal cell fate clade is expanded when compared with the Arabidopsis and rice MYB subfamilies. Two anthocyanin MYBA related clusters were identified in chromosomes 2 and 14, one of which includes the previously described grape colour locus. Tannin related loci were also detected with eight candidate homologues in chromosomes 4, 9 and 11. This genome wide transcription factor analysis in Vitis suggests that clade-specific grape R2R3 MYB genes are expanded while other MYB genes could be well conserved compared to Arabidopsis. MYB gene abundance, homology and orientation within particular loci also suggests that expanded MYB clades conferring quality attributes of grapes and wines, such as colour and astringency, could possess redundant, overlapping and cooperative functions.

  19. Analysis of the grape MYB R2R3 subfamily reveals expanded wine quality-related clades and conserved gene structure organization across Vitis and Arabidopsis genomes

    PubMed Central

    Matus, José Tomás; Aquea, Felipe; Arce-Johnson, Patricio

    2008-01-01

    Background The MYB superfamily constitutes the most abundant group of transcription factors described in plants. Members control processes such as epidermal cell differentiation, stomatal aperture, flavonoid synthesis, cold and drought tolerance and pathogen resistance. No genome-wide characterization of this family has been conducted in a woody species such as grapevine. In addition, previous analysis of the recently released grape genome sequence suggested expansion events of several gene families involved in wine quality. Results We describe and classify 108 members of the grape R2R3 MYB gene subfamily in terms of their genomic gene structures and similarity to their putative Arabidopsis thaliana orthologues. Seven gene models were derived and analyzed in terms of gene expression and their DNA binding domain structures. Despite low overall sequence homology in the C-terminus of all proteins, even in those with similar functions across Arabidopsis and Vitis, highly conserved motif sequences and exon lengths were found. The grape epidermal cell fate clade is expanded when compared with the Arabidopsis and rice MYB subfamilies. Two anthocyanin MYBA related clusters were identified in chromosomes 2 and 14, one of which includes the previously described grape colour locus. Tannin related loci were also detected with eight candidate homologues in chromosomes 4, 9 and 11. Conclusion This genome wide transcription factor analysis in Vitis suggests that clade-specific grape R2R3 MYB genes are expanded while other MYB genes could be well conserved compared to Arabidopsis. MYB gene abundance, homology and orientation within particular loci also suggests that expanded MYB clades conferring quality attributes of grapes and wines, such as colour and astringency, could possess redundant, overlapping and cooperative functions. PMID:18647406

  20. Chitosan-plasmid DNA nanoparticles encoding small hairpin RNA targeting MMP-3 and -13 to inhibit the expression of dedifferentiation related genes in expanded chondrocytes.

    PubMed

    Zhao, Jingxin; Fan, Xiangli; Zhang, Qiang; Sun, Fangfei; Li, Xiaojian; Xiong, Chuan; Zhang, Chunli; Fan, Hongbin

    2014-02-01

    Overexpression of matrix metalloproteinase (MMP)-3 and -13 can lead to the dedifferentiation of expanded chondrocytes. After implanting dedifferentiated cells for cartilage defect repair, graft failure may occur. Short hairpin RNA (shRNA) is a powerful genetic tool to reduce the expression of target genes. This study investigated the effects of chitosan-plasmid DNA (pDNA) nanoparticles encoding shRNA targeting MMP-3 and -13 on the dedifferentiation of expanded chondrocytes. The objective was to optimize the parameters of chitosan-pDNA formulation for achieving higher efficiency of pDNA delivery and gene silencing. The chitosan-pDNA nanoparticles were prepared using a complex coacervation process. Then the characteristics including size, shape, stability, and transfection efficiency were compared in different groups. The results indicated that chitosan of 800 kDa at N/P ratio of 4 and pH 7.0 was optimal to prepare chitosan-pDNA nanoparticles. These nanoparticles showed high DNA loading efficiency (95.8 ± 1.5%) and high gene transfection efficiency (24.5 ± 1.6%). After the expanded chondrocytes were transfected by chitosan-pDNA nanoparticles, MMP-3-610 and MMP-13-2024 groups showed greater suppression in mRNA and protein levels. The results indicated that chitosan-pDNA nanoparticles encoding shRNA targeting MMP-3 and -13 had great potential in silencing the dedifferentiation-related genes for regenerating prolonged and endurable cartilage.

  1. Analysis of conifer FLOWERING LOCUS T/TERMINAL FLOWER1-like genes provides evidence for dramatic biochemical evolution in the angiosperm FT lineage.

    PubMed

    Klintenäs, Maria; Pin, Pierre A; Benlloch, Reyes; Ingvarsson, Pär K; Nilsson, Ove

    2012-12-01

    In flowering plants, homologs of the Arabidopsis phosphatidylethanolamine-binding protein (PEBP) FLOWERING LOCUS T (FT) are key components in controlling flowering time. We show here that, although FT homologs are found in all angiosperms with completed genome sequences, there is no evidence to date that FT-like genes exist in other groups of plants. Through phylogeny reconstructions and heterologous expression, we examined the biochemical function of the Picea (spruces) and Pinus (pines) PEBP families - two gymnosperm taxa phylogenetically distant from the angiosperms. We have defined a lineage of gymnosperm PEBP genes, termed the FT/TERMINAL FLOWER1 (TFL1)-like genes, that share sequence characteristics with both the angiosperm FT- and TFL1-like clades. When expressed in Arabidopsis, FT/TFL1-like genes repressed flowering, indicating that the proteins are biochemically more similar to the angiosperm TFL1-like proteins than to the FT-like proteins. This suggests that the regulation of the vegetative-to-reproductive switch might differ in gymnosperms compared with angiosperms. Molecular evolution studies suggest that plasticity at exon 4 contributes to the divergence of FT-like function in floral promotion. In addition, the presence of FT-like genes in basal angiosperms indicates that the FT-like function emerged at an early stage during the evolution of flowering plants as a means to regulate flowering time.

  2. Graft-versus-leukemia Effect of HLA-haploidentical Central-memory T-cells Expanded With Leukemic APCs and Modified With a Suicide Gene

    PubMed Central

    Casucci, Monica; Perna, Serena Kimi; Falcone, Laura; Camisa, Barbara; Magnani, Zulma; Bernardi, Massimo; Crotta, Alessandro; Tresoldi, Cristina; Fleischhauer, Katharina; Ponzoni, Maurilio; Gregori, Silvia; Caligaris Cappio, Federico; Ciceri, Fabio; Bordignon, Claudio; Cignetti, Alessandro; Bondanza, Attilio; Bonini, Chiara

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-haploidentical family donor (haplo-HSCT) is a readily available and potentially curative option for high-risk leukemia. In haplo-HSCT, alloreactivity plays a major role in the graft-versus-leukemia (GVL) effect, which, however, is frequently followed by relapse due to emerging leukemic cell variants that have lost the unshared HLA haplotype as a mechanism of immune escape. We report that stimulation of HLA-haploidentical donor T lymphocytes with leukemic antigen-presenting cells (L-APCs) expands a population of leukemia-reactive T cells, which, besides alloreactivity to unshared HLAs, contain leukemia-associated specificities restricted by shared HLAs. According to a preferential central-memory (TCM) phenotype and to high interleukin (IL)-7Rα expression, these T cells persist in vivo and sustain a major GVL effect in a clinically relevant xenograft model. Moreover, we demonstrate that modifying L-APC–expanded T cells to express the herpes simplex virus thymidine kinase (HSV-tk) suicide gene enables their elimination with the prodrug ganciclovir (GCV), therefore providing a safety switch in case of graft-versus-host disease (GVHD). These results warrant the clinical investigation of L-APC–expanded T cells modified with a suicide gene in the setting of haplo-HSCT. PMID:23299798

  3. Graft-versus-leukemia effect of HLA-haploidentical central-memory T-cells expanded with leukemic APCs and modified with a suicide gene.

    PubMed

    Casucci, Monica; Perna, Serena Kimi; Falcone, Laura; Camisa, Barbara; Magnani, Zulma; Bernardi, Massimo; Crotta, Alessandro; Tresoldi, Cristina; Fleischhauer, Katharina; Ponzoni, Maurilio; Gregori, Silvia; Caligaris Cappio, Federico; Ciceri, Fabio; Bordignon, Claudio; Cignetti, Alessandro; Bondanza, Attilio; Bonini, Chiara

    2013-02-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-haploidentical family donor (haplo-HSCT) is a readily available and potentially curative option for high-risk leukemia. In haplo-HSCT, alloreactivity plays a major role in the graft-versus-leukemia (GVL) effect, which, however, is frequently followed by relapse due to emerging leukemic cell variants that have lost the unshared HLA haplotype as a mechanism of immune escape. We report that stimulation of HLA-haploidentical donor T lymphocytes with leukemic antigen-presenting cells (L-APCs) expands a population of leukemia-reactive T cells, which, besides alloreactivity to unshared HLAs, contain leukemia-associated specificities restricted by shared HLAs. According to a preferential central-memory (T(CM)) phenotype and to high interleukin (IL)-7Rα expression, these T cells persist in vivo and sustain a major GVL effect in a clinically relevant xenograft model. Moreover, we demonstrate that modifying L-APC-expanded T cells to express the herpes simplex virus thymidine kinase (HSV-tk) suicide gene enables their elimination with the prodrug ganciclovir (GCV), therefore providing a safety switch in case of graft-versus-host disease (GVHD). These results warrant the clinical investigation of L-APC-expanded T cells modified with a suicide gene in the setting of haplo-HSCT.

  4. Targeted next-generation sequencing detects novel gene-phenotype associations and expands the mutational spectrum in cardiomyopathies.

    PubMed

    Forleo, Cinzia; D'Erchia, Anna Maria; Sorrentino, Sandro; Manzari, Caterina; Chiara, Matteo; Iacoviello, Massimo; Guaricci, Andrea Igoren; De Santis, Delia; Musci, Rita Leonarda; La Spada, Antonino; Marangelli, Vito; Pesole, Graziano; Favale, Stefano

    2017-01-01

    Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity and mortality. These diseases are genetically diverse and associated with rare mutations in a large number of genes, many of which overlap among the phenotypes. To better investigate the genetic overlap between these three phenotypes and to identify new genotype-phenotype correlations, we designed a custom gene panel consisting of 115 genes known to be associated with cardiomyopathic phenotypes and channelopathies. A cohort of 38 unrelated patients, 16 affected by DCM, 14 by HCM and 8 by ARVC, was recruited for the study on the basis of more severe phenotypes and family history of cardiomyopathy and/or sudden death. We detected a total of 142 rare variants in 40 genes, and all patients were found to be carriers of at least one rare variant. Twenty-eight of the 142 rare variants were also predicted as potentially pathogenic variants and found in 26 patients. In 23 out of 38 patients, we found at least one novel potential gene-phenotype association. In particular, we detected three variants in OBSCN gene in ARVC patients, four variants in ANK2 gene and two variants in DLG1, TRPM4, and AKAP9 genes in DCM patients, two variants in PSEN2 gene and four variants in AKAP9 gene in HCM patients. Overall, our results confirmed that cardiomyopathic patients could carry multiple rare gene variants; in addition, our investigation of the genetic overlap among cardiomyopathies revealed new gene-phenotype associations. Furthermore, as our study confirms, data obtained using targeted next-generation sequencing could provide a remarkable contribution to the molecular diagnosis of cardiomyopathies, early identification of patients at risk for arrhythmia development, and better clinical management of cardiomyopathic patients.

  5. Chemical-Gene Interactions from ToxCast Bioactivity Data Expands Universe of Literature Network-Based Associations (SOT)

    EPA Science Inventory

    Characterizing the effects of chemicals in biological systems is often summarized by chemical-gene interactions, which have sparse coverage in the literature. The ToxCast chemical screening program has produced bioactivity data for nearly 2000 chemicals and over 450 gene targets....

  6. F-box gene family is expanded in herbaceous annual plants Arabidopsis and rice relative to woody perennial plant Populus

    SciTech Connect

    Yang, Xiaohan; Kalluri, Udaya C; Jawdy, Sara; Gunter, Lee E; Yin, Tongming; Tschaplinski, Timothy J; Weston, David; Ranjan, Priya; Tuskan, Gerald A

    2008-01-01

    F-box proteins are generally responsible for substrate recognition in the Skp1-Cullin-F-box complexes that are involved in protein degradation via the ubiquitin-26S proteosome pathway. In plants, F-box genes influence a variety of biological processes such as leaf senescence, branching, self-incompatibility and responses to biotic and abiotic stresses. The number of F-box genes in Populus (~320) is less than half that found in Arabidopsis (~660) or rice (~680), even though the total number of genes in Populus is equivalent to that in rice and 1.5 times that in Arabidopsis. We performed comparative genomic analysis between the woody perennial plant Populus and the herbaceous annual plants Arabidopsis and rice in order to explicate the functional implications of this large gene family. Our analyses reveal interspecific differences in genomic distribution, orthologous relationship, intron evolution, protein domain structure and gene expression. The set of F-box genes shared by these three species appear to be involved in core biological processes essential for plant growth and development; lineage-specific differences primarily occurred because of an expansion of the F-box genes via tandem duplications in Arabidopsis and rice. The present study provides insights into the relationship between the structure and composition of the F-box gene family in herbaceous and woody species and their associated developmental and physiological features.

  7. Identification of expanded alleles of the FMR1 gene among high-risk population in Indonesia by using blood spot screening.

    PubMed

    Winarni, Tri Indah; Utari, Agustini; Mundhofir, Farmaditya E P; Tong, Tzuhan; Durbin-Johnson, Blythe; Faradz, Sultana M H; Tassone, Flora

    2012-03-01

    The prevalence of Fragile X Syndrome (FXS) is 1 in 4000 in males and 1 in 2500 in males and females, respectively, in the general population. Several screening studies aimed at determining the prevalence of FXS have been conducted in individuals with intellectual disabilities (IDs) with a prevalence varying from 1.15% to 6.3% across different ethnic groups. A previous study in Indonesia showed an FXS prevalence of 1.9% among the ID population. A rapid, effective, and inexpensive method for FMR1 screening, using dried blood spots capable of detecting an expanded FMR1 allele in both males and females, was recently reported. We used this approach to screen 176 blood spots, collected from Central Java, Indonesia, for the presence of expanded FMR1 gene alleles. Samples were collected from high-risk populations: 112 individuals with ID, 32 obtained from individuals with diagnosis of autism spectrum disorders, and 32 individuals with a known family history of FXS. Fourteen subjects carrying an FMR1 expanded allele were identified including 7 premutations (55-200 CGG repeats) and 7 full mutations (>200 repeats). Of the seven subjects identified with a full mutation, one subject was from a non-fragile X family, and six from were families with a history of FXS.

  8. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements

    PubMed Central

    Mi, Huaiyu; Huang, Xiaosong; Muruganujan, Anushya; Tang, Haiming; Mills, Caitlin; Kang, Diane; Thomas, Paul D.

    2017-01-01

    The PANTHER database (Protein ANalysis THrough Evolutionary Relationships, http://pantherdb.org) contains comprehensive information on the evolution and function of protein-coding genes from 104 completely sequenced genomes. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments. In the past year, major improvements include a large expansion of classification information available in PANTHER, as well as significant enhancements to the analysis tools. Protein subfamily functional classifications have more than doubled due to progress of the Gene Ontology Phylogenetic Annotation Project. For human genes (as well as a few other organisms), PANTHER now also supports enrichment analysis using pathway classifications from the Reactome resource. The gene list enrichment tools include a new ‘hierarchical view’ of results, enabling users to leverage the structure of the classifications/ontologies; the tools also allow users to upload genetic variant data directly, rather than requiring prior conversion to a gene list. The updated coding single-nucleotide polymorphisms (SNP) scoring tool uses an improved algorithm. The hidden Markov model (HMM) search tools now use HMMER3, dramatically reducing search times and improving accuracy of E-value statistics. Finally, the PANTHER Tree-Attribute Viewer has been implemented in JavaScript, with new views for exploring protein sequence evolution. PMID:27899595

  9. PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements.

    PubMed

    Mi, Huaiyu; Huang, Xiaosong; Muruganujan, Anushya; Tang, Haiming; Mills, Caitlin; Kang, Diane; Thomas, Paul D

    2017-01-04

    The PANTHER database (Protein ANalysis THrough Evolutionary Relationships, http://pantherdb.org) contains comprehensive information on the evolution and function of protein-coding genes from 104 completely sequenced genomes. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments. In the past year, major improvements include a large expansion of classification information available in PANTHER, as well as significant enhancements to the analysis tools. Protein subfamily functional classifications have more than doubled due to progress of the Gene Ontology Phylogenetic Annotation Project. For human genes (as well as a few other organisms), PANTHER now also supports enrichment analysis using pathway classifications from the Reactome resource. The gene list enrichment tools include a new 'hierarchical view' of results, enabling users to leverage the structure of the classifications/ontologies; the tools also allow users to upload genetic variant data directly, rather than requiring prior conversion to a gene list. The updated coding single-nucleotide polymorphisms (SNP) scoring tool uses an improved algorithm. The hidden Markov model (HMM) search tools now use HMMER3, dramatically reducing search times and improving accuracy of E-value statistics. Finally, the PANTHER Tree-Attribute Viewer has been implemented in JavaScript, with new views for exploring protein sequence evolution.

  10. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency

    PubMed Central

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R

    2014-01-01

    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient–mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (Treg) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID. PMID:24666246

  11. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.

    PubMed

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R

    2014-06-01

    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

  12. Interferon-Induced Genes of the Expanded IFIT Family Show Conserved Antiviral Activities in Non-Mammalian Species

    PubMed Central

    Pereiro, Patricia; Forn-Cuní, Gabriel; Costa, Maria M.; Dios, Sonia; Romero, Alejandro; Figueras, Antonio; Novoa, Beatriz

    2014-01-01

    Interferon-induced proteins with tetratricopeptide repeats (IFITs) are involved in the protective response to viral infection, although the precise mechanism of IFITs for reducing viral proliferation is currently unknown. The interaction with the translation initiation factor eIF-3 or viral proteins and the sequestering of viral RNA have been proposed as potential antiviral functions for these proteins. In humans, four members of this family have been characterized. Nevertheless, information about these proteins in fish is almost non-existent. Exploiting the conservation of synteny between human and zebrafish genomes, we have identified ten members of the IFIT family located on four different chromosomes. The induction of these genes was examined both in vitro and in vivo after interferon (IFN) administration and rhabdovirus challenge. Whereas an induction of IFIT genes was observed after interferon treatments (IFNΦ1, IFNΦ2 and IFNΦ3), the viral infection did not affect these IFN-induced genes in vitro, and even reduced the IFN-induced expression of these genes. The response was largely different in vivo, with a broad up-regulation of IFIT genes after viral challenge. In addition, three selected IFITs were cloned in an expression vector and microinjected into zebrafish larvae to examine the protective effect of IFITs upon viral infection. Reduction in the mortality rate was observed confirming a conserved antiviral function in non-mammalian species. PMID:24950240

  13. EasyClone 2.0: expanded toolkit of integrative vectors for stable gene expression in industrial Saccharomyces cerevisiae strains.

    PubMed

    Stovicek, Vratislav; Borja, Gheorghe M; Forster, Jochen; Borodina, Irina

    2015-11-01

    Saccharomyces cerevisiae is one of the key cell factories for production of chemicals and active pharmaceuticals. For large-scale fermentations, particularly in biorefinery applications, it is desirable to use stress-tolerant industrial strains. However, such strains are less amenable for metabolic engineering than the standard laboratory strains. To enable easy delivery and overexpression of genes in a wide range of industrial S. cerevisiae strains, we constructed a set of integrative vectors with long homology arms and dominant selection markers. The vectors integrate into previously validated chromosomal locations via double cross-over and result in homogenous stable expression of the integrated genes, as shown for several unrelated industrial strains. Cre-mediated marker rescue is possible for removing markers positioned on different chromosomes. To demonstrate the applicability of the presented vector set for metabolic engineering of industrial yeast, we constructed xylose-utilizing strains overexpressing xylose isomerase, xylose transporter and five genes of the pentose phosphate pathway.

  14. The Expanding Role of MBD Genes in Autism: Identification of a MECP2 Duplication and Novel Alterations in MBD5, MBD6, and SETDB1

    PubMed Central

    Cukier, Holly N.; Lee, Joycelyn M.; Ma, Deqiong; Young, Juan I.; Mayo, Vera; Butler, Brittany L.; Ramsook, Sandhya S.; Rantus, Joseph A.; Abrams, Alexander J.; Whitehead, Patrice L.; Wright, Harry H.; Abramson, Ruth K.; Haines, Jonathan L.; Cuccaro, Michael L.; Pericak-Vance, Margaret A.; Gilbert, John R.

    2012-01-01

    The methyl-CpG-binding domain (MBD) gene family was first linked to autism over a decade ago when Rett syndrome, which falls under the umbrella of autism spectrum disorders (ASDs), was revealed to be predominantly caused by MECP2 mutations. Since that time, MECP2 alterations have been recognized in idiopathic ASD patients by us and others. Individuals with deletions across the MBD5 gene also present with ASDs, impaired speech, intellectual difficulties, repetitive behaviors, and epilepsy. These findings suggest that further investigations of the MBD gene family may reveal additional associations related to autism. We now describe the first study evaluating individuals with ASD for rare variants in four autosomal MBD family members, MBD5, MBD6, SETDB1, and SETDB2, and expand our initial screening in the MECP2 gene. Each gene was sequenced over all coding exons and evaluated for copy number variations in 287 patients with ASD and an equal number of ethnically matched control individuals. We identified 186 alterations through sequencing, approximately half of which were novel (96 variants, 51.6%). We identified seventeen ASD specific, nonsynonymous variants, four of which were concordant in multiplex families: MBD5 Tyr1269Cys, MBD6 Arg883Trp, MECP2 Thr240Ser, and SETDB1 Pro1067del. Furthermore, a complex duplication spanning the MECP2 gene was identified in two brothers who presented with developmental delay and intellectual disability. From our studies, we provide the first examples of autistic patients carrying potentially detrimental alterations in MBD6 and SETDB1, thereby demonstrating that the MBD gene family potentially plays a significant role in rare and private genetic causes of autism. PMID:23055267

  15. Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease

    PubMed Central

    Beltran, William A.; Cideciyan, Artur V.; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S.; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

    2015-01-01

    Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP. PMID:26460017

  16. Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease.

    PubMed

    Beltran, William A; Cideciyan, Artur V; Iwabe, Simone; Swider, Malgorzata; Kosyk, Mychajlo S; McDaid, Kendra; Martynyuk, Inna; Ying, Gui-Shuang; Shaffer, James; Deng, Wen-Tao; Boye, Sanford L; Lewin, Alfred S; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

    2015-10-27

    Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP.

  17. An expanded maize gene expression atlas based on RNA sequencing and its use to explore root development

    DOE PAGES

    Stelpflug, Scott C.; Sekhon, Rajandeep S.; Vaillancourt, Brieanne; ...

    2015-12-30

    Comprehensive and systematic transcriptome profiling provides valuable insight into biological and developmental processes that occur throughout the life cycle of a plant. We have enhanced our previously published microarray-based gene atlas of maize (Zea mays L.) inbred B73 to now include 79 distinct replicated samples that have been interrogated using RNA sequencing (RNA-seq). The current version of the atlas includes 50 original array-based gene atlas samples, a time-course of 12 stalk and leaf samples postflowering, and an additional set of 17 samples from the maize seedling and adult root system. The entire dataset contains 4.6 billion mapped reads, with anmore » average of 20.5 million mapped reads per biological replicate, allowing for detection of genes with lower transcript abundance. As the new root samples represent key additions to the previously examined tissues, we highlight insights into the root transcriptome, which is represented by 28,894 (73.2%) annotated genes in maize. Additionally, we observed remarkable expression differences across both the longitudinal (four zones) and radial gradients (cortical parenchyma and stele) of the primary root supported by fourfold differential expression of 9353 and 4728 genes, respectively. Among the latter were 1110 genes that encode transcription factors, some of which are orthologs of previously characterized transcription factors known to regulate root development in Arabidopsis thaliana (L.) Heynh., while most are novel, and represent attractive targets for reverse genetics approaches to determine their roles in this important organ. As a result, this comprehensive transcriptome dataset is a powerful tool toward understanding maize development, physiology, and phenotypic diversity.« less

  18. An expanded maize gene expression atlas based on RNA sequencing and its use to explore root development

    SciTech Connect

    Stelpflug, Scott C.; Sekhon, Rajandeep S.; Vaillancourt, Brieanne; Hirsch, Candice N.; Buell, C. Robin; de Leon, Natalia; Kaeppler, Shawn M.

    2015-12-30

    Comprehensive and systematic transcriptome profiling provides valuable insight into biological and developmental processes that occur throughout the life cycle of a plant. We have enhanced our previously published microarray-based gene atlas of maize (Zea mays L.) inbred B73 to now include 79 distinct replicated samples that have been interrogated using RNA sequencing (RNA-seq). The current version of the atlas includes 50 original array-based gene atlas samples, a time-course of 12 stalk and leaf samples postflowering, and an additional set of 17 samples from the maize seedling and adult root system. The entire dataset contains 4.6 billion mapped reads, with an average of 20.5 million mapped reads per biological replicate, allowing for detection of genes with lower transcript abundance. As the new root samples represent key additions to the previously examined tissues, we highlight insights into the root transcriptome, which is represented by 28,894 (73.2%) annotated genes in maize. Additionally, we observed remarkable expression differences across both the longitudinal (four zones) and radial gradients (cortical parenchyma and stele) of the primary root supported by fourfold differential expression of 9353 and 4728 genes, respectively. Among the latter were 1110 genes that encode transcription factors, some of which are orthologs of previously characterized transcription factors known to regulate root development in Arabidopsis thaliana (L.) Heynh., while most are novel, and represent attractive targets for reverse genetics approaches to determine their roles in this important organ. As a result, this comprehensive transcriptome dataset is a powerful tool toward understanding maize development, physiology, and phenotypic diversity.

  19. Alternative Splicing in the Cytochrome P450 Superfamily Expands Protein Diversity to Augment Gene Function and Redirect Human Drug Metabolism.

    PubMed

    Annalora, Andrew J; Marcus, Craig B; Iversen, Patrick L

    2017-04-01

    The human genome encodes 57 cytochrome P450 genes, whose enzyme products metabolize hundreds of drugs, thousands of xenobiotics, and unknown numbers of endogenous compounds, including steroids, retinoids, and eicosanoids. Indeed, P450 genes are the first line of defense against daily environmental chemical challenges in a manner that parallels the immune system. Several National Institutes of Health databases, including PubMed, AceView, and Ensembl, were queried to establish a comprehensive analysis of the full human P450 transcriptome. This review describes a remarkable diversification of the 57 human P450 genes, which may be alternatively processed into nearly 1000 distinct mRNA transcripts to shape an individual's P450 proteome. Important P450 splice variants from families 1A, 1B, 2C, 2D, 3A, 4F, 19A, and 24A have now been documented, with some displaying alternative subcellular distribution or catalytic function directly linked to a disease pathology. The expansion of P450 transcript diversity involves tissue-specific splicing factors, transformation-sensitive alternate splicing, trans-splicing between gene transcripts, single-nucleotide polymorphisms, and epigenetic regulation of alternate splicing. Homeostatic regulation of variant P450 expression is influenced also by nuclear receptor signaling, suppression of nonsense-mediated decay or premature termination codons, mitochondrial dysfunction, or host infection. This review focuses on emergent aspects of the adaptive gene-splicing process, which when viewed through the lens of P450-nuclear receptor gene interactions, resembles a primitive immune-like system that can rapidly monitor, respond, and diversify to acclimate to fluctuations in endo-xenobiotic exposure. Insights gained from this review should aid future drug discovery and improve therapeutic management of personalized drug regimens. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Candidate genes, pathways and mechanisms for bipolar (manic-depressive) and related disorders: an expanded convergent functional genomics approach.

    PubMed

    Ogden, C A; Rich, M E; Schork, N J; Paulus, M P; Geyer, M A; Lohr, J B; Kuczenski, R; Niculescu, A B

    2004-11-01

    Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood stabilizer--valproate), with human data (linkage loci from human genetic studies, changes in postmortem brains from patients), as a bayesian strategy of crossvalidating findings. Topping the list of candidate genes, we have DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) located at 17q12, PENK (preproenkephalin) located at 8q12.1, and TAC1 (tachykinin 1, substance P) located at 7q21.3. These data suggest that more primitive molecular mechanisms involved in pleasure and pain may have been recruited by evolution to play a role in higher mental functions such as mood. The analysis also revealed other high-probability candidates genes (neurogenesis, neurotrophic, neurotransmitter, signal transduction, circadian, synaptic, and myelin related), pathways and mechanisms of likely importance in pathophysiology.

  1. Preferred analysis methods for Affymetrix GeneChips. II. An expanded, balanced, wholly-defined spike-in dataset

    PubMed Central

    2010-01-01

    Background Concomitant with the rise in the popularity of DNA microarrays has been a surge of proposed methods for the analysis of microarray data. Fully controlled "spike-in" datasets are an invaluable but rare tool for assessing the performance of various methods. Results We generated a new wholly defined Affymetrix spike-in dataset consisting of 18 microarrays. Over 5700 RNAs are spiked in at relative concentrations ranging from 1- to 4-fold, and the arrays from each condition are balanced with respect to both total RNA amount and degree of positive versus negative fold change. We use this new "Platinum Spike" dataset to evaluate microarray analysis routes and contrast the results to those achieved using our earlier Golden Spike dataset. Conclusions We present updated best-route methods for Affymetrix GeneChip analysis and demonstrate that the degree of "imbalance" in gene expression has a significant effect on the performance of these methods. PMID:20507584

  2. A glimpse into the expanded genome content of Vibrio cholerae through identification of genes present in environmental strains.

    PubMed

    Purdy, Alexandra; Rohwer, Forest; Edwards, Rob; Azam, Farooq; Bartlett, Douglas H

    2005-05-01

    Vibrio cholerae has multiple survival strategies which are reflected both in its broad distribution in many aquatic environments and its high genotypic diversity. To obtain additional information regarding the content of the V. cholerae genome, suppression subtractive hybridization (SSH) was used to prepare libraries of DNA sequences from two southern California coastal isolates which are divergent or absent in the clinical strain V. cholerae O1 El Tor N16961. More than 1,400 subtracted clones were sequenced. This revealed the presence of novel sequences encoding functions related to cell surface structures, transport, metabolism, signal transduction, luminescence, mobile elements, stress resistance, and virulence. Flanking sequence information was determined for loci of interest, and the distribution of these sequences was assessed for a collection of V. cholerae strains obtained from southern California and Mexican environments. This led to the surprising observation that sequences related to the toxin genes toxA, cnf1, and exoY are widespread and more common in these strains than those of the cholera toxin genes which are a hallmark of the pandemic strains of V. cholerae. Gene transfer among these strains could be facilitated by a 4.9-kbp plasmid discovered in one isolate, which possesses similarity to plasmids from other environmental vibrios. By investigating some of the nucleotide sequence basis for V. cholerae genotypic diversity, DNA fragments have been uncovered which could promote survival in coastal environments. Furthermore, a set of genes has been described which could be involved in as yet undiscovered interactions between V. cholerae and eukaryotic organisms.

  3. Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.

    PubMed

    Tetzlaff, Michael T; Teh, Bin S; Timme, Terry L; Fujita, Tetsuo; Satoh, Takefumi; Tabata, Ken-Ichi; Mai, Wei-Yuan; Vlachaki, Maria T; Amato, Robert J; Kadmon, Dov; Miles, Brian J; Ayala, Gustavo; Wheeler, Thomas M; Aguilar-Cordova, Estuardo; Thompson, Timothy C; Butler, E Brian

    2006-02-01

    The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.

  4. Evaluation of an Expanded Microarray for Detecting Antibiotic Resistance Genes in a Broad Range of Gram-Negative Bacterial Pathogens

    PubMed Central

    Card, Roderick; Zhang, Jiancheng; Das, Priya; Cook, Charlotte; Woodford, Neil

    2013-01-01

    A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure. PMID:23129055

  5. Using viral-mediated gene delivery to model Parkinson's disease: do nonhuman primate investigations expand our understanding?

    PubMed

    Fiandaca, Massimo S; Federoff, Howard J

    2014-06-01

    In this review, we consider the use of nonhuman primate (NHP) models of Parkinson's disease (PD) produced using viral-mediated gene delivery and information they provide in comparison to other model systems in rodents and NHPs. To date, rodent and NHP PD models have found it difficult to fully recapitulate the human disorder and, therefore, provide little actual insight into disease progression. The viral-mediated gene delivery method for α-synuclein has been shown to produce a parkinsonian rodent and NHP. This novel viral-mediated gene transfer model in the NHP appears to provide a significant advance beyond neurotoxicant models, by more closely mimicking the more chronic time course of developed behavioral deterioration and neuropathology. Although we agree that the use of these novel methods inducing parkinsonian NHPs may provide relevant treatment insights, beyond those of more standard PD models, we remain cautious as to the preclinical models' ability to predict outcomes in human trials. In specific cases of certain novel medical therapeutics, therefore, we also consider the phase 0 clinical trial as offering an alternative to the currently non-predictive preclinical models, including those in the NHP.

  6. Evaluation of an expanded microarray for detecting antibiotic resistance genes in a broad range of gram-negative bacterial pathogens.

    PubMed

    Card, Roderick; Zhang, Jiancheng; Das, Priya; Cook, Charlotte; Woodford, Neil; Anjum, Muna F

    2013-01-01

    A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.

  7. Identification of I-7 expands the repertoire of genes for resistance to Fusarium wilt in tomato to three resistance gene classes

    USDA-ARS?s Scientific Manuscript database

    The tomato I-3 and I-7 genes confer resistance to Fusarium oxysporum f. sp. lycopersici (Fol) race 3 and both genes were introgressed into the cultivated tomato, Solanum lycopersicum, from the wild relative Solanum pennellii. I-3 was identified previously and encodes a S-receptor-like kinase, but li...

  8. The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain

    PubMed Central

    Datson, Nicole A.; González-Barriga, Anchel; Kourkouta, Eleni; Weij, Rudie; van de Giessen, Jeroen; Mulders, Susan; Kontkanen, Outi; Heikkinen, Taneli; Lehtimäki, Kimmo; van Deutekom, Judith C. T.

    2017-01-01

    The aim of these studies was to demonstrate the therapeutic capacity of an antisense oligonucleotide with the sequence (CUG)7 targeting the expanded CAG repeat in huntingtin (HTT) mRNA in vivo in the R6/2 N-terminal fragment and Q175 knock-in Huntington’s disease (HD) mouse models. In a first study, R6/2 mice received six weekly intracerebroventricular infusions with a low and high dose of (CUG)7 and were sacrificed 2 weeks later. A 15–60% reduction of both soluble and aggregated mutant HTT protein was observed in striatum, hippocampus and cortex of (CUG)7-treated mice. This correction at the molecular level resulted in an improvement of performance in multiple motor tasks, increased whole brain and cortical volume, reduced levels of the gliosis marker myo-inositol, increased levels of the neuronal integrity marker N-aceyl aspartate and increased mRNA levels of the striatal marker Darpp-32. These neuroanatomical and neurochemical changes, together with the improved motor performance, suggest that treatment with (CUG)7 ameliorates basal ganglia dysfunction. The HTT-lowering was confirmed by an independent study in Q175 mice using a similar (CUG)7 AON dosing regimen, further demonstrating a lasting reduction of mutant HTT protein in striatum, hippocampus and cortex for up to 18 weeks post last infusion along with an increase in motor activity. Based on these encouraging results, (CUG)7 may thus offer an interesting alternative HTT-lowering strategy for HD. PMID:28182673

  9. Expanded Dengue.

    PubMed

    Kadam, D B; Salvi, Sonali; Chandanwale, Ajay

    2016-07-01

    The World Health Organization (WHO) has coined the term expanded dengue to describe cases which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. This has incorporated several atypical findings of dengue. Dengue virus has not been enlisted as a common etiological agent in several conditions like encephalitis, Guillain Barre syndrome. Moreover it is a great mimic of co-existing epidemics like Malaria, Chikungunya and Zika virus disease, which are also mosquito-borne diseases. The atypical manifestations noted in dengue can be mutisystemic and multifacetal. In clinical practice, the occurrence of atypical presentation should prompt us to investigate for dengue. Knowledge of expanded dengue helps to clinch the diagnosis of dengue early, especially during ongoing epidemics, avoiding further battery of investigations. Dengue has proved to be the epidemic with the ability to recur and has a diverse array of presentation as seen in large series from India, Srilanka, Indonesia and Taiwan. WHO has given the case definition of dengue fever in their comprehensive guidelines. Accordingly, a probable case is defined as acute febrile illness with two or more of any findings viz. headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia and supportive serology. There have been cases of patients admitted with fever, altered mentation with or without neck stiffness and pyramidal tract signs. Some had seizures or status epilepticus as presentation. When they were tested for serology, dengue was positive. After ruling out other causes, dengue remained the only culprit. We have come across varied presentations of dengue fever in clinical practice and the present article throws light on atypical manifestations of dengue. © Journal of the Association of Physicians of India 2011.

  10. Rett-like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5-related disease.

    PubMed

    Allou, L; Julia, S; Amsallem, D; El Chehadeh, S; Lambert, L; Thevenon, J; Duffourd, Y; Saunier, A; Bouquet, P; Pere, S; Moustaïne, A; Ruaud, L; Roth, V; Jonveaux, P; Philippe, C

    2017-03-01

    Several genes have been implicated in Rett syndrome (RTT) in its typical and variant forms. We applied next-generation sequencing (NGS) to evaluate for mutations in known or new candidate genes in patients with variant forms of Rett or Rett-like phenotypes of unknown molecular aetiology. In the first step, we used NGS with a custom panel including MECP2, CDKL5, FOXG1, MEF2C and IQSEC2. In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free. This missense was maternally inherited with opposite allele expression ratios in the proband and her mother. In the asymptomatic mother, the mutated copy of the CDKL5 gene was inactivated in 90% of blood cells. We also identified a premature stop codon (p.Arg926*) in IQSEC2 in a patient with a Rett-like phenotype. Finally, exome sequencing enabled us to characterize a heterozygous de novo missense (p.Val408Ala) in KCNA2 encoding the potassium channel Kv 1.2 in a girl with infantile-onset seizures variant of RTT. Our study expands the genetic heterogeneity of RTT and RTT-like phenotypes. Moreover, we report the first familial case of CDKL5-related disease.

  11. Townes-Brocks syndrome versus expanded spectrum hemifacial microsomia: review of eight patients and further evidence of a "hot spot" for mutation in the SALL1 gene.

    PubMed

    Keegan, C E; Mulliken, J B; Wu, B L; Korf, B R

    2001-01-01

    It can be difficult to differentiate clinically between hemifacial microsomia (HFM) and Townes-Brocks syndrome (TBS). The distinction is important because TBS is inherited as an autosomal dominant trait, whereas HFM is sporadic. We performed a retrospective analysis of eight patients with HFM-expanded spectrum and anal anomalies to determine whether this subset has TBS. Two patients had major phenotypic findings of TBS. Sequencing of SALL1, the gene mutated in TBS, in four of the eight patients revealed one with a C --> T transition (resulting in a nonsense mutation R276X) at a previously identified mutational "hot spot." Patients with overlapping features of both syndromes should be screened for SALL1 mutations.

  12. The fragile x mental retardation syndrome 20 years after the FMR1 gene discovery: an expanding universe of knowledge.

    PubMed

    Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

    2011-08-01

    The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations.

  13. The Fragile X Mental Retardation Syndrome 20 Years After the FMR1 Gene Discovery: an Expanding Universe of Knowledge

    PubMed Central

    Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

    2011-01-01

    The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations. PMID:21912443

  14. Instability of the expanded (CTG){sub n} repeats in the myotonin protein kinase gene in cultured lymphoblastoid cell lines from patients with myotonic dystrophy

    SciTech Connect

    Ashizawa, Tetsuo; Patel, B.J.; Monckton, D.G.

    1996-08-15

    The mutation associated with myotonic dystrophy (DM) is the expansion of an unstable trinucleotide repeat, (CTG){sub n}, in the 3{prime}-untranslated region of the myotonin protein kinase gene. Although expanded repeats show both germline and somatic instability, the mechanisms of the instability are poorly understood. To establish a model system in which somatic instability of the DM repeat could be studied in more detail, we established lymphoblastoid cell lines (LBCL) from DM patients. Analysis of the DNA from DM LBCL using Southern blotting showed that the (CTG). repeats were apparently stable up to 29 passages in culture. To study infrequent repeat size mutations that are undetectable due to the size heterogeneity, we established LBCL of single-cell origins by cloning using multiple steps of limiting dilution. After expansion to approximately 10{sup 6} cells (equivalent to approximately 20 cell cycles), the DNAs of these cell lines were analyzed by the small pool PCR technique using primers flanking the (CTG), repeat region. Two types of mutations of the expanded (CTG){sub n} repeat alleles were detected: (1) frequent mutations that show small changes of the (CTG){sub n} repeat size, resulting in alleles in a normal distribution around the progenitor allele, and (2) relatively rare mutations with large changes of the (CTG){sub n} repeat size, with a bias toward contraction. The former may represent the mechanism responsible for the so matic heterogeneity of the (CTG), repeat size observe in blood cells of DM patients. This in vitro experimental system will be useful for further studies on mechanisms involved in the regulation of the somatic stability of the (CTG). repeats in DM. 24 refs., 4 figs.

  15. Spliced Leader RNAs, Mitochondrial Gene Frameshifts and Multi-Protein Phylogeny Expand Support for the Genus Perkinsus as a Unique Group of Alveolates

    PubMed Central

    Zhang, Huan; Campbell, David A.; Sturm, Nancy R.; Dungan, Christopher F.; Lin, Senjie

    2011-01-01

    The genus Perkinsus occupies a precarious phylogenetic position. To gain a better understanding of the relationship between perkinsids, dinoflagellates and other alveolates, we analyzed the nuclear-encoded spliced-leader (SL) RNA and mitochondrial genes, intron prevalence, and multi-protein phylogenies. In contrast to the canonical 22-nt SL found in dinoflagellates (DinoSL), P. marinus has a shorter (21-nt) and a longer (22-nt) SL with slightly different sequences than DinoSL. The major SL RNA transcripts range in size between 80–83 nt in P. marinus, and ∼83 nt in P. chesapeaki, significantly larger than the typical ≤56-nt dinoflagellate SL RNA. In most of the phylogenetic trees based on 41 predicted protein sequences, P. marinus branched at the base of the dinoflagellate clade that included the ancient taxa Oxyrrhis and Amoebophrya, sister to the clade of apicomplexans, and in some cases clustered with apicomplexans as a sister to the dinoflagellate clade. Of 104 Perkinsus spp. genes examined 69.2% had introns, a higher intron prevalence than in dinoflagellates. Examination of Perkinsus spp. mitochondrial cytochrome B and cytochrome C oxidase subunit I genes and their cDNAs revealed no mRNA editing, but these transcripts can only be translated when frameshifts are introduced at every AGG and CCC codon as if AGGY codes for glycine and CCCCU for proline. These results, along with the presence of the numerous uncharacterized ‘marine alveolate group I' and Perkinsus-like lineages separating perkinsids from core dinoflagellates, expand support for the affiliation of the genus Perkinsus with an independent lineage (Perkinsozoa) positioned between the phyla of Apicomplexa and Dinoflagellata. PMID:21629701

  16. Evolution of high cellulolytic activity in symbiotic Streptomyces through selection of expanded gene content and coordinated gene expression

    SciTech Connect

    Book, Adam J.; Lewin, Gina R.; McDonald, Bradon R.; Takasuka, Taichi E.; Wendt-Pienkowski, Evelyn; Doering, Drew T.; Suh, Steven; Raffa, Kenneth F.; Fox, Brian G.; Currie, Cameron R.

    2016-06-08

    In this study, the evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology.

  17. Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay.

    PubMed

    Gous, Natasha; Scott, Lesley; Berrie, Leigh; Stevens, Wendy

    2016-01-01

    Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert's random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32-0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services.

  18. Ectoine alters subcellular localization of inclusions and reduces apoptotic cell death induced by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch.

    PubMed

    Furusho, Kentaro; Yoshizawa, Toshihiro; Shoji, Shinichi

    2005-10-01

    Protein misfolding is considered a key event in the pathogenesis of polyglutamine disease such as Machado-Joseph disease (MJD). Overexpression of chaperone proteins and the application of chemical chaperones are reported to suppress polyglutamine induced cytotoxicity in vitro and in vivo. The effects of compatible solutes, which are osmoprotectants in bacteria and possess the action in stabilizing proteins under stress, have not, to our knowledge, been studied. We explored the protective effects of the compatible solutes ectoine, hydroxyectoine, and betaine on apoptotic cell death produced by the truncated MJD gene product with an expanded polyglutamine tract in cultured neuro2a cells. Ectoine, but not hydroxyectoine or betaine, decreased large cytoplasmic inclusions and increased the frequency of nuclear inclusions. Immunoblot analysis showed that ectoine reduced the total amount of aggregates. Despite the presence of nuclear inclusions, apoptotic features were less frequently observed after ectoine application. Our findings suggest that ectoine, a natural osmoprotectant in bacteria, may function as a novel molecule protecting cells from polyglutamine-induced toxicity.

  19. Three FT and multiple CEN and BFT genes regulate maturity, flowering, and vegetative phenology in kiwifruit

    PubMed Central

    Voogd, Charlotte; Brian, Lara A.; Wang, Tianchi; Allan, Andrew C.

    2017-01-01

    Abstract Kiwifruit is a woody perennial horticultural crop, characterized by excessive vegetative vigor, prolonged juvenility, and low productivity. To understand the molecular factors controlling flowering and winter dormancy, here we identify and characterize the kiwifruit PEBP (phosphatidylethanolamine-binding protein) gene family. Five CEN-like and three BFT-like genes are differentially expressed and act as functionally conserved floral repressors, while two MFT-like genes have no impact on flowering time. FT-like genes are differentially expressed, with AcFT1 confined to shoot tip and AcFT2 to mature leaves. Both act as potent activators of flowering, but expression of AcFT2 in Arabidopsis resulted in a greater impact on plant morphology than that of AcFT1. Constitutive expression of either construct in kiwifruit promoted in vitro flowering, but AcFT2 displayed a greater flowering activation efficiency than AcFT1, leading to immediate floral transition and restriction of leaf development. Both leaf and flower differentiation were observed in AcFT1 kiwifruit lines. Sequential activation of specific PEBP genes in axillary shoot buds during growth and dormancy cycles indicated specific roles in regulation of kiwifruit vegetative and reproductive phenologies. AcCEN and AcCEN4 marked active growth, AcBFT2 was associated with suppression of latent bud growth during winter, and only AcFT was activated after cold accumulation and dormancy release. PMID:28369532

  20. In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial.

    PubMed Central

    Economou, J S; Belldegrun, A S; Glaspy, J; Toloza, E M; Figlin, R; Hobbs, J; Meldon, N; Kaboo, R; Tso, C L; Miller, A; Lau, R; McBride, W; Moen, R C

    1996-01-01

    Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears to produce dramatic regressions in patients with metastatic melanoma and renal cancer. However, the in vivo mechanism of TIL function is not known. We conducted an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee, and FDA-approved clinical trial using genetically-marked TIL to test the hypothesis that these cells have unique, tumor-specific in vivo trafficking patterns. TIL and PBL (as a control effector cell population) were isolated and expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the expansion, TIL and PBL were separately transduced with the amphotropic retroviral vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and their respective numbers measured in tumor, peripheral blood, and normal tissues; integrated provirus could be quantitated and distinguished by DNA PCR. Nine patients were treated (six melanoma, three renal) and received between 4.5 x 10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected circulating in the peripheral blood, in some patients for up to 99 d after infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of nine patients as early as day 6 and as late as day 99 after infusion. No convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted. Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence of TIL/PBL in comparable or greater numbers than in tumor in five patients. The results of this double gene marking trial provide interesting insights into the life span and trafficking of adoptively transferred lymphocytes, but do not support the hypothesis that TIL specifically traffic to tumor deposits. PMID:8567975

  1. Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay

    PubMed Central

    Gous, Natasha; Scott, Lesley; Berrie, Leigh; Stevens, Wendy

    2016-01-01

    Background Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert’s random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Method Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Results Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32–0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. Conclusion The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services. PMID:27992495

  2. The 3; 21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1

    SciTech Connect

    Nucifora, G.; Begy, C.R.; Rowley, J.D. ); Erickson, P.; Drabkin, H.A. )

    1993-08-15

    In the 8;21 translocation, the AML1 gene, located at chromosome band 21q22, is translocated to chromosome 8 (q22), where it is fused to the ETO gene and transcribed as a chimeric gene. AML1 is the human homolog of the recently cloned mouse gene pebp2[alpha]B, homologous to the DNA binding [alpha] subunit of the polyoma enhancer factor pebp2. AML1 is also involved in a translocation with chromosome 3 that is seen in patients with therapy-related acute myeloid leukemia and myelodysplastic syndrome and in chronic myelogenous leukemia in blast crisis. The authors have isolated a fusion cDNA clone from a t(3;21) library derived from a patient with therapy-related myelodysplastic syndrome; this clone contains sequences from AML1 and from EAP, which have now been localized to ban 3q26. EAP has previously been characterized as a highly expressed small nuclear protein of 128 residues (EBER 1) associated with Epstein-Barr virus small RNA. The fusion clone contains the DNA binding 5[prime] part of AML1 that is fused to ETO in the t(8;21) and, in addition, at least one other exon. The translocation replaces the last nine codons of AML1 with the last 96 codons of EAP. The fusion does not maintain the correct reading frame of EAP and may not lead to a functional chimeric protein. 23 refs., 6 figs.

  3. Phylogenic analysis revealed an expanded C₂H₂-homeobox subfamily and expression profiles of C₂H₂ zinc finger gene family in Verticillium dahliae.

    PubMed

    Xiong, Dianguang; Wang, Yonglin; Deng, Chenglin; Hu, Ruowen; Tian, Chengming

    2015-05-15

    C2H2 zinc finger (CZF) proteins are a major class of transcription factors that play crucial roles in fungal growth, development, various stress responses, and virulence. Little genome-wide data is available regarding the roles of CZF proteins in Verticillium dahliae, a destructive pathogen that causes vascular wilt disease in more than 200 plant species. We identified a total of 79 typical CZF genes in V. dahliae. Comparative analysis revealed that four plant pathogenic fungi, V. dahliae, Fusarium oxysporum, Magnaporthe oryzae, and Botrytis cinerea, have comparable numbers of predicted CZF genes with similar characteristics. Phylogenetic analysis identified a C2H2-homeobox subfamily in V. dahliae containing seven genes with similar gene structures. V. dahliae and F. oxysporum (Hypocreomycetidae) have more genes of this subfamily than M. oryzae (Sordariomycetidae) and B. cinerea (Leotiomycetes). Furthermore, gene-expression analysis of the smoke tree wilt fungus V. dahliae strain XS11 using digital gene-expression profiling and RT-qPCR revealed that a number of CZF genes were differentially expressed during microsclerotia formation, nutritional starvation, and simulated in planta conditions. Furthermore, the expression profiles revealed that some CZF genes were overrepresented during multiple stages, indicating that they might play diverse roles. Our results provide useful information concerning the functions of CZF genes in microsclerotia formation, nutritional stress responses, and pathogenicity in V. dahliae, and form a basis for future functional studies of these genes.

  4. What Expands in an Expanding Universe?

    PubMed

    Pacheco, José A De Freitas

    2015-01-01

    In the present investigation, the possible effects of the expansion of the Universe on systems bonded either by gravitational or electromagnetic forces, are reconsidered. It will be shown that the acceleration (positive or negative) of the expanding background, is the determinant factor affecting planetary orbits and atomic sizes. In the presently accepted cosmology (ΛCDM) all bonded systems are expanding at a decreasing rate that tends to be zero as the universe enters in a de Sitter phase. It is worth mentioning that the estimated expansion rates are rather small and they can be neglected for all practical purposes.

  5. Comparison of human chromosome 6p25 with mouse chromosome 13 reveals a greatly expanded ov-serpin gene repertoire in the mouse.

    PubMed

    Kaiserman, Dion; Knaggs, Susan; Scarff, Katrina L; Gillard, Anneliese; Mirza, Ghazala; Cadman, Matthew; McKeone, Richard; Denny, Paul; Cooley, Jessica; Benarafa, Charaf; Remold-O'Donnell, Eileen; Ragoussis, Jiannis; Bird, Phillip I

    2002-03-01

    Ov-serpins are intracellular proteinase inhibitors implicated in the regulation of tumor progression, inflammation, and cell death. The 13 human ov-serpin genes are clustered at 6p25 (3 genes) and 18q21 (10 genes), and share common structures. We show here that a 1-Mb region on mouse chromosome 13 contains at least 15 ov-serpin genes compared with the three ov-serpin genes within 0.35 Mb at human 6p25 (SERPINB1 (MNEI), SERPINB6 (PI-6), SER-PINB9 (PI-9)). The mouse serpins have characteristics of functional inhibitors and fall into three groups on the basis of similarity to MNEI, PI-6, or PI-9. The genes map between the mouse orthologs of the Werner helicase interacting protein and NAD(P)H menadioine oxidoreductase 2 genes, in a region that contains the markers D13Mit136 and D13Mit116. They have the seven-exon structure typical of human 6p25 ov-serpin genes, with identical intron phasing. Most show restricted patterns of expression, with common sites of synthesis being the placenta and immune tissue. Compared with human, this larger mouse serpin repertoire probably reflects the need to regulate a larger proteinase repertoire arising from differing evolutionary pressures on the reproductive and immune systems.

  6. Expanding our understanding of sequence-function relationships of type II polyketide biosynthetic gene clusters: bioinformatics-guided identification of Frankiamicin A from Frankia sp. EAN1pec.

    PubMed

    Ogasawara, Yasushi; Yackley, Benjamin J; Greenberg, Jacob A; Rogelj, Snezna; Melançon, Charles E

    2015-01-01

    A large and rapidly increasing number of unstudied "orphan" natural product biosynthetic gene clusters are being uncovered in sequenced microbial genomes. An important goal of modern natural products research is to be able to accurately predict natural product structures and biosynthetic pathways from these gene cluster sequences. This requires both development of bioinformatic methods for global analysis of these gene clusters and experimental characterization of select products produced by gene clusters with divergent sequence characteristics. Here, we conduct global bioinformatic analysis of all available type II polyketide gene cluster sequences and identify a conserved set of gene clusters with unique ketosynthase α/β sequence characteristics in the genomes of Frankia species, a group of Actinobacteria with underexploited natural product biosynthetic potential. Through LC-MS profiling of extracts from several Frankia species grown under various conditions, we identified Frankia sp. EAN1pec as producing a compound with spectral characteristics consistent with the type II polyketide produced by this gene cluster. We isolated the compound, a pentangular polyketide which we named frankiamicin A, and elucidated its structure by NMR and labeled precursor feeding. We also propose biosynthetic and regulatory pathways for frankiamicin A based on comparative genomic analysis and literature precedent, and conduct bioactivity assays of the compound. Our findings provide new information linking this set of Frankia gene clusters with the compound they produce, and our approach has implications for accurate functional prediction of the many other type II polyketide clusters present in bacterial genomes.

  7. Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

    PubMed

    Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Nakade, Shota; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

    2017-05-04

    The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer ( http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively.

  8. A Family with Craniofrontonasal Syndrome and a Mutation (p.G151S) in the EFNB1 Gene: Expanding the Phenotype

    PubMed Central

    Toral-López, Jaime; González-Huerta, Luz M.; Messina Baas, Olga; Cuevas-Covarrubias, Sergio A.

    2016-01-01

    Craniofrontonasal syndrome (CFNS) is a rare genetic entity with X-linked dominant inheritance. CFNS is due to mutations in the Ephrin-B1 (EFNB1) gene. It is characterized by brachycephaly, frontonasal dysplasia, palate/lip defects, dental malocclusion, short neck, split nails, syndactyly, toe and finger defects, and minor skeletal defects. Intelligence is usually unaffected. CFNS exhibits unexpected manifestations between males and females as the latter are more affected. Cellular or metabolic interference due to X inactivation explains the more severe phenotype in heterozygous females. One family with several members affected with CFNS and 100 healthy controls were examined. DNA from leukocytes was isolated to analyze the EFNB1 gene. We did molecular modeling to assess the impact of the mutation on the EFNB1-encoded protein. DNA sequencing analysis of the EFNB1 gene of the affected members showed the heterozygous missense mutation c.451G>A in the EFNB1 gene (GRcH38, chrX: 68,839,708; GERP score in hg38 of 9.961). This transition mutation resulted in the substitution of Gly at position 151 by Ser. Analysis of the healthy members of the family and 100 unrelated controls showed a normal sequence of the EFNB1 gene. Phenotypes of the patients in this family differ from the classical CFNS due to the decreased size of sulci and fissures, subarachnoid space and ventricles, and the absence of a cleft lip/palate. PMID:27194971

  9. A Family with Craniofrontonasal Syndrome and a Mutation (p.G151S) in the EFNB1 Gene: Expanding the Phenotype.

    PubMed

    Toral-López, Jaime; González-Huerta, Luz M; Messina Baas, Olga; Cuevas-Covarrubias, Sergio A

    2016-04-01

    Craniofrontonasal syndrome (CFNS) is a rare genetic entity with X-linked dominant inheritance. CFNS is due to mutations in the Ephrin-B1 (EFNB1) gene. It is characterized by brachycephaly, frontonasal dysplasia, palate/lip defects, dental malocclusion, short neck, split nails, syndactyly, toe and finger defects, and minor skeletal defects. Intelligence is usually unaffected. CFNS exhibits unexpected manifestations between males and females as the latter are more affected. Cellular or metabolic interference due to X inactivation explains the more severe phenotype in heterozygous females. One family with several members affected with CFNS and 100 healthy controls were examined. DNA from leukocytes was isolated to analyze the EFNB1 gene. We did molecular modeling to assess the impact of the mutation on the EFNB1-encoded protein. DNA sequencing analysis of the EFNB1 gene of the affected members showed the heterozygous missense mutation c.451G>A in the EFNB1 gene (GRcH38, chrX: 68,839,708; GERP score in hg38 of 9.961). This transition mutation resulted in the substitution of Gly at position 151 by Ser. Analysis of the healthy members of the family and 100 unrelated controls showed a normal sequence of the EFNB1 gene. Phenotypes of the patients in this family differ from the classical CFNS due to the decreased size of sulci and fissures, subarachnoid space and ventricles, and the absence of a cleft lip/palate.

  10. Expanding the Repertoire of Gene Tools for Precise Manipulation of the Clostridium difficile Genome: Allelic Exchange Using pyrE Alleles

    PubMed Central

    Philip, Sheryl; Collery, Mark M.; Janoir, Clare; Collignon, Anne; Cartman, Stephen T.; Minton, Nigel P.

    2013-01-01

    Sophisticated genetic tools to modify essential biological processes at the molecular level are pivotal in elucidating the molecular pathogenesis of Clostridium difficile, a major cause of healthcare associated disease. Here we have developed an efficient procedure for making precise alterations to the C. difficile genome by pyrE-based allelic exchange. The robustness and reliability of the method was demonstrated through the creation of in-frame deletions in three genes (spo0A, cwp84, and mtlD) in the non-epidemic strain 630Δerm and two genes (spo0A and cwp84) in the epidemic PCR Ribotype 027 strain, R20291. The system is reliant on the initial creation of a pyrE deletion mutant, using Allele Coupled Exchange (ACE), that is auxotrophic for uracil and resistant to fluoroorotic acid (FOA). This enables the subsequent modification of target genes by allelic exchange using a heterologous pyrE allele from Clostridium sporogenes as a counter-/negative-selection marker in the presence of FOA. Following modification of the target gene, the strain created is rapidly returned to uracil prototrophy using ACE, allowing mutant phenotypes to be characterised in a PyrE proficient background. Crucially, wild-type copies of the inactivated gene may be introduced into the genome using ACE concomitant with correction of the pyrE allele. This allows complementation studies to be undertaken at an appropriate gene dosage, as opposed to the use of multicopy autonomous plasmids. The rapidity of the ‘correction’ method (5–7 days) makes pyrE− strains attractive hosts for mutagenesis studies. PMID:23405251

  11. Induced Variations in Brassinosteroid Genes Define Barley Height and Sturdiness, and Expand the Green Revolution Genetic Toolkit1[C][W][OPEN

    PubMed Central

    Dockter, Christoph; Gruszka, Damian; Braumann, Ilka; Druka, Arnis; Druka, Ilze; Franckowiak, Jerome; Gough, Simon P.; Janeczko, Anna; Kurowska, Marzena; Lundqvist, Joakim; Lundqvist, Udda; Marzec, Marek; Matyszczak, Izabela; Müller, André H.; Oklestkova, Jana; Schulz, Burkhard; Zakhrabekova, Shakhira; Hansson, Mats

    2014-01-01

    Reduced plant height and culm robustness are quantitative characteristics important for assuring cereal crop yield and quality under adverse weather conditions. A very limited number of short-culm mutant alleles were introduced into commercial crop cultivars during the Green Revolution. We identified phenotypic traits, including sturdy culm, specific for deficiencies in brassinosteroid biosynthesis and signaling in semidwarf mutants of barley (Hordeum vulgare). This set of characteristic traits was explored to perform a phenotypic screen of near-isogenic short-culm mutant lines from the brachytic, breviaristatum, dense spike, erectoides, semibrachytic, semidwarf, and slender dwarf mutant groups. In silico mapping of brassinosteroid-related genes in the barley genome in combination with sequencing of barley mutant lines assigned more than 20 historic mutants to three brassinosteroid-biosynthesis genes (BRASSINOSTEROID-6-OXIDASE, CONSTITUTIVE PHOTOMORPHOGENIC DWARF, and DIMINUTO) and one brassinosteroid-signaling gene (BRASSINOSTEROID-INSENSITIVE1 [HvBRI1]). Analyses of F2 and M2 populations, allelic crosses, and modeling of nonsynonymous amino acid exchanges in protein crystal structures gave a further understanding of the control of barley plant architecture and sturdiness by brassinosteroid-related genes. Alternatives to the widely used but highly temperature-sensitive uzu1.a allele of HvBRI1 represent potential genetic building blocks for breeding strategies with sturdy and climate-tolerant barley cultivars. PMID:25332507

  12. Did Androgen-Binding Protein Paralogs Undergo Neo- and/or Subfunctionalization as the Abp Gene Region Expanded in the Mouse Genome?

    PubMed Central

    Karn, Robert C.; Chung, Amanda G.; Laukaitis, Christina M.

    2014-01-01

    The Androgen-binding protein (Abp) region of the mouse genome contains 30 Abpa genes encoding alpha subunits and 34 Abpbg genes encoding betagamma subunits, their products forming dimers composed of an alpha and a betagamma subunit. We endeavored to determine how many Abp genes are expressed as proteins in tears and saliva, and as transcripts in the exocrine glands producing them. Using standard PCR, we amplified Abp transcripts from cDNA libraries of C57BL/6 mice and found fifteen Abp gene transcripts in the lacrimal gland and five in the submandibular gland. Proteomic analyses identified proteins corresponding to eleven of the lacrimal gland transcripts, all of them different from the three salivary ABPs reported previously. Our qPCR results showed that five of the six transcripts that lacked corresponding proteins are expressed at very low levels compared to those transcripts with proteins. We found 1) no overlap in the repertoires of expressed Abp paralogs in lacrimal gland/tears and salivary glands/saliva; 2) substantial sex-limited expression of lacrimal gland/tear expressed-paralogs in males but no sex-limited expression in females; and 3) that the lacrimal gland/tear expressed-paralogs are found exclusively in ancestral clades 1, 2 and 3 of the five clades described previously while the salivary glands/saliva expressed-paralogs are found only in clade 5. The number of instances of extremely low levels of transcription without corresponding protein production in paralogs specific to tears and saliva suggested the role of subfunctionalization, a derived condition wherein genes that may have been expressed highly in both glands ancestrally were down-regulated subsequent to duplication. Thus, evidence for subfunctionalization can be seen in our data and we argue that the partitioning of paralog expression between lacrimal and salivary glands that we report here occurred as the result of adaptive evolution. PMID:25531410

  13. A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients.

    PubMed

    Morales, Fernando; Vásquez, Melissa; Santamaría, Carolina; Cuenca, Patricia; Corrales, Eyleen; Monckton, Darren G

    2016-04-01

    Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age-dependent, tissue-specific and expansion-biased, contributing toward the tissue-specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex-dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target.

  14. Functionalized expanded porphyrins

    DOEpatents

    Sessler, Jonathan L; Pantos, Patricia J

    2013-11-12

    Disclosed are functionalized expanded porphyrins that can be used as spectrometric sensors for high-valent actinide cations. The disclosed functionalized expanded porphyrins have the advantage over unfunctionalized systems in that they can be immobilized via covalent attachment to a solid support comprising an inorganic or organic polymer or other common substrates. Substrates comprising the disclosed functionalized expanded porphyrins are also disclosed. Further, disclosed are methods of making the disclosed compounds (immobilized and free), methods of using them as sensors to detect high valent actinides, devices that comprise the disclosed compounds, and kits.

  15. G-quadruplex structures formed by expanded hexanucleotide repeat RNA and DNA from the neurodegenerative disease-linked C9orf72 gene efficiently sequester and activate heme.

    PubMed

    Grigg, Jason C; Shumayrikh, Nisreen; Sen, Dipankar

    2014-01-01

    The expansion of a (G(4)C(2))n repeat within the human C9orf72 gene has been causally linked to a number of neurodegenerative diseases, most notably familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies have shown that the repeat expansion alters gene function in four ways, disrupting the gene's normal cellular roles and introducing toxic gain of function at the level of both DNA and RNA. (G(4)C(2))n DNA, as well as the RNA transcribed from it, are found to fold into four-stranded G-quadruplex structures. It has been shown that the toxicity of the RNA G-quadruplexes, often localized in intracellular RNA foci, lies in their ability to sequester many important RNA binding proteins. Herein we propose that a distinct toxic property of such RNA and DNA G-quadruplexes from the C9orf72 gene may arise from their ability to bind and oxidatively activate cellular heme. We show that G-quadruplexes formed by both (G(4)C(2))(4) RNA and DNA not only complex tightly with heme but also enhance its intrinsic peroxidase and oxidase propensities. By contrast, the antisense (C(4)G(2))(4) RNA and DNA neither bind heme nor influence its oxidative activity. Curiously, the ability of C9orf72 DNA and transcripts to bind and activate heme mirror similar properties that have been reported for the Aβ peptide and its oligomers in Alzheimer's disease neurons. It is therefore conceivable that C9orf72 RNA G-quadruplex tangles play roles in sequestering intracellular heme and promoting oxidative damage in ALS and FTD analogous to those proposed for Aβ peptide and its tangles in Alzheimer's Disease. Given that neurodegenerative diseases in general are characterized by mitochondrial and respiratory malfunctions, the role of C9orf72 DNA and RNA in heme sequestration as well as its inappropriate activation in ALS and FTD neurons may warrant examination.

  16. Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option.

    PubMed

    Gilabert, Aude; Curran, David M; Harvey, Simon C; Wasmuth, James D

    2016-06-27

    Signalling pathways underlie development, behaviour and pathology. To understand patterns in the evolution of signalling pathways, we undertook a comprehensive investigation of the pathways that control the switch between growth and developmentally quiescent dauer in 24 species of nematodes spanning the phylum. Our analysis of 47 genes across these species indicates that the pathways and their interactions are not conserved throughout the Nematoda. For example, the TGF-β pathway was co-opted into dauer control relatively late in a lineage that led to the model species Caenorhabditis elegans. We show molecular adaptations described in C. elegans that are restricted to its genus or even just to the species. Similarly, our analyses both identify species where particular genes have been lost and situations where apparently incorrect orthologues have been identified. Our analysis also highlights the difficulties of working with genome sequences from non-model species as reliance on the published gene models would have significantly restricted our understanding of how signalling pathways evolve. Our approach therefore offers a robust standard operating procedure for genomic comparisons.

  17. Expanding the Universe

    NASA Astrophysics Data System (ADS)

    Sterken, Christiaan; Leedjärv, Laurits; Tempel, Elmo

    2011-12-01

    Proceedings of the International Conference EXPANDING THE UNIVERSE, On the occasion of the 200th anniversary of the Tartu Observatory, Tartu, Estonia 2011 April 27-29. C. Sterken, L. Leedjarv, E. Tempel (Eds.)

  18. Identification of precursor transcripts for 6 novel miRNAs expands the diversity on the genomic organisation and expression of miRNA genes in rice

    PubMed Central

    Lacombe, Séverine; Nagasaki, Hiroshi; Santi, Carole; Duval, David; Piégu, Benoît; Bangratz, Martine; Breitler, Jean-Christophe; Guiderdoni, Emmanuel; Brugidou, Christophe; Hirsch, Judith; Cao, Xiaofeng; Brice, Claire; Panaud, Olivier; Karlowski, Wojciech M; Sato, Yutaka; Echeverria, Manuel

    2008-01-01

    Background The plant miRNAs represent an important class of endogenous small RNAs that guide cleavage of an mRNA target or repress its translation to control development and adaptation to stresses. MiRNAs are nuclear-encoded genes transcribed by RNA polymerase II, producing a primary precursor that is subsequently processed by DCL1 an RNase III Dicer-like protein. In rice hundreds of miRNAs have been described or predicted, but little is known on their genes and precursors which are important criteria to distinguish them from siRNAs. Here we develop a combination of experimental approaches to detect novel miRNAs in rice, identify their precursor transcripts and genes and predict or validate their mRNA targets. Results We produced four cDNA libraries from small RNA fractions extracted from distinct rice tissues. By in silico analysis we selected 6 potential novel miRNAs, and confirmed that their expression requires OsDCL1. We predicted their targets and used 5'RACE to validate cleavage for three of them, targeting a PPR, an SPX domain protein and a GT-like transcription factor respectively. In addition, we identified precursor transcripts for the 6 miRNAs expressed in rice, showing that these precursors can be efficiently processed using a transient expression assay in transfected Nicotiana benthamiana leaves. Most interestingly, we describe two precursors producing tandem miRNAs, but in distinct arrays. We focus on one of them encoding osa-miR159a.2, a novel miRNA produced from the same stem-loop structure encoding the conserved osa-miR159a.1. We show that this dual osa-miR159a.2-osa-miR159a.1 structure is conserved in distant rice species and maize. Finally we show that the predicted mRNA target of osa-miR159a.2 encoding a GT-like transcription factor is cleaved in vivo at the expected site. Conclusion The combination of approaches developed here identified six novel miRNAs expressed in rice which can be clearly distinguished from siRNAs. Importantly, we show that

  19. Expanding the repertoire of deadenylases.

    PubMed

    Skeparnias, Ilias; Αnastasakis, Dimitrios; Shaukat, Athanasios-Nasir; Grafanaki, Katerina; Stathopoulos, Constantinos

    2017-03-07

    Deadenylases belong to an expanding family of exoribonucleases involved mainly in mRNA stability and turnover, with the exception of PARN which has additional roles in the biogenesis of several important non-coding RNAs, including miRNAs and piRNAs. Recently, PARN in C. elegans and its homolog PNLDC1 in B. mori were reported as the elusive trimmers mediating piRNA biogenesis. In addition, characterization of mammalian PNLDC1 in comparison to PARN, showed that is specifically expressed in embryonic stem and germ cells, as well as during early embryo development. Moreover, its expression is correlated with epigenetic events mediated by the de novo DNMT3b methyltransferase and knockdown in stem cells upregulates important genes that regulate multipotency. The recent data suggest that at least some new deadenylases may have expanded roles in cell metabolism as regulators of gene expression, through mRNA deadenylation, ncRNAs biogenesis and ncRNA-mediated mRNA targeting, linking essential mechanisms that regulate epigenetic control and transition events during differentiation. The possible roles of mammalian PNLDC1 along those dynamic networks are discussed in the light of new extremely important findings.

  20. Silicon microfabricated beam expander

    SciTech Connect

    Othman, A. Ibrahim, M. N.; Hamzah, I. H.; Sulaiman, A. A.; Ain, M. F.

    2015-03-30

    The feasibility design and development methods of silicon microfabricated beam expander are described. Silicon bulk micromachining fabrication technology is used in producing features of the structure. A high-precision complex 3-D shape of the expander can be formed by exploiting the predictable anisotropic wet etching characteristics of single-crystal silicon in aqueous Potassium-Hydroxide (KOH) solution. The beam-expander consist of two elements, a micromachined silicon reflector chamber and micro-Fresnel zone plate. The micro-Fresnel element is patterned using lithographic methods. The reflector chamber element has a depth of 40 µm, a diameter of 15 mm and gold-coated surfaces. The impact on the depth, diameter of the chamber and absorption for improved performance are discussed.

  1. Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive architecture in Arabidopsis

    PubMed Central

    Coelho, Carla P.; Minow, Mark A. A.; Chalfun-Júnior, Antonio; Colasanti, Joseph

    2014-01-01

    Agriculturally important grasses such as rice, maize, and sugarcane are evolutionarily distant from Arabidopsis, yet some components of the floral induction process are highly conserved. Flowering in sugarcane is an important factor that negatively affects cane yield and reduces sugar/ethanol production from this important perennial bioenergy crop. Comparative studies have facilitated the identification and characterization of putative orthologs of key flowering time genes in sugarcane, a complex polyploid plant whose genome has yet to be sequenced completely. Using this approach we identified phosphatidylethanolamine-binding protein (PEBP) gene family members in sugarcane that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play an essential role in controlling the transition from vegetative to reproductive growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral repressors, showed transcripts in developing leaves surrounding the shoot apex but not at the apex itself. ScFT1 was detected in immature leaves and apical regions of vegetatively growing plants and, after the floral transition, expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a gene related to TFL1. In addition, lines with the latest flowering phenotype exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which has greatest similarity to the florigen-encoding FT, also caused a delay in flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene family members from Saccharum spp. suggests that their expression patterns and roles in the floral transition has diverged from the predicted role of similar PEBP family members. PMID:24904616

  2. An Expanded Role for HLA Genes: HLA-B Encodes a microRNA that Regulates IgA and Other Immune Response Transcripts.

    PubMed

    Chitnis, Nilesh; Clark, Peter M; Kamoun, Malek; Stolle, Catherine; Brad Johnson, F; Monos, Dimitri S

    2017-01-01

    We describe a novel functional role for the HLA-B locus mediated by its intron-encoded microRNA (miRNA), miR-6891-5p. We show that in vitro inhibition of miR-6891-5p impacts the expression of nearly 200 transcripts within the B-lymphoblastoid cell line (B-LCL) COX, affecting a large number of metabolic pathways, including various immune response networks. The top affected transcripts following miR-6891-5p inhibition are those encoding the heavy chain of IgA. We identified a conserved miR-6891-5p target site on the 3'UTR of both immunoglobulin heavy chain alpha 1 and 2 (IGHA1 and IGHA2) transcripts and demonstrated that this miRNA modulates the expression of IGHA1 and IGHA2. B-LCLs from IgA-deficient patients expressed significantly elevated levels of miR-6891-5p when compared with unaffected family members. Upon inhibition of miR-6891-5p, IgA mRNA expression levels were increased, and IgA secretion was restored in the B-LCL of an IgA-deficient patient. These findings indicate that miR-6891-5p regulates IGHA1 and IGHA2 gene expression at the posttranscriptional level and suggest that increase in miR-6891-5p levels may contribute to the etiology of selective IgA deficiency.

  3. Expanding Views on Transition.

    ERIC Educational Resources Information Center

    Repetto, Jeanne B.; Correa, Vivian I.

    1996-01-01

    This position paper proposes an expanded definition of transition, based on common components of early childhood and secondary perspectives. It advocates for a seamless model of transition service delivery for students with disabilities, including program planning, from birth through age 21. The model addresses curriculum, location of services,…

  4. Expanded Roles for HRD.

    ERIC Educational Resources Information Center

    1998

    This document contains three papers from a symposium on expanded roles for human resource development (HRD). "The Roles of Consultants in Gainsharing Firms: Empirical Results" (Eunsang Cho, Gary N. McLean) reports findings that consultants are moderately involved at the separation, preparation, evaluation, and design stages and have low…

  5. Expand Your Hiring Horizons.

    ERIC Educational Resources Information Center

    Leske, Lucy Apthorp; Archer-Martin, Nancy

    1999-01-01

    To succeed in recruiting development officers, colleges and universities must use more aggressive methods to reach alumni, people with ties to the campus, and local business people; expand their selection criteria, perhaps including candidates with little or no experience; streamline the hiring process; and train new professionals. (MSE)

  6. ExpandED Options: Learning beyond High School Walls

    ERIC Educational Resources Information Center

    ExpandED Schools, 2014

    2014-01-01

    Through ExpandED Options by TASC, New York City high school students get academic credit for learning career-related skills that lead to paid summer jobs. Too many high school students--including those most likely to drop out--are bored or see classroom learning as irrelevant. ExpandED Options students live the connection between mastering new…

  7. Characterisation of betalain biosynthesis in Parakeelya flowers identifies the key biosynthetic gene DOD as belonging to an expanded LigB gene family that is conserved in betalain-producing species

    PubMed Central

    Chung, Hsiao-Hang; Schwinn, Kathy E.; Ngo, Hanh M.; Lewis, David H.; Massey, Baxter; Calcott, Kate E.; Crowhurst, Ross; Joyce, Daryl C.; Gould, Kevin S.; Davies, Kevin M.; Harrison, Dion K.

    2015-01-01

    Plant betalain pigments are intriguing because they are restricted to the Caryophyllales and are mutually exclusive with the more common anthocyanins. However, betalain biosynthesis is poorly understood compared to that of anthocyanins. In this study, betalain production and betalain-related genes were characterized in Parakeelya mirabilis (Montiaceae). RT-PCR and transcriptomics identified three sequences related to the key biosynthetic enzyme Dopa 4,5-dioxgenase (DOD). In addition to a LigB gene similar to that of non-Caryophyllales species (Class I genes), two other P. mirabilis LigB genes were found (DOD and DOD-like, termed Class II). PmDOD and PmDOD-like had 70% amino acid identity. Only PmDOD was implicated in betalain synthesis based on transient assays of enzyme activity and correlation of transcript abundance to spatio-temporal betalain accumulation. The role of PmDOD-like remains unknown. The striking pigment patterning of the flowers was due to distinct zones of red betacyanin and yellow betaxanthin production. The major betacyanin was the unglycosylated betanidin rather than the commonly found glycosides, an occurrence for which there are a few previous reports. The white petal zones lacked pigment but had DOD activity suggesting alternate regulation of the pathway in this tissue. DOD and DOD-like sequences were also identified in other betalain-producing species but not in examples of anthocyanin-producing Caryophyllales or non-Caryophyllales species. A Class I LigB sequence from the anthocyanin-producing Caryophyllaceae species Dianthus superbus and two DOD-like sequences from the Amaranthaceae species Beta vulgaris and Ptilotus spp. did not show DOD activity in the transient assay. The additional sequences suggests that DOD is part of a larger LigB gene family in betalain-producing Caryophyllales taxa, and the tandem genomic arrangement of two of the three B. vulgaris LigB genes suggests the involvement of duplication in the gene family evolution

  8. Grazing incidence beam expander

    SciTech Connect

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  9. Grazing incidence beam expander

    NASA Astrophysics Data System (ADS)

    Akkapeddi, P. R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V. K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  10. Expandable LED array interconnect

    DOEpatents

    Yuan, Thomas Cheng-Hsin; Keller, Bernd

    2011-03-01

    A light emitting device that can function as an array element in an expandable array of such devices. The light emitting device comprises a substrate that has a top surface and a plurality of edges. Input and output terminals are mounted to the top surface of the substrate. Both terminals comprise a plurality of contact pads disposed proximate to the edges of the substrate, allowing for easy access to both terminals from multiple edges of the substrate. A lighting element is mounted to the top surface of the substrate. The lighting element is connected between the input and output terminals. The contact pads provide multiple access points to the terminals which allow for greater flexibility in design when the devices are used as array elements in an expandable array.

  11. Discovering the Expanding Universe

    NASA Astrophysics Data System (ADS)

    Nussbaumer, Harry; Bieri, Lydia; Sandage, Foreword by Allan

    2009-03-01

    Acknowledgments; Foreword; 1. Introduction; 2. Cosmological concepts at the end of the Middle Ages; 3. Nebulae as a new astronomical phenomenon; 4. On the construction of the Heavens; 5. Island universes turn into astronomical facts: a universe of galaxies; 6. The early cosmology of Einstein and de Sitter; 7. The dynamical universe of Friedmann; 8. Redshifts: how to reconcile Slipher and de Sitter?; 9. Lemaître discovers the expanding universe; 10. Hubble's contribution of 1929; 11. The breakthrough for the expanding universe; 12. Hubble's anger about de Sitter; 13. Robertson and Tolman join the game; 14. The Einstein-de Sitter universe; 15. Are Sun and Earth older than the universe?; 16. In search of alternative tracks; 17. The seed for the Big Bang; 18. Summary and Postscript; Appendix; References; Index.

  12. Expanding the HAWC Observatory

    SciTech Connect

    Mori, Johanna

    2016-08-17

    The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

  13. Changes in Growth CO2 Result in Rapid Adjustments of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Small Subunit Gene Expression in Expanding and Mature Leaves of Rice1

    PubMed Central

    Gesch, Russ W.; Boote, Kenneth J.; Vu, Joseph C.V.; Hartwell Allen, L.; Bowes, George

    1998-01-01

    The accumulation of soluble carbohydrates resulting from growth under elevated CO2 may potentially signal the repression of gene activity for the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcS). To test this hypothesis we grew rice (Oryza sativa L.) under ambient (350 μL L−1) and high (700 μL L−1) CO2 in outdoor, sunlit, environment-controlled chambers and performed a cross-switching of growth CO2 concentration at the late-vegetative phase. Within 24 h, plants switched to high CO2 showed a 15% and 23% decrease in rbcS mRNA, whereas plants switched to ambient CO2 increased 27% and 11% in expanding and mature leaves, respectively. Ribulose-1,5-bisphosphate carboxylase/oxygenase total activity and protein content 8 d after the switch increased up to 27% and 20%, respectively, in plants switched to ambient CO2, but changed very little in plants switched to high CO2. Plants maintained at high CO2 showed greater carbohydrate pool sizes and lower rbcS transcript levels than plants kept at ambient CO2. However, after switching growth CO2 concentration, there was not a simple correlation between carbohydrate and rbcS transcript levels. We conclude that although carbohydrates may be important in the regulation of rbcS expression, changes in total pool size alone could not predict the rapid changes in expression that we observed. PMID:9765537

  14. Expanding hollow metal rings

    DOEpatents

    Peacock, Harold B [Evans, GA; Imrich, Kenneth J [Grovetown, GA

    2009-03-17

    A sealing device that may expand more planar dimensions due to internal thermal expansion of a filler material. The sealing material is of a composition such that when desired environment temperatures and internal actuating pressures are reached, the sealing materials undergoes a permanent deformation. For metallic compounds, this permanent deformation occurs when the material enters the plastic deformation phase. Polymers, and other materials, may be using a sealing mechanism depending on the temperatures and corrosivity of the use. Internal pressures are generated by either rapid thermal expansion or material phase change and may include either liquid or solid to gas phase change, or in the gaseous state with significant pressure generation in accordance with the gas laws. Sealing material thickness and material composition may be used to selectively control geometric expansion of the seal such that expansion is limited to a specific facing and or geometric plane.

  15. Mechanically expandable annular seal

    DOEpatents

    Gilmore, R.F.

    1983-07-19

    A mechanically expandable annular reusable seal assembly to form an annular hermetic barrier between two stationary, parallel, and planar containment surfaces is described. A rotatable ring, attached to the first surface, has ring wedges resembling the saw-tooth array of a hole saw. Matching seal wedges are slidably attached to the ring wedges and have their motion restricted to be perpendicular to the second surface. Each seal wedge has a face parallel to the second surface. An annular elastomer seal has a central annular region attached to the seal wedges' parallel faces and has its inner and outer circumferences attached to the first surface. A rotation of the ring extends the elastomer seal's central region perpendicularly towards the second surface to create the fluid tight barrier. A counter rotation removes the barrier. 6 figs.

  16. Mechanically expandable annular seal

    DOEpatents

    Gilmore, Richard F.

    1983-01-01

    A mechanically expandable annular reusable seal assembly to form an annular hermetic barrier between two stationary, parallel, and planar containment surfaces. A rotatable ring, attached to the first surface, has ring wedges resembling the saw-tooth array of a hole saw. Matching seal wedges are slidably attached to the ring wedges and have their motion restricted to be perpendicular to the second surface. Each seal wedge has a face parallel to the second surface. An annular elastomer seal has a central annular region attached to the seal wedges' parallel faces and has its inner and outer circumferences attached to the first surface. A rotation of the ring extends the elastomer seal's central region perpendicularly towards the second surface to create the fluidtight barrier. A counterrotation removes the barrier.

  17. Soviet gas processing expands

    SciTech Connect

    Sagers, M.J.

    1987-09-01

    The Soviet gas processing industry expanded with the recent completion of two new gas processing plants, the Krasnoleninskiy and Noyabr'sk plants, both located in West Siberia. Both process associated gas from nearby oil fields to remove valuable liquid hydrocarbons before putting the dry gas into pipelines; previously the gas was flared or vented. These plants represent part of a major program, ongoing since the 1970s, to increase the level of utilization of the tremendous amount of valuable associated gas now being produced in West Siberia. Another major effort to develop gas processing is under way in western Kazakhstan at the Tengiz and Zhanazhol' fields. At Zhanazhol', a small gas recovery plant went into operation in late 1984 in conjunction with a separation plant with a processing capacity of 1 million tons of oil per year. A much larger enterprise to refine oil and process associated gas is under construction at the Tengiz field. This enterprise is different from the major petrochemical operation planned to use feedstocks from Tengiz; the petrochemical operation will be constructed at Kulsary, 120 kilometers from Tengiz, and produce polyethylene, polypropylene, and other plastics.

  18. Expanding contraceptive options.

    PubMed

    1989-01-01

    The goals of Family Health International (FHI) have been to introduce a variety of birth control options to people in developing countries, and to provide information to the user on the advantages and disadvantages of each method. FHI has worked with many developing countries in clinical trials of established as well as new contraceptive methods. These trials played an important part in making 2 sterilization procedures, laparoscopy and minilaparotomy popular for women. Further research improved the methods and have made them the most popular in the world, chosen by 130 million users. FHI is doing clinical trials on a new IUD, that is a copper bearing T-shaped device called the TCu380A. they have collected data on over 10,000 women using IUD's and early analysis indicates TCu380A is more effective than others. FHI is also evaluating devices such as Norplant that will prevent pregnancy up to 5 years by implanting the capsules in the arm. More than 8,000 women are being tested to determine the acceptability of implants in different geographical locations. Other research groups are doing work in 10 additional countries: Bangladesh will expand its program to 24,000 women and Nepal to 8,000 women. Trials are also being conducted on progestogen pills, since they do not lesson the volume of milk in breast feeding. FHI has also worked to introduce creative community-based distribution channels. In one case, specially trained health workers delivered contraceptives door-to-door in over 150,000 households. They found that 2 of 3 women accepted the pills and in a follow up survey 90% were still using them. FHI is now focusing on ways to improve moving new contraceptives from clinical testing on everyday use. They will coordinate training programs, educational material, media campaigns, and efforts with other international organizations, government agencies, and family planning groups.

  19. The Artful Universe Expanded

    NASA Astrophysics Data System (ADS)

    Barrow, John D.

    2005-07-01

    Our love of art, writes John Barrow, is the end product of millions of years of evolution. How we react to a beautiful painting or symphony draws upon instincts laid down long before humans existed. Now, in this enhanced edition of the highly popular The Artful Universe , Barrow further explores the close ties between our aesthetic appreciation and the basic nature of the Universe. Barrow argues that the laws of the Universe have imprinted themselves upon our thoughts and actions in subtle and unexpected ways. Why do we like certain types of art or music? What games and puzzles do we find challenging? Why do so many myths and legends have common elements? In this eclectic and entertaining survey, Barrow answers these questions and more as he explains how the landscape of the Universe has influenced the development of philosophy and mythology, and how millions of years of evolutionary history have fashioned our attraction to certain patterns of sound and color. Barrow casts the story of human creativity and thought in a fascinating light, considering such diverse topics as our instinct for language, the origins and uses of color in nature, why we divide time into intervals as we do, the sources of our appreciation of landscape painting, and whether computer-generated fractal art is really art. Drawing on a wide variety of examples, from the theological questions raised by St. Augustine and C.S. Lewis to the relationship between the pure math of Pythagoras and the music of the Beatles, The Artful Universe Expanded covers new ground and enters a wide-ranging debate about the meaning and significance of the links between art and science.

  20. Advanced expander test bed program

    NASA Technical Reports Server (NTRS)

    Masters, A. I.; Mitchell, J. C.

    1991-01-01

    The Advanced Expander Test Bed (AETB) is a key element in NASA's Chemical Transfer Propulsion Program for development and demonstration of expander cycle oxygen/hydrogen engine technology component technology for the next space engine. The AETB will be used to validate the high-pressure expander cycle concept, investigate system interactions, and conduct investigations of advanced missions focused components and new health monitoring techniques. The split-expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust.

  1. Advanced expander test bed engine

    NASA Technical Reports Server (NTRS)

    Mitchell, J. P.

    1992-01-01

    The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high pressure expander cycle concept, study system interactions, and conduct studies of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust.

  2. Responsible implementation of expanded carrier screening.

    PubMed

    Henneman, Lidewij; Borry, Pascal; Chokoshvili, Davit; Cornel, Martina C; van El, Carla G; Forzano, Francesca; Hall, Alison; Howard, Heidi C; Janssens, Sandra; Kayserili, Hülya; Lakeman, Phillis; Lucassen, Anneke; Metcalfe, Sylvia A; Vidmar, Lovro; de Wert, Guido; Dondorp, Wybo J; Peterlin, Borut

    2016-06-01

    This document of the European Society of Human Genetics contains recommendations regarding responsible implementation of expanded carrier screening. Carrier screening is defined here as the detection of carrier status of recessive diseases in couples or persons who do not have an a priori increased risk of being a carrier based on their or their partners' personal or family history. Expanded carrier screening offers carrier screening for multiple autosomal and X-linked recessive disorders, facilitated by new genetic testing technologies, and allows testing of individuals regardless of ancestry or geographic origin. Carrier screening aims to identify couples who have an increased risk of having an affected child in order to facilitate informed reproductive decision making. In previous decades, carrier screening was typically performed for one or few relatively common recessive disorders associated with significant morbidity, reduced life-expectancy and often because of a considerable higher carrier frequency in a specific population for certain diseases. New genetic testing technologies enable the expansion of screening to multiple conditions, genes or sequence variants. Expanded carrier screening panels that have been introduced to date have been advertised and offered to health care professionals and the public on a commercial basis. This document discusses the challenges that expanded carrier screening might pose in the context of the lessons learnt from decades of population-based carrier screening and in the context of existing screening criteria. It aims to contribute to the public and professional discussion and to arrive at better clinical and laboratory practice guidelines.

  3. Responsible implementation of expanded carrier screening

    PubMed Central

    Henneman, Lidewij; Borry, Pascal; Chokoshvili, Davit; Cornel, Martina C; van El, Carla G; Forzano, Francesca; Hall, Alison; Howard, Heidi C; Janssens, Sandra; Kayserili, Hülya; Lakeman, Phillis; Lucassen, Anneke; Metcalfe, Sylvia A; Vidmar, Lovro; de Wert, Guido; Dondorp, Wybo J; Peterlin, Borut

    2016-01-01

    This document of the European Society of Human Genetics contains recommendations regarding responsible implementation of expanded carrier screening. Carrier screening is defined here as the detection of carrier status of recessive diseases in couples or persons who do not have an a priori increased risk of being a carrier based on their or their partners' personal or family history. Expanded carrier screening offers carrier screening for multiple autosomal and X-linked recessive disorders, facilitated by new genetic testing technologies, and allows testing of individuals regardless of ancestry or geographic origin. Carrier screening aims to identify couples who have an increased risk of having an affected child in order to facilitate informed reproductive decision making. In previous decades, carrier screening was typically performed for one or few relatively common recessive disorders associated with significant morbidity, reduced life-expectancy and often because of a considerable higher carrier frequency in a specific population for certain diseases. New genetic testing technologies enable the expansion of screening to multiple conditions, genes or sequence variants. Expanded carrier screening panels that have been introduced to date have been advertised and offered to health care professionals and the public on a commercial basis. This document discusses the challenges that expanded carrier screening might pose in the context of the lessons learnt from decades of population-based carrier screening and in the context of existing screening criteria. It aims to contribute to the public and professional discussion and to arrive at better clinical and laboratory practice guidelines. PMID:26980105

  4. The expanding family Marseilleviridae.

    PubMed

    Aherfi, Sarah; La Scola, Bernard; Pagnier, Isabelle; Raoult, Didier; Colson, Philippe

    2014-10-01

    The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in 2007, 7 new marseilleviruses have been observed, including 3 from environmental freshwater, one from a dipteran, and two from symptom-free humans. Marseilleviruses have ≈250-nm-large icosahedral capsids and 346-386-kb-long mosaic genomes that encode 444-497 predicted proteins. They share a small set of core genes with Mimivirus and other large and giant DNA viruses that compose a monophyletic group, first described in 2001. Comparative genomics analyses indicate that the family Marseilleviridae currently includes three lineages and a pan-genome composed of ≈600 genes. Antibodies against marseilleviruses and viral DNA have been observed in a significant proportion of asymptomatic individuals and in the blood and lymph nodes of a child with adenitis; these observations suggest that these giant viruses may be blood borne and question if they may be pathogenic in humans.

  5. Genome-Wide Comparative Analysis of Flowering-Related Genes in Arabidopsis, Wheat, and Barley

    PubMed Central

    Peng, Fred Y.; Hu, Zhiqiu; Yang, Rong-Cai

    2015-01-01

    Early flowering is an important trait influencing grain yield and quality in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) in short-season cropping regions. However, due to large and complex genomes of these species, direct identification of flowering genes and their molecular characterization remain challenging. Here, we used a bioinformatic approach to predict flowering-related genes in wheat and barley from 190 known Arabidopsis (Arabidopsis thaliana (L.) Heynh.) flowering genes. We identified 900 and 275 putative orthologs in wheat and barley, respectively. The annotated flowering-related genes were clustered into 144 orthologous groups with one-to-one, one-to-many, many-to-one, and many-to-many orthology relationships. Our approach was further validated by domain and phylogenetic analyses of flowering-related proteins and comparative analysis of publicly available microarray data sets for in silico expression profiling of flowering-related genes in 13 different developmental stages of wheat and barley. These further analyses showed that orthologous gene pairs in three critical flowering gene families (PEBP, MADS, and BBX) exhibited similar expression patterns among 13 developmental stages in wheat and barley, suggesting similar functions among the orthologous genes with sequence and expression similarities. The predicted candidate flowering genes can be confirmed and incorporated into molecular breeding for early flowering wheat and barley in short-season cropping regions. PMID:26435710

  6. Discovery of gene-gene interactions across multiple independent datasets of Late Onset Alzheimer Disease from the Alzheimer Disease Genetics Consortium

    PubMed Central

    Hohman, Timothy J.; Bush, William S.; Jiang, Lan; Brown-Gentry, Kristin D.; Torstenson, Eric S.; Dudek, Scott M.; Mukherjee, Shubhabrata; Naj, Adam; Kunkle, Brian W.; Ritchie, Marylyn D.; Martin, Eden R.; Schellenberg, Gerard D.; Mayeux, Richard; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Thornton-Wells, Tricia A.

    2015-01-01

    Late-onset Alzheimer disease (LOAD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance and gene-gene interactions; however, the investigation of interactions in recent GWAS has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across thirteen datasets from the Alzheimer Disease Genetics Consortium. Fifteen SNP-SNP pairs within three gene-gene combinations were identified: SIRT1 x ABCB1, PSAP x PEBP4, and GRIN2B x ADRA1A. Additionally, we extend a previously identified interaction from an endophenotype analysis between RYR3 x CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this manuscript highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis. PMID:26827652

  7. Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium.

    PubMed

    Hohman, Timothy J; Bush, William S; Jiang, Lan; Brown-Gentry, Kristin D; Torstenson, Eric S; Dudek, Scott M; Mukherjee, Shubhabrata; Naj, Adam; Kunkle, Brian W; Ritchie, Marylyn D; Martin, Eden R; Schellenberg, Gerard D; Mayeux, Richard; Farrer, Lindsay A; Pericak-Vance, Margaret A; Haines, Jonathan L; Thornton-Wells, Tricia A

    2016-02-01

    Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 × ABCB1, PSAP × PEBP4, and GRIN2B × ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3 × CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis.

  8. Expanding CEP290 mutational spectrum in ciliopathies

    PubMed Central

    Travaglini, Lorena; Brancati, Francesco; Attie-Bitach, Tania; Audollent, Sophie; Bertini, Enrico; Kaplan, Josseline; Perrault, Isabelle; Iannicelli, Miriam; Mancuso, Brunella; Rigoli, Luciana; Rozet, Jean-Michel; Swistun, Dominika; Tolentino, Jerlyn; Dallapiccola, Bruno; Gleeson, Joseph G.; Valente, Enza Maria

    2015-01-01

    Ciliopathies are an expanding group of rare conditions characterised by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus, that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified. PMID:19764032

  9. Expanding CEP290 mutational spectrum in ciliopathies.

    PubMed

    Travaglini, Lorena; Brancati, Francesco; Attie-Bitach, Tania; Audollent, Sophie; Bertini, Enrico; Kaplan, Josseline; Perrault, Isabelle; Iannicelli, Miriam; Mancuso, Brunella; Rigoli, Luciana; Rozet, Jean-Michel; Swistun, Dominika; Tolentino, Jerlyn; Dallapiccola, Bruno; Gleeson, Joseph G; Valente, Enza Maria; Zankl, A; Leventer, R; Grattan-Smith, P; Janecke, A; D'Hooghe, M; Sznajer, Y; Van Coster, R; Demerleir, L; Dias, K; Moco, C; Moreira, A; Kim, C Ae; Maegawa, G; Petkovic, D; Abdel-Salam, G M H; Abdel-Aleem, A; Zaki, M S; Marti, I; Quijano-Roy, S; Sigaudy, S; de Lonlay, P; Romano, S; Touraine, R; Koenig, M; Lagier-Tourenne, C; Messer, J; Collignon, P; Wolf, N; Philippi, H; Kitsiou Tzeli, S; Halldorsson, S; Johannsdottir, J; Ludvigsson, P; Phadke, S R; Udani, V; Stuart, B; Magee, A; Lev, D; Michelson, M; Ben-Zeev, B; Fischetto, R; Benedicenti, F; Stanzial, F; Borgatti, R; Accorsi, P; Battaglia, S; Fazzi, E; Giordano, L; Pinelli, L; Boccone, L; Bigoni, S; Ferlini, A; Donati, M A; Caridi, G; Divizia, M T; Faravelli, F; Ghiggeri, G; Pessagno, A; Briguglio, M; Briuglia, S; Salpietro, C D; Tortorella, G; Adami, A; Castorina, P; Lalatta, F; Marra, G; Riva, D; Scelsa, B; Spaccini, L; Uziel, G; Del Giudice, E; Laverda, A M; Ludwig, K; Permunian, A; Suppiej, A; Signorini, S; Uggetti, C; Battini, R; Di Giacomo, M; Cilio, M R; Di Sabato, M L; Leuzzi, V; Parisi, P; Pollazzon, M; Silengo, M; De Vescovi, R; Greco, D; Romano, C; Cazzagon, M; Simonati, A; Al-Tawari, A A; Bastaki, L; Mégarbané, A; Sabolic Avramovska, V; de Jong, M M; Stromme, P; Koul, R; Rajab, A; Azam, M; Barbot, C; Martorell Sampol, L; Rodriguez, B; Pascual-Castroviejo, I; Teber, S; Anlar, B; Comu, S; Karaca, E; Kayserili, H; Yüksel, A; Akcakus, M; Al Gazali, L; Sztriha, L; Nicholl, D; Woods, C G; Bennett, C; Hurst, J; Sheridan, E; Barnicoat, A; Hennekam, R; Lees, M; Blair, E; Bernes, S; Sanchez, H; Clark, A E; DeMarco, E; Donahue, C; Sherr, E; Hahn, J; Sanger, T D; Gallager, T E; Dobyns, W B; Daugherty, C; Krishnamoorthy, K S; Sarco, D; Walsh, C A; McKanna, T; Milisa, J; Chung, W K; De Vivo, D C; Raynes, H; Schubert, R; Seward, A; Brooks, D G; Goldstein, A; Caldwell, J; Finsecke, E; Maria, B L; Holden, K; Cruse, R P; Swoboda, K J; Viskochil, D

    2009-10-01

    Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected. To assess whether genomic rearrangements involving the CEP290 gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290 heterozygous patients, including five JSRD/MKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290 C-terminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290 genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290 mutated allele was identified.

  10. Monolithical aspherical beam expanding systems

    NASA Astrophysics Data System (ADS)

    Fuchs, U.; Matthias, Sabrina

    2014-10-01

    Beam expanding is a common task, where Galileo telescopes are preferred. However researches and customers have found limitations when using these systems. A new monolithical solution which is based on the usage of only one aspherical component will be presented. It will be shown how to combine up to five monolithical beam expanding systems and to keep the beam quality at diffraction limitation. Insights will be given how aspherical beam expanding systems will help using larger incoming beams and reducing the overall length of such a system. Additionally an add-on element for divergence and wavelength adaption will be presented.

  11. Advanced expander test bed program

    NASA Technical Reports Server (NTRS)

    Riccardi, D. P.; Mitchell, J. C.

    1993-01-01

    The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high-pressure expander cycle concept, investigate system interactions, and conduct investigations of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust. Contract work began 27 Apr. 1990. During 1992, a major milestone was achieved with the review of the final design of the oxidizer turbopump in Sep. 1992.

  12. The expanding universe of p53 targets.

    PubMed

    Menendez, Daniel; Inga, Alberto; Resnick, Michael A

    2009-10-01

    The p53 tumour suppressor is modified through mutation or changes in expression in most cancers, leading to the altered regulation of hundreds of genes that are directly influenced by this sequence-specific transcription factor. Central to the p53 master regulatory network are the target response element (RE) sequences. The extent of p53 transactivation and transcriptional repression is influenced by many factors, including p53 levels, cofactors and the specific RE sequences, all of which contribute to the role that p53 has in the aetiology of cancer. This Review describes the identification and functionality of REs and highlights the inclusion of non-canonical REs that expand the universe of genes and regulation mechanisms in the p53 tumour suppressor network.

  13. Teleteach Expanded Delivery System: Evaluation.

    ERIC Educational Resources Information Center

    Christopher, G. Ronald; Milam, Alvin L.

    In order to meet the demand for Air Force Institute of Technology (AFIT) professional continuing education (PCE) courses within the School of Systems and Logistics and the School of Engineering, the Teleteach Expanded Delivery System (TEDS) for instruction of Air Force personnel at remote locations was developed and evaluated. TEDS uses a device…

  14. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G

    2015-02-03

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  15. Expanding the eukaryotic genetic code

    DOEpatents

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2017-02-28

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  16. Expanding Frontiers of Humanoid Robotics

    DTIC Science & Technology

    2000-08-01

    From the IEEE Intelligent Systems Special Issue on Humanoid Robotics , July/August 2000 GUEST EDITORS’ Expanding Frontiers of Humanoid Robotics ...Mark L. Swinson, DARPA David J. Bruemmer, Strategic Analysis Mobile robots pose a unique set of challenges to artificial intelligence researchers...the constraints of logical correctness but also some assortment of crosscutting, physical constraints. Particularly interesting among these robots

  17. Common Ground: Expanding Our Horizons.

    ERIC Educational Resources Information Center

    McDevitt, Michele J.

    In "Common Ground: Dialogue, Understanding, and the Teaching of Composition," Kurt Spellmeyer seeks to familiarize students and teachers with the linguistic and cultural no-man's-land separating them. Reinstating the value of two writing conventions often used by traditional students--expressive and commonplaces--can help expand on the…

  18. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W; Cropp, T Ashton; Anderson, J Christopher; Schultz, Peter G

    2012-05-08

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  19. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2013-01-22

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  20. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W; Cropp, T Ashton; Anderson, J Christopher; Schultz, Peter G

    2012-02-14

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  1. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2010-09-14

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  2. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2009-12-01

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  3. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W; Cropp, T Ashton; Anderson, J Christopher; Schultz, Peter G

    2009-10-27

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  4. Expanding the eukaryotic genetic code

    SciTech Connect

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2009-11-17

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  5. Expanding the Universe of Education.

    ERIC Educational Resources Information Center

    Parsons, Elizabeth

    1996-01-01

    Definitions of "education" and "rural" are debunked and expanded. The three major tasks of rural education are educating people to understand their own needs, the unavoidable changes that will transform rural Australia within their lifetimes, and the range of technologies that can enhance their well-being. Presents a strategy…

  6. Emotional Giftedness: An Expanded View.

    ERIC Educational Resources Information Center

    Piechowski, Michael M.

    This paper discusses an expanded definition of the concept of emotional giftedness in children as defined by Annemarie Roeper. In contrast to examples of academic and artistic prodigies, cases are reviewed that illustrate less tangibly measured examples of children's giftedness, such as expressions of compassion, moral sensitivity, positive…

  7. Tree Decay - An Expanded Concept

    Treesearch

    Alex L. Shigo

    1979-01-01

    The purpose of this publication is to clarify further the tree decay concept that expands the classical concept to include the orderly response of the tree to wounding and infection-compartmentalization-and the orderly infection of wounds by many microorganisms-successions. The heartrot concept must be abandoned because it deals only with decay-causing fungi and it...

  8. Tree decay an expanded concept

    Treesearch

    Alex L. Shigo

    1979-01-01

    This publication is the final one in a series on tree decay developed in cooperation with Harold G. Marx, Research Application Staff Assistant, U.S. Department of Agriculture, Forest Service, Washington, D.C. The purpose of this publication is to clarify further the tree decay concept that expands the classical concept to include the orderly response of the tree to...

  9. The Expanding Frontier of Pluralism.

    ERIC Educational Resources Information Center

    King, Edmund

    1983-01-01

    Looks at the expanding frontier of pluralism in terms of reappraising the relationship of formal education to the advent of the constant change (occupational and social) accelerated by the microprocessor revolution and readjusting provisions in educational systems to meet the different needs of different populations. (AH)

  10. Expandable Shelter/Container Report.

    DTIC Science & Technology

    1973-06-01

    without removing whatever payload might be in the contai ner. Equ i pment located in the expanded porti on of the ES/C durin g norma l operat i ons is...and Supply BattalIon , Div isi on Support Coianand. In addition , divisional avIation battalions have an A Irc raft Maintenance Company. The TOE

  11. Expanded civil judicial referral procedures

    SciTech Connect

    Not Available

    1986-08-28

    The directive provides guidance on procedures for civil judicial referrals to the Department of Justice. The memorandum expands the current direct referral program, indicates that Headquarters should not establish mandatory requirements for pre-referral negotiations, mandates use of hold action cases only for strategic or tactical reasons and offers guidance on the preparation of bankruptcy cases.

  12. Finite simple groups as expanders

    PubMed Central

    Kassabov, Martin; Lubotzky, Alexander; Nikolov, Nikolay

    2006-01-01

    We prove that there exist k ∈ ℕ and 0 < ε ∈ ℝ such that every non-abelian finite simple group G, which is not a Suzuki group, has a set of k generators for which the Cayley graph Cay(G; S) is an ε-expander. PMID:16601101

  13. Monolithical aspherical beam expanding systems

    NASA Astrophysics Data System (ADS)

    Fuchs, U.

    2014-02-01

    In complex laser systems, such as those for material processing, and in basically all laboratory applications passive optical components are indispensable. Matching beam diameters is a common task, where Galileo type telescopes are preferred for beam expansion. Nevertheless researches and customers have found various limitations when using these systems. Some of them are the complicated adjustment, very small diameter for the incoming beam (1/e2), fixed and non-modifiable magnifications. Above that, diffraction-limitation is only assured within the optical design and not for the real world setup of the beam expanding system. Therefore, we will discuss limitations of currently used beam expanding systems to some extent. We will then present a new monolithical solution, which is based on the usage of only one aspherical component. It will be shown theoretically how the beam quality can be significantly improved by using aspherical lenses. As it is in the nature of things aspheres are working diffraction limited in the design, it will be shown how to combine up to five monolithical beam expanding systems and to keep the beam quality at diffraction limitation. Data of the culminated wavefront error will be presented. Last but not least insights will be given how beam expanding systems based on aspheres will help to use larger incoming beams and to reduce the overall length of such a system.

  14. Expanding the genetic heterogeneity of intellectual disability.

    PubMed

    Anazi, Shams; Maddirevula, Sateesh; Salpietro, Vincenzo; Asi, Yasmine T; Alsahli, Saud; Alhashem, Amal; Shamseldin, Hanan E; AlZahrani, Fatema; Patel, Nisha; Ibrahim, Niema; Abdulwahab, Firdous M; Hashem, Mais; Alhashmi, Nadia; Al Murshedi, Fathiya; Al Kindy, Adila; Alshaer, Ahmad; Rumayyan, Ahmed; Al Tala, Saeed; Kurdi, Wesam; Alsaman, Abdulaziz; Alasmari, Ali; Banu, Selina; Sultan, Tipu; Saleh, Mohammed M; Alkuraya, Hisham; Salih, Mustafa A; Aldhalaan, Hesham; Ben-Omran, Tawfeg; Al Musafri, Fatima; Ali, Rehab; Suleiman, Jehan; Tabarki, Brahim; El-Hattab, Ayman W; Bupp, Caleb; Alfadhel, Majid; Al Tassan, Nada; Monies, Dorota; Arold, Stefan T; Abouelhoda, Mohamed; Lashley, Tammaryn; Houlden, Henry; Faqeih, Eissa; Alkuraya, Fowzan S

    2017-09-22

    Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.

  15. The highly polymorphic CYP6M7 cytochrome P450 gene partners with the directionally selected CYP6P9a and CYP6P9b genes to expand the pyrethroid resistance front in the malaria vector Anopheles funestus in Africa.

    PubMed

    Riveron, Jacob M; Ibrahim, Sulaiman S; Chanda, Emmanuel; Mzilahowa, Themba; Cuamba, Nelson; Irving, Helen; Barnes, Kayla G; Ndula, Miranda; Wondji, Charles S

    2014-09-27

    Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies. Here, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country. Pyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies.

  16. Seal-less cryogenic expander

    SciTech Connect

    Faria, L.E.; Christopher, E.H.

    1987-12-08

    In an expander for use in a split Stirling cycle refrigeration system of the type wherein a displacer moves with reciprocating motion inside an expander housing, and wherein a plunger force and a regenerator force are formed on the displacer, the plunger force cyclically varying and having a time of minimum and maximum plunger force amplitude, and the regenerator force cyclically varying and having a time of minimum and maximum regenerator force amplitude, the improvement is described comprising: (a) means for maintaining displacer forces, such that the maximum plunger force amplitude is substantially equal to the maximum regenerator force amplitude; and (b) means for adjusting a time difference, the time difference being the time between the time of maximum plunger force and the time of maximum regenerator force such that a measure of the cooling power of the refrigeration system is maximized.

  17. Helical screw expander evaluation project

    NASA Technical Reports Server (NTRS)

    Mckay, R.

    1982-01-01

    A one MW helical rotary screw expander power system for electric power generation from geothermal brine was evaluated. The technology explored in the testing is simple, potentially very efficient, and ideally suited to wellhead installations in moderate to high enthalpy, liquid dominated field. A functional one MW geothermal electric power plant that featured a helical screw expander was produced and then tested with a demonstrated average performance of approximately 45% machine efficiency over a wide range of test conditions in noncondensing, operation on two-phase geothermal fluids. The Project also produced a computer equipped data system, an instrumentation and control van, and a 1000 kW variable load bank, all integrated into a test array designed for operation at a variety of remote test sites. Data are presented for the Utah testing and for the noncondensing phases of the testing in Mexico. Test time logged was 437 hours during the Utah tests and 1101 hours during the Mexico tests.

  18. Helical screw expander evaluation project

    NASA Astrophysics Data System (ADS)

    McKay, R.

    1982-03-01

    A one MW helical rotary screw expander power system for electric power generation from geothermal brine was evaluated. The technology explored in the testing is simple, potentially very efficient, and ideally suited to wellhead installations in moderate to high enthalpy, liquid dominated field. A functional one MW geothermal electric power plant that featured a helical screw expander was produced and then tested with a demonstrated average performance of approximately 45% machine efficiency over a wide range of test conditions in noncondensing, operation on two-phase geothermal fluids. The Project also produced a computer equipped data system, an instrumentation and control van, and a 1000 kW variable load bank, all integrated into a test array designed for operation at a variety of remote test sites. Data are presented for the Utah testing and for the noncondensing phases of the testing in Mexico. Test time logged was 437 hours during the Utah tests and 1101 hours during the Mexico tests.

  19. Echinocandins: The Expanding Antifungal Armamentarium.

    PubMed

    Aguilar-Zapata, Daniel; Petraitiene, Ruta; Petraitis, Vidmantas

    2015-12-01

    The echinocandins are large lipopeptide molecules that, since their discovery approximately 41 years ago, have emerged as important additions to the expanding armamentarium against invasive fungal diseases. Echinocandins exert in vitro and in vivo fungicidal action against most Candida species and fungistatic action against Aspergillus species. However, the population of patients at risk for developing invasive fungal infections continues to increase. New therapeutic strategies using echinocandins are needed to improve clinical outcomes in patients with invasive fungal disease.

  20. Entropy in an expanding universe.

    PubMed

    Frautschi, S

    1982-08-13

    The question of how the observed evolution of organized structures from initial chaos in the expanding universe can be reconciled with the laws of statistical mechanics is studied, with emphasis on effects of the expansion and gravity. Some major sources of entropy increase are listed. An expanding "causal" region is defined in which the entropy, though increasing, tends to fall further and further behind its maximum possible value, thus allowing for the development of order. The related questions of whether entropy will continue increasing without limit in the future, and whether such increase in the form of Hawking radiation or radiation from positronium might enable life to maintain itself permanently, are considered. Attempts to find a scheme for preserving life based on solid structures fail because events such as quantum tunneling recurrently disorganize matter on a very long but fixed time scale, whereas all energy sources slow down progressively in an expanding universe. However, there remains hope that other modes of life capable of maintaining themselves permanently can be found.

  1. Entropy in an expanding universe

    NASA Astrophysics Data System (ADS)

    Frautschi, S.

    1982-08-01

    The evolution of organized structures from initial chaos in the expanding universe is demonstrated to be reconcilable with the second law of thermodynamics, and the effects of expansion and gravity on this problem are emphasized. Numerical estimates of the major sources of entropy increase are calculated, including the entropy increase in stars, the earth, black hole formation and decay, quantum tunneling of matter into black holes, positronium formation and decay, etc. An expanding 'causal' region is defined in which the entropy, though increasing, tends to fall further and further behind its maximum possible value, thus allowing for the development of order. That is, the classical heat death argument does not hold, because an expanding universe never achieves equilibrium and never reaches a constant temperature. Also considered are questions of whether entropy will continue increasing without limit in the future, and whether such increase in the form of Hawking radiation or radiation from positronium might enable life to maintain itself permanently. Attempts to find a scheme for preserving life based on solid structures fail because events such as quantum tunneling recurrently disorganize matter on a very long but fixed time scale.

  2. Genes

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Genes URL of this page: //medlineplus.gov/ency/article/ ...

  3. Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

    PubMed

    Nurden, Alan T; Pillois, Xavier; Fiore, Mathieu; Alessi, Marie-Christine; Bonduel, Mariana; Dreyfus, Marie; Goudemand, Jenny; Gruel, Yves; Benabdallah-Guerida, Schéhérazade; Latger-Cannard, Véronique; Négrier, Claude; Nugent, Diane; Oiron, Roseline D; Rand, Margaret L; Sié, Pierre; Trossaert, Marc; Alberio, Lorenzo; Martins, Nathalie; Sirvain-Trukniewicz, Peggy; Couloux, Arnaud; Canault, Mathias; Fronthroth, Juan Pablo; Fretigny, Mathilde; Nurden, Paquita; Heilig, Roland; Vinciguerra, Christine

    2015-05-01

    We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin. © 2015 WILEY PERIODICALS, INC.

  4. Three FLOWERING LOCUS T-like genes function as potential florigens and mediate photoperiod response in sorghum.

    PubMed

    Wolabu, Tezera W; Zhang, Fei; Niu, Lifang; Kalve, Shweta; Bhatnagar-Mathur, Pooja; Muszynski, Michael G; Tadege, Million

    2016-05-01

    Sorghum is a typical short-day (SD) plant and its use in grain or biomass production in temperate regions depends on its flowering time control, but the underlying molecular mechanism of floral transition in sorghum is poorly understood. Here we characterized sorghum FLOWERING LOCUS T (SbFT) genes to establish a molecular road map for mechanistic understanding. Out of 19 PEBP genes, SbFT1, SbFT8 and SbFT10 were identified as potential candidates for encoding florigens using multiple approaches. Phylogenetic analysis revealed that SbFT1 clusters with the rice Hd3a subclade, while SbFT8 and SbFT10 cluster with the maize ZCN8 subclade. These three genes are expressed in the leaf at the floral transition initiation stage, expressed early in grain sorghum genotypes but late in sweet and forage sorghum genotypes, induced by SD treatment in photoperiod-sensitive genotypes, cooperatively repressed by the classical sorghum maturity loci, interact with sorghum 14-3-3 proteins and activate flowering in transgenic Arabidopsis plants, suggesting florigenic potential in sorghum. SD induction of these three genes in sensitive genotypes is fully reversed by 1 wk of long-day treatment, and yet, some aspects of the SD treatment may still make a small contribution to flowering in long days, indicating a complex photoperiod response mediated by SbFT genes.

  5. Shell may expand detergent alcohols

    SciTech Connect

    1996-10-23

    Shell Chemical is studying plans to expand detergent alcohols capacity in the US, CW has learned. The company is considering adding capacity for about 80 million lbs/year. If the project is approved, it would be implemented at the company`s Geismar, LA site. Shell will make a final decision on whether to proceed with the project within six months. It has been rumored to be considering a capacity addition as a result of tightening supply of natural and synthetic detergent alcohols.

  6. Advanced Expander Test Bed Engine

    DTIC Science & Technology

    1992-03-01

    performance data will be provided to NASA -LeRC for verifying the ROCETS computer model and evaluating various RLI0 modifications. 22 SECTION IV CURRENT...RL10 modeling data for the ROCETS computer program. 23 NASA Report Documentation Page Nafi~aj AfWflWuIC Wd Sow@ Ad-lvhlsto, 1 eport No. 2. Government... NASA have identified the need for a new Space Transfer Vehicle (STV) Propulsion System. The new system will be an oxygen/hydrogen expander cycle engine

  7. Unconventional microfluidics: expanding the discipline.

    PubMed

    Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

    2013-04-21

    Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

  8. Semigroup Actions of Expanding Maps

    NASA Astrophysics Data System (ADS)

    Carvalho, Maria; Rodrigues, Fagner B.; Varandas, Paulo

    2017-01-01

    We consider semigroups of Ruelle-expanding maps, parameterized by random walks on the free semigroup, with the aim of examining their complexity and exploring the relation between intrinsic properties of the semigroup action and the thermodynamic formalism of the associated skew-product. In particular, we clarify the connection between the topological entropy of the semigroup action and the growth rate of the periodic points, establish the main properties of the dynamical zeta function of the semigroup action and relate these notions to recent research on annealed and quenched thermodynamic formalism. Meanwhile, we examine how the choice of the random walk in the semigroup unsettles the ergodic properties of the action.

  9. Unconventional microfluidics: expanding the discipline

    PubMed Central

    Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S.; Huang, Tony Jun

    2014-01-01

    Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields—and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such “unconventional” microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline. PMID:23478651

  10. Severe and rapidly progressing cognitive phenotype in a SCA17-family with only marginally expanded CAG/CAA repeats in the TATA-box binding protein gene: A case report

    PubMed Central

    2012-01-01

    Background The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease. Case presentation We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype. Conclusions The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based. PMID:22889412

  11. Expanding Your School. Is It Worth It?

    ERIC Educational Resources Information Center

    Friedberg, Richard; And Others

    1986-01-01

    Identifies concerns and potential problems that will surface while trying to expand a school. The decision to expand and the criterion to be considered in reaching that critical judgment is comprehensively discussed. (CT)

  12. Expanding Your School. Is It Worth It?

    ERIC Educational Resources Information Center

    Friedberg, Richard; And Others

    1986-01-01

    Identifies concerns and potential problems that will surface while trying to expand a school. The decision to expand and the criterion to be considered in reaching that critical judgment is comprehensively discussed. (CT)

  13. Bigelow Expandable Activity Module (BEAM) Monitoring System

    NASA Technical Reports Server (NTRS)

    Wells, Nathan

    2017-01-01

    What is Bigelow Expandable Activity Module (BEAM)? The Bigelow Expandable Activity Module (BEAM) is an expandable habitat technology demonstration on ISS; increase human-rated inflatable structure Technology Readiness Level (TRL) to level 9. NASA managed ISS payload project in partnership with Bigelow Aerospace. Launched to ISS on Space X 8 (April 8th, 2016). Fully expanded on May 28th, 2016. Jeff Williams/Exp. 48 Commander first entered BEAM on June 5th, 2016.

  14. Expandable Lunar Habitat (X-Hab)

    NASA Image and Video Library

    2010-09-23

    Expandable Lunar Habitat (X-Hab).ILC Dover, under contract by NASA Langley Research Center, and in cooperation with NASA Johnson Space Center has designed and manufactured an expandable lunar habitat. This cylindrical habitat, or Expandable Lunar Habitat (X-Hab) is a hybrid system with two hard end caps and a deployable softgoods section in the center.

  15. Leak detection with expandable coatings

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Developed and evaluated is a system for leak detection that can be easily applied over separable connectors and that expands into a bubble or balloon if a leak is present. This objective is accomplished by using thin films of Parafilm tape wrapped over connectors, which are then overcoated with a special formulation. The low yield strength and the high elongation of the envelope permit bubble formation if leakage occurs. This system is appropriate for welds and other hardware besides separable connectors. The practical limit of this system appears to be for leaks exceeding 0.000001 cc/sec. If this envelope is used to trap gases for mass spectrometer inspection, leaks in the range of ten to the minus 8th power cc/sec. may be detectable.

  16. OCT Expanded Clinical Data Analysis

    NASA Technical Reports Server (NTRS)

    Van Baalen, Mary; Tafreshi, Ali; Patel, Nimesh; Young, Millennia; Mason, Sara; Otto, Christian; Samuels, Brian; Koslovsky, Matthew; Schaefer, Caroline; Taiym, Wafa; hide

    2017-01-01

    Vision changes identified in long duration space fliers has led to a more comprehensive clinical monitoring protocol. Optical Coherence Tomography (OCT) was recently implemented on board the International Space Station in 2013. NASA is collaborating with Heidelberg Engineering to expand our current OCT data analysis capability by implementing a volumetric approach. Volumetric maps will be created by combining the circle scan, the disc block scan, and the radial scan. This assessment may provide additional information about the optic nerve and further characterize changes related microgravity exposure. We will discuss challenges with collection and analysis of OCT data, present the results of this reanalysis and outline the potential benefits and limitations of the additional data.

  17. Expanding Human Cognition and Communication

    SciTech Connect

    Spohrer, Jim; Pierce, Brian M.; Murray, Cherry A.; Golledge, Reginald G.; Horn, Robert E.; Turkle, Sherry; Yonas, Gerold; Glicken Turnley, Jessica; Pollack, Jordan; Burger, Rudy; Robinett, Warren; Wilson, Larry Todd; Bainbridge, W. S.; Canton, J.; Kuekes, P.; Loomis, J.; Penz, P.

    2013-01-01

    To be able to chart the most profitable future directions for societal transformation and corresponding scientific research, five multidisciplinary themes focused on major goals have been identified to fulfill the overall motivating vision of convergence described in the previous pages. The first, “Expanding Human Cognition and Communication,” is devoted to technological breakthroughs that have the potential to enhance individuals’ mental and interaction abilities. Throughout the twentieth century, a number of purely psychological techniques were offered for strengthening human character and personality, but evaluation research has generally failed to confirm the alleged benefits of these methods (Druckman and Bjork 1992; 1994). Today, there is good reason to believe that a combination of methods, drawing upon varied branches of converging science and technology, would be more effective than attempts that rely upon mental training alone.

  18. Shear Acceleration in Expanding Flows

    NASA Astrophysics Data System (ADS)

    Rieger, F. M.; Duffy, P.

    2016-12-01

    Shear flows are naturally expected to occur in astrophysical environments and potential sites of continuous non-thermal Fermi-type particle acceleration. Here we investigate the efficiency of expanding relativistic outflows to facilitate the acceleration of energetic charged particles to higher energies. To this end, the gradual shear acceleration coefficient is derived based on an analytical treatment. The results are applied to the context of the relativistic jets from active galactic nuclei. The inferred acceleration timescale is investigated for a variety of conical flow profiles (i.e., power law, Gaussian, Fermi-Dirac) and compared to the relevant radiative and non-radiative loss timescales. The results exemplify that relativistic shear flows are capable of boosting cosmic-rays to extreme energies. Efficient electron acceleration, on the other hand, requires weak magnetic fields and may thus be accompanied by a delayed onset of particle energization and affect the overall jet appearance (e.g., core, ridge line, and limb-brightening).

  19. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  20. Preventive Ethics Through Expanding Education.

    PubMed

    Ho, Anita; MacDonald, Lisa Mei-Hwa; Unger, David

    2016-03-01

    Healthcare institutions have been making increasing efforts to standardize consultation methodology and to accredit both bioethics training programs and the consultants accordingly. The focus has traditionally been on the ethics consultation as the relevant unit of ethics intervention. Outcome measures are studied in relation to consultations, and the hidden assumption is that consultations are the preferred or best way to address day-to-day ethical dilemmas. Reflecting on the data from an internal quality improvement survey and the literature, we argue that having general ethics education as a key function of ethics services may be more important in meeting the contemporaneous needs of acute care settings. An expanded and varied ethics education, with attention to the time constraints of healthcare workers' schedules, was a key recommendation brought forward by survey respondents. Promoting ethical reflection and creating a culture of ethics may serve to prevent ethical dilemmas or mitigate their effects.

  1. Expanding the Trilinos developer community.

    SciTech Connect

    Heroux, Michael Allen

    2010-10-01

    The Trilinos Project started approximately nine years ago as a small effort to enable research, development and ongoing support of small, related solver software efforts. The 'Tri' in Trilinos was intended to indicate the eventual three packages we planned to develop. In 2007 the project expanded its scope to include any package that was an enabling technology for technical computing. Presently the Trilinos repository contains over 55 packages covering a broad spectrum of reusable tools for constructing full-featured scalable scientific and engineering applications. Trilinos usage is now worldwide, and many applications have an explicit dependence on Trilinos for essential capabilities. Users come from other US laboratories, universities, industry and international research groups. Awareness and use of Trilinos is growing rapidly outside of Sandia. Members of the external research community are becoming more familiar with Trilinos, its design and collaborative nature. As a result, the Trilinos project is receiving an increasing number of requests from external community members who want to contribute to Trilinos as developers. To-date we have worked with external developers in an ad hoc fashion. Going forward, we want to develop a set of policies, procedures, tools and infrastructure to simplify interactions with external developers. As we go forward with multi-laboratory efforts such as CASL and X-Stack, and international projects such as IESP, we will need a more streamlined and explicit process for making external developers 'first-class citizens' in the Trilinos development community. This document is intended to frame the discussion for expanding the Trilinos community to all strategically important external members, while at the same time preserving Sandia's primary leadership role in the project.

  2. An experimental reciprocating expander for cryocooler application

    NASA Technical Reports Server (NTRS)

    Minta, M.; Smith, J. L., Jr.

    1985-01-01

    An experimental reciprocating expander was designed with features appropriate for cryocooler cycles. The expander has a displacer piston, simple valves, and a hydraulic/pneumatic stroking mechanism. The expander has a valve in head configuration with the valves extending out the bottom of the vacuum enclosure while the piston extends out the top. The expander was tested using a CTI 1400 liquefier to supply 13 atm in the temperature range 4.2 to 12 K. Expander efficiency was measured in the range 84 to 93% while operating the apparatus as a supercritical wet expander and in the range 91 to 93% aa a single phase expander. The apparatus can also be modified to operate as a compressor for saturated helium vapor.

  3. Production of biodiesel using expanded gas solvents

    SciTech Connect

    Ginosar, Daniel M; Fox, Robert V; Petkovic, Lucia M

    2009-04-07

    A method of producing an alkyl ester. The method comprises providing an alcohol and a triglyceride or fatty acid. An expanding gas is dissolved into the alcohol to form a gas expanded solvent. The alcohol is reacted with the triglyceride or fatty acid in a single phase to produce the alkyl ester. The expanding gas may be a nonpolar expanding gas, such as carbon dioxide, methane, ethane, propane, butane, pentane, ethylene, propylene, butylene, pentene, isomers thereof, and mixtures thereof, which is dissolved into the alcohol. The gas expanded solvent may be maintained at a temperature below, at, or above a critical temperature of the expanding gas and at a pressure below, at, or above a critical pressure of the expanding gas.

  4. An expanded role for mTORC1 in autophagy.

    PubMed

    Kim, Young-Mi; Park, Ji-Man; Grunwald, Douglas; Kim, Do-Hyung

    2016-01-01

    Mechanistic target of rapamycin complex 1 (mTORC1) negatively regulates autophagy at early stages by phosphorylating Unc51-like kinase 1 (ULK1). Our recent study expanded the roles of mTORC1 in autophagy by identifying ultraviolet radiation resistance-associated gene product (UVRAG) as a substrate of mTORC1. This finding has provided new insight into the roles of mTORC1 in cellular membrane processes and cancer.

  5. Model of An Expanding Heliosphere

    NASA Astrophysics Data System (ADS)

    Song, P.; Vasyliunas, V. M.

    2015-12-01

    Conventional models of the heliosphere assume that the heliopause is formed, similarly to the magnetopause of a planet, at the location where the total pressure of the exterior (interstellar) medium is balanced by the total pressure of the interior (heliospheric) medium. The heliosphere, however, differs greatly from a planetary magnetosphere in being dominated by a continuous interior source of mass (present in some planetary magnetospheres, notably Jupiter and Saturn, but not to anything like the same extent), and it differs as well from systems with large interior mass sources such as comets (to which it has also been compared) in being threaded by magnetic flux from its central object (the Sun). The heliosphere must thus expand continually as more and more mass is put into it by the solar wind, with the heliopause marching into the interstellar medium at some non-zero speed while maintaining the plasma total (thermal plus magnetic) pressure equal to that of the interstellar medium. A steady state heliosphere is, strictly speaking, impossible unless and until the distinction between the heliospheric and the interstellar medium has disappeared. The geometry of the expansion can be visualized in different ways. Conventionally it is taken for granted that the expansion is deflected by interstellar flow sideways and channeled into an extended wake/tail region, the rest of the heliosphere being in apparently steady state. Even if this may occur, it would be at a distance much larger than commonly assumed. We explore the alternative possibility of a heliosphere expanding predominantly in the radial direction and describe some of its properties. The input from solar wind and interplanetary magnetic field during each solar cycle forms a shell, with subsequent cycles adding shells of alternating magnetic polarities. The ultimate extent of the heliosphere (in all directions) and the number of shells can be limited by the time until either the solar output or the

  6. Cat Scratch Disease: Expanded Spectrum

    PubMed Central

    Aziz, Hassan A.; Plesec, Thomas P.; Sabella, Camille; Udayasankar, Unni K.; Singh, Arun D.

    2016-01-01

    Background To expand the spectrum of ophthalmic manifestations in cat scratch disease. Methods Case report. Results A 7-year-old male was referred for evaluation of his left optic disc after failing vision screening test at school. His visual acuity was 20/20 OD and light perception OS. Fundus examination showed a left optic disc lesion associated with an exudative retinal detachment and vitreous seeding. Ultrasonography revealed a 7 × 7.5 × 3.8 mm lesion with a possible 6.3 mm of retrolaminar extension into the substance of the optic nerve. Brain MRI did not show evidence of optic nerve involvement but revealed a 6-mm nodule of the pineal gland suggestive of a pineoblastoma. Enucleation was performed and histopathology revealed a suppurative granulomatous inflammation suggestive of Bartonella infection. Upon further questioning, the patient had recent exposure to kittens with areas of cat scratches along both of his arms. He was subsequently referred to and treated with a 2-week course of trimethoprim-sulfamethoxazole and rifampin by the pediatric infectious disease specialist. Repeat brain MRI showed interval total resolution of enlarged pineal gland. Conclusion: Optic nerve granulomas are a rare presentation of cat scratch disease and could potentially masquerade as retinoblastoma. PMID:27843905

  7. Male contraception: expanding reproductive choice.

    PubMed

    Rajalakshmi, M

    2005-11-01

    The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable, safe and effective male contraceptive, scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen, thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently, a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view, while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men, using sperm surface epitopes not expressed in female reproductive tract as source, still requires considerable research efforts.

  8. Chronic Expanding Hematoma Following Abdominoplasty.

    PubMed

    Tatsuta, Sayo; Morioka, Daichi; Murakami, Naoki; Ohkubo, Fumio

    2017-02-01

    Chronic expanding hematoma (CEH) is a relatively rare complication of trauma or surgery. We report a patient with CEH as a late complication of abdominoplasty. A 58-year-old woman underwent conventional abdominoplasty and thereafter refused to use a compression binder, citing discomfort. One month postoperatively, she presented with a gradually enlarging, painful abdominal mass. The results of ultrasonography and computed tomography were highly suspicious for CEH. The lesion was completely removed, together with surrounding fibrous tissue. Histopathology revealed a chronic hemorrhage collection with a fibrous capsule, consistent with CEH. This condition as a late complication of abdominoplasty has not previously been reported in the literature. However, an online medical consultation site features several abdominoplasty patients asking about persistent hematomas that sound suspicious for CEH. CEH might be underdiagnosed by surgeons. Although a postoperative binder may increase the risk of skin necrosis and deep vein thrombosis, appropriate compression treatment is necessary to prevent hematoma formation. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  9. Cat Scratch Disease: Expanded Spectrum.

    PubMed

    Aziz, Hassan A; Plesec, Thomas P; Sabella, Camille; Udayasankar, Unni K; Singh, Arun D

    2016-10-01

    To expand the spectrum of ophthalmic manifestations in cat scratch disease. Case report. A 7-year-old male was referred for evaluation of his left optic disc after failing vision screening test at school. His visual acuity was 20/20 OD and light perception OS. Fundus examination showed a left optic disc lesion associated with an exudative retinal detachment and vitreous seeding. Ultrasonography revealed a 7 × 7.5 × 3.8 mm lesion with a possible 6.3 mm of retrolaminar extension into the substance of the optic nerve. Brain MRI did not show evidence of optic nerve involvement but revealed a 6-mm nodule of the pineal gland suggestive of a pineoblastoma. Enucleation was performed and histopathology revealed a suppurative granulomatous inflammation suggestive of Bartonella infection. Upon further questioning, the patient had recent exposure to kittens with areas of cat scratches along both of his arms. He was subsequently referred to and treated with a 2-week course of trimethoprim-sulfamethoxazole and rifampin by the pediatric infectious disease specialist. Repeat brain MRI showed interval total resolution of enlarged pineal gland. Conclusion: Optic nerve granulomas are a rare presentation of cat scratch disease and could potentially masquerade as retinoblastoma.

  10. FMC: Expanding its chemical universe

    SciTech Connect

    Wood, A.

    1992-12-23

    With a portfolio ranging from defense systems to gold to food machinery - the source of its name - FMC Corp. (Chicago) ranks as a diversified conglomerate. The company's industrial chemicals operation consists of alkali chemicals, chiefly soda ash and derivatives: peroxygen chemicals, made up of hydrogen peroxide and other peroxygens; and phosphorus chemicals. FMC has about a 30% market share in each of these three. It also includes the Foret (Barcelona) division, part of FMC Europe. Moving lithium into FMC's specialties group reflects the R D-intensive nature of many lithium compounds, explains F. Wyman Morgan, director/group technology for the chemical product and specialty chemicals groups. FMC is also involved in collaborative research programs to develop lithium-based batteries and fuel cells. We have a decentralized business-oriented R D focus, Morgan says. The main thrusts in lithium are in developing organolithiums for drug synthesis. FMC also has a major industrial lithium business; it recently added a new butyl lithium unit in Texas and is looking to expand production through the development of lithium deposits in Latin America. But lithium is growing fastest in the downstream areas, says W. Reginald Hall, v.p. and group manager/specialty chemicals group. It has an unbelievable range of uses, he says, including catalytic applications in the pharmaceuticals industry. We are working on lithium compounds that allow you to drop a functional organic group into a molecule in a reliable way.

  11. Towards expanding megasonic cleaning capability

    NASA Astrophysics Data System (ADS)

    Han, Zhenxing; Ferstl, Berthold; Oetter, Günter; Dietze, Uwe; Samayoa, Martin; Dattilo, Davide

    2016-10-01

    Megasonic cleaning remains the industry's workhorse technology for particle removal on advanced 193i and extreme ultraviolet (EUV) photomasks. Several megasonic cleaning technologies and chemistries have been proposed and implemented over the years in diverse production environments. The operational range of these process technologies, over a wide array of applications, is ultimately defined by measurable capability limits. As geometries continue to scale-down and new materials are introduced, existing cleaning technologies will naturally fade out of range and new capability is ultimately required. This paper presents a novel fundamental approach for expanding cleaning capability by use of high-frequency megasonics and tenside-based additives (BASF SELECTIPUR C-series). To this end, a sonoluminescence-based experimental test bench was configured to characterize and study the effects of various process parameters on cleaning performance, with a particular emphasis on cavitation-induced damage and enhancement of particle removal capabilities. The results from the fundamental studies provide a path forward towards delivering new cleaning capability by enabling high-frequency megasonic systems and tenside-based additives.

  12. The expanding role of immunotherapy.

    PubMed

    Martin-Liberal, Juan; Ochoa de Olza, María; Hierro, Cinta; Gros, Alena; Rodon, Jordi; Tabernero, Josep

    2017-02-11

    The use of agents able to modulate the immune system to induce or potentiate its anti-tumour activity is not a new strategy in oncology. However, the development of new agents such as immune checkpoint inhibitors has achieved unprecedented efficacy results in a wide variety of tumours, dramatically changing the landscape of cancer treatment in recent years. Ipilimumab, nivolumab, pembrolizumab or atezolizumab are now standard of care options in several malignancies and new indications are being approved on a regular basis in different tumours. Moreover, there are many other novel immunotherapy strategies that are currently being assessed in clinical trials. Agonists of co-stimulatory signals, adoptive cell therapies, vaccines, virotherapy and others have raised interest as therapeutic options against cancer. In addition, many of these novel approaches are being developed both in monotherapy and as part of combinatory regimes in order to synergize their activity. The results from those studies will help to define the expanding role of immunotherapy in cancer treatment in a forthcoming future.

  13. Expanding the yeast prion world

    PubMed Central

    Suzuki, Genjiro; Tanaka, Motomasa

    2013-01-01

    Mammalian and fungal prion proteins form self-perpetuating β-sheet-rich fibrillar aggregates called amyloid. Prion inheritance is based on propagation of the regularly oriented amyloid structures of the prion proteins. All yeast prion proteins identified thus far contain aggregation-prone glutamine/asparagine (Gln/Asn)-rich domains, although the mammalian prion protein and fungal prion protein HET-s do not contain such sequences. In order to fill this gap, we searched for novel yeast prion proteins lacking Gln/Asn-rich domains via a genome-wide screen based on cross-seeding between two heterologous proteins and identified Mod5, a yeast tRNA isopentenyltransferase, as a novel non-Gln/Asn-rich yeast prion protein. Mod5 formed self-propagating amyloid fibers in vitro and the introduction of Mod5 amyloids into non-prion yeast induced dominantly and cytoplasmically heritable prion state [MOD+], which harbors aggregates of endogenous Mod5. [MOD+] yeast showed an increased level of membrane lipid ergosterol and acquired resistance to antifungal agents. Importantly, enhanced de novo formation of [MOD+] was observed when non-prion yeast was grown under selective pressures from antifungal drugs. Our findings expand the family of yeast prions to non-Gln/Asn-rich proteins and reveal the acquisition of a fitness advantage for cell survival through active prion conversion. PMID:23117914

  14. Attitudes toward expanding nurses' authority.

    PubMed

    Kerzman, Hana; Van Dijk, Dina; Eizenberg, Limor; Khaikin, Rut; Phridman, Shoshi; Siman-Tov, Maya; Goldberg, Shoshi

    2015-01-01

    In recent years, an increasing number of care procedures previously under the physician's authority have been placed in the hands of registered nurses. The purpose of this study was to examine the attitudes of nurses towards expanding nurses' authority and the relationships between these attitudes and job satisfaction facets, professional characteristics, and demographics. A cross-sectional study was conducted between 2010 and 2011 in three major medical centers in Israel. Participants included 833 nurses working in 89 departments. Attitudes toward the expansion of nurses' authority were assessed by self-report questionnaire, as well as job satisfaction facets including perception of professional autonomy, nurse-physician working relations, workload and burnout, perceptions of quality of care, and nursing staff satisfaction at work. Nurses reported positive attitudes toward the expansion of nurses' authority and moderate attitudes for interpretation of diagnostic tests in selected situations. The results of multivariate regression analyses demonstrate that the nurses' satisfaction from professional autonomy and work relations were the most influential factors in explaining their attitudes toward the expansion of nurses' authority. In addition, professionally young nurses tend to be more positive regarding changes in nurses' authority. In the Israeli reality of a nurse's shortage, we are witnessing professional transitions toward expansion of the scope of nurses' accountability and decision-making authority. The current research contributes to our understanding of attitudes toward the expansion of nurses' authority among the nursing staffs. The findings indicate the necessity of redefining the scope of nursing practice within the current professional context.

  15. Expanding discourse repertoires with hybridity

    NASA Astrophysics Data System (ADS)

    Kelly, Gregory J.

    2012-09-01

    In "Hybrid discourse practice and science learning" Kamberelis and Wehunt present a theoretically rich argument about the potential of hybrid discourses for science learning. These discourses draw from different forms of "talk, social practice, and material practices" to create interactions that are "intertextually complex" and "interactionally dynamic." The hybrid discourse practices are described as involving the dynamic interplay of at least three key elements: "the lamination of multiple cultural frames, the shifting relations between people and their discourse, and the shifting power relations between and among people." Each of these elements requires a respective unit of analysis and are often mutually reinforcing. The authors present a theoretically cogent argument for the study of hybrid discourse practices and identify the potential such discourses may have for science education. This theoretical development leads to an analysis of spoken and written discourse around a set of educational events concerning the investigation of owl pellets by two fifth grade students, their classmates, and teacher. Two discourse segments are presented and analyzed by the authors in detail. The first is a discourse analysis of the dissection of the owl pellet by two students, Kyle and Max. The second analysis examines the science report of these same two students. In this article, I pose a number of questions about the study with the hope that by doing so I expand the conversation around the insightful analysis presented.

  16. Galactose Epimerase Deficiency: Expanding the Phenotype.

    PubMed

    Dias Costa, Filipa; Ferdinandusse, Sacha; Pinto, Carla; Dias, Andrea; Keldermans, Liesbeth; Quelhas, Dulce; Matthijs, Gert; Mooijer, Petra A; Diogo, Luísa; Jaeken, Jaak; Garcia, Paula

    2017-03-01

    Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a dysmorphic syndrome. Failure to thrive was noticed during the first year. Episodes of heart failure due to dilated cardiomyopathy, followed by liver failure, occurred between 12 and 42 months. The finding of a serum transferrin isoelectrofocusing (IEF) type 1 pattern led to the suspicion of a congenital disorder of glycosylation (CDG). Follow-up disclosed psychomotor disability, deafness, and nuclear cataracts.Patient 2: The sibling of patient 1 was born with short limbs and hip dysplasia. She is deceased in the neonatal period due to intraventricular hemorrhage in the context of liver failure. Investigation disclosed galactosuria and normal transferrin glycosylation.Next-generation sequence panel analysis for CDG syndrome revealed the previously reported c.280G>A (p.[V94M]) homozygous mutation in the GALE gene. Enzymatic studies in erythrocytes (patient 1) and fibroblasts (patients 1 and 2) revealed markedly reduced GALE activity confirming generalized GALE deficiency. This report describes the fourth family with generalized GALE deficiency, expanding the clinical spectrum of this disorder, since major cardiac involvement has not been reported before.

  17. Neuroimaging of Parkinson's disease: Expanding views.

    PubMed

    Weingarten, Carol P; Sundman, Mark H; Hickey, Patrick; Chen, Nan-kuei

    2015-12-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Expanding the knowledge translation metaphor.

    PubMed

    Engebretsen, Eivind; Sandset, Tony Joakim; Ødemark, John

    2017-03-13

    Knowledge translation (KT) is a buzzword in modern medical science. However, there has been little theoretical reflection on translation as a process of meaning production in KT. In this paper, we argue that KT will benefit from the incorporation of a more theoretical notion of translation as an entangled material, textual and cultural process. We discuss and challenge fundamental assumptions in KT, drawing on theories of translation from the human sciences. We show that the current construal of KT as separate from and secondary to the original scientific message is close to the now deeply compromised literary view of translation as the simple act of copying the original. Inspired by recent theories of translation, we claim that KT can be more adequately understood in terms of a 'double supplement' - on the one hand, KT offers new approaches to the communication of scientific knowledge to different groups in the healthcare system with the aim of supplementing a lack of knowledge among clinicians (and patients). On the other, it demonstrates that a textual and cultural supplement, namely a concern with target audiences (clinicians and patients), is inevitable in the creation of an 'autonomous' science. Hence, the division between science and its translation is unproductive and impossible to maintain. We discuss some possible implications of our suggested shift in concept by drawing on pharmaceutical interventions for the prevention of HIV as a case. We argue that such interventions are based on a supplementary and paradoxical relation to the target audiences, both presupposing and denying their existence. More sophisticated theories of translation can lay the foundation for an expanded model of KT that incorporates a more adequate and reflective description of the interdependency of scientific, cultural, textual and material practices.

  19. 24 CFR 3285.502 - Expanding rooms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.502 Expanding rooms. The... the home manufacturer or prepared by a registered professional engineer or registered architect,...

  20. 24 CFR 3285.502 - Expanding rooms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.502 Expanding rooms. The... the home manufacturer or prepared by a registered professional engineer or registered architect,...

  1. 24 CFR 3285.502 - Expanding rooms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Optional Features § 3285.502 Expanding rooms. The... the home manufacturer or prepared by a registered professional engineer or registered architect,...

  2. Studies of an expanded trinucleotide repeat in transgenic mice

    SciTech Connect

    Bingham, P.; Wang, S.; Merry, D.

    1994-09-01

    Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

  3. Expanding genomics of mycorrhizal symbiosis

    SciTech Connect

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; Grigoriev, Igor V.

    2014-11-04

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolve through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism.

  4. Expanding genomics of mycorrhizal symbiosis

    DOE PAGES

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; ...

    2014-11-04

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolvemore » through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism.« less

  5. Expanding genomics of mycorrhizal symbiosis

    PubMed Central

    Kuo, Alan; Kohler, Annegret; Martin, Francis M.; Grigoriev, Igor V.

    2014-01-01

    The mycorrhizal symbiosis between soil fungi and plant roots is a ubiquitous mutualism that plays key roles in plant nutrition, soil health, and carbon cycling. The symbiosis evolved repeatedly and independently as multiple morphotypes [e.g., arbuscular mycorrhizae (AM), ectomycorrhizal (ECM)] in multiple fungal clades (e.g., phyla Glomeromycota, Ascomycota, Basidiomycota). The accessibility and cultivability of many mycorrhizal partners make them ideal models for symbiosis studies. Alongside molecular, physiological, and ecological investigations, sequencing led to the first three mycorrhizal fungal genomes, representing two morphotypes and three phyla. The genome of the ECM basidiomycete Laccaria bicolor showed that the mycorrhizal lifestyle can evolve through loss of plant cell wall-degrading enzymes (PCWDEs) and expansion of lineage-specific gene families such as short secreted protein (SSP) effectors. The genome of the ECM ascomycete Tuber melanosporum showed that the ECM type can evolve without expansion of families as in Laccaria, and thus a different set of symbiosis genes. The genome of the AM glomeromycete Rhizophagus irregularis showed that despite enormous phylogenetic distance and morphological difference from the other two fungi, symbiosis can involve similar solutions as symbiosis-induced SSPs and loss of PCWDEs. The three genomes provide a solid base for addressing fundamental questions about the nature and role of a vital mutualism. PMID:25408690

  6. Expanding Enceladus' Impact Crater Database

    NASA Astrophysics Data System (ADS)

    Kirchoff, M. R.; Schenk, P.

    2016-12-01

    Enceladus is a mid-sized, icy satellite of Saturn with a diameter of 500 km. Most of its surface has been modified by the formation of tectonic grooves and ridges throughout Enceladus' history and only a relatively small area of ancient cratered terrain remains - mostly in the northern latitudes. Examining impact crater density variations is currently the only way to constrain how old the cratered terrains are and when tectonic activity occurred. Analyzing crater distributions also provides insight into other types of activity modifying craters, such as viscous relaxation due to increased heat flow and burial by plume material [e.g., 1,2]. Since the original release of our Enceladus crater database in [1], which only covered the trailing hemisphere, there have been several new images from the Cassini Imaging Science Subsystem cameras at pixel scales of 100 m/pixel or better, including complete coverage of the leading hemisphere. Therefore, we are recording the diameter and location of craters 1 km and larger in these new images to expand the areal coverage of the database. We are also aligning the original database to the new coordinate system [3], which has changed by a few degrees longitude and also has a minor latitude shift. Finally, we are adding the following information for all craters: crater morphology, crater degradation (or preservation) class, observer confidence that the feature is a crater, and if the crater is cut by tectonic features. This additional information will increase the scientific usefulness of the crater database. We report on progress and similarity/differences to crater distributions derived in previous work [1,4-6].References: [1] Kirchoff, M. R. & P. Schenk. Icarus 202 (2009): 656-68. [2] Bland, M. T., et al. GRL 39 (2012): L17204, doi:10.1029/2012GL052736. [3] Roatsch, Th., et al. PSS 77 (2013): 118-25. [4] Plescia, J. B. & J. M. Boyce. Nature 301 (1983): 666-70. [5] Pozio, S. & J. S. Kargel. LPSC XXI (1990): 975-76. [6] Kinczyk, M

  7. Expanding your horizons in science and mathematics

    NASA Technical Reports Server (NTRS)

    Palmer, Cynthia E. A.

    1995-01-01

    The purpose of the 'Expanding Your Horizons in Science and Mathematics' program is to interest young women in grades six through twelve in a variety of careers where mathematics and science are important. Progress in encouraging young women to take courses in mathematics, science, and technological subjects is discussed. Also included are adult, student, and organizational information packets used for 'Expanding Your Horizons' conferences.

  8. Screw expander for light duty diesel engines

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Preliminary selection and sizing of a positive displacement screw compressor-expander subsystem for a light-duty adiabatic diesel engine; development of a mathematical model to describe overall efficiencies for the screw compressor and expander; simulation of operation to establish overall efficiency for a range of design parameters and at given engine operating points; simulation to establish potential net power output at light-duty diesel operating points; analytical determination of mass moments of inertia for the rotors and inertia of the compressor-expander subsystem; and preparation of engineering layout drawings of the compressor and expander are discussed. As a result of this work, it was concluded that the screw compressor and expander designed for light-duty diesel engine applications are viable alternatives to turbo-compound systems, with acceptable efficiencies for both units, and only a moderate effect on the transient response.

  9. Expanding roles for lipid droplets

    PubMed Central

    Welte, Michael A.

    2015-01-01

    Summary Lipid droplets are the intracellular sites for neutral lipid storage. They are critical for lipid metabolism and energy homeostasis, and their dysfunction has been linked to many diseases. Accumulating evidence suggests that the roles lipid droplets play in biology are significantly broader than previously anticipated. Lipid droplets are the source of molecules important in the nucleus: they can sequester transcription factors and chromatin components and generate the lipid ligands for certain nuclear receptors. Lipid droplets have also emerged as important nodes for fatty acid trafficking, both inside the cell and between cells. In immunity, new roles for droplets, not directly linked to lipid metabolism, have been uncovered, as assembly platforms for specific viruses and as reservoirs for proteins that fight intracellular pathogens. Until recently, knowledge about droplets in the nervous system has been minimal, but now there are multiple links between lipid droplets and neurodegeneration: Many candidate genes for Hereditary Spastic Paraplegia also have central roles in lipid-droplet formation and maintenance, and mitochondrial dysfunction in neurons can lead to transient accumulating of lipid droplets in neighboring glial cells, an event that may, in turn, contribute to neuronal damage. As the cell biology and biochemistry of lipid droplets are increasingly well understood, the next few years should yield many new mechanistic insights into these novel functions of lipid droplets. PMID:26035793

  10. The Expanding Family of Virophages

    PubMed Central

    Bekliz, Meriem; Colson, Philippe; La Scola, Bernard

    2016-01-01

    Virophages replicate with giant viruses in the same eukaryotic cells. They are a major component of the specific mobilome of mimiviruses. Since their discovery in 2008, five other representatives have been isolated, 18 new genomes have been described, two of which being nearly completely sequenced, and they have been classified in a new viral family, Lavidaviridae. Virophages are small viruses with approximately 35–74 nm large icosahedral capsids and 17–29 kbp large double-stranded DNA genomes with 16–34 genes, among which a very small set is shared with giant viruses. Virophages have been isolated or detected in various locations and in a broad range of habitats worldwide, including the deep ocean and inland. Humans, therefore, could be commonly exposed to virophages, although currently limited evidence exists of their presence in humans based on serology and metagenomics. The distribution of virophages, the consequences of their infection and the interactions with their giant viral hosts within eukaryotic cells deserve further research. PMID:27886075

  11. The "expanding universe" of piroplasms.

    PubMed

    Criado-Fornelio, A; Gónzalez-del-Río, M A; Buling-Saraña, A; Barba-Carretero, J C

    2004-02-06

    The present paper is the continuation of our previous studies dealing with the genetic characterization of piroplasmid species found in southern Europe. We report in this work new data concerning sequences of the 18s rRNA gene in Spanish piroplasms not studied (or not totally sequenced) in our former surveys. Molecular data analysis indicated that Spanish Cytauxzoon felis (cat isolate) has 98% identity with Cytauxzoon sp. from Mongolia and 95% identity compared to African C. felis. There are at least two main genetic variants of Babesia caballi in Spain: The first variety (isolate Spain 1) shows a relatively low homology with the African genotype (97% identity). The second variety (represented by two isolates, Spain 2 and Spain 3, differing by a single base) shows high genetic similarity with the African genotype (99.7-100% identity). There are also two genetic variants of Babesia equi (isolates Spain 1 and Spain 2, differing by four bases) in Spain, sharing 99% identity with the African genotype. At least one of them (Spain 1) can infect dogs. All of the phylogenetic analysis procedures employed indicated that Spanish isolates of C. felis, B. caballi (Spain 1) and B. equi (Spain 1 and Spain 2) are genetically different from their African relatives, all those dichotomies showing very high bootstrap support. Nonetheless, the lack of information on their morphology and the fact that the sequences were obtained in a single isolate preclude any conclusion about their definitive taxonomic status.

  12. The Expanding Family of Virophages.

    PubMed

    Bekliz, Meriem; Colson, Philippe; La Scola, Bernard

    2016-11-23

    Virophages replicate with giant viruses in the same eukaryotic cells. They are a major component of the specific mobilome of mimiviruses. Since their discovery in 2008, five other representatives have been isolated, 18 new genomes have been described, two of which being nearly completely sequenced, and they have been classified in a new viral family, Lavidaviridae. Virophages are small viruses with approximately 35-74 nm large icosahedral capsids and 17-29 kbp large double-stranded DNA genomes with 16-34 genes, among which a very small set is shared with giant viruses. Virophages have been isolated or detected in various locations and in a broad range of habitats worldwide, including the deep ocean and inland. Humans, therefore, could be commonly exposed to virophages, although currently limited evidence exists of their presence in humans based on serology and metagenomics. The distribution of virophages, the consequences of their infection and the interactions with their giant viral hosts within eukaryotic cells deserve further research.

  13. ExpandED Schools National Demonstration: Lessons for Scale and Sustainability

    ERIC Educational Resources Information Center

    Russell, Christina A.; Hildreth, Jeanine L.; Stevens, Pamela

    2016-01-01

    The ExpandED Schools model for expanded learning is designed to transform schools by changing the use of time, both as experienced by students in learning and by teachers in instruction. The model is grounded in the belief that strategically adding time to the school day can enhance skills and knowledge and broaden horizons by engaging students in…

  14. Time to Grow: Year Two Report on ExpandED Schools. A TASC Report

    ERIC Educational Resources Information Center

    Traill, Saskia; Brohawn, Katie

    2014-01-01

    An analysis of data from the second year of The After-School Corporation's (TASC's) national demonstration of an expanded school day for elementary and middle school students shows that ExpandED Schools improved school culture, decreased rates of students' chronic absenteeism and helped students develop positive learning habits and attitudes.…

  15. Time to Grow: Year Two Report on ExpandED Schools. A TASC Report

    ERIC Educational Resources Information Center

    Traill, Saskia; Brohawn, Katie

    2014-01-01

    An analysis of data from the second year of The After-School Corporation's (TASC's) national demonstration of an expanded school day for elementary and middle school students shows that ExpandED Schools improved school culture, decreased rates of students' chronic absenteeism and helped students develop positive learning habits and attitudes.…

  16. The expanding regulatory universe of p53 in gastrointestinal cancer.

    PubMed

    Fesler, Andrew; Zhang, Ning; Ju, Jingfang

    2016-01-01

    Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes in gastrointestinal cancers. As a transcription factor, p53 regulates a number of important protein coding genes to control cell cycle, cell death, DNA damage/repair, stemness, differentiation and other key cellular functions. In addition, p53 is also able to activate the expression of a number of small non-coding microRNAs (miRNAs) through direct binding to the promoter region of these miRNAs.  Many miRNAs have been identified to be potential tumor suppressors by regulating key effecter target mRNAs. Our understanding of the regulatory network of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like miRNA, lncRNAs have been found to play important roles in cancer biology.  With our increased understanding of the important functions of these non-coding RNAs and their relationship with p53, we are gaining exciting new insights into the biology and function of cells in response to various growth environment changes. In this review we summarize the current understanding of the ever expanding involvement of non-coding RNAs in the p53 regulatory network and its implications for our understanding of gastrointestinal cancer.

  17. Optimization of the use of skin expanders.

    PubMed

    Pamplona, D C; Weber, H I; Leta, F R

    2014-11-01

    Skin expansion is a physiological process that is defined as the ability of the human skin to increase its superficial area in response to stress or to a given deformation. Skin expanders are silicon bags that are implanted underneath the skin. Because the skin presents creep or relaxation, the resulting stress decreases after a time due to the imposed deformation. Skin expansions are used to reconstruct burned areas and breasts after a mastectomy or to hide scars. The question that constantly arises during skin expansion is whether it creates a sufficient amount of skin or, in other words, whether the achieved expansion is sufficient to resurface the defect. These questions are answered with information about how much new tissue is required to achieve the reconstruction in a given context and calculating the required tissue (surface area) in relationship with the volume infiltrated. Surface formulas for round and rectangular, and finite elements method for crescent skin expanders are used to calculate the relation between infiltrated volume and surface area. Those results were corrected or validated by an experimental work using 3D scanners to calculate the relation between surface area and internal volumes for the three types of expanders in question. The research provides information to determine the type, number, and volume of skin expanders necessary to obtain an extra amount of skin to repair a specific medical condition and to determine the amount of skin obtained even in cases when the expansion does not come to term. fci, Correcting factor, which corrects the mathematical formulas using the experimental results, for i skin expander; i, geometry of the expander, round (c), rectangular (r), or crescent (cresc/cr); Sd , surface of the defect; Sds , surface area of the donor site; Sfi, surface area obtained using a mathematical calculation for the i skin expander; S¯fi, surface area obtained experimentally for the i skin expander; Sfi∗, corrected surface

  18. 24 CFR 3285.502 - Expanding rooms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... support and anchoring systems for expanding rooms must be installed in accordance with designs provided by the home manufacturer or prepared by a registered professional engineer or registered architect,...

  19. Dual-action expanded-latch mechanism

    NASA Technical Reports Server (NTRS)

    Spencer, R. A.; Tewell, J. R.; Tobey, W. H.

    1978-01-01

    Single drive actuator operates novel mechanism that expands, attaches to object, and withdraws to latch object firmly to another part. Packaging is extremely simple and compact, and eliminates need for machined parts or close tolerances.

  20. PROLANG: an expandable software in protein chemistry.

    PubMed

    Petrilli, P; Caporale, C; Sepe, C

    1990-04-01

    PROLANG is an improved version of the PROSOFT program. Improvements to the old commands were made and new ones were added, PROLANG is an open software that users with BASIC programming experience can easily expand.

  1. An Expanded Classification of the Plant Kingdom.

    ERIC Educational Resources Information Center

    Rushton, B. S.

    1981-01-01

    Presents an expanded classification of the plant kingdom, emphasizing major evolutionary steps and differences in levels of complexity. Describes subdivisions and suggests that this classification, reflecting unity and diversity, may be logical, understandable, and useful to students. (JN)

  2. Properties of hot expanded liquid aluminum

    SciTech Connect

    Gathers, G.R.; Ross, M.

    1983-07-01

    Measurements of temperature, volume, enthalpy, and electrical resistivity have been made on aluminum expanded isobarically by 50% in volume to temperatures of about 4000/sup 0/K. These measurements are compared with the predictions of liquid-metal pseudopotential theory.

  3. Expanding European markets for immunotherapy drugs.

    PubMed

    1992-11-01

    Exploding markets for immunotherapeutics have hastened research and development of new drugs to treat patients in institutions and at home. Recent figures reveal just how quickly this market is expanding.

  4. Heroin Epidemic Expands Its Grip on America

    MedlinePlus

    ... gov/news/fullstory_164350.html Heroin Epidemic Expands Its Grip on America Use of the narcotic grew ... people transition from painkillers to heroin, Martins explained. It is also related to availability, lower cost and ...

  5. Helical rotary screw expander power system

    NASA Technical Reports Server (NTRS)

    Mckay, R. A.; Sprankle, R. S.

    1974-01-01

    An energy converter for the development of wet steam geothermal fields is described. A project to evaluate and characterize a helical rotary screw expander for geothermal applications is discussed. The helical screw expander is a positive displacement machine which can accept untreated corrosive mineralized water of any quality from a geothermal well. The subjects of corrosion, mineral deposition, the expansion process, and experience with prototype devices are reported.

  6. Joule-Thomson Expander Without Check Valves

    NASA Technical Reports Server (NTRS)

    Chan, C. K.; Gatewood, J. R.

    1989-01-01

    Cooling effected by bidirectional, reciprocating flow of gas. Type of Joule-Thomson (J-T) expander for cryogenic cooling requires no check valves to prevent reverse flow of coolant. More reliable than conventional J-T expander, containing network of check valves, each potential source of failure. Gas flows alternately from left to right and right to left. Heat load cooled by evaporation of liquid from left or right compartment, whichever at lower pressure.

  7. Exceedingly expanded retroauricular flaps for microtia reconstruction.

    PubMed

    Chen, Zhenyu; Zhang, Weina; Huang, Jinjun; Ren, Jizhen; Zhu, Yuehua

    2011-11-01

    The authors propose here a new strategy to obtain exceedingly expanded retroauricular mastoid skin for sufficient coverage of the three-dimensional autogenous costal cartilage framework generally used in auricular reconstruction surgery. From February 2000 to September 2009, 42 microtia reconstructions were performed using this new strategy. Auricular reconstruction was performed in three surgical stages. In the first stage, a 50-ml kidney-shaped expander was inserted subcutaneously in the retroauricular mastoid region. From 5 to 8 ml saline was then injected into the expander every 4 days until the final volume of the expander reached 100-120 ml. In the second stage, we divided the expanded mastoid skin into a superior two-third region (flap A) and an inferior one-third region (flap B, rotation flap). Autogenous costal cartilage framework was then enveloped by these expanded flaps. Tragus construction and conchal excavation was performed in the third stage. All patients were followed up from 6 months to 4 years after reconstruction. A total of 36 cases reported to be satisfied with the appearance of good shape, accurate size, right orientation, and duplication of well-detailed structures. Further revision was requested by six of the total. Complications in this series includes one case of haematoma, two cases of partial evection of the expanded skin and two cases of partial skin necrosis of the helix. All the complications were treated appropriately. Exceeding expansion can provide sufficient retroauricular non-hair-bearing skin tissues for draping the auricular cartilage framework. Skin grafts and retroauricular fascial flap are not needed any more. Patients are usually satisfied with their reconstructive auricles as regards the size, location, projection, convolution, skin-colour matching, etc. Exceedingly expanded retroauricular flaps are the appropriate envelope for the auricular cartilage framework. Copyright © 2011 British Association of Plastic

  8. Hand-Operated Hydraulic Tube Expander

    NASA Technical Reports Server (NTRS)

    Hagan, David W.; Wolff, Edwin D.

    1995-01-01

    Hand-operated tool expands end portion of narrow metal or plastic tube to slightly larger diameter. Used on tubes with original inner diameters as small as 0.060 in. Includes replaceable tip comprising ferrule and tubular expansion sleeve sized for sliding fit into tube to be expanded. Expansion sleeve swells in response to internal hydraulic pressure generated by turning handle and thereby advancing piston.

  9. Planning the milking center in expanding dairies.

    PubMed

    Smith, J F; Armstrong, D V; Gamroth, M J; Martin, J G

    1997-08-01

    This paper focuses on dairies that want to expand and milk more cows through an existing parlor or by building new parlor. The expansion process can be divided into the following three phases: 1) financial evaluation, 2) design, and 3) construction. A financial evaluation should be carried out first to determine the resources that are available for expanding the dairy operation. This phase is extremely important, considering that 68% of the dairies that expand have cash flow problems within the first 2 yr of operation. The next phase is to design the milking center, and options include expanding the present parlor or constructing a new parlor. The present parlor can be expanded by addition of stalls, but group size must also expand to maintain cow flow at the larger parlor size. Group size can often be increased by combining corrals or free-stall alleys. The third phase in the expansion is to determine the most efficient milking procedure during the construction or remodeling of the facilities.

  10. Quantification Assays for Total and Polyglutamine-Expanded Huntingtin Proteins

    PubMed Central

    Boogaard, Ivette; Smith, Melanie; Pulli, Kristiina; Szynol, Agnieszka; Albertus, Faywell; Lamers, Marieke B. A. C.; Dijkstra, Sipke; Kordt, Daniel; Reindl, Wolfgang; Herrmann, Frank; McAllister, George; Fischer, David F.; Munoz-Sanjuan, Ignacio

    2014-01-01

    The expansion of a CAG trinucleotide repeat in the huntingtin gene, which produces huntingtin protein with an expanded polyglutamine tract, is the cause of Huntington's disease (HD). Recent studies have reported that RNAi suppression of polyglutamine-expanded huntingtin (mutant HTT) in HD animal models can ameliorate disease phenotypes. A key requirement for such preclinical studies, as well as eventual clinical trials, aimed to reduce mutant HTT exposure is a robust method to measure HTT protein levels in select tissues. We have developed several sensitive and selective assays that measure either total human HTT or polyglutamine-expanded human HTT proteins on the electrochemiluminescence Meso Scale Discovery detection platform with an increased dynamic range over other methods. In addition, we have developed an assay to detect endogenous mouse and rat HTT proteins in pre-clinical models of HD to monitor effects on the wild type protein of both allele selective and non-selective interventions. We demonstrate the application of these assays to measure HTT protein in several HD in vitro cellular and in vivo animal model systems as well as in HD patient biosamples. Furthermore, we used purified recombinant HTT proteins as standards to quantitate the absolute amount of HTT protein in such biosamples. PMID:24816435

  11. Enhancing microbial production of biofuels by expanding microbial metabolic pathways.

    PubMed

    Yu, Ping; Chen, Xingge; Li, Peng

    2016-08-10

    Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to produce biofuels. By introducing three genes, atfA, adhE, and pdc, into Escherichia coli to expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl esters can be achieved. The isoprenoid pathway can be expanded to produce bisabolene with a high titer of 900 mg/L in Saccharomyces cerevisiae. Short- and long-chain alcohols can also be effectively biosynthesized by extending the carbon chain of ketoacids with an engineered "+1" alcohol pathway. Thus, it can be concluded that expanding microbial metabolic pathways has enormous potential for enhancing microbial production of biofuels for future industrial applications. However, some major challenges for microbial production of biofuels should be overcome to compete with traditional fossil fuels: lowering production costs, reducing the time required to construct genetic elements and to increase their predictability and reliability, and creating reusable parts with useful and predictable behavior. To address these challenges, several aspects should be further considered in future: mining and transformation of genetic elements related to metabolic pathways, assembling biofuel elements and coordinating their functions, enhancing the tolerance of host cells to biofuels, and creating modular subpathways that can be easily interconnected. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  12. TFClass: an expandable hierarchical classification of human transcription factors

    PubMed Central

    Wingender, Edgar; Schoeps, Torsten; Dönitz, Jürgen

    2013-01-01

    TFClass (http://tfclass.bioinf.med.uni-goettingen.de/) provides a comprehensive classification of human transcription factors based on their DNA-binding domains. Transcription factors constitute a large functional family of proteins directly regulating the activity of genes. Most of them are sequence-specific DNA-binding proteins, thus reading out the information encoded in cis-regulatory DNA elements of promoters, enhancers and other regulatory regions of a genome. TFClass is a database that classifies human transcription factors by a six-level classification schema, four of which are abstractions according to different criteria, while the fifth level represents TF genes and the sixth individual gene products. Altogether, nine superclasses have been identified, comprising 40 classes and 111 families. Counted by genes, 1558 human TFs have been classified so far or >2900 different TFs when including their isoforms generated by alternative splicing or protein processing events. With this classification, we hope to provide a basis for deciphering protein–DNA recognition codes; moreover, it can be used for constructing expanded transcriptional networks by inferring additional TF-target gene relations. PMID:23180794

  13. Molecular Cloning and Functional Analysis of Three FLOWERING LOCUS T (FT) Homologous Genes from Chinese Cymbidium

    PubMed Central

    Huang, Weiting; Fang, Zhongming; Zeng, Songjun; Zhang, Jianxia; Wu, Kunlin; Chen, Zhilin; Teixeira da Silva, Jaime A.; Duan, Jun

    2012-01-01

    The FLOWERING LOCUS T (FT) gene plays crucial roles in regulating the transition from the vegetative to reproductive phase. To understand the molecular mechanism of reproduction, three homologous FT genes were isolated and characterized from Cymbidium sinense “Qi Jian Bai Mo”, Cymbidium goeringii and Cymbidium ensifolium “Jin Si Ma Wei”. The three genes contained 618-bp nucleotides with a 531-bp open reading frame (ORF) of encoding 176 amino acids (AAs). Alignment of the AA sequences revealed that CsFT, CgFT and CeFT contain a conserved domain, which is characteristic of the PEBP-RKIP superfamily, and which share high identity with FT of other plants in GenBank: 94% with OnFT from Oncidium Gower Ramsey, 79% with Hd3a from Oryza sativa, and 74% with FT from Arabidopsis thaliana. qRT-PCR analysis showed a diurnal expression pattern of CsFT, CgFT and CeFT following both long day (LD, 16-h light/8-h dark) and short day (SD, 8-h light/16-h dark) treatment. While the transcripts of both CsFT and CeFT under LD were significantly higher than under SD, those of CgFT were higher under SD. Ectopic expression of CgFT in transgenic Arabidopsis plants resulted in early flowering compared to wild-type plants and significant up-regulation of APETALA1 (AP1) expression. Our data indicates that CgFT is a putative phosphatidylethanolamine-binding protein gene in Cymbidium that may regulate the vegetative to reproductive transition in flowers, similar to its Arabidopsis ortholog. PMID:23109860

  14. Giant viruses with an expanded complement of translation system components.

    PubMed

    Schulz, Frederik; Yutin, Natalya; Ivanova, Natalia N; Ortega, Davi R; Lee, Tae Kwon; Vierheilig, Julia; Daims, Holger; Horn, Matthias; Wagner, Michael; Jensen, Grant J; Kyrpides, Nikos C; Koonin, Eugene V; Woyke, Tanja

    2017-04-07

    The discovery of giant viruses blurred the sharp division between viruses and cellular life. Giant virus genomes encode proteins considered as signatures of cellular organisms, particularly translation system components, prompting hypotheses that these viruses derived from a fourth domain of cellular life. Here we report the discovery of a group of giant viruses (Klosneuviruses) in metagenomic data. Compared with other giant viruses, the Klosneuviruses encode an expanded translation machinery, including aminoacyl transfer RNA synthetases with specificities for all 20 amino acids. Notwithstanding the prevalence of translation system components, comprehensive phylogenomic analysis of these genes indicates that Klosneuviruses did not evolve from a cellular ancestor but rather are derived from a much smaller virus through extensive gain of host genes. Copyright © 2017, American Association for the Advancement of Science.

  15. Improved Chondrogenic Capacity of Collagen Hydrogel-Expanded Chondrocytes: In Vitro and in Vivo Analyses.

    PubMed

    Sanz-Ramos, Patricia; Duart, Julio; Rodríguez-Goñi, María Victoria; Vicente-Pascual, Mikel; Dotor, Javier; Mora, Gonzalo; Izal-Azcárate, Iñigo

    2014-07-02

    The use of autologous chondrocytes in cartilage repair is limited because of loss of the cartilage phenotype during expansion. The mechanosensing capacity of chondrocytes suggests evaluating the use of soft substrates for in vitro expansion. Our aim was to test the expansion of chondrocytes on collagen hydrogels to improve their capacity for chondrogenesis after a number of passages. Rat cartilage cells were expanded on collagen hydrogels and on plastic, and the preservation of their chondrogenic capacity was tested both in vitro and in vivo. The expression of relevant markers during expansion on each surface was measured by real-time PCR (polymerase chain reaction). Expanded cells were then implanted in focal lesions in the medial femoral condyle of healthy sheep, and the newly formed tissue was analyzed by histomorphometry. Compared with cells cultured on plastic, cells cultured on hydrogels had better maintenance of the expression of the Sox9, Col2 (type-II collagen), FGFR3, and Alk-5 genes and decreased expression of Alk-1 and BMP-2. Pellets also showed increased expression of the cartilage marker genes aggrecan, Sox9, and Col2, and decreased expression of Col1 and Col10 (type-I and type-X collagen). ELISA (enzyme-linked immunosorbent assay) also showed a higher ratio of type-II to type-I collagen in pellets formed from cells expanded on hydrogels. When sheep chondrocytes were expanded and implanted in cartilage lesions in the femoral condyle of healthy sheep, hydrogel-expanded cells produced histologically better tissue compared with plastic-expanded cells. The expansion of chondrocytes on collagen hydrogels yielded cells with an improved chondrogenic capacity compared with cells expanded on plastic. The study results favor the use of hydrogel-expanded cells over the traditional plastic-expanded cells for autologous chondrocyte implantation. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

  16. Expanded Schools: Developing Mindsets to Support Academic Success. Research Brief

    ERIC Educational Resources Information Center

    ExpandED Schools, 2014

    2014-01-01

    The national demonstration of ExpandED Schools, The After-School Corporation's (TASC) expanded learning model, was launched in 2011-12 in New York City, Baltimore, and New Orleans. The ExpandED Schools demonstration is being evaluated by Policy Studies Associates (PSA) and is rolling out at a time when there is heightened awareness among…

  17. Evaluation of injury to expanded and expanding leaves of peas exposed to sulfur dioxide and ozone

    SciTech Connect

    Olszyk, D.M.; Tibbitts, T.W.

    1982-03-01

    Necrosis, chlorophyll concentration, dry weight and surface area measurements were made to evaluate injury to leaves of Pisum sativum L. cv Alsweet grown under controlled environments and exposed to sulfur dioxide, ozone and combinations of sulfur dioxide plus ozone. Injury evaluations were made at low pollutant levels causing slight necrotic injury and high levels causing severe necrotic injury. At low levels, expanded leaves with a trace of necrotic injury had a 10% reduction in chlorophyll concentration but no reductions in dry weight or surface area, while expanding leaves, also with a trace of necrotic injury, had a reduction in chlorophyll concentration accompanied by reductions in dry weight and surface area. At high pollutant levels, expanded leaves with severe necrotic injury had a 70% reduction in chlorophyll concentration and significant reductions in dry weight and surface area, while expanding leaves had a smaller amount of necrotic injury and a smaller reduction in chlorophyll concentration, but reductions in dry weight and surface area similar to those in expanded leaves. Thus, the following measurements are proposed as reliable indicators of injury at pollutant concentrations just above the threshold for injury: chlorophyll concentration for expanded leaves and surface area for expanding leaves. Reliable indicators of injury at higher concentrations causing serious injury to leaves are: necrosis for expanded leaves and chlorophyll concentration, dry weight, and surface area for expanding leaves. 19 references, 4 figures, 3 tables.

  18. Expanding your horizons in science and mathematics

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Through the presentation of its Expanding Your Horizons in Science and Mathematics career education conferences for secondary school young women, the Math/Science Network continues its efforts to remove the educational, psychological, and cultural barriers which prevent women from entering math-and science-based careers. The Expanding Your Horizons conferences were presented on 77 college, university and high school campuses across the United States. This year, these unique one day conferences reached 15,500 students, 3,000 parents and educators, and involved 3,000 career women who volunteered their services as conference planners, workshop leaders, speakers, and role models.

  19. Negative energy particle as an expanding wormhole

    NASA Astrophysics Data System (ADS)

    Culetu, Hristu

    2015-04-01

    The properties of a dynamic wormhole are investigated. Using a particular equation of state for the fluid on the wormhole throat, we reached an equation of motion for the throat (a hyperbola) that leads to a negative surface energy density σ. The throat expands with the same acceleration 2π|σ| as the Ipser-Sikivie domain wall. We found the Lagrangian leading to the above equation of motion of the throat. The associated Hamiltonian corresponds to a relativistic free particle of a time-dependent negative energy -ℏc/R, where R is the throat radius, similar in form with the Casimir energy inside an expanding spherical box.

  20. DYNAMICAL MODEL OF AN EXPANDING SHELL

    SciTech Connect

    Pe'er, Asaf

    2012-06-10

    Expanding blast waves are ubiquitous in many astronomical sources, such as supernova remnants, X-ray emitting binaries, and gamma-ray bursts. I consider here the dynamics of such an expanding blast wave, both in the adiabatic and the radiative regimes. As the blast wave collects material from its surroundings, it decelerates. A full description of the temporal evolution of the blast wave requires consideration of both the energy density and the pressure of the shocked material. The obtained equation is different from earlier works in which only the energy was considered. The solution converges to the familiar results in both the ultrarelativistic and the sub-relativistic (Newtonian) regimes.

  1. Transition Metal Complexes of Expanded Porphyrins

    PubMed Central

    Sessler, Jonathan L.; Tomat, Elisa

    2008-01-01

    Over the last two decades, the rapid development of new synthetic routes for the preparation of expanded porphyrin macrocycles has allowed exploration of a new frontier consisting of “porphyrin-like” coordination chemistry. In this Account, we summarize our exploratory forays into the still relatively poorly explored area of oligopyrrolic macrocycle metalation chemistry. Specifically, we describe our successful formation of both mono- and binuclear complexes and in doing so highlight the diversity of coordination modes available to expanded porphyrin-type ligands. The nature of the inserted cation, the emerging role of tautomeric equilibria, and the importance of hydrogen-bonding interactions in regulating this chemistry are also discussed. PMID:17397134

  2. Expanding Arts Education in a Digital Age

    ERIC Educational Resources Information Center

    Choi, Haeryun; Piro, Joseph M.

    2009-01-01

    This article proposes a way to expand the study of arts education within new contexts of technology and globalization. Drawing upon theories that have informed arts and aesthetic education in the past, the authors suggest new applications for these ideas to ensure that arts education sustains its significance in twenty-first-century society. The…

  3. Expanding the Boundaries of Adult Religious Education

    ERIC Educational Resources Information Center

    Isaac, E. Paulette

    2012-01-01

    Religious institutions wear many hats. In addition to meeting spiritual needs, they also serve as educational, cultural, political, and social centers. Like the world in general, many of them have responded to societal changes. They have expanded their contextual, geographical, and physical boundaries. Also, as demonstrated throughout this…

  4. Consonant confusions in amplitude-expanded speech.

    PubMed

    Freyman, R L; Nerbonne, G P

    1996-12-01

    The perceptual consequences of expanding the amplitude variations in speech were studied under conditions in which spectral information was obscured by signal correlated noise that had an envelope correlated with the speech envelope, but had a flat amplitude spectrum. The noise samples, created individually from 22 vowel-consonant-vowel nonsense words, were used as maskers of those words, with signal-to-noise ratios ranging from -15 to 0 dB. Amplitude expansion was by a factor of 3.0 in terms of decibels. In the first experiment, presentation level for speech peaks was 80 dB SPL. Consonant recognition performance for expanded speech by 50 listeners with normal hearing was as much as 30 percentage points poorer than for unexpanded speech and the types of errors were dramatically different, especially in the midrange of S-N ratios. In a second experiment presentation level was varied to determine whether reductions in consonant levels produced by expansion were responsible for the differences between conditions. Recognition performance for unexpanded speech at 40 dB SPL was nearly equivalent to that for expanded speech at 80 dB SPL. The error patterns obtained in these two conditions were different, suggesting that the differences between conditions in Experiment 1 were due largely to expanded amplitude envelopes rather than differences in audibility.

  5. Expanding the Reader Landscape of Histone Acylation.

    PubMed

    Khan, Abid; Bridgers, Joseph B; Strahl, Brian D

    2017-04-04

    In this issue of Structure,Klein et al. (2017) expand our understanding of what reader domains bind to by showing that MORF, a double PHD domain containing lysine acetyltransferase, is a preferential reader of histone lysine acylation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. An Expanding Universe in the Classroom.

    ERIC Educational Resources Information Center

    Chandler, David

    1991-01-01

    Two computer-generated star charts that can be used as overlay transparencies to show an expanding universe are presented. Directions on how to use the star charts to determine the Hubble constant and the age of the universe are provided. (KR)

  7. Improving Accountability through Expanded Measures of Performance

    ERIC Educational Resources Information Center

    Hamilton, Laura S.; Schwartz, Heather L.; Stecher, Brian M.; Steele, Jennifer L.

    2013-01-01

    Purpose: The purpose of this paper is to examine how test-based accountability has influenced school and district practices and explore how states and districts might consider creating expanded systems of measures to address the shortcomings of traditional accountability. It provides research-based guidance for entities that are developing or…

  8. Virginia expands HIV testing, licenses viatical firms.

    PubMed

    1997-05-02

    Virginia Governor George Allen signed H.B. 2174, H.B. 871, and S.B. 788 on March 25, 1997. The legislation expands HIV testing of criminal defendants, requires viatical settlement companies to obtain licenses, and imposes civil penalties for physician-assisted suicides.

  9. Virginia rejects assisted suicide, expands mandatory testing.

    PubMed

    1997-03-07

    Virginia legislators ended their 1997 session by adopting measures that impact AIDS patients, physicians, advocates, and their families. Gov. George Allen may sign into law bills imposing penalties for doctor-assisted suicide, requiring viatical settlement companies to obtain licenses, and expanding mandatory HIV testing of criminal defendants. Republican lawmakers are working to rescind Virginia's medical marijuana law.

  10. Heat expanded starch-based compositions.

    PubMed

    Glenn, Gregory M; Klamczynski, Artur K; Holtman, Kevin M; Shey, Justin; Chiou, Bor-Sen; Berrios, Jose; Wood, Delilah; Orts, William J; Imam, Syed H

    2007-05-16

    A heat expansion process similar to that used for expanded bead polystyrene was used to expand starch-based compositions. Foam beads made by solvent extraction had the appearance of polystyrene beads but did not expand when heated due to an open-cell structure. Nonporous beads, pellets, or particles were made by extrusion or by drying and milling cooked starch slurries. The samples expanded into a low-density foam by heating 190-210 degrees C for more than 20 s at ambient pressures. Formulations containing starch (50-85%), sorbitol (5-15%), glycerol (4-12%), ethylene vinyl alcohol (EVAL, 5-15%), and water (10-20%) were studied. The bulk density was negatively correlated to sorbitol, glycerol, and water content. Increasing the EVAL content increased the bulk density, especially at concentrations higher than 15%. Poly(vinyl alcohol) (PVAL) increased the bulk density more than EVAL. The bulk density was lowest in samples made of wheat and potato starch as compared to corn starch. The expansion temperature for the starch pellets decreased more than 20 degrees C as the moisture content was increased from 10 to 25%. The addition of EVAL in the formulations decreased the equilibrium moisture content of the foam and reduced the water absorption during a 1 h soaking period.

  11. Women Engineering Faculty: Expanding the Pipeline

    ERIC Educational Resources Information Center

    Greni, Nadene Deiterman

    2006-01-01

    The purpose for this case study was to explore the features of undergraduate engineering departmental and college support that influenced the persistence of women students. Women engineering faculty members were among the participants at three Land Grant universities in the Midwest. The data revealed the theme, Expanding the Pipeline, and…

  12. Utilities expand baseload power plant plans

    SciTech Connect

    Smock, R.

    1993-04-01

    This article examines the plans being made by electric utilities to expand the number of baseload plants to accommodate increasing power demands. The results of a survey of utility's construction plans is presented. The topics include current construction, construction planning in the Southeast, current baseload technology, nuclear potential, and incorporation of environmental externalities impact in planning.

  13. Properties of extruded expandable breadfruit products

    USDA-ARS?s Scientific Manuscript database

    Dried breadfruit was extruded with a twin screw extruder to develop a value-added expanded fruit product. This research studied the effects of barrel temperature (120-160°C), moisture content (13-25%), feeding rate (13-25 kg/h) and screw speed (115-175rpm) on physicochemical properties (bulk densit...

  14. A Curriculum Model for the Expanded Role

    ERIC Educational Resources Information Center

    Zornow, Ruth Ann

    1977-01-01

    If the expanded role is conceived in terms of five levels of functioning, organizing theoretical instruction and clinical preparation within a school's program is facilitated. The levels are: Basic nursing level, assessment level, screening level, management level, and diagnostic level. (Editor/TA)

  15. Expanding the Boundaries of Adult Religious Education

    ERIC Educational Resources Information Center

    Isaac, E. Paulette

    2012-01-01

    Religious institutions wear many hats. In addition to meeting spiritual needs, they also serve as educational, cultural, political, and social centers. Like the world in general, many of them have responded to societal changes. They have expanded their contextual, geographical, and physical boundaries. Also, as demonstrated throughout this…

  16. Digital Storytelling: Expanding Media Possibilities for Learning

    ERIC Educational Resources Information Center

    McLellan, Hilary, Ed.

    2008-01-01

    Stories offer a powerful framework for engagement, reflection, and other important skills that young people need to learn. As digital media have expanded, so have the possibilities for creating stories. Here, several examples of those new possibilities are examined, examples that highlight student-produced online broadcasting initiatives,…

  17. Expanding Perspectives on HRD Research. Symposium.

    ERIC Educational Resources Information Center

    2002

    This document contains three papers from a symposium on expanding perspectives in human resource development (HRD) research. "The Concept of Culture in International and Comparative HRD Research: Methodological Problems and Possible Solutions" (Alexander Ardichvili, K. Peter Kuchinke) discusses the following topics: (1) alternative…

  18. E-Books: Expanding the School Library

    ERIC Educational Resources Information Center

    Cavanaugh, Terence

    2005-01-01

    E-Books are books or other forms of text in digital form, an enhanced book without paper and at little or no cost, technologies that are already available at most schools can be used to expand the library media center's collection of books, at the same time making many books more accessible to students. Many tools are available for free to convert…

  19. Parachute Line Hook Includes Integral Loop Expander

    NASA Technical Reports Server (NTRS)

    Bayless, G. B.

    1983-01-01

    Parachute packing simplified with modified line hook. One person packs parachutes for test recovery vehicles faster than previously two-person team. New line hook includes expander that opens up two locking loops so parachute lines are pulled through them. Parachutes are packed at high pressure to be compressed into limited space available in test vehicles.

  20. Successful educational geophysics field program expands

    NASA Astrophysics Data System (ADS)

    The Summer of Applied Geophysical Experience (SAGE), a program that gives students an opportunity to apply a variety of modern geophysical methods in a challenging geologic environment, has expanded.A 2-year grant awarded in 1993 by the National Science Foundation's Research Experiences for Undergraduate's (REU) initiative allowed the program to include fourteen U.S. undergraduate students last summer.

  1. An Expanding Universe in the Classroom.

    ERIC Educational Resources Information Center

    Chandler, David

    1991-01-01

    Two computer-generated star charts that can be used as overlay transparencies to show an expanding universe are presented. Directions on how to use the star charts to determine the Hubble constant and the age of the universe are provided. (KR)

  2. Expanded Learning the LA's BEST Way

    ERIC Educational Resources Information Center

    Sanger, Carla; Heckman, Paul E.

    2011-01-01

    As federal and state policymakers and many education researchers and experts suggest, expanding the learning day for students makes sense. Given the demographic trends--women increasingly entering the workforce and low-income families working multiple jobs--children and youth need supervision and opportunities to learn in the hours between 3:00…

  3. Digital Storytelling: Expanding Media Possibilities for Learning

    ERIC Educational Resources Information Center

    McLellan, Hilary, Ed.

    2008-01-01

    Stories offer a powerful framework for engagement, reflection, and other important skills that young people need to learn. As digital media have expanded, so have the possibilities for creating stories. Here, several examples of those new possibilities are examined, examples that highlight student-produced online broadcasting initiatives,…

  4. Replicating an expanded genetic alphabet in cells.

    PubMed

    Chaput, John C

    2014-09-05

    Recent advances in synthetic biology have made it possible to replicate an unnatural base pair in living cells. This study highlights the technologies developed to create a semisynthetic organism with an expanded genetic alphabet and the potential challenges of moving forward. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Expanding the Focus of Career Assessment.

    ERIC Educational Resources Information Center

    Lock, Jared D.; Hogan, Robert

    2000-01-01

    Issues affecting career assessment include change in the focus and definition of career, emphasis on quality of work life, expansion of career paths, increased amount of career information available on the Internet, and questionable quality of online assessment. An expanded model of career assessment now includes technical fit, personal fit,…

  6. Expanding Analytic Possibilities of Rokeach Values Data.

    ERIC Educational Resources Information Center

    Chapman, David W.; And Others

    1983-01-01

    This study investigated the validity of Hayes's formula for converting rank-ordered Rokeach Values data to a normal distribution theoretically achieved through the use of rated data. Findings support the validity of Hayes's formula and expand the analytic possibilities of data collected on the Rokeach instrument. (Author/PN)

  7. E-Books: Expanding the School Library

    ERIC Educational Resources Information Center

    Cavanaugh, Terence

    2005-01-01

    E-Books are books or other forms of text in digital form, an enhanced book without paper and at little or no cost, technologies that are already available at most schools can be used to expand the library media center's collection of books, at the same time making many books more accessible to students. Many tools are available for free to convert…

  8. Expanding CTE Opportunities through Blended Learning

    ERIC Educational Resources Information Center

    McKinstry, Elizabeth

    2012-01-01

    The global economy, 21st century skills, knowledge society, college and career readiness, digital and project-based learning are all common terms to educators who are expanding their learning environments beyond the classroom to meet the needs of all students. It is common knowledge that the rapid technological advances of this century have…

  9. Expanding the Audience for the Performing Arts.

    ERIC Educational Resources Information Center

    Andreasen, Alan R.

    Becoming involved in the arts is a process that involves movement through several stages, from disinterest to active attendance at and enthusiasm for performing arts events. Since target consumers at any time will differ in their placement on this continuum, marketing programs to expand arts audiences must first identify where each target segment…

  10. Expanding Educational Excellence: The Power of Schools

    ERIC Educational Resources Information Center

    Coleman, Mary Ruth; Winn, Donna-Marie; Harradine, Christine

    2012-01-01

    In this paper, the authors explore four major barriers to academic success that must be addressed, briefly describe two projects that have worked to address these barriers, and make recommendations for moving forward as they work to expand educational excellence for all students. They provide examples of the myriad ways in which schools have the…

  11. Smaragdyrins: emeralds of expanded porphyrin family.

    PubMed

    Pareek, Yogita; Ravikanth, M; Chandrashekar, T K

    2012-10-16

    Porphyrins are tetrapyrrolic 18 π electron conjugated macrocycles with wide applications that range from materials to medicine. Expanded porphyrins, synthetic analogues of porphyrins that contain more than 18 π electrons in the conjugated pathway, have an increased number of pyrroles or other heterocyles or multiple meso-carbon bridges. The expanded porphyrins have attracted tremendous attention because of unique features such as anion binding or transport that are not present in porphyrins. Expanded porphyrins exhibit wide applications that include their use in the coordination of large metal ions, as contrasting agents in magnetic resonance imaging (MRI), as sensitizers for photodynamic therapy (PDT) and as materials for nonlinear optical (NLO) studies. Pentaphyrin 1, sapphyrin 2, and smaragdyrin 3 are expanded porphyrins that include five pyrroles or heterocyclic rings. They differ from each other in the number of bridging carbons and direct bonds that connect the five heterocyclic rings. Sapphyrins were the first stable expanded porphyrins reported in the literature and remain one of the most extensively studied macrocycles. The strategies used to synthesize sapphyrins are well established, and these macrocycles are versatile anion binding agents. They possess rich porphyrin-like coordination chemistry and have been used in diverse applications. This Account reviews developments in smaragdyrin chemistry. Although smaragdyrins were discovered at the same time as sapphyrins, the chemistry of smaragdyrins remained underdeveloped because of synthetic difficulties and their comparative instability. Earlier efforts resulted in the isolation of stable β-substituted smaragdyrins and meso-aryl isosmaragdyrins. Recently, researchers have synthesized stable meso-aryl smaragdyrins by [3 + 2] oxidative coupling reactions. These results have stimulated renewed research interest in the exploration of these compounds for anion and cation binding, energy transfer

  12. Refrigeration generation using expander-generator units

    NASA Astrophysics Data System (ADS)

    Klimenko, A. V.; Agababov, V. S.; Koryagin, A. V.; Baidakova, Yu. O.

    2016-05-01

    The problems of using the expander-generator unit (EGU) to generate refrigeration, along with electricity were considered. It is shown that, on the level of the temperatures of refrigeration flows using the EGU, one can provide the refrigeration supply of the different consumers: ventilation and air conditioning plants and industrial refrigerators and freezers. The analysis of influence of process parameters on the cooling power of the EGU, which depends on the parameters of the gas expansion process in the expander and temperatures of cooled environment, was carried out. The schematic diagram of refrigeration generation plant based on EGU is presented. The features and advantages of EGU to generate refrigeration compared with thermotransformer of steam compressive and absorption types were shown, namely: there is no need to use the energy generated by burning fuel to operate the EGU; beneficial use of the heat delivered to gas from the flow being cooled in equipment operating on gas; energy production along with refrigeration generation, which makes it possible to create, using EGU, the trigeneration plants without using the energy power equipment. It is shown that the level of the temperatures of refrigeration flows, which can be obtained by using the EGU on existing technological decompression stations of the transported gas, allows providing the refrigeration supply of various consumers. The information that the refrigeration capacity of an expander-generator unit not only depends on the parameters of the process of expansion of gas flowing in the expander (flow rate, temperatures and pressures at the inlet and outlet) but it is also determined by the temperature needed for a consumer and the initial temperature of the flow of the refrigeration-carrier being cooled. The conclusion was made that the expander-generator units can be used to create trigeneration plants both at major power plants and at small energy.

  13. A new alternative to expandable pedicle screws: Expandable poly-ether-ether-ketone shell.

    PubMed

    Demir, Teyfik

    2015-05-01

    Screw pullout is a very common problem in the fixation of sacrum with pedicle screws. The principal cause of this problem is that the cyclic micro motions in the fixation of sacrum are higher than the other regions of the vertebrae that limit the osteo-integration between bone and screw. In addition to that, the bone quality is very poor at sacrum region. This study investigated a possible solution to the pullout problem without the expandable screws' handicaps. Newly designed poly-ether-ether-ketone expandable shell and classical pedicle screws were biomechanically compared. Torsion test, pullout tests, fatigue tests, flexion/extension moment test, axial gripping capacity tests and torsional gripping capacity tests were conducted in accordance with ASTM F543, F1798 and F1717. Standard polyurethane foam and calf vertebrae were used as embedding medium for pullout tests. Classical pedicle screw pullout load on polyurethane foam was 564.8 N compared to the failure load for calf vertebrae's 1264 N. Under the same test conditions, expandable poly-ether-ether-ketone shell system's pullout loads from polyurethane foam and calf vertebrae were 1196.3 and 1890 N, respectively. The pullout values for expandable poly-ether-ether-ketone shell were 33% and 53% higher than classical pedicle screw on polyurethane foam and calf vertebrae, respectively. The expandable poly-ether-ether-ketone shell exhibited endurance on its 90% of yield load. Contrary to poly-ether-ether-ketone shell, classical pedicle screw exhibited endurance on 70% of its yield load. Expandable poly-ether-ether-ketone shell exhibited much higher pullout performance than classical pedicle screw. Fatigue performance of expandable poly-ether-ether-ketone shell is also higher than classical pedicle screw due to damping the micro motion capacity of the poly-ether-ether-ketone. Expandable poly-ether-ether-ketone shell is a safe alternative to all other expandable pedicle screw systems on mechanical perspective.

  14. Reasons for Declining Preconception Expanded Carrier Screening Using Genome Sequencing.

    PubMed

    Gilmore, Marian J; Schneider, Jennifer; Davis, James V; Kauffman, Tia L; Leo, Michael C; Bergen, Kellene; Reiss, Jacob A; Himes, Patricia; Morris, Elissa; Young, Carol; McMullen, Carmit; Wilfond, Benjamin S; Goddard, Katrina A B

    2017-03-17

    Genomic carrier screening can identify more disease-associated variants than existing carrier screening methodologies, but its utility from patients' perspective is not yet established. A randomized controlled trial for preconception genomic carrier screening provided an opportunity to understand patients' decisions about whether to accept or decline testing. We administered a survey to potential genomic carrier screening recipients who declined participation (N = 240) to evaluate their reasons for doing so. Two thirds of women declined participation. We identified major themes describing reasons these individuals declined to participate; the most common were time limitation, lack of interest, not wanting to know the information, and potential cause of worry or anxiety. Most women eligible for genomic carrier screening indicated that their reasons for opting out were due to logistical issues rather than opposing the rationale for testing. As expanded carrier screening and genomic sequencing become a more routine part of clinical care, it is anticipated there will be variable uptake from individuals for this testing. Thus, the advancement of clinical carrier screening from single genes, to expanded screening panels, to an exome- or genome-wide platform, will require approaches that respect individual choice to receive genetic testing for reproductive risk assessment.

  15. The radiological findings in chronic expanding hematoma.

    PubMed

    Aoki, T; Nakata, H; Watanabe, H; Maeda, H; Toyonaga, T; Hashimoto, H; Nakamura, T

    1999-07-01

    To identify the characteristic MRI findings of chronic expanding hematoma correlated with the pathology. Three patients who had a chronic expanding hematoma involving the musculoskeletal system were reviewed retrospectively. Huge soft tissue masses suggestive of malignancy with destruction of the bony structure were revealed on radiography and computed tomography. MRI showed the masses to exhibit heterogeneous signal intensity on both T1 and T2-weighted images with a peripheral rim of low signal intensity, reflecting the central zones of fluid collection due to fresh and altered blood with a wall of collagenous fibrous tissue. These MRI findings were seen in all three patients and are considered to be characteristic; they assist in differentiation from neoplasm in consideration of the history of trauma or surgery.

  16. Controlling the statistical properties of expanding maps

    NASA Astrophysics Data System (ADS)

    Galatolo, Stefano; Pollicott, Mark

    2017-07-01

    How can one change a system, in order to change its statistical properties in a prescribed way? In this note we consider a control problem related to the theory of linear response. Given an expanding map of the unit circle with an associated invariant density, we can consider the inverse problem of finding which first order changes in the transformation can achieve a given first order perturbation in the density. We show the general mathematical structure of the problem, the existence of many solutions in the case of expanding maps of the circle and the existence of optimal ones. We investigate in depth the example of the doubling map, where we give a complete solution of the problem.

  17. Expanding and collapsing scalar field thin shell

    NASA Astrophysics Data System (ADS)

    Sharif, M.; Abbas, G.

    2012-09-01

    This paper deals with the dynamics of scalar field thin shell in the Reissner-Nordstr öm geometry. The Israel junction conditions between Reissner-Nordstr öm spacetimes are derived, which lead to the equation of motion of scalar field shell and Klien-Gordon equation. These equations are solved numerically by taking scalar field model with the quadratic scalar potential. It is found that solution represents the expanding and collapsing scalar field shell. For the better understanding of this problem, we investigate the case of massless scalar field (by taking the scalar field potential zero). Also, we evaluate the scalar field potential when p is an explicit function of R. We conclude that both massless as well as massive scalar field shell can expand to infinity at constant rate or collapse to zero size forming a curvature singularity or bounce under suitable conditions.

  18. Black holes in an expanding universe.

    PubMed

    Gibbons, Gary W; Maeda, Kei-ichi

    2010-04-02

    An exact solution representing black holes in an expanding universe is found. The black holes are maximally charged and the universe is expanding with arbitrary equation of state (P = w rho with -1 < or = for all w < or = 1). It is an exact solution of the Einstein-scalar-Maxwell system, in which we have two Maxwell-type U(1) fields coupled to the scalar field. The potential of the scalar field is an exponential. We find a regular horizon, which depends on one parameter [the ratio of the energy density of U(1) fields to that of the scalar field]. The horizon is static because of the balance on the horizon between gravitational attractive force and U(1) repulsive force acting on the scalar field. We also calculate the black hole temperature.

  19. Expanding the genetic code of mammalian cells.

    PubMed

    Italia, James S; Zheng, Yunan; Kelemen, Rachel E; Erickson, Sarah B; Addy, Partha S; Chatterjee, Abhishek

    2017-04-15

    In the last two decades, unnatural amino acid (UAA) mutagenesis has emerged as a powerful new method to probe and engineer protein structure and function. This technology enables precise incorporation of a rapidly expanding repertoire of UAAs into predefined sites of a target protein expressed in living cells. Owing to the small footprint of these genetically encoded UAAs and the large variety of enabling functionalities they offer, this technology has tremendous potential for deciphering the delicate and complex biology of the mammalian cells. Over the last few years, exciting progress has been made toward expanding the toolbox of genetically encoded UAAs in mammalian cells, improving the efficiency of their incorporation and developing innovative applications. Here, we provide our perspective on these recent developments and highlight the current challenges that must be overcome to realize the full potential of this technology. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  20. Expanding Advanced Civilizations in the Universe

    NASA Astrophysics Data System (ADS)

    Gros, C.

    The 1950 lunch-table remark by Enrico Fermi `Where is everybody' has started intensive scientific and philosophical discussions about what we call nowadays the `Fermi paradox': If there had been ever a single advanced civilization in the cosmological history of our galaxy, dedicated to expansion, it would have had plenty of time to colonize the entire galaxy via exponential growth. No evidence of present or past alien visits to earth are known to us, leading to the standard conclusion that no advanced expanding civilization has ever existed in the milky-way. This conclusion rest fundamentally on the ad-hoc assumption, that any alien civilizations dedicated to expansion at one time would remain dedicated to expansions forever. Considering our limited knowledge about alien civilizations we need however to relax this basic assumption. Here we show that a substantial and stable population of expanding advanced civilization might consequently exist in our galaxy.

  1. Outsourcing meets expanded plant`s requirements

    SciTech Connect

    Haas, W.E.

    1997-03-01

    This article describes a system provided and operated by outside contractor that converts treated sewage water to high-purity makeup for expanded gas-turbine plant with minimal environmental impact. Florida Power Corp. (FPC), St. Petersburg, Fla., faced various challenges when planning to expand the Intercession City gas-turbine plant located near Kissimmee, Fla. One challenge was dealing with water for NO{sub x} emissions reduction supplied from the Kissimmee sanitary sewage treatment plant. Another was to minimize or eliminate wastewater generated by chemical cleaning of the reverse-osmosis (RO) system envisioned for the plant. Because of the substantial capital investment needed to meet these challenges, FPC outsourced the design, construction, and operation of the water treatment system to Ecolochem Inc., Norfolk, VA. After three years of operation, the system is meeting all design requirements and is saving the utility about $250,000/yr.

  2. Expanding the NATO Movement Control Network

    DTIC Science & Technology

    2016-05-17

    stationed in Es- tonia, Latvia, Lithuania, and Poland, an opportunity to expand the Strong Europe movement network by as- signing its Soldiers to embed...Lithuania. Therefore, Poland drives the diplo- matic clearance process with its 30- day requirement because everything must cross its borders. The...millimeter rail gauge for its railroad network. Estonia, Latvia, and Lithuania all have the Russian rail gauge of 1,520 millimeters. In order to use

  3. Joule-Thomson expander and heat exchanger

    NASA Technical Reports Server (NTRS)

    Norman, R. H.

    1976-01-01

    The Joule-Thomson Expander and Heat Exchanger Program was initiated to develop an assembly (JTX) which consists of an inlet filter, counterflow heat exchanger, Joule-Thomson expansion device, and a low pressure jacket. The program objective was to develop a JTX which, when coupled to an open cycle supercritical helium refrigerating system (storage vessel), would supply superfluid helium (He II) at 2 K or less for cooling infrared detectors.

  4. Short wavelength striations on expanding plasma clouds

    SciTech Connect

    Winske, D.; Gary, S.P.

    1989-01-01

    The growth and evolution of short wavelength (expanding across an ambient magnetic field have been actively studied in recent years, both by means of experiments in the laboratory as well as in space and through numerical simulations. We review the relevant observations and simulations results, discuss the instability mechanism and related linear theory, and describe recent work to bring experiments and theory into better agreement. 30 refs., 6 figs.

  5. Metagenome of a Versatile Chemolithoautotroph from Expanding Oceanic Dead Zones

    SciTech Connect

    Walsh, David A.; Zaikova, Elena; Howes, Charles L.; Song, Young; Wright, Jody; Tringe, Susannah G.; Tortell, Philippe D.; Hallam, Steven J.

    2009-07-15

    Oxygen minimum zones (OMZs), also known as oceanic"dead zones", are widespread oceanographic features currently expanding due to global warming and coastal eutrophication. Although inhospitable to metazoan life, OMZs support a thriving but cryptic microbiota whose combined metabolic activity is intimately connected to nutrient and trace gas cycling within the global ocean. Here we report time-resolved metagenomic analyses of a ubiquitous and abundant but uncultivated OMZ microbe (SUP05) closely related to chemoautotrophic gill symbionts of deep-sea clams and mussels. The SUP05 metagenome harbors a versatile repertoire of genes mediating autotrophic carbon assimilation, sulfur-oxidation and nitrate respiration responsive to a wide range of water column redox states. Thus, SUP05 plays integral roles in shaping nutrient and energy flow within oxygen-deficient oceanic waters via carbon sequestration, sulfide detoxification and biological nitrogen loss with important implications for marine productivity and atmospheric greenhouse control.

  6. An Expanded Lateral Interactive Clonal Selection Algorithm and Its Application

    NASA Astrophysics Data System (ADS)

    Gao, Shangce; Dai, Hongwei; Zhang, Jianchen; Tang, Zheng

    Based on the clonal selection principle proposed by Burnet, in the immune response process there is no crossover of genetic material between members of the repertoire, i. e., there is no knowledge communication during different elite pools in the previous clonal selection models. As a result, the search performance of these models is ineffective. To solve this problem, inspired by the concept of the idiotypic network theory, an expanded lateral interactive clonal selection algorithm (LICS) is put forward. In LICS, an antibody is matured not only through the somatic hypermutation and the receptor editing from the B cell, but also through the stimuli from other antibodies. The stimuli is realized by memorizing some common gene segment on the idiotypes, based on which a lateral interactive receptor editing operator is also introduced. Then, LICS is applied to several benchmark instances of the traveling salesman problem. Simulation results show the efficiency and robustness of LICS when compared to other traditional algorithms.

  7. An Expanded Genomic Representation of the Phylum Cyanobacteria

    PubMed Central

    Soo, Rochelle M.; Skennerton, Connor T.; Sekiguchi, Yuji; Imelfort, Michael; Paech, Samuel J.; Dennis, Paul G.; Steen, Jason A.; Parks, Donovan H.; Tyson, Gene W.; Hugenholtz, Philip

    2014-01-01

    Molecular surveys of aphotic habitats have indicated the presence of major uncultured lineages phylogenetically classified as members of the Cyanobacteria. One of these lineages has recently been proposed as a nonphotosynthetic sister phylum to the Cyanobacteria, the Melainabacteria, based on recovery of population genomes from human gut and groundwater samples. Here, we expand the phylogenomic representation of the Melainabacteria through sequencing of six diverse population genomes from gut and bioreactor samples supporting the inference that this lineage is nonphotosynthetic, but not the assertion that they are strictly fermentative. We propose that the Melainabacteria is a class within the phylogenetically defined Cyanobacteria based on robust monophyly and shared ancestral traits with photosynthetic representatives. Our findings are consistent with theories that photosynthesis occurred late in the Cyanobacteria and involved extensive lateral gene transfer and extends the recognized functionality of members of this phylum. PMID:24709563

  8. Expanding the metabolic engineering toolbox: more options to engineer cells.

    PubMed

    Tyo, Keith E; Alper, Hal S; Stephanopoulos, Gregory N

    2007-03-01

    Metabolic engineering exploits an integrated, systems-level approach for optimizing a desired cellular property or phenotype; and great strides have been made within this scope and context during the past fifteen years. However, due to limitations in the concepts and techniques, these have relied on a focused, pathway-oriented view. Recent advances in 'omics' technologies and computational systems biology have brought the foundational systems approach of metabolic engineering into focus. At the same time, protein engineering and synthetic biology have expanded the breadth and precision of the methods available to metabolic engineers to improve strain properties. Examples are presented that illustrate this broader perspective of tools and concepts, including a recent approach for global transcriptional machinery engineering (gTME), which has demonstrated the ability to elicit multigenic transcriptional changes that have improved phenotypes compared with single-gene perturbations.

  9. Direct reprogramming of human fibroblasts to functional and expandable hepatocytes.

    PubMed

    Huang, Pengyu; Zhang, Ludi; Gao, Yimeng; He, Zhiying; Yao, Dan; Wu, Zhitao; Cen, Jin; Chen, Xiaotao; Liu, Changcheng; Hu, Yiping; Lai, Dongmei; Hu, Zhenlei; Chen, Li; Zhang, Ying; Cheng, Xin; Ma, Xiaojun; Pan, Guoyu; Wang, Xin; Hui, Lijian

    2014-03-06

    The generation of large numbers of functional human hepatocytes for cell-based approaches to liver disease is an important and unmet goal. Direct reprogramming of fibroblasts to hepatic lineages could offer a solution to this problem but so far has only been achieved with mouse cells. Here, we generated human induced hepatocytes (hiHeps) from fibroblasts by lentiviral expression of FOXA3, HNF1A, and HNF4A. hiHeps express hepatic gene programs, can be expanded in vitro, and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance. Upon transplantation into mice with concanavalin-A-induced acute liver failure and fatal metabolic liver disease due to fumarylacetoacetate dehydrolase (Fah) deficiency, hiHeps restore the liver function and prolong survival. Collectively, our results demonstrate successful lineage conversion of nonhepatic human cells into mature hepatocytes with potential for biomedical and pharmaceutical applications.

  10. Metagenome of a versatile chemolithoautotroph from expanding oceanic dead zones.

    PubMed

    Walsh, David A; Zaikova, Elena; Howes, Charles G; Song, Young C; Wright, Jody J; Tringe, Susannah G; Tortell, Philippe D; Hallam, Steven J

    2009-10-23

    Oxygen minimum zones, also known as oceanic "dead zones," are widespread oceanographic features currently expanding because of global warming. Although inhospitable to metazoan life, they support a cryptic microbiota whose metabolic activities affect nutrient and trace gas cycling within the global ocean. Here, we report metagenomic analyses of a ubiquitous and abundant but uncultivated oxygen minimum zone microbe (SUP05) related to chemoautotrophic gill symbionts of deep-sea clams and mussels. The SUP05 metagenome harbors a versatile repertoire of genes mediating autotrophic carbon assimilation, sulfur oxidation, and nitrate respiration responsive to a wide range of water-column redox states. Our analysis provides a genomic foundation for understanding the ecological and biogeochemical role of pelagic SUP05 in oxygen-deficient oceanic waters and its potential sensitivity to environmental changes.

  11. Expanding the metabolic engineering toolbox with directed evolution.

    PubMed

    Abatemarco, Joseph; Hill, Andrew; Alper, Hal S

    2013-12-01

    Cellular systems can be engineered into factories that produce high-value chemicals from renewable feedstock. Such an approach requires an expanded toolbox for metabolic engineering. Recently, protein engineering and directed evolution strategies have started to play a growing and critical role within metabolic engineering. This review focuses on the various ways in which directed evolution can be applied in conjunction with metabolic engineering to improve product yields. Specifically, we discuss the application of directed evolution on both catalytic and non-catalytic traits of enzymes, on regulatory elements, and on whole genomes in a metabolic engineering context. We demonstrate how the goals of metabolic pathway engineering can be achieved in part through evolving cellular parts as opposed to traditional approaches that rely on gene overexpression and deletion. Finally, we discuss the current limitations in screening technology that hinder the full implementation of a metabolic pathway-directed evolution approach.

  12. An expanded genomic representation of the phylum cyanobacteria.

    PubMed

    Soo, Rochelle M; Skennerton, Connor T; Sekiguchi, Yuji; Imelfort, Michael; Paech, Samuel J; Dennis, Paul G; Steen, Jason A; Parks, Donovan H; Tyson, Gene W; Hugenholtz, Philip

    2014-05-01

    Molecular surveys of aphotic habitats have indicated the presence of major uncultured lineages phylogenetically classified as members of the Cyanobacteria. One of these lineages has recently been proposed as a nonphotosynthetic sister phylum to the Cyanobacteria, the Melainabacteria, based on recovery of population genomes from human gut and groundwater samples. Here, we expand the phylogenomic representation of the Melainabacteria through sequencing of six diverse population genomes from gut and bioreactor samples supporting the inference that this lineage is nonphotosynthetic, but not the assertion that they are strictly fermentative. We propose that the Melainabacteria is a class within the phylogenetically defined Cyanobacteria based on robust monophyly and shared ancestral traits with photosynthetic representatives. Our findings are consistent with theories that photosynthesis occurred late in the Cyanobacteria and involved extensive lateral gene transfer and extends the recognized functionality of members of this phylum.

  13. Measurements of an expanding surface flashover plasma

    SciTech Connect

    Harris, J. R.

    2014-05-21

    A better understanding of vacuum surface flashover and the plasma produced by it is of importance for electron and ion sources, as well as advanced accelerators and other vacuum electronic devices. This article describes time-of-flight and biased-probe measurements made on the expanding plasma generated from a vacuum surface flashover discharge. The plasma expanded at velocities of 1.2–6.5 cm/μs, and had typical densities of 10{sup 10}–10{sup 12} cm{sup −3}. The expansion velocity of the plasma leading edge often exhibited a sharp increase at distances of about 50 mm from the discharge site. Comparison with biased-probe data suggests that, under most conditions, the plasma leading edge was dominated by negative ions, with the apparent increase in velocity being due to fast H{sup −} overtaking slower, heavier ions. In some cases, biased-probe data also showed abrupt discontinuities in the plasma energy distribution co-located with large changes in the intercepted plasma current, suggesting the presence of a shock in the leading edge of the expanding plasma.

  14. Expandable Metal Liner For Downhole Components

    DOEpatents

    Hall, David R.; Fox, Joe R.

    2004-10-05

    A liner for an annular downhole component is comprised of an expandable metal tube having indentations along its surface. The indentations are formed in the wall of the tube either by drawing the tube through a die, by hydroforming, by stamping, or roll forming and may extend axially, radially, or spirally along its wall. The indentations accommodate radial and axial expansion of the tube within the downhole component. The tube is inserted into the annular component and deformed to match an inside surface of the component. The tube may be expanded using a hydroforming process or by drawing a mandrel through the tube. The tube may be expanded in such a manner so as to place it in compression against the inside wall of the component. The tube is useful for improving component hydraulics, shielding components from contamination, inhibiting corrosion, and preventing wear to the downhole component during use. It may also be useful for positioning conduit and insulated conductors within the component. An insulating material may be disposed between the tube and the component in order to prevent galvanic corrosion of the downhole component.

  15. Expanding soft tissue with Osmed tissue expanders in the goat maxilla.

    PubMed

    Uijlenbroek, Henri J J; Liu, Yuelian; He, Jian Feng; Visscher, Corine; van Waas, Marinus A J; Wismeyer, Daniel

    2011-01-01

    soft tissue limitations are encountered in implant dentistry, due to the loss of alveolar bone. The aim of this study is to compare the outcome of soft tissue preparation using Osmed self-inflating soft tissue expanders with different in situ times in two implantation techniques. Osmed self-inflating soft tissue expanders were implanted in goats using a tunnel approach and a flap approach. The animals were sacrificed after 1h (controls) and 40 days (treated). A tattoo technique for stereographic measurements was used to look for soft tissue surface gain. Histological and histomorphometric analyses were performed to quantify and compare the changes in soft tissue volume and bone volume after 1h and 40 days of implantation. after 40 days, the expansion was visible and none of the goats had shown any inflammation. The space between the soft tissue and the bone was filled by the completely expanded expander and surrounding connective tissue. Between the test groups and the control groups, there was no histological difference in the structure of the soft tissue. all the tissue expanders expanded to their maximum size (2.8 times) and were a reliable product for creating a space between soft tissue and bone. The overlying soft tissue remained in excellent shape. There was no difference in the soft tissue volume and the bone volume between the tunnel and the flap approach after 40 days.

  16. Expanded mode lasers for telecommunications applications

    NASA Astrophysics Data System (ADS)

    Lealman, Ian F.

    This thesis describes the development of a long wavelength (1.55 μm) expanded mode semiconductor laser. The increased spot size of the laser improves both the coupling efficiency to cleaved fibre and fibre alignment tolerances and reduces packaging cost. In this type of device the strength of the waveguide is gradually reduced towards the front facet allowing the mode to adiabatically expand so that the laser mode is better matched in size to that of a cleaved fibre. This can be achieved by either reducing the refractive index of the guide or reducing the amount of material in the core. The structure chosen was a buried heterostructure laser that utilised a twin guide consisting of an upper higher refractive index guide (the active region of the laser) above a weak passive guide. The width of the active region was reduced along part of the device allowing the mode to expand into the weak underlying guide. The guide structure was optimised using a variable grid finite difference mode solver, and the taper length calculated by an approximation to Love's method. Detailed results are presented for the measured light-current characteristic, farfield and coupling loss to cleaved fibre. These coupling losses were compared to the calculated data thus allowing the waveguide design to be optimised. Several iterations in the design of the device were undertaken, with the aim of reducing the coupling loss to cleaved single mode fibre without significantly compromising the laser performance. The final device design had extremely low coupling losses as low as 1.2 dB to cleaved fibre. Finally, the positive impact this device had on passive alignment using a silicon motherboard is examined, and the application this technology to a range of other optoelectronic components is discussed.

  17. Transplantation of ex vivo expanded cord blood.

    PubMed

    Shpall, Elizabeth J; Quinones, Ralph; Giller, Roger; Zeng, Chan; Baron, Anna E; Jones, Roy B; Bearman, Scott I; Nieto, Yago; Freed, Brian; Madinger, Nancy; Hogan, Christopher J; Slat-Vasquez, Vicki; Russell, Peggy; Blunk, Betsy; Schissel, Deborah; Hild, Elaine; Malcolm, Janet; Ward, William; McNiece, Ian K

    2002-01-01

    Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.

  18. Entangling power of an expanding universe

    SciTech Connect

    Steeg, Greg Ver; Menicucci, Nicolas C.

    2009-02-15

    We show that entanglement can be used to detect spacetime curvature. Quantum fields in the Minkowski vacuum are entangled with respect to local field modes. This entanglement can be swapped to spatially separated quantum systems using standard local couplings. A single, inertial field detector in the exponentially expanding (de Sitter) vacuum responds as if it were bathed in thermal radiation in a Minkowski universe. We show that using two inertial detectors, interactions with the field in the thermal case will entangle certain detector pairs that would not become entangled in the corresponding de Sitter case. The two universes can thus be distinguished by their entangling power.

  19. Short wavelength striations on expanding plasma clouds

    NASA Technical Reports Server (NTRS)

    Winske, D.; Gary, S. P.

    1990-01-01

    The present evaluation of current understanding of the growth and evolution of less-than-1 ion gyroradius 'flute modes' on a plasma as it expands across and ambient magnetic field notes that the mechanism by which the instability is generated, and its approximate linear theory (encompassing nonlocal, finite-beta, and collisional effects), have reached a satisfactory degree of development. AMPTE Ba releases have been the bases of most of the observational studies. Substantial progress is also noted in the development of a nonlinear mode-coupling theory which can resolve remaining differences between theory and observation.

  20. Expanding health literacy: indigenous youth creating videos.

    PubMed

    Stewart, Suzanne; Riecken, Ted; Scott, Tish; Tanaka, Michele; Riecken, Janet

    2008-03-01

    How can creating videos contribute to expanding health literacy? This article describes a participatory action research project with a group of Canadian Indigenous youth and their teachers. As the youth explored their interests about health and wellness through the artistic creation of videos, they developed a critical consciousness about community, culture, confidence, and control. They became mobilized and obtained information about health and wellness that allowed for the development and expansion of their notion of health literacy that included cultural conceptions of health and wellness.

  1. Painful Na-channelopathies: an expanding universe.

    PubMed

    Waxman, Stephen G

    2013-07-01

    The universe of painful Na-channelopathies--human disorders caused by mutations in voltage-gated sodium channels--has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic 'model disorders' such as inherited erythromelalgia and channelopathy-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic.

  2. Expanding Slayer Statutes to Elder Abuse.

    PubMed

    Piel, Jennifer

    2015-09-01

    Common law has a dictum that people must not benefit from their crimes. In years past, states have enacted slayer rules to prevent killers from inheriting from their victims. The specific criteria and applicability of slayer rules vary by jurisdiction. Recently, several states, including Washington, have expanded their slayer rules to disqualify persons from inheriting if they have been involved in abuse or financial exploitation of the deceased. Reviewed herein are the abuse disinheritance laws, the relationship of the laws to concepts of testamentary capacity and undue influence, and the relevance to forensic psychiatric evaluations.

  3. Expanding Lorentzian Wormholes in R2 Gravity

    NASA Astrophysics Data System (ADS)

    Sajadi, S. N.; Riazi, N.

    2011-10-01

    We present traversable, Lorentzian wormholes in the framework of R^{2} gravity. These wormholes are obtained by assuming constant Ricci scalar and trace-less equation of state. The metric is asymptotically RW, and locally that of a Lorentzian wormhole. Dynamics of the cosmological background, as well as the expanding wormhole are discussed. Weak energy condition near the wormhole throat is also examined. It is shown that the positive energy density condition can be satisfied all-over a spacelike hypersurface at large enough cosmological times and small enough, positive cosmological constant.

  4. Emergence of oscillons in an expanding background

    SciTech Connect

    Farhi, E.; Guth, A. H.; Iqbal, N.; Graham, N.; Rosales, R. R.; Stamatopoulos, N.

    2008-04-15

    We consider a (1+1) dimensional scalar field theory that supports oscillons, which are localized, oscillatory, stable solutions to nonlinear equations of motion. We study this theory in an expanding background and show that oscillons now lose energy, but at a rate that is exponentially small when the expansion rate is slow. We also show numerically that a universe that starts with (almost) thermal initial conditions will cool to a final state where a significant fraction of the energy of the universe--on the order of 50%--is stored in oscillons. If this phenomenon persists in realistic models, oscillons may have cosmological consequences.

  5. FOAM: Expanding the horizons of climate modeling

    SciTech Connect

    Tobis, M.; Foster, I.T.; Schafer, C.M.

    1997-10-01

    We report here on a project that expands the applicability of dynamic climate modeling to very long time scales. The Fast Ocean Atmosphere Model (FOAM) is a coupled ocean atmosphere model that incorporates physics of interest in understanding decade to century time scale variability. It addresses the high computational cost of this endeavor with a combination of improved ocean model formulation, low atmosphere resolution, and efficient coupling. It also uses message passing parallel processing techniques, allowing for the use of cost effective distributed memory platforms. The resulting model runs over 6000 times faster than real time with good fidelity, and has yielded significant results.

  6. Expandable tubulars for use in geologic structures

    DOEpatents

    Spray, Jeffery A.; Svedeman, Steven; Walter, David; Mckeighan, Peter; Siebanaler, Shane; Dewhurst, Peter; Hobson, Steven; Foss, Doug; Wirz, Holger; Sharpe, Aaron; Apostal, Michael

    2014-08-12

    An expandable tubular includes a plurality of leaves formed from sheet material that have curved surfaces. The leaves extend around a portion or fully around the diameter of the tubular structure. Some of the adjacent leaves of the tubular are coupled together. The tubular is compressed to a smaller diameter so that it can be inserted through previously deployed tubular assemblies. Once the tubular is properly positioned, it is deployed and coupled or not coupled to a previously deployed tubular assembly. The tubular is useful for all types of wells and boreholes.

  7. Common but different: The expanding realm of Cladosporium.

    PubMed

    Bensch, K; Groenewald, J Z; Braun, U; Dijksterhuis, J; de Jesús Yáñez-Morales, M; Crous, P W

    2015-09-01

    The genus Cladosporium (Cladosporiaceae, Dothideomycetes), which represents one of the largest genera of dematiaceous hyphomycetes, has been intensively investigated during the past decade. In the process, three major species complexes (C. cladosporioides, C. herbarum and C. sphaerospermum) were resolved based on morphology and DNA phylogeny, and a monographic revision of the genus (s. lat.) published reflecting the current taxonomic status quo. In the present study a further 19 new species are described based on phylogenetic characters (nuclear ribosomal RNA gene operon, including the internal transcribed spacer regions ITS1 and ITS2, as well as partial actin and translation elongation factor 1-α gene sequences) and morphological differences. For a selection of the species with ornamented conidia, scanning electron microscopic photos were prepared to illustrate the different types of surface ornamentation. Surprisingly, during this study Cladosporium ramotenellum was found to be a quite common saprobic species, being widely distributed and occurring on various substrates. Therefore, an emended species description is provided. Furthermore, the host range and distribution data for several previously described species are also expanded.

  8. Common but different: The expanding realm of Cladosporium

    PubMed Central

    Bensch, K.; Groenewald, J.Z.; Braun, U.; Dijksterhuis, J.; de Jesús Yáñez-Morales, M.; Crous, P.W.

    2015-01-01

    The genus Cladosporium (Cladosporiaceae, Dothideomycetes), which represents one of the largest genera of dematiaceous hyphomycetes, has been intensively investigated during the past decade. In the process, three major species complexes (C. cladosporioides, C. herbarum and C. sphaerospermum) were resolved based on morphology and DNA phylogeny, and a monographic revision of the genus (s. lat.) published reflecting the current taxonomic status quo. In the present study a further 19 new species are described based on phylogenetic characters (nuclear ribosomal RNA gene operon, including the internal transcribed spacer regions ITS1 and ITS2, as well as partial actin and translation elongation factor 1-α gene sequences) and morphological differences. For a selection of the species with ornamented conidia, scanning electron microscopic photos were prepared to illustrate the different types of surface ornamentation. Surprisingly, during this study Cladosporium ramotenellum was found to be a quite common saprobic species, being widely distributed and occurring on various substrates. Therefore, an emended species description is provided. Furthermore, the host range and distribution data for several previously described species are also expanded. PMID:26955200

  9. Retinoic acid expands the evolutionarily reduced dentition of zebrafish

    PubMed Central

    Seritrakul, Pawat; Samarut, Eric; Lama, Tenzing T. S.; Gibert, Yann; Laudet, Vincent; Jackman, William R.

    2012-01-01

    Zebrafish lost anterior teeth during evolution but retain a posterior pharyngeal dentition that requires retinoic acid (RA) cell-cell signaling for its development. The purposes of this study were to test the sufficiency of RA to induce tooth development and to assess its role in evolution. We found that exposure of embryos to exogenous RA induces a dramatic anterior expansion of the number of pharyngeal teeth that later form and shifts anteriorly the expression patterns of genes normally expressed in the posterior tooth-forming region, such as pitx2 and dlx2b. After RA exposure, we also observed a correlation between cartilage malformations and ectopic tooth induction, as well as abnormal cranial neural crest marker gene expression. Additionally, we observed that the RA-induced zebrafish anterior teeth resemble in pattern and number the dentition of fish species that retain anterior pharyngeal teeth such as medaka but that medaka do not express the aldh1a2 RA-synthesizing enzyme in tooth-forming regions. We conclude that RA is sufficient to induce anterior ectopic tooth development in zebrafish where teeth were lost in evolution, potentially by altering neural crest cell development, and that changes in the location of RA synthesis correlate with evolutionary changes in vertebrate dentitions.—Seritrakul, P., Samarut, E., Lama, T. T. S., Gibert, Y., Laudet, V., Jackman, W. R. Retinoic acid expands the evolutionarily reduced dentition of zebrafish. PMID:22942074

  10. Expanding the mutation and clinical spectrum of Roberts syndrome.

    PubMed

    Afifi, Hanan H; Abdel-Salam, Ghada M H; Eid, Maha M; Tosson, Angie M S; Shousha, Wafaa Gh; Abdel Azeem, Amira A; Farag, Mona K; Mehrez, Mennat I; Gaber, Khaled R

    2016-07-01

    Roberts syndrome and SC phocomelia syndrome are rare autosomal recessive genetic disorders representing the extremes of the spectrum of severity of the same condition, caused by mutations in ESCO2 gene. We report three new patients with Roberts syndrome from three unrelated consanguineous Egyptian families. All patients presented with growth retardation, mesomelic shortening of the limbs more in the upper than in the lower limbs and microcephaly. Patients were subjected to clinical, cytogenetic and radiologic examinations. Cytogenetic analysis showed the characteristic premature separation of centromeres and puffing of heterochromatic regions. Further, sequencing of the ESCO2 gene identified a novel mutation c.244_245dupCT (p.T83Pfs*20) in one family besides two previously reported mutations c.760_761insA (p.T254Nfs*27) and c.764_765delTT (p.F255Cfs*25). All mutations were in homozygous state, in exon 3. The severity of the mesomelic shortening of the limbs and craniofacial anomalies showed variability among patients. Interestingly, patient 1 had abnormal skin hypopigmentation. Serial fetal ultrasound examinations and measurements of long bones diagnosed two affected fetuses in two of the studied families. A literature review and case comparison was performed. In conclusion, we report a novel ESCO2 mutation and expand the clinical spectrum of Roberts syndrome.

  11. Unintended Consequences of Expanding the Genetic Alphabet.

    PubMed

    Pollum, Marvin; Ashwood, Brennan; Jockusch, Steffen; Lam, Minh; Crespo-Hernández, Carlos E

    2016-09-14

    The base pair d5SICS·dNaM was recently reported to incorporate and replicate in the DNA of a modified strain of Escherichia coli, thus making the world's first stable semisynthetic organism. This newly expanded genetic alphabet may allow organisms to store considerably more information in order to translate proteins with unprecedented enzymatic activities. Importantly, however, there is currently no knowledge of the photochemical properties of d5SICS or dNaM-properties that are central to the chemical integrity of cellular DNA. In this contribution, it is shown that excitation of d5SICS or dNaM with near-visible light leads to efficient trapping of population in the nucleoside's excited triplet state in high yield. Photoactivation of these long-lived, reactive states is shown to photosensitize cells, leading to the generation of reactive oxygen species and to a marked decrease in cell proliferation, thus warning scientists of the potential phototoxic side effects of expanding the genetic alphabet.

  12. Tracing transient charges in expanding clusters

    NASA Astrophysics Data System (ADS)

    Schütte, Bernd; Vrakking, Marc J. J.; Rouzée, Arnaud

    2017-06-01

    We study transient charges formed in methane clusters following ionization by intense near-infrared laser pulses. Cluster ionization by 400-fs (I =1 ×1014 W /cm2) pulses is highly efficient, resulting in the observation of a dominant C3 + ion contribution. The C4 + ion yield is very small but is strongly enhanced by applying a time-delayed weak near-infrared pulse. We conclude that most of the valence electrons are removed from their atoms during the laser-cluster interaction and that electrons from the nanoplasma recombine with ions and populate Rydberg states when the cluster expands, leading to a decrease of the average charge state of individual ions. Furthermore, we find clear bound-state signatures in the electron kinetic energy spectrum, which we attribute to Auger decay taking place in expanding clusters. Such nonradiative processes lead to an increase of the final average ion charge state that is measured in experiments. Our results suggest that it is crucial to include both recombination and nonradiative decay processes for the understanding of recorded ion charge spectra.

  13. Expanding ester biosynthesis in Escherichia coli

    PubMed Central

    Rodriguez, Gabriel M; Tashiro, Yohei; Atsumi, Shota

    2015-01-01

    To expand the capabilities of whole-cell biocatalysis, we have engineered Escherichia coli to produce various esters. The alcohol O-acyltransferase (ATF) class of enzyme uses acyl-CoA units for ester formation. The release of free CoA upon esterification with an alcohol provides the free energy to facilitate ester formation. The diversity of CoA molecules found in nature in combination with various alcohol biosynthetic pathways allows for the biosynthesis of a multitude of esters. Small to medium volatile esters have extensive applications in the flavor, fragrance, cosmetic, solvent, paint and coating industries. The present work enables the production of these compounds by designing several ester pathways in E. coli. The engineered pathways generated acetate esters of ethyl, propyl, isobutyl, 2-methyl-1-butyl, 3-methyl-1-butyl and 2-phenylethyl alcohols. In particular, we achieved high-level production of isobutyl acetate from glucose (17.2 g l−1). This strategy was expanded to realize pathways for tetradecyl acetate and several isobutyrate esters. PMID:24609358

  14. Interactive Exploration for Continuously Expanding Neuron Databases.

    PubMed

    Li, Zhongyu; Metaxas, Dimitris N; Lu, Aidong; Zhang, Shaoting

    2017-02-15

    This paper proposes a novel framework to help biologists explore and analyze neurons based on retrieval of data from neuron morphological databases. In recent years, the continuously expanding neuron databases provide a rich source of information to associate neuronal morphologies with their functional properties. We design a coarse-to-fine framework for efficient and effective data retrieval from large-scale neuron databases. In the coarse-level, for efficiency in large-scale, we employ a binary coding method to compress morphological features into binary codes of tens of bits. Short binary codes allow for real-time similarity searching in Hamming space. Because the neuron databases are continuously expanding, it is inefficient to re-train the binary coding model from scratch when adding new neurons. To solve this problem, we extend binary coding with online updating schemes, which only considers the newly added neurons and update the model on-the-fly, without accessing the whole neuron databases. In the fine-grained level, we introduce domain experts/users in the framework, which can give relevance feedback for the binary coding based retrieval results. This interactive strategy can improve the retrieval performance through re-ranking the above coarse results, where we design a new similarity measure and take the feedback into account. Our framework is validated on more than 17,000 neuron cells, showing promising retrieval accuracy and efficiency. Moreover, we demonstrate its use case in assisting biologists to identify and explore unknown neurons.

  15. Cam shaft with expanded hollow shaft

    SciTech Connect

    Hughes, R.W.; Brisson, R.H.; Brisson, G.R.

    1987-09-15

    This patent describes a camshaft having lobes with irregularly shaped apertures spaced along the longitudinal axis of a hollow tubular shaft. The lobes are orientated radially and axially in predetermined positions along the hollow tubular shaft. The camshaft is characterized by the walls of the hollow shaft expanded outwardly into aperture portions in irregular engagement with the interior of the apertures of the lobes and the walls expanded outwardly radially farther into ballooned portions between adjacent lobes to create corresponding outside and inside shoulders extending between the aperture and ballooned portions. The outside shoulders are disposed immediately adjacent and abutting each side of the lobes circumferentially about the apertures therein to secure the lobes axially upon the shaft, the inside shoulders disposed directly opposite the outside shoulders to that shoulder extend annularly about each end of each of the apertures and the ballooned portions extend between shoulders at adjacent lobes, the exterior circumferences of the lobes being furnished to closer tolerances than the interior apertures and the exterior surfaces of the lobes being positioned radially relative to the longitudinal axis with the radial positions of the interior apertures being offset among adjacent lobes.

  16. Expanding ester biosynthesis in Escherichia coli.

    PubMed

    Rodriguez, Gabriel M; Tashiro, Yohei; Atsumi, Shota

    2014-04-01

    To expand the capabilities of whole-cell biocatalysis, we have engineered Escherichia coli to produce various esters. The alcohol O-acyltransferase (ATF) class of enzyme uses acyl-CoA units for ester formation. The release of free CoA upon esterification with an alcohol provides the free energy to facilitate ester formation. The diversity of CoA molecules found in nature in combination with various alcohol biosynthetic pathways allows for the biosynthesis of a multitude of esters. Small to medium volatile esters have extensive applications in the flavor, fragrance, cosmetic, solvent, paint and coating industries. The present work enables the production of these compounds by designing several ester pathways in E. coli. The engineered pathways generated acetate esters of ethyl, propyl, isobutyl, 2-methyl-1-butyl, 3-methyl-1-butyl and 2-phenylethyl alcohols. In particular, we achieved high-level production of isobutyl acetate from glucose (17.2 g l(-1)). This strategy was expanded to realize pathways for tetradecyl acetate and several isobutyrate esters.

  17. Familiarity expands space and contracts time

    PubMed Central

    Spiers, Hugo

    2016-01-01

    ABSTRACT When humans draw maps, or make judgments about travel‐time, their responses are rarely accurate and are often systematically distorted. Distortion effects on estimating time to arrival and the scale of sketch‐maps reveal the nature of mental representation of time and space. Inspired by data from rodent entorhinal grid cells, we predicted that familiarity to an environment would distort representations of the space by expanding the size of it. We also hypothesized that travel‐time estimation would be distorted in the same direction as space‐size, if time and space rely on the same cognitive map. We asked international students, who had lived at a college in London for 9 months, to sketch a south‐up map of their college district, estimate travel‐time to destinations within the area, and mark their everyday walking routes. We found that while estimates for sketched space were expanded with familiarity, estimates of the time to travel through the space were contracted with familiarity. Thus, we found dissociable responses to familiarity in representations of time and space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27770476

  18. Historical Notes on the Expanding Universe

    NASA Technical Reports Server (NTRS)

    Way, Michael J.; Belenkyi, Ari; Nussbaumer, Harry; Peacock, John

    2014-01-01

    The article Measuring the Hubble constant by Mario Livio and Adam Riess (Physics Today, October 2013, page 41) reviewed studies of the expanding universe from the 1920s to the present. Although the history of the subject underwent considerable compression to fit the length of a magazine article, we think it may leave a misleading impression of some of the key steps to our current understanding. We therefore offer the following clarifications. Most significantly, papers by Arthur Eddington and by Willem de Sitter in 1930, who successfully promoted Georges Lematres 1927 article for the Scientific Society of Brussels, effected a paradigm shift in interpretation of extragalactic redshifts in 1930. Before then, the astronomical community was generally unaware of the existence of nonstatic cosmological solutions and did not broadly appreciate that redshifts could be thought of locally as Doppler shifts in an expanding matter distribution. Certainly, in 1929 Edwin Hubble referred only to the de Sitter solution of 1917. At the time, the relation between distance and redshift predicted in that model was generally seen purely as a manifestation of static spacetime curvature.

  19. Familiarity expands space and contracts time.

    PubMed

    Jafarpour, Anna; Spiers, Hugo

    2017-01-01

    When humans draw maps, or make judgments about travel-time, their responses are rarely accurate and are often systematically distorted. Distortion effects on estimating time to arrival and the scale of sketch-maps reveal the nature of mental representation of time and space. Inspired by data from rodent entorhinal grid cells, we predicted that familiarity to an environment would distort representations of the space by expanding the size of it. We also hypothesized that travel-time estimation would be distorted in the same direction as space-size, if time and space rely on the same cognitive map. We asked international students, who had lived at a college in London for 9 months, to sketch a south-up map of their college district, estimate travel-time to destinations within the area, and mark their everyday walking routes. We found that while estimates for sketched space were expanded with familiarity, estimates of the time to travel through the space were contracted with familiarity. Thus, we found dissociable responses to familiarity in representations of time and space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  20. Expanding Global Mindedness through a 4-H International Village

    ERIC Educational Resources Information Center

    Seal, Susan D.; Peterson, Donna J.; Iwata, Chieko; Kobia, Caroline; Reddy, Raja

    2017-01-01

    With expanding global interdependence, it is vital that 4-H youths learn more about the ever-increasing diverse cultures in their own communities as well as expand their global mindedness and understanding of globalization. The 4-H International Village (a) offers a comfortable yet engaging avenue for youths to expand their knowledge of and…

  1. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  2. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  3. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  4. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  5. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  6. 46 CFR 56.30-15 - Expanded or rolled joints.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Expanded or rolled joints. 56.30-15 Section 56.30-15... APPURTENANCES Selection and Limitations of Piping Joints § 56.30-15 Expanded or rolled joints. (a) Expanded or rolled joints may be used where experience or test has demonstrated that the joint is suitable for the...

  7. 46 CFR 56.30-15 - Expanded or rolled joints.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Expanded or rolled joints. 56.30-15 Section 56.30-15... APPURTENANCES Selection and Limitations of Piping Joints § 56.30-15 Expanded or rolled joints. (a) Expanded or rolled joints may be used where experience or test has demonstrated that the joint is suitable for the...

  8. 46 CFR 56.30-15 - Expanded or rolled joints.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Expanded or rolled joints. 56.30-15 Section 56.30-15... APPURTENANCES Selection and Limitations of Piping Joints § 56.30-15 Expanded or rolled joints. (a) Expanded or rolled joints may be used where experience or test has demonstrated that the joint is suitable for the...

  9. The Expanding Marketplace for Applied Geophysics

    NASA Astrophysics Data System (ADS)

    Carlson, N.; Sirles, P.

    2012-12-01

    While the image of geophysics for the proverbial "layman" often seems limited to volcanoes and earthquakes, and to the geoscientist this image enlarges to include oil or minerals exploration and whole earth studies, there has been a steady increase in the application of geophysics into the realm of "daily life", such as real estate deals, highway infrastructure, and flood protection. This expansion of applications can be attributed to the improved economics from advances in equipment and interpretation. Traditional geophysical methods that at one time often only fit within the budgets of oil, gas, and minerals exploration programs can now be economically applied to much smaller scale needs like contaminant mapping, landfill delineation, and levee investigations. A real-world, economic example of this expanding marketplace is our company, which began very small and was aimed almost exclusively at the minerals exploration market. Most of our growth has been in the last 10 years, when we have expanded to five offices and a staff with almost 40 geoscientist degrees (21 in geophysics); much of this growth has been in the non-oil, non-minerals arenas. While much of our work still includes minerals exploration, other projects this year include wind-farm foundation studies, cavity detection above underground nuclear tests, landfill studies, acid mine drainage problems, and leaks in evaporation ponds. A methodology example of this expanding market is the induced polarization (IP) survey, once primarily used for minerals exploration, particularly large porphyry copper deposits, but now efficient enough to also use in environmental studies. The IP method has been particularly useful in delineating and characterizing old, poorly documented landfills, and recent research suggests it may also be useful in monitoring the accelerated biodegradation processes used in some cases to rehabilitate the sites. Compared to temperature monitoring systems, IP may be more useful in providing

  10. Optical cavity resonator in an expanding universe

    NASA Astrophysics Data System (ADS)

    Kopeikin, Sergei M.

    2015-02-01

    We study the cosmological evolution of frequency of a standing electromagnetic wave in a resonant optical cavity placed to the expanding manifold described by the Robertson-Walker metric. Because of the Einstein principle of equivalence (EEP), one can find a local coordinate system (a local freely falling frame), in which spacetime is locally Minkowskian. However, due to the conformal nature of the Robertson-Walker metric the conventional transformation to the local inertial coordinates introduces ambiguity in the physical interpretation of the local time coordinate, . Therefore, contrary to a common-sense expectation, a straightforward implementation of EEP alone does not allow us to unambiguously decide whether atomic clocks based on quantum transitions of atoms, ticks at the same rate as the clocks based on electromagnetic modes of a cavity. To resolve this ambiguity we have to analyse the cavity rigidity and the oscillation of its electromagnetic modes in an expanding universe by employing the full machinery of the Maxwell equations irrespectively of the underlying theory of gravity. We proceed in this way and found out that the size of the cavity and the electromagnetic frequency experience an adiabatic drift in conformal (unphysical) coordinates as the universe expands in accordance with the Hubble law. We set up the oscillation equation for the resonant electromagnetic modes, solve it by the WKB approximation, and reduce the coordinate-dependent quantities to their counterparts measured by a local observer who counts time with atomic clock. The solution shows that there is a perfect mutual cancellation of the adiabatic drift of cavity's frequency by space transformation to local coordinates and the time counted by the clocks based on electromagnetic modes of cavity has the same rate as that of atomic clocks. We conclude that if general relativity is correct and the local expansion of space is isotropic there should be no cosmological drift of frequency of a

  11. Expression of the leukemia-associated CBF{beta}/SMMHC chimeric gene causes transformation of 3T3 cells

    SciTech Connect

    Hajra, A.; Liu, P.; Collins, E.S.

    1994-09-01

    A pericentric inversion of chromosome 16 (inv(16)(p13;q22)) is consistently seen in acute myeloid leukemia of the M4Eo subtype. This inversion fuses almost the entire coding region of the gene encoding of the {beta} subunit of the heterodimeric transcription factor CBF/PEBP2 to the region of the MYH11 gene encoding the rod domain for the smooth muscle myosin heavy chain (SMMHC). To investigate the biological properties of the CBF{beta}/SMMHC fusion protein, we have generated 3T3 cell lines that stably express the CBF{beta}/SMMHC chimeric cDNA or the normal, nonchimeric CBF{beta} and SMMHC cDNAs. 3T3 cells expressing CBF{beta}/SMMHC acquire a transformed phenotype, as indicated by altered cell morphology, formation of foci, and growth in soft agar. Cells constitutively overexpressing the normal CBF{beta} cDNA or the rod region of SMMHC remain nontransformed. Western blot analysis using antibodies to CBF{beta} and the SMMHC rod demonstrates that stably transfected cells express the appropriate chimeric or normal protein. Electrophoretic mobility shift assays reveal that cells transformed by the chimeric cDNA do not have a CBF-DNA complex of the expected mobility, but instead contain a large complex with CBF DNA-binding activity that fails to migrate out of the gel wells. In order to define the regions of CBF{beta}/SMMHC necessary for 3T3 transformation, we have stably transfected cells with mutant CBF{beta}/SMMHC cDNAs containing various deletions of the coding region. Analysis of these cell lines indicates that the transformation property of CBF{beta}/SMMHC requires regions of CBF{beta} known to be necessary for association with the DNA-binding CBF{alpha} subunit, and also requires an intact SMMHC carboxyl terminus, which is necessary for formation of the coiled coil domain of the myosin rod.

  12. Overexpression of PaFT gene in the wild orchid Phalaenopsis amabilis (L.) Blume

    NASA Astrophysics Data System (ADS)

    Semiarti, Endang; Mercuriani, Ixora S.; Rizal, Rinaldi; Slamet, Agus; Utami, Bekti S.; Bestari, Ida A.; Aziz-Purwantoro, Moeljopawiro, S.; Jang, Soenghoe; Machida, Y.; Machida, C.

    2015-09-01

    To shorten vegetative stage and induce transition from vegetative to reproductive stage in orchids, we overexpressed Phalaenopsis amabilis Flowering LocusT (PaFT) gene under the control of Ubiquitin promoter into protocorm of Indonesian Wild Orchid Phalaenopsis amabilis (L.) Blume. The dynamic expression of vegetative gene Phalaenopsis Homeobox1 (POH1) and flowering time gene PaFT has been analyzed. Accumulation of mRNA was detected in shoot and leaves of both transgenic and non transgenic plants by using Reverse transcriptase-PCR (RT-PCR) with specific gene primers for POH1 and PaFT in 24 months old plants. To analyze the POH1 and PaFT genes, three pairs of degenerate primers PaFT degF1R1, F2R2 and F3R3 that amplified 531 bp PaFT cDNA were used. We detected 700 bp PaFTcDNA from leaves and shoots of transgenic plants, but not in NT plants. POH1 mRNA was detected in plants. PaFT protein consists of Phospatidyl Ethanolamine-Binding Protein (PEBP) in interval base 73-483 and CETS family protein at base 7-519, which are important motif for transmembrane protein. We inserted Ubipro::PaFT/pGAS101 into P. amabilis protocorm using Agrobacterium. Analysis of transgenic plants showed that PaFTmRNA was accumulated in leaves of 12 months after sowing, although it is not detected in non transgeic plants. Compare to the wild type (NT plants), ectopic expression of PaFT shows alter phenotype as follows: 31% normal, 19% with short-wavy leaves, 5% form rosette leaves and 45% produced multishoots. Analysis of protein profiles of trasgenic plants showed that a putative PaFT protein (MW 19,7 kDa) was produced in 1eaves and shoots.This means that at 12 months, POH1 gene expression gradually decreased/negatively regulated, the expression of PaFT gene was activated, although there is no flower initiation yet. Some environmental factors might play a role to induce inflorescens. This experiment is in progress.

  13. Financing Expanded Learning Time in Schools: A Look at Five District-Expanded Time Schools

    ERIC Educational Resources Information Center

    Kaplan, Claire; Farbman, David A.; Deich, Sharon; Padgette, Heather Clapp

    2014-01-01

    Over the last several years, public education in the U.S. has experienced a remarkable growth in the number of schools that have expanded their schedules beyond the conventional calendar of 180 6.5-hour days. Spurred by significant policy activity at the federal, state, and local levels, more and more educators have capitalized on opportunities to…

  14. Expandable pallet for space station interface attachments

    NASA Technical Reports Server (NTRS)

    Wesselski, Clarence J. (Inventor)

    1989-01-01

    A foldable expandable pallet having a basic square configuration is disclosed. Each pallet is comprised of a plurality of struts, joined together by node point fittings to make a rigid structure. Some of the struts have hinge fittings and are spring loaded to permit collapse of the module for stowage and transport to a space station. Dimensions of the pallet are selected to provide convenient, closely spaced attachment points between the relatively widely spaced trusses of a space station platform. A pallet is attached to a truss at four points; one close fitting hole; two oversize holes; and a slot; to allow for thermal expansion/contraction and for manufacturing tolerances. Applications of the pallet include its use in rotary or angular joints; servicing of splints; with gridded plates; as an instrument mounting bases; and as a roadbed for a Mobile Service Center (MSC).

  15. High temperature expanding cement composition and use

    DOEpatents

    Nelson, Erik B.; Eilers, Louis H.

    1982-01-01

    A hydratable cement composition useful for preparing a pectolite-containing expanding cement at temperatures above about 150.degree. C. comprising a water soluble sodium salt of a weak acid, a 0.1 molar aqueous solution of which salt has a pH of between about 7.5 and about 11.5, a calcium source, and a silicon source, where the atomic ratio of sodium to calcium to silicon ranges from about 0.3:0.6:1 to about 0.03:1:1; aqueous slurries prepared therefrom and the use of such slurries for plugging subterranean cavities at a temperature of at least about 150.degree. C. The invention composition is useful for preparing a pectolite-containing expansive cement having about 0.2 to about 2 percent expansion, by volume, when cured at at least 150.degree. C.

  16. [Measurement of Affect Regulation Styles (MARS) expanded].

    PubMed

    Rovira, Darío Páez; Martínez Sánchez, Francisco; Sevillano Triguero, Verónica; Mendiburo Seguel, Andrés; Campos, Miriam

    2012-05-01

    An expanded Spanish version of the Measure of Affect Regulation Styles (MARS), was applied to episodes of anger and sadness, in a sample of 355 graduate students from Chile, Spain, and Mexico. The study examines the association between affective regulation, adaptation to episodes and dispositional coping and emotional regulation, and psychological well-being. With regard to perceived improvement of adaptive goals, the following adaptive affect regulation strategies were confirmed: Instrumental coping, seeking social support, positive reappraisal, distraction, rumination, self-comfort, self-control, and emotional expression were functional; whereas inhibition and suppression were dysfunctional. Adaptive strategies were positively associated with psychological well-being, reappraisal and humor as a coping strategy. Negative associations were found between adaptive strategies and suppression and alexithymia. Maladaptive strategies show the opposite profile. Confrontation, instrumental coping, social support as well as social isolation were more frequently found in anger, an approach emotion.

  17. Expandable and reconfigurable instrument node arrays

    NASA Technical Reports Server (NTRS)

    Hilliard, Lawrence M. (Inventor); Deshpande, Manohar (Inventor)

    2012-01-01

    An expandable and reconfigurable instrument node includes a feature detection means and a data processing portion in communication with the feature detection means, the data processing portion configured and disposed to process feature information. The instrument node further includes a phase locked loop (PLL) oscillator in communication with the data processing portion, the PLL oscillator configured and disposed to provide PLL information to the processing portion. The instrument node further includes a single tone transceiver and a pulse transceiver in communication with the PLL oscillator, the single tone transceiver configured and disposed to transmit or receive a single tone for phase correction of the PLL oscillator and the pulse transceiver configured and disposed to transmit and receive signals for phase correction of the PLL oscillator. The instrument node further includes a global positioning (GPA) receiver in communication with the processing portion, the GPS receiver configured and disposed to establish a global position of the instrument node.

  18. Expandable pallet for space station interface attachments

    NASA Technical Reports Server (NTRS)

    Wesselski, Clarence J. (Inventor)

    1988-01-01

    Described is a foldable expandable pallet for Space Station interface attachments with a basic square configuration. Each pallet consists of a series of struts joined together by node point fittings to make a rigid structure. The struts have hinge fittings which are spring loaded to permit collapse of the module for stowage transport to a Space Station in the payload bay of the Space Shuttle, and development on orbit. Dimensions of the pallet are selected to provide convenient, closely spaced attachment points between the node points of the relatively widely spaced trusses of a Space Station platform. A pallet is attached to a strut at four points: one close fitting hole, two oversize holes, and a slot to allow for thermal expansion/contraction and for manufacturing tolerances. Applications of the pallet include its use in rotary or angular joints; servicing of splints; with gridded plates; as instrument mounting bases; and as a roadbed for a Mobile Service Center (MSC).

  19. Microfluidics Expanding the Frontiers of Microbial Ecology

    PubMed Central

    Rusconi, Roberto; Garren, Melissa; Stocker, Roman

    2014-01-01

    The ability afforded by microfluidics to observe the behaviors of microbes in highly controlled and confined microenvironments, across scales from a single cell to mixed communities, has significantly contributed to expand the frontiers of microbial ecology over the last decade. Spatially and temporally varying distributions of organisms and chemical cues that mimic natural microbial habitats can now be established by exploiting physics at the micrometer scale and by incorporating structures with specific geometries and materials. Here we review applications of microfluidics that have resulted in highly insightful discoveries on fundamental aspects of microbial life, ranging from growth and sensing to cell-cell interactions and population dynamics. We anticipate that this flexible, multidisciplinary technology will continue to facilitate discoveries regarding the ecology of microorganisms and help uncover strategies to control phenomena such as biofilm formation and antibiotic resistance. PMID:24773019

  20. An Expanded View of Progressive Cardiorenal Disorders.

    PubMed

    Re, Richard N

    2016-06-01

    Chronic renal diseases and congestive heart failure are progressive disorders, which cannot be completely controlled by established therapies. It has been argued that intracrine biology involving the formation of self-sustaining intracrine regulatory loops accounts for the progression of these disorders and for the inability of standard therapies to stop disease spread. The renin-angiotensin system is a prime candidate to be involved in any such process, and an amplifying role for mineralocorticoid activation is also consistent with this view. Here, the notion of intracrine participation in congestive heart failure and chronic renal disease is expanded to include consideration of the participation of other intracrines including transforming growth factor beta 1, parathyroid hormone-related protein and vascular endothelial growth factor among others. The possibility that intracrine expression patterns account for disease phenotypes is explored. The therapeutic implications of this view are discussed. Copyright © 2016. Published by Elsevier Inc.

  1. The law's interface with expanding technology

    NASA Technical Reports Server (NTRS)

    Green, H. P.

    1972-01-01

    The role of the law in technology assessment is described in generalized terms of a legal system as it confronts expanding technology. The functions of a technology assessment are considered to be twofold; provide for legislative action designed to channel technological advance along lines which are regarded as optimal from the standpoint of society's interests; and encourage and promote legislative action which will deal decisively with the potential disruptions and injuries caused by technology at a much earlier stage of the growth of the technology than is feasible under the present legal system. It is concluded that since new law always has a disruptive effect on expectations and commitments arrived at under old law, it is generally desirable that new legislation should make the least possible change in the law consistant with accomplishing the desired objective.

  2. Expandable mixing section gravel and cobble eductor

    DOEpatents

    Miller, Arthur L.; Krawza, Kenneth I.

    1997-01-01

    In a hydraulically powered pump for excavating and transporting slurries in hich it is immersed, the improvement of a gravel and cobble eductor including an expandable mixing section, comprising: a primary flow conduit that terminates in a nozzle that creates a water jet internal to a tubular mixing section of the pump when water pressure is applied from a primary supply flow; a tubular mixing section having a center line in alignment with the nozzle that creates a water jet; a mixing section/exit diffuser column that envelopes the flexible liner; and a secondary inlet conduit that forms an opening at a bas portion of the column and adjacent to the nozzle and water jet to receive water saturated gravel as a secondary flow that mixes with the primary flow inside of the mixing section to form a combined total flow that exits the mixing section and decelerates in the exit diffuser.

  3. Towards an expanded definition of value.

    PubMed

    Smith, Matthew J; Standaert, Christopher J

    2013-11-01

    Much of the change being sought in the United State's health-care system is predicated on improving value. Value is most simply defined as quality divided by cost, and physicians increasingly rely on the quality-adjusted life year as the numerical measure to justify their services. However, there are many other definitions of value being advocated by various stakeholders in the health-care reform effort. Incentive programs and pilot studies implemented by private and public payers are steering much of the current change. Expanding our understanding of how value is defined by health-care economists and policy makers can help spine providers navigate the evolving health-care landscape. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Henry Norris Russell and the Expanding Universe

    NASA Astrophysics Data System (ADS)

    DeVorkin, D.

    2013-04-01

    Henry Norris Russell, one of the most influential American astronomers of the first half of the 20th Century, had a special place in his heart for the Lowell Observatory. Although privately critical of the founder for his pronouncements about life on Mars and the superiority of the Mars Hill observing site, he always supported the Observatory in public and professional circles. He staunchly supported Tombaugh's detection of a planet as leading from Lowell's prediction, and always promoted V. M. Slipher's spectroscopic investigations of planetary and stellar phenomena. But how did he react to Slipher's puzzling detection of the extreme radial velocities of spiral nebulae starting in 1912, and how did he regard the extension and interpretation of those observations by Hubble and others in following decades? Here we describe the arc of Russell's reactions, dating from Slipher's first detection, as an indicator of how mainstream stellar astronomers reacted to the concept of an expanding universe.

  5. Expanding the role of the oncology nurse

    PubMed Central

    Quinn, A

    2008-01-01

    Oncology nursing continues to evolve in response to advances in cancer treatment, information and biotechnology. As new scientific and technological discoveries are integrated into cancer care, oncology nurses need to play a key role in the management of this patient population. The role of the oncology nurse has expanded significantly and can differ greatly across cultures. Sophisticated treatments and the growth of targeted therapies will create the challenge of ensuring that all nurses working in this arena are well-educated, independent thinkers. Thus the future success of oncology nurses will focus on enhancement of nursing practice through advanced education. The increased globalisation of healthcare offers exciting opportunities to accomplish this goal by allowing for collaborative relationships among oncology nurses across the globe. PMID:21611002

  6. Electron Cooling in a Magnetically Expanding Plasma.

    PubMed

    Little, J M; Choueiri, E Y

    2016-11-25

    Electron cooling in a magnetically expanding plasma, which is a fundamental process for plasma flow and detachment in magnetic nozzles, is experimentally investigated using a radio frequency plasma source and magnetic nozzle (MN). Probe measurements of the plasma density, potential, and electron temperature along the center line of the MN indicate that the expansion follows a polytropic law with exponent γ_{e}=1.15±0.03. This value contradicts isothermal electron expansion, γ_{e}=1, which is commonly assumed in MN models. The axial variation of the measured quantities can be described by a simple quasi-1D fluid model with classical electron thermal conduction, for which it has been previously shown that a value of γ_{e}≈1.19 is expected in the weakly collisional limit. A new criterion, derived from the model, ensures efficient ion acceleration when a critical value for the ratio of convected to conducted power is exceeded.

  7. Web Content Analysis: Expanding the Paradigm

    NASA Astrophysics Data System (ADS)

    Herring, Susan C.

    Are established methods of content analysis (CA) adequate to analyze web content, or should new methods be devised to address new technological developments? This article addresses this question by contrasting narrow and broad interpretations of the concept of web content analysis. The utility of a broad interpretation that subsumes the narrow one is then illustrated with reference to research on weblogs (blogs), a popular web format in which features of HTML documents and interactive computer-mediated communication converge. The article concludes by proposing an expanded Web Content Analysis (WebCA) paradigm in which insights from paradigms such as discourse analysis and social network analysis are operationalized and implemented within a general content analytic framework.

  8. Expanding the principle of local distinguishability

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Heinosaari, Teiko; Schultz, Jussi; Toigo, Alessandro

    2015-04-01

    The principle of local distinguishability states that an arbitrary physical state of a bipartite system can be determined by the combined statistics of local measurements performed on the subsystems. A necessary and sufficient requirement for the local measurements is that each one must be able to distinguish between all pairs of states of the respective subsystems. We show that, if the task is changed into the determination of an arbitrary bipartite pure state, then at least in certain cases it is possible to restrict to local measurements which can distinguish all pure states but not all states. Moreover, we show that, if the local measurements are such that the purity of the bipartite state can be verified from the statistics without any prior assumption, then in these special cases also this property is carried over to the composite measurement. These surprising facts give evidence that the principle of local distinguishability may be expanded beyond its usual applicability.

  9. Study of an expanding magnetic cloud

    NASA Astrophysics Data System (ADS)

    Nakwacki, M. S.; Dasso, S.; Mandrini, C. H.; Démoulin, P.

    Magnetic Clouds (MCs) transport into the interplanetary medium the magnetic flux and helicity released in coronal mass ejections by the Sun. At 1 AU from the Sun, MCs are generally modelled as static flux ropes. However, the velocity profile of some MCs presents signatures of expansion. We analise here the magnetic structure of an expanding magnetic cloud observed by Wind spacecraft. We consider a dynamical model, based on a self-similar behaviour for the cloud radial velocity. We assume a free expansion for the cloud, and a cylindrical linear force free field (i.e., the Lundquist's field) as the initial condition for its magnetic configuration. We derive theoretical expressions for the magnetic flux across a surface perpendicular to the cloud axis, for the magnetic helicity and magnetic energy per unit length along the tube using the self-similar model. Finally, we compute these magntitudes with the fitted parameters. FULL TEXT IN SPANISH

  10. Alice and Bob in an expanding spacetime

    NASA Astrophysics Data System (ADS)

    Alexander, Helder; de Souza, Gustavo; Mansfield, Paul; Sampaio, Marcos

    2015-09-01

    We investigate the teleportation of a qubit between two observers Alice and Bob in an asymptotically flat Robertson-Walker expanding spacetime. We use scalar or fermionic field modes inside Alice's and Bob's ideal cavities and show the degradation of the teleportation quality, as measured by the fidelity, through a mechanism governed by spacetime expansion. This reduction is demonstrated to increase with the rapidity of the expansion and to be highly sensitive to the coupling of the field to spacetime curvature, becoming considerably stronger as it reduces from conformal to minimal. We explore a perturbative approach in the cosmological parameters to compute the Bogoliubov coefficients in order to evaluate and compare the fidelity degradation of fermionic and scalar fields.

  11. Expanding the role of nurses in Armenia.

    PubMed

    Jenkins, D L; Brush, K; McGonagle, E; Vartanian, M; Levy, K

    2000-01-01

    The dissolution of the Soviet Union and the declaration of Independence by the Republic of Armenia created the need for significant changes in the healthcare delivery system in Armenia. The desire to raise the level of health care presented challenges and opportunities for nurses within the Republic. Members of the departments of nursing at Boston City Hospital/Boston Medical Center in Boston, Massachusetts, University of Massachusetts Medical Center, Worcester, Massachusetts, and the Emergency Scientific Medical Center of Yerevan, Armenia, joined forces through a grant written by Boston University School of Medicine and sponsored by the American International Health Alliance under a cooperative agreement with the United States Agency for International Development to expand the role of nursing. This article describes the assessment, planning, implementation, and evaluation of changes to the role of nursing and the development of new roles for nurses within a hospital in the capital city of Yerevan.

  12. Emergency management: expanding the disaster plan.

    PubMed

    Ross, Kevin L; Bing, Caryn M

    2007-06-01

    A comprehensive emergency management plan (CEMP) is key to minimizing the disruption of patient care and services during and after a natural or man-made disaster. The home health nurse can play a key role in enhancing, expanding, and evaluating the effectiveness of the organization's disaster plan. The components of a CEMP and lessons learned from actual implementation of disaster plans in home care are addressed. The disasters and emergencies of the past few years, such as threats of terrorism, hurricanes, floods, wildfires, tornadoes, and earthquakes, have validated the need to extend the emergency preparedness plan to a more comprehensive approach to emergency management. Communities, healthcare providers, and individuals/families all have been urged to take a more comprehensive look at their readiness for these types of events. Home healthcare organizations, including home health agencies, hospice providers, infusion providers, and medical equipment companies, can take a fresh and comprehensive look at their emergency management plan.

  13. A temperature correction method for expanding atmospheres

    NASA Astrophysics Data System (ADS)

    Hamann, W.-R.; Gräfener, G.

    2003-11-01

    Model atmospheres form the basis for the interpretation of stellar spectra. A major problem in those model calculations is to establish the temperature stratification from the condition of radiative equilibrium. Dealing with non-LTE models for spherically expanding atmospheres of Wolf-Rayet stars, we developed a new temperature correction method. Its basic idea dates back to 1955 when it was proposed by Unsöld for grey, static and plane-parallel atmospheres in LTE. The equations were later generalized to the non-grey case by Lucy. In the present paper we furthermore drop the Eddington approximation, proceed to spherical geometry and allow for expansion of the atmosphere. Finally the concept of an ``approximate lambda operator'' is employed to speed up the convergence. Tests for Wolf-Rayet type models demonstrate that the method works fine even in situations of strong non-LTE.

  14. Expanding forensic science through forensic intelligence.

    PubMed

    Ribaux, Olivier; Talbot Wright, Benjamin

    2014-12-01

    Research and Development ('R&D') in forensic science currently focuses on innovative technologies improving the efficiency of existing forensic processes, from the detection of marks and traces at the scene, to their presentation in Court. R&D approached from this perspective provides no response to doubts raised by recent criminological studies, which question the effective contribution of forensic science to crime reduction, and to policing in general. Traces (i.e. forensic case data), as remnants of criminal activity are collected and used in various forms of crime monitoring and investigation. The aforementioned doubts therefore need to be addressed by expressing how information is conveyed by traces in these processes. Modelling from this standpoint expands the scope of forensic science and provides new R&D opportunities. Twelve propositions for R&D are stated in order to pave the way.

  15. An expandable radiocollar for elk calves

    USGS Publications Warehouse

    Smith, B.L.; Burger, W.P.; Singer, F.J.

    1998-01-01

    Expandable radiocollars, designed to monitor juvenile survival and movements, were placed on 132 neonatal elk (Cervus elaphus) in Yellowstone National Park during 1987-1990. A modified design of the same collar was placed on 164 neonates of the Jackson elk herd in northwest Wyoming during 1990-1992. One of the Yellowstone calves and 19 of the Jackson calves cast their collars before 15 July of their birth year. General deterioration of collar materials resulted in loss of the Yellowstone collars 12-18 months post-deployment. Separation of breakaway tabs resulted in loss of 13 collars from Jackson elk 504 ?? 60 days post-deployment, but the remaining collars remained on elk for ???4 years. These light-weight and adaptable collar designs achieved study objectives. We provide design recommendations for future monitoring of juvenile elk.

  16. Withdrawal: Expanding a Key Addiction Construct

    PubMed Central

    2015-01-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  17. Roots Air Management System with Integrated Expander

    SciTech Connect

    Stretch, Dale; Wright, Brad; Fortini, Matt; Fink, Neal; Ramadan, Bassem; Eybergen, William

    2016-07-06

    PEM fuel cells remain an emerging technology in the vehicle market with several cost and reliability challenges that must be overcome in order to increase market penetration and acceptance. The DOE has identified the lack of a cost effective, reliable, and efficient air supply system that meets the operational requirements of a pressurized PEM 80kW fuel cell as one of the major technological barriers that must be overcome. This project leveraged Roots positive displacement development advancements and demonstrated an efficient and low cost fuel cell air management system. Eaton built upon its P-Series Roots positive displacement design and shifted the peak efficiency making it ideal for use on an 80kW PEM stack. Advantages to this solution include: • Lower speed of the Roots device eliminates complex air bearings present on other systems. • Broad efficiency map of Roots based systems provides an overall higher drive cycle fuel economy. • Core Roots technology has been developed and validated for other transportation applications. Eaton modified their novel R340 Twin Vortices Series (TVS) Roots-type supercharger for this application. The TVS delivers more power and better fuel economy in a smaller package as compared to other supercharger technologies. By properly matching the helix angle with the rotor’s physical aspect ratio, the supercharger’s peak efficiency can be moved to the operating range where it is most beneficial for the application. The compressor was designed to meet the 90 g/s flow at a pressure ratio of 2.5, similar in design to the P-Series 340. A net shape plastic expander housing with integrated motor and compressor was developed to significantly reduce the cost of the system. This integrated design reduced part count by incorporating an overhung expander and motor rotors into the design such that only four bearings and two shafts were utilized.

  18. The expanding universe of alkaloid biosynthesis.

    PubMed

    De Luca, V; Laflamme, P

    2001-06-01

    Characterization of many of the major gene families responsible for the generation of central intermediates and for their decoration, together with the development of large genomics and proteomics databases, has revolutionized our capability to identify exotic and interesting natural-product pathways. Over the next few years, these tools will facilitate dramatic advances in our knowledge of the biosynthesis of alkaloids, which will far surpass that which we have learned in the past 50 years. These tools will also be exploited for the rapid characterization of regulatory genes, which control the development of specialized cell factories for alkaloid biosynthesis.

  19. Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

    PubMed

    Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

    2011-10-01

    Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

  20. BOOK REVIEW: The Artful Universe Expanded

    NASA Astrophysics Data System (ADS)

    Bassett, B. A.

    2005-07-01

    The cosmos is an awfully big place and there is no better guide to its vast expanse and fascinating nooks and crannies than John Barrow. A professor of mathematical sciences at Cambridge University, Barrow embodies that rare combination of highly polished writer and expert scientist. His deft touch brings together the disparate threads of human knowledge and weaves them into a tapestry as rich and interesting for the expert as it is for the layperson. The Artful Universe Expanded is an updated edition of this popular book first published in 1995. It explores the deeply profound manner in which natural law and the nature of the cosmos have moulded and shaped us, our cultures and the very form of our arts and music—a new type of `cosmic' anthropology. The main themes Barrow chooses for revealing this new anthropology are the subjects of evolution, the size of things, the heavens and the nature of music. The book is a large, eclectic repository of knowledge often unavailable to the layperson,\\endcolumn hidden in esoteric libraries around the world. It rivals The Da Vinci Code for entertainment value and insights, but this time it is Nature’s code that is revealed. It is rare indeed to find common threads drawn through topics as diverse as The Beetles, Bach and Beethoven or between Jackson Pollock, the Aztecs, Kant, Picasso, Byzantine mosaics, uranium-235 and the helix nebula. Barrow unerringly binds them together, presenting them in a stimulating, conversational style that belies the amount of time that must have gone into researching this book. Dip into it at random, or read it from cover to cover, but do read it. The Artful Universe Expanded is an entertaining antidote to the oft-lamented pressures to know more and more about less and less and the apparently inexorable march of specialization. On reading this book one can, for a short time at least, hold in one’s mind a vision that unifies science, art and culture and glimpse a universal tapestry of great

  1. Expanding Taylor bubble under constant heat flux

    NASA Astrophysics Data System (ADS)

    Voirand, Antoine; Benselama, Adel M.; Ayel, Vincent; Bertin, Yves

    2016-09-01

    Modelization of non-isothermal bubbles expanding in a capillary, as a contribution to the understanding of the physical phenomena taking place in Pulsating Heat Pipes (PHPs), is the scope of this paper. The liquid film problem is simplified and solved, while the thermal problem takes into account a constant heat flux density applied at the capillary tube wall, exchanging with the liquid film surrounding the bubble and also with the capillary tube outside medium. The liquid slug dynamics is solved using the Lucas-Washburn equation. Mass and energy balance on the vapor phase allow governing equations of bubble expansion to be written. The liquid and vapor phases are coupled only through the saturation temperature associated with the vapor pressure, assumed to be uniform throughout the bubble. Results show an over-heating of the vapor phase, although the particular thermal boundary condition used here always ensures an evaporative mass flux at the liquid-vapor interface. Global heat exchange is also investigated, showing a strong decreasing of the PHP performance to convey heat by phase change means for large meniscus velocities.

  2. Expandable Purge Chambers Would Protect Cryogenic Fittings

    NASA Technical Reports Server (NTRS)

    Townsend, Ivan I., III

    2004-01-01

    Expandable ice-prevention and cleanliness-preservation (EIP-CP) chambers have been proposed to prevent the accumulation of ice or airborne particles on quick-disconnect (QD) fittings, or on ducts or tubes that contain cryogenic fluids. In the original application for which the EIP-CP chambers were conceived, there is a requirement to be able to disconnect and reconnect the QD fittings in rapid succession. If ice were to form on the fittings by condensation and freezing of airborne water vapor on the cold fitting surfaces, the ice could interfere with proper mating of the fittings, making it necessary to wait an unacceptably long time for the ice to thaw before attempting reconnection. By keeping water vapor away from the cold fitting surfaces, the EIP-CP chambers would prevent accumulation of ice, preserving the ability to reconnect as soon as required. Basically, the role of an EIP-CP chamber would be to serve as an enclosure for a flow of dry nitrogen gas that would keep ambient air away from QD cryogenic fittings. An EIP-CP chamber would be an inflatable device made of a fabriclike material. The chamber would be attached to an umbilical plate holding a cryogenic QD fitting.

  3. Branching instability in expanding bacterial colonies

    PubMed Central

    Giverso, Chiara; Verani, Marco; Ciarletta, Pasquale

    2015-01-01

    Self-organization in developing living organisms relies on the capability of cells to duplicate and perform a collective motion inside the surrounding environment. Chemical and mechanical interactions coordinate such a cooperative behaviour, driving the dynamical evolution of the macroscopic system. In this work, we perform an analytical and computational analysis to study pattern formation during the spreading of an initially circular bacterial colony on a Petri dish. The continuous mathematical model addresses the growth and the chemotactic migration of the living monolayer, together with the diffusion and consumption of nutrients in the agar. The governing equations contain four dimensionless parameters, accounting for the interplay among the chemotactic response, the bacteria–substrate interaction and the experimental geometry. The spreading colony is found to be always linearly unstable to perturbations of the interface, whereas branching instability arises in finite-element numerical simulations. The typical length scales of such fingers, which align in the radial direction and later undergo further branching, are controlled by the size parameters of the problem, whereas the emergence of branching is favoured if the diffusion is dominant on the chemotaxis. The model is able to predict the experimental morphologies, confirming that compact (resp. branched) patterns arise for fast (resp. slow) expanding colonies. Such results, while providing new insights into pattern selection in bacterial colonies, may finally have important applications for designing controlled patterns. PMID:25652464

  4. Filtration application from recycled expanded polystyrene.

    PubMed

    Shin, C

    2006-10-01

    Water-in-oil emulsion with drop size less than 100 mum is difficult to separate. Coalescence filtration is economical and effective for separation of secondary dispersions. Coalescence performance depends on flow rate, bed depth, fiber surface properties, and drop size. The amount of surface area of the fibers directly affects the efficiency. A new recycling method was investigated in the previous work in which polystyrene (PS) sub-mum fibers were electro-spun from recycled expanded polystyrene (EPS). These fibers are mixed with micro glass fibers to modify the glass fiber filter media. The filter media are tested in the separation of water droplets from an emulsion of water droplets in oil. The experimental results in this work show that adding nanofibers to conventional micron sized fibrous filter media improves the separation efficiency of the filter media but also increases the pressure drop. An optimum in the performance occurs (significant increase in efficiency with minimal increase in pressure drop) with the addition of about 4% by mass of 500 nm diameter PS nanofibers to glass fibers for the filters.

  5. Expanded polylactide bead foaming - A new technology

    NASA Astrophysics Data System (ADS)

    Nofar, M.; Ameli, A.; Park, C. B.

    2015-05-01

    Bead foaming technology with double crystal melting peak structure has been recognized as a promising method to produce low-density foams with complex geometries. During the molding stage of the bead foams, the double peak structure generates a strong bead-to-bead sintering and maintains the overall foam structure. During recent years, polylactide (PLA) bead foaming has been of the great interest of researchers due to its origin from renewable resources and biodegradability. However, due to the PLA's low melt strength and slow crystallization kinetics, the attempts have been limited to the manufacturing methods used for expanded polystyrene. In this study, for the first time, we developed microcellular PLA bead foams with double crystal melting peak structure. Microcellular PLA bead foams were produced with expansion ratios and average cell sizes ranging from 3 to 30-times and 350 nm to 15 µm, respectively. The generated high melting temperature crystals during the saturation significantly affected the expansion ratio and cell density of the PLA bead foams by enhancing the PLA's poor melt strength and promoting heterogeneous cell nucleation around the crystals.

  6. Exposing medical students to expanding populations.

    PubMed

    Lindenthal, J J; DeLisa, J A; Heinrich, G F; Calderón Gerstein, W S

    2015-01-01

    Physicians are required to advocate for and counsel patients based on the best science and the interests of the individual while avoiding discrimination, ensuring equal access to health and mental services. Nonetheless, the communication gap between physician and patients has long been observed. To this end, the Institute for the Public Understanding of Health and Medicine of the Rutgers University New Jersey Medical School has expanded its efforts. This report describes two new programs: a legacy lecture series for medical students and an international "experience", in Huancayo, Peru, for medical students and faculty. The MiniMed outreach program, now in its ninth year and first described in this journal in 2012, was designed to empower the powerless to communicate more effectively with clinicians, thus improving both the effectiveness of the physician-patient relationship and health care outcomes. The approach of the two new programs and their effects on patients, particularly the underserved, and medical students and faculty, are outlined in the following article.

  7. Exposing medical students to expanding populations

    PubMed Central

    Lindenthal, JJ; DeLisa, JA; Heinrich, GF; Calderón Gerstein, WS

    2015-01-01

    Physicians are required to advocate for and counsel patients based on the best science and the interests of the individual while avoiding discrimination, ensuring equal access to health and mental services. Nonetheless, the communication gap between physician and patients has long been observed. To this end, the Institute for the Public Understanding of Health and Medicine of the Rutgers University New Jersey Medical School has expanded its efforts. This report describes two new programs: a legacy lecture series for medical students and an international “experience”, in Huancayo, Peru, for medical students and faculty. The MiniMed outreach program, now in its ninth year and first described in this journal in 2012, was designed to empower the powerless to communicate more effectively with clinicians, thus improving both the effectiveness of the physician–patient relationship and health care outcomes. The approach of the two new programs and their effects on patients, particularly the underserved, and medical students and faculty, are outlined in the following article. PMID:25834472

  8. Expanding on Successful Concepts, Models, and ...

    EPA Pesticide Factsheets

    If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead, the outcome we promote is broader use of an organizational framework for exposure science. The framework would support improved generation, organization, and interpretation of data as well as modeling and prediction, not replacement of models. The field of toxicology has seen the benefits of wide use of one or more organizational frameworks (e.g., mode and mechanism of action, adverse outcome pathway). These frameworks influence how experiments are designed, data are collected, curated, stored and interpreted and ultimately how data are used in risk assessment. Exposure science is poised to similarly benefit from broader use of a parallel organizational framework, which Dr. von Göetz correctly points out, is currently used in the exposure modeling community. In our view, the concepts used so effectively in the exposure modeling community, expanded upon in the AEP framework, could see wider adoption by the field as a whole. The value of such a framework was recognized by the National Academy of Sciences.1Replacement of models, databases, or any application with the AEP framework was not proposed in our article. The positive role such a framework might have in enabling and advancing “general activities such as data acquisition, organization…,” and exposure modeling was discussed

  9. Helical Screw Expander Evaluation Project. Final report

    SciTech Connect

    McKay, R.

    1982-03-01

    A functional 1-MW geothermal electric power plant that featured a helical screw expander was produced and then tested in Utah in 1978 to 1979 with a demonstrated average performance of approximately 45% machine efficiency over a wide range of test conditions in noncondensing operation on two-phase geothermal fluids. The Project also produced a computer-equipped data system, an instrumentation and control van, and a 1000-kW variable load bank, all integrated into a test array designed for operation at a variety of remote test sites. Additional testing was performed in Mexico in 1980 under a cooperative test program using the same test array, and machine efficiency was measured at 62% maximum with the rotors partially coated with scale, compared with approximately 54% maximum in Utah with uncoated rotors, confirming the importance of scale deposits within the machine on performance. Data are presented for the Utah testing and for the noncondensing phases of the testing in Mexico. Test time logged was 437 hours during the Utah tests and 1101 hours during the Mexico tests.

  10. The expanding universe of noncoding RNAs.

    PubMed

    Hannon, G J; Rivas, F V; Murchison, E P; Steitz, J A

    2006-01-01

    The 71st Cold Spring Harbor Symposium on Quantitative Biology celebrated the numerous and expanding roles of regulatory RNAs in systems ranging from bacteria to mammals. It was clearly evident that noncoding RNAs are undergoing a renaissance, with reports of their involvement in nearly every cellular process. Previously known classes of longer noncoding RNAs were shown to function by every possible means-acting catalytically, sensing physiological states through adoption of complex secondary and tertiary structures, or using their primary sequences for recognition of target sites. The many recently discovered classes of small noncoding RNAs, generally less than 35 nucleotides in length, most often exert their effects by guiding regulatory complexes to targets via base-pairing. With the ability to analyze the RNA products of the genome in ever greater depth, it has become clear that the universe of noncoding RNAs may extend far beyond the boundaries we had previously imagined. Thus, as much as the Symposium highlighted exciting progress in the field, it also revealed how much farther we must go to understand fully the biological impact of noncoding RNAs.

  11. The expanding universe of prion diseases.

    PubMed

    Watts, Joel C; Balachandran, Aru; Westaway, David

    2006-03-01

    Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C). Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE) the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases--including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and Nor98 of sheep--have been identified in the last ten years, and chronic wasting disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America. While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk) can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

  12. Expandable Image Compression System, A Modular Approach

    NASA Astrophysics Data System (ADS)

    Ho, Bruce K.; Chan, K. K.; Ishimitsu, Yoshiyuki; Lo, Shih C.; Huang, H. K.

    1987-01-01

    The full-frame bit allocation algorithm for radiological image compression developed in our laboratory can achieve compression ratios as high as 30:1. The software development and clinical evaluation of this algorithm has been completed. It involves two stages of operations: a two-dimensional discrete cosine transform and pixel quantization in the transform space with pixel depth kept accountable by a bit allocation table. The greatest engineering challenge in implementing a hardware version of the compression system lies in the fast cosine transform of 1Kx1K images. Our design took an expandable modular approach based on the VME bus system which has a maximum data transfer rate of 48 Mbytes per second and a Motorola 68020 microprocessor as the master controller. The transform modules are based on advanced digital signal processor (DSP) chips microprogrammed to perform fast cosine transforms. Four DSP's built into a single-board transform module can process an 1K x 1K image in 1.7 seconds. Additional transform modules working in parallel can be added if even greater speeds are desired. The flexibility inherent in the microcode extends the capabilities of the system to incorporate images of variable sizes. Our design allows fof a maximum image size of 2K x 2K.

  13. Massive Fermi gas in the expanding universe

    NASA Astrophysics Data System (ADS)

    Trautner, Andreas

    2017-03-01

    The behavior of a decoupled ideal Fermi gas in a homogeneously expanding three-dimensional volume is investigated, starting from an equilibrium spectrum. In case the gas is massless and/or completely degenerate, the spectrum of the gas can be described by an effective temperature and/or an effective chemical potential, both of which scale down with the volume expansion. In contrast, the spectrum of a decoupled massive and non-degenerate gas can only be described by an effective temperature if there are strong enough self-interactions such as to maintain an equilibrium distribution. Assuming perpetual equilibration, we study a decoupled gas which is relativistic at decoupling and then is red-shifted until it becomes non-relativistic. We find expressions for the effective temperature and effective chemical potential which allow us to calculate the final spectrum for arbitrary initial conditions. This calculation is enabled by a new expansion of the Fermi-Dirac integral, which is for our purpose superior to the well-known Sommerfeld expansion. We also compute the behavior of the phase space density under expansion and compare it to the case of real temperature and real chemical potential. Using our results for the degenerate case, we also obtain the mean relic velocity of the recently proposed non-thermal cosmic neutrino background.

  14. Coiled tubing 1994 update: Expanding applications

    SciTech Connect

    Teel, M.E.

    1994-06-01

    The coiled tubing (CT) resurgence, which began in late 1989 shows little sign of moderating in spite of lower oil and gas prices. In fact, this so-called revolution continues to expand into major new services and applications. CT units are replacing workover rigs and snubbing units in some areas and have recently started to replace drilling rigs even outside Alaska's North Slope Prudhoe Bay field. Activity is reaching record levels in many areas. Although drilling, completions and flowlines generate a lot of interest, these are currently only a small part of total CT business. About 75% of activity is split evenly between nitrogen, acidizing and cleanouts. The other 25% includes newer services like cementing, fishing, sliding sleeves, logging, underreaming to remove scale or cement and drilling. CT is used to drill slimholes and reentry drainholes up to 6 1/8-in. CT has been used as casing and more casing applications are planned. CT ODs to 3 1/2-in. are produced and 4 1/2-in. OD CT production is scheduled later this year. Larger ODs make CT feasible for replacing conventional jointed tubing and welded flowlines.

  15. Expanded polytetrafluoroethylene augmentation of the lower face.

    PubMed

    Sherris, D A; Larrabee, W F

    1996-05-01

    Most options for rejuvenation of the lower face use soft-tissue fillers that augment the appropriate sites. Each of these options has associated risks and benefits. The U.S. Food and Drug Administration recently approved the use of expanded polytetrafluoroethylene (E-PTFE) as a soft-tissue filler in the face. From January 1991 through December 1993, the authors used E-PTFE soft-tissue patches for lower facial augmentation in 41 patients at 115 implant sites. Postsurgical follow-up has ranged from 2.5 to 4.5 years; during this time, complications have occurred in 4 patients. One implant had to be removed because of a seroma (1 patient), 4 implants required further secondary augmentation (2 patients), and 1 implant required revision because of malposition (1 patient). There have been no cases of implant infection, extrusion, long-term inflammation, or capsule formation. In this article, the authors review the technical aspects of E-PTFE use and discuss issues relating to the long-term efficacy of this new option for soft-tissue augmentation. The technique is also compared with other options for rejuvenation of the lower face.

  16. Implications of coccolithophores expanding to polar waters

    NASA Astrophysics Data System (ADS)

    Winter, A.; Henderiks, J.; Beaufort, L.

    2008-12-01

    There is much debate about the response of coccolithophores to decreased carbonate saturation state and decreased pH in the ocean as a result of increased CO2 partial pressure. It is still not known whether coccolithophores act as a sink or source for CO CO2. Nor is it known whether calcification will be reduced or increased in response to climate change. A proper understanding of the relationship between calcification and climate change is important not only because coccolithophores play an important role in determining the PIC:POC ratio of particle export into the deep ocean but also because climate change may affect the overall biodiversity of phytoplankton and the marine food chain. Because ocean acidification strongly affects polar regions, initially it seems unlikely that coccolithophores should prefer polar waters or even be a major component of phytoplankton in these regions. Yet there is much recent evidence that coccolithophores are increasingly expanding their range into polar oceans. This observation could be pivotal in improving our understanding of the mechanisms and rates of climatic adaptation by natural coccolithophore populations. We postulate that coccolithophores may be more sensitive to recent environmental changes, such as SSTs and salinity, than to factors more directly linked to changing ocean carbonate chemistry

  17. Expanded Small-Scale Shock Reactivity Test

    NASA Astrophysics Data System (ADS)

    Granholm, Richard

    2005-07-01

    Explosives react from a strong shock, even in quantities too small for detonation. The potential for a new material to be an explosive can be evaluated from this shock reactivity. The recently developed small-scale shock reactivity test (SSRT)ootnotetextH. W. Sandusky, R. H. Granholm, D. G. Bohl, ``Small-Scale Shock Reactivity Test,'' NSWC Technical Report (in publication), Naval Surface Warfare Center, Indian Head, MD 20640 uses very high confinement to allow prompt reactions to occur in less than half-gram samples well below critical diameter, with the reactions quantified by a dent in a soft aluminum witness block. This test has been expanded to simultaneously measure both early and late-time reactions from a single sample subjected to the output from an RP-80 detonator. The sample apparatus is further confined within a small chamber instrumented with a pressure gage for internal air blast. This provides a measure of late-time reactions, such as from fuel/air combustion. Results are shown from several simultaneous early- and late-reaction measurements.

  18. The expanding fireball of Nova Delphini 2013.

    PubMed

    Schaefer, G H; ten Brummelaar, T; Gies, D R; Farrington, C D; Kloppenborg, B; Chesneau, O; Monnier, J D; Ridgway, S T; Scott, N; Tallon-Bosc, I; McAlister, H A; Boyajian, T; Maestro, V; Mourard, D; Meilland, A; Nardetto, N; Stee, P; Sturmann, J; Vargas, N; Baron, F; Ireland, M; Baines, E K; Che, X; Jones, J; Richardson, N D; Roettenbacher, R M; Sturmann, L; Turner, N H; Tuthill, P; van Belle, G; von Braun, K; Zavala, R T; Banerjee, D P K; Ashok, N M; Joshi, V; Becker, J; Muirhead, P S

    2014-11-13

    A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common-envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 ± 0.59 kiloparsecs from the Sun.

  19. The Expanding Universe of Prion Diseases

    PubMed Central

    Watts, Joel C; Balachandran, Aru; Westaway, David

    2006-01-01

    Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrPC. Several mammalian species are affected by the diseases, and in the case of “mad cow disease” (BSE) the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases—including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and Nor98 of sheep—have been identified in the last ten years, and chronic wasting disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America. While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk) can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of “sporadic” disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded. PMID:16609731

  20. Is Space Really Expanding? A Counterexample

    NASA Astrophysics Data System (ADS)

    Chodorowski, Michał J.

    2007-03-01

    In all Friedman models, the cosmological redshift is widely interpreted as a consequence of the general-relativistic phenomenon of expansion of space. Other commonly believed consequences of this phenomenon are superluminal recession velocities of distant galaxies, and the distance to the particle horizon greater than ct (where t is the age of the Universe), in apparent conflict with special relativity. Here, we study a particular Friedman model: empty universe. This model exhibits both cosmological redshift, superluminal velocities and infinite distance to the horizon. However, we show that the cosmological redshift is there simply a relativistic Doppler shift. Moreover, apparently superluminal velocities and ‘acausal’ distance to the horizon are in fact a direct consequence of special-relativistic phenomenon of time dilation, as well as of the adopted definition of distance in cosmology. There is no conflict with special relativity, whatsoever. In particular, inertial recession velocities are subluminal. Since in the real Universe, sufficiently distant galaxies recede with relativistic velocities, these special-relativistic effects must be at least partly responsible for the cosmological redshift and the aforementioned ‘superluminalities’, commonly attributed to the expansion of space. Let us finish with a question resembling a Buddhism-Zen ‘koan’: in an empty universe, what is expanding?

  1. Phenotypic characterization of culture expanded rabbit limbal corneal keratocytes.

    PubMed

    Abd Ghafar, Norzana; Chua, Kien Hui; Wan Ngah, Wan Zurinah; Che Hamzah, Jemaima; Othman, Fauziah; Abd Rahman, Ropilah; Hj Idrus, Ruszymah

    2014-03-01

    The in vivo quiescent corneal stroma keratocytes need to be transformed to activated state in order to obtain sufficient number of cells either for monolayer evaluation or corneal stroma reconstruction. This study aimed to investigate the phenotypic characterization of corneal stromal cells during culture expansion from the limbal region of the cornea. Isolated corneal keratocytes from limbal tissue of New Zealand White Strain rabbits' corneas (n = 6) were culture expanded until three passages. Keratocytes morphology was examined daily with viability, growth rate, number of cell doubling and population doubling time were recorded at each passage. The expression of collagen type 1, aldehyde dehydrogenase (ALDH), lumican and alpha smooth muscle actin (α-SMA) were detected by RT-PCR. Immunocytochemistry was also used to detect ALDH, α-SMA, collagen type I and Cytokeratin-3 (CK3). Growth kinetic study revealed that the growth rate was low at the initial passage but increase to about two folds with concomitant reduction in population doubling time in later passages. Freshly isolated and cultured keratocytes expressed collagen type 1, ALDH and lumican but α-SMA expression was absent. However, α-SMA was expressed along with the other genes during culture expansion. Keratocytes at P1 expressed all the proteins except CK3. These results suggest that cultured keratocytes maintained most of the gene expression profile of native keratocytes while the emergence of α-SMA in serial passages showed a mix population of various phenotypes. The phenotypic characterization of monolayer keratocytes provides useful information before reconstruction of bioengineered tissue or in vitro pharmaceutical applications.

  2. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  3. Neuroimaging of Parkinson’s Disease: Expanding views

    PubMed Central

    Weingarten, Carol P.; Sundman, Mark H.; Hickey, Patrick; Chen, Nankuei

    2015-01-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. PMID:26409344

  4. Functional diversification of Argonautes in nematodes: an expanding universe.

    PubMed

    Buck, Amy H; Blaxter, Mark

    2013-08-01

    In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism.

  5. Functional diversification of Argonautes in nematodes: an expanding universe

    PubMed Central

    Buck, Amy H.; Blaxter, Mark

    2013-01-01

    In the last decade, many diverse RNAi (RNA interference) pathways have been discovered that mediate gene silencing at epigenetic, transcriptional and post-transcriptional levels. The diversity of RNAi pathways is inherently linked to the evolution of Ago (Argonaute) proteins, the central protein component of RISCs (RNA-induced silencing complexes). An increasing number of diverse Agos have been identified in different species. The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. Recent research in the nematode Caenorhabditis elegans has expanded the breadth of RNAi functions to include transgenerational epigenetic memory and, possibly, environmental sensing. These functions are inherently linked to the production of secondary siRNAs (small interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos). In the present article, we review briefly what is known about the evolution and function of Ago proteins in eukaryotes, including the expansion of WAGOs in nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional functional plasticity of nematodes, including their capacity for parasitism. PMID:23863149

  6. Prevention of necrosis of adjacent expanded flaps by surgical delay.

    PubMed

    Zhu, Hainan; Xie, Yun; Xie, Feng; Gu, Bin; Liu, Kai; Zan, Tao; Li, QingFeng

    2014-11-01

    Although expanded flaps have been shown to survive longer than unexpanded flaps, flap necrosis still occurs, particularly when a deep back cut has been made. Overcautious design can avoid necrosis but leads to inefficient usage of the expanded flap. In this study, we tested a surgical delay method to prevent partial necrosis and maximize the use of the expanded flap. Ten patients with 13 expanders were included in this series. The surgical delay was performed 2 weeks before the final flap transfer. The survival of the delayed flaps was compared with that in previous cases without surgical delay. All 13 expanded flaps exhibited complete survival, which was significantly better than the 27.5% partial flap necrosis observed in nondelayed cases. Surgical delay can decrease the risk of necrosis in an expanded flap caused by a back cut and can thus maximize flap use.

  7. Expanding on Successful Concepts, Models, and Organization

    SciTech Connect

    Teeguarden, Justin G.; Tan, Yu-Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Kile, Molly L.; L. Massey Simonich, Staci; Stone, David; Tanguay, Robert L.; Waters, Katrina M.; Harper, Stacey L.; Williams, David E.

    2016-09-06

    In her letter to the editor1 regarding our recent Feature Article “Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework” 2, Dr. von Göetz expressed several concerns about terminology, and the perception that we propose the replacement of successful approaches and models for exposure assessment with a concept. We are glad to have the opportunity to address these issues here. If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead, the outcome we promote is broader use of an organizational framework for exposure science. The framework would support improved generation, organization, and interpretation of data as well as modeling and prediction, not replacement of models. The field of toxicology has seen the benefits of wide use of one or more organizational frameworks (e.g., mode and mechanism of action, adverse outcome pathway). These frameworks influence how experiments are designed, data are collected, curated, stored and interpreted and ultimately how data are used in risk assessment. Exposure science is poised to similarly benefit from broader use of a parallel organizational framework, which Dr. von Göetz correctly points out, is currently used in the exposure modeling community. In our view, the concepts used so effectively in the exposure modeling community, expanded upon in the AEP framework, could see wider adoption by the field as a whole. The value of such a framework was recognized by the National Academy of Sciences.3 Replacement of models, databases, or any application with the AEP framework was not proposed in our article. The positive role broader more consistent use of such a framework might have in enabling and advancing “general activities such as data acquisition, organization…,” and exposure modeling was discussed

  8. AstroCom NYC: Expanding the Partnership

    NASA Astrophysics Data System (ADS)

    Paglione, Timothy; Ford, Saavik; Agueros, Marcel A.; Mac Low, Mordecai-Mark; Robbins, Dennis

    2015-01-01

    AstroCom NYC is an undergraduate mentoring program designed to improve urban minority student access to opportunities in astrophysical research by greatly enhancing partnerships between research astronomers in New York City (City University of New York - an MSI, American Museum of Natural History, and Columbia). AstroCom NYC provides centralized, personalized mentoring as well as financial and academic support, to CUNY undergraduates throughout their studies, plus the resources and opportunities to further CUNY faculty research with students. The goal is that students' residency at AMNH helps them build a sense of belonging in the field, and readies and inspires them for graduate study. AstroCom NYC provides a rigorous Methods of Scientific Research course developed specifically to this purpose, a laptop, research and career mentors, outreach activities, scholarships and stipends, Metrocards, and regular assessment for maximum effectiveness. Stipends in part alleviate the burdens at home typical for CUNY students so they may concentrate on their academic success. AMNH serves as the central hub for our faculty and students, who are otherwise dispersed among all five boroughs of the City. For our second cohort, we dramatically improved the application and screening process, implemented a number of tools to evaluate their potential for grad school, and began growing a network of potential hosts for summer internships around NY State and the US. We review these implementations and outcomes, as well as plans for Year 3, when we expect many of our current students to compete for external summer REUs, and after greatly expanding the program reach through a NASA community college initiative.

  9. Expanding the scope of the turnover flap.

    PubMed

    Mitra, Avir; Spears, Julie; Newsome, Edward; McCampbell, Beth; Kiran, Ravi; Mitra, Amit

    2006-07-01

    Turnover flaps are often utilized as alternatives to more traditional flaps, especially in situations where traditional flap viability is limited. Most turnover flaps are currently used in the lower extremities. This study examined the senior author's use of the turnover flap in 103 cases between 1987 and 2004. Postoperative follow-up ranged from 3 months to 10 years, with an average follow-up of 9 months. The majority (n = 90) of the cases involved the lower extremities and carried high success rates; there were 72 successful operations (complete graft take), 10 partial flap losses (partial graft take that could be treated postoperatively without surgery), and eight complete flap losses (no graft take and the necessity of additional surgery). Three of the partial flap losses and two of the complete flap losses involved patients with end-stage vascular disease. End-stage vascular disease cases represented 20.0 percent of the lower extremity cases and carried a significantly higher percentage of partial or complete flap loss (27.8 percent). These circumstances were examined in detail; the authors found that the turnover flap provided improved outcome to such end-stage patients who otherwise would have undergone amputation. In 13 cases, turnover flaps were utilized in nontraditional regions, such as the chest wall, abdominal wall, head and neck region, and upper extremities, with a high degree of success (zero partial or complete flap losses). These approaches are discussed in detail. The surgical approach is examined with recommendations regarding preferred wound size and type and overall flap design. This study indicates that turnover flaps are effective and useful as an alternative and, in some cases, primary procedure. In addition, the results serve to expand the present scope of the turnover flap by examining nontraditional regions in which the flap was highly successful. The authors believe the turnover flap should be given higher priority as a reconstructive

  10. Equations of motion in an Expanding Universe

    NASA Astrophysics Data System (ADS)

    Kopeikin, Sergei M.; Petrov, Alexander N.

    2015-06-01

    We make use of an effective field-theoretical approach to derive post-Newtonian equations of motion of hydrodynamical inhomogeneities in cosmology. The matter Lagrangian for the perturbed cosmological model includes dark matter, dark energy, and ordinary baryonic matter. The Lagrangian is expanded in an asymptotic Taylor series around a Friedmann-Lemaître-Robertson-Walker background. The small parameter of the decomposition is the magnitude of the metric tensor perturbation. Each term of the expansion series is gauge-invariant and all of them together form a basis for the successive post-Newtonian approximations around the background metric. The approximation scheme is covariant and the asymptotic nature of the Lagrangian decomposition does not require the post-Newtonian perturbations to be small though computationally it works the most effectively when the perturbed metric is close enough to the background metric. Temporal evolution of the background metric is governed by dark matter and dark energy and we associate the large-scale inhomogeneities of matter as those generated by the primordial cosmological perturbations in these two components with δρ/ρ ≤ 1. The small scale inhomogeneities are generated by the baryonic matter which is considered as a bare perturbation of the background gravitational field, dark matter and energy. Mathematically, the large scale structure inhomogeneities are given by the homogeneous solution of the post-Newtonian equations while the small scale inhomogeneities are described by a particular solution of these equations with the stress-energy tensor of the baryonic matter that admits δρ/ρ ≫ 1. We explicitly work out the field equations of the first post-Newtonian approximation in cosmology and derive the post-Newtonian equations of motion of the large and small scale inhomogeneities which generalize the covariant law of conservation of stress-energy-momentum tensor of matter in asymptotically-flat spacetime.

  11. Expanding Lookout Capabilities for Architectural Analysis

    NASA Astrophysics Data System (ADS)

    Shick, B.

    SMC/SYSW/ENY's Lookout tool provides a M&S capability for architectural analysis. It models the contributions of ground and space-based assets in several mission threads and scenarios to quantify overall Space Situational Awareness (SSA) capability. Plotting performance results versus costs enables decision makers to identify and evaluate Best Value families of systems and combinations of architectures. Currently, SMC intends to use Lookout to impact the Fiscal Year 2012 budget programming cycle, the National SSA Initial Capabilities Document (ICD) and Architecture definition effort, planning for programs of record, and AFSPC & SMC leadership. Ultimately, Lookout will enable additional space superiority analysis. Previous Lookout work focused on modeling the metric tracking capabilities of the Space Surveillance Network (detecting and tracking) and proposed concepts to close identified collection shortfalls. SMC/SYSW/ENY leveraged some of the lessons learned in developing and implementing the metric tracking models to expand Lookout to develop an initial characterization capability, including non-resolved space object identification (SOI), imaging, and Foreign Instrumentation and Signals (FIS) Intelligence. Characterization collection phenomenologies added in FY08 and FY09 include mechanical tracking and phased array radars, visible telescopes, and signals collection. Lookout enables evaluating the characterization collections for quantity, quality, and timeliness. Capturing the Tasking, Collection, Processing, Exploitation, and Dissemination processes represent one of the biggest challenges in including characterization capabilities in mission thread and scenario-based analysis. The SMC/SYSW/ENY team met with several representatives of the community and held community-wide Technical Interchange Meetings. Based on feedback from these meetings, SMC created an infrastructure for modeling the tasking processes and scales to relate collection quality to intelligence

  12. PROFAM expands Mexican family planning clinics.

    PubMed

    1983-01-01

    Mexico's private, nonprofit social marketing company, known as PROFAM, intends to expand its family planning clinics to marginal urban areas. The clinics are part of PROFAM's push to diversify social marketing outlets for contraceptive products and other birth control methods. PROFAM expects to establish 3 new clinics, possibly including a pregnancy test laboratory, a small 1-doctor clinic, and a large clinic housing an operating room. 1 clinic will be located outside the Mexico City area, the program's traditional boundaries. The company currently runs 2 small clinics and a pregnancy testing laboratory in Ciudad Netzahualcoyti, a community of 3.5 million on Mexico City's outskirts. PROFAM recently obtaine d government approval to sell condoms in food stores, which should increase distribtuion and sales. Currently, the company sells over 1 million high quality, lubricated condoms each month, accounting for over half of the Mexican market. Distribution covers 85% of the country's drugstore. Program setbacks occurred in 1981, when the Mexican government cancelled PROFAM's sales permits for all contraceptive products except condoms. Cancelled products included an oral contraceptive and 3 vaginal spermicides. These 4 products had provided nearly 100,000 couple years of protection in 1979 and an estimated 120,000 CYP 1980. During 1979 and 1980, condoms provided about 27,000 and 60,000 CYP, respectively. PROFAM had relied heavily on the pill and spermicides because its early studies showed condoms had a negative image in Mexico, due largely to the product's association with extramarital affairs. To counter this, PROFAM launched a widespread, free product sampling program in 1979, along with a continuing educational and advertising drive. Subsequent consumer surveys revealed a marked increase in product acceptance, with PROFAM's condom becoming the most widely known brand available in Mexico.

  13. The chimeric genes AML1/DS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties

    SciTech Connect

    Zent, C.S.; Matheiu, C.; Rowley, J.D.

    1996-02-06

    The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the {alpha} subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the {beta} subunit (CBFB) is involved in the inv(16). These are two of the most common recurring chromosomal rearrangements in acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF binding sites are found in a number of eukaryotic and viral enhancers and promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter by using reporter gene assays, and we analyzed the consequences of the expression of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in culture and after injection into athymic nude mice. Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AMLI (CBFA2). AML1/EAP and AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of growth, and expression of AML1/MDS1 was associated with acquisition of the ability to grow in suspension culture. Expression of AML1/MDS1 increased the tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP expression provented tumor growth. These results suggest that expression of AML1/MDS1 can interfere with normal AML1 function, and that AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell line. 26 refs., 5 figs.

  14. GeneCards Version 3: the human gene integrator.

    PubMed

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-08-05

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  15. Nutrition and genetics: an expanding frontier.

    PubMed

    Olson, Robert E

    2003-08-01

    The age of molecular biology began in 1953 with the discovery of the structure of DNA. By 1961 the genetic code for the translation of the sequence of bases in DNA to amino acids in proteins was underway, and a model for the genetic regulation of protein synthesis was proposed. My interest in the genetic regulation of nutrient metabolism began in that year during my sabbatical leave in the laboratory of Sir Hans Krebs at Oxford University. In the present article, I describe 2 episodes in my career during which I used genetic concepts to explain a nutritional phenomenon; the first episode occurred before doing the experimental work, and the second occurred after the experimental work was completed. My first brainstorm, which occurred in 1961, was to investigate the hypothesis that all of the fat-soluble vitamins act by the regulation of a cluster of genes. Unfortunately, I selected vitamin K as my model and discovered that it is the only fat-soluble vitamin that does not work in full or in part by the regulation of a set of genes. In 1967 I undertook a second problem, which was to determine the mode of action of polyunsaturated fatty acids in lowering plasma lipid concentrations in humans. We discovered that linoleic acid reduced the storage and enhanced the oxidation of fatty acids. The genetic interpretation of this study has come only recently: polyunsaturated fats have been shown to down-regulate enzymes that accomplish storage of fatty acids and to up-regulate genes that enhance fatty acid oxidation.

  16. A low absolute number of expanded transcripts is involved in myotonic dystrophy type 1 manifestation in muscle

    PubMed Central

    Gudde, Anke E. E. G.; González-Barriga, Anchel; van den Broek, Walther J. A. A.; Wieringa, Bé; Wansink, Derick G.

    2016-01-01

    Muscular manifestation of myotonic dystrophy type 1 (DM1), a common inheritable degenerative multisystem disorder, is mainly caused by expression of RNA from a (CTG·CAG)n-expanded DM1 locus. Here, we report on comparative profiling of expression of normal and expanded endogenous or transgenic transcripts in skeletal muscle cells and biopsies from DM1 mouse models and patients in order to help us in understanding the role of this RNA-mediated toxicity. In tissue of HSALR mice, the most intensely used ‘muscle-only’ model in the DM1 field, RNA from the α-actin (CTG)250 transgene was at least 1000-fold more abundant than that from the Dmpk gene, or the DMPK gene in humans. Conversely, the DMPK transgene in another line, DM500/DMSXL mice, was expressed ∼10-fold lower than the endogenous gene. Temporal regulation of expanded RNA expression differed between models. Onset of expression occurred remarkably late in HSALR myoblasts during in vitro myogenesis whereas Dmpk or DMPK (trans)genes were expressed throughout proliferation and differentiation phases. Importantly, quantification of absolute transcript numbers revealed that normal and expanded Dmpk/DMPK transcripts in mouse models and DM1 patients are low-abundance RNA species. Northern blotting, reverse transcriptase–quantitative polymerase chain reaction, RNA-sequencing and fluorescent in situ hybridization analyses showed that they occur at an absolute number between one and a few dozen molecules per cell. Our findings refine the current RNA dominance theory for DM1 pathophysiology, as anomalous factor binding to expanded transcripts and formation of soluble or insoluble ribonucleoprotein aggregates must be nucleated by only few expanded DMPK transcripts and therefore be a small numbers game. PMID:26908607

  17. Small silencing RNAs: an expanding universe.

    PubMed

    Ghildiyal, Megha; Zamore, Phillip D

    2009-02-01

    Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.

  18. An expanding universe of noncoding RNAs.

    PubMed

    Storz, Gisela

    2002-05-17

    Noncoding RNAs (ncRNAs) have been found to have roles in a great variety of processes, including transcriptional regulation, chromosome replication, RNA processing and modification, messenger RNA stability and translation, and even protein degradation and translocation. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined. These findings raise several fundamental questions: How many ncRNAs are encoded by a genome? Given the absence of a diagnostic open reading frame, how can these genes be identified? How can all the functions of ncRNAs be elucidated?

  19. Small silencing RNAs: an expanding universe

    PubMed Central

    Ghildiyal, Megha; Zamore, Phillip D.

    2009-01-01

    Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats. PMID:19148191

  20. Infrastructure Requirements for an Expanded Fuel Ethanol Industry

    SciTech Connect

    Reynolds, Robert E.

    2002-01-15

    This report provides technical information specifically related to ethanol transportation, distribution, and marketing issues. This report required analysis of the infrastructure requirements for an expanded ethanol industry.

  1. Exploring the expanded practice roles of community mental health nurses.

    PubMed

    Elsom, Stephen; Happell, Brenda; Manias, Elizabeth

    2007-04-01

    Significant changes to the delivery of mental health services have resulted in the expansion of the community mental health nursing role. This qualitative study was undertaken to explore the extent to which community mental health nurses are currently engaged in expanded forms of practice. Focus groups were undertaken with community mental health nurses (n = 27) from metropolitan and rural Victoria, Australia. Thematic analysis identified the following major themes: reported practice, consumers as beneficiaries of expanded practice, risk of harm and litigation, and barriers to expanded practice. The findings emphasize the need for significant changes in current legislation if expanded practice for nurses is to become a reality.

  2. Expanding Ring for the DWPF Melter Pour Spout

    SciTech Connect

    Imrich, K.J.

    2002-09-23

    The Materials Technology Section was requested to develop a novel concept, namely that of an expanding ring, to restore the upper knife edge in the DWPF melter pour spout. The expanding ring is a unit that, when deployed in the DPWF pour spout, will self-expand against the inner diameter of the 3-inch section of the pour spout providing a seal against glass leakage and a new knife edge that will mate with a Type 3A insert. This report provides a summary of the final design features of the expanding ring and an overview of its development.

  3. Structural state of expanded graphite prepared from intercalation compounds

    SciTech Connect

    Teplykh, A. E. Bogdanov, S. G.; Dorofeev, Yu. A.; Pirogov, A. N.; Skryabin, Yu. N.; Makotchenko, V. G.; Nazarov, A. S.; Fedorov, V. E.

    2006-12-15

    The structural state of nanocrystalline samples of expanded graphite is investigated using X-ray diffraction and neutron diffraction analyses. The expanded graphite samples are prepared by a rapid thermal decomposition of intercalation compounds of oxidized graphite based on fluorinated graphite, graphite oxide, and graphite aminofluoride. It is established that the main phase of expanded graphite belongs to the hexagonal crystal system (space group P6{sub 3}/mmc) and that carbon atoms in the structure occupy the 2b and 2c positions. The unit cell parameters and the unit cell volume in the structure of expanded graphite samples are larger than those in the structure of massive graphite.

  4. Alterations in gp37 expand the host range of a T4-like phage.

    PubMed

    Chen, Mianmian; Zhang, Lei; Abdelgader, Sheikheldin A; Yu, Li; Xu, Juntian; Yao, Huochun; Lu, Chengping; Zhang, Wei

    2017-09-22

    The use of phages as antibacterial agents is limited by their generally narrow host range. The aim of this study was to make a T4-like phage, WG01, obtain the host range of another T4-like phage, QL01, by replacing its host determinant gene region with that of QL01. This process triggered a direct expansion of the WG01 host range. The offspring of WG01 obtained the host ranges of both QL01 and WG01, as well as the ability to infect eight additional host bacteria in comparison to the wildtype strains. WQD had the widest host range; therefore, the corresponding QD fragments could be used for constructing a homologous sequence library. Moreover, after a sequencing analysis of gene37, we identified two different mechanisms responsible for the expanded host range: 1) the first generation of WG01 formed chimeras without mutations; and 2) the second generation of WG01 mutants formed from the chimeras. The expansion of the host range indicated that regions other than the C-terminal region may indirectly change the receptor specificity by altering the supportive capacity of the binding site. Additionally, we also found that the subsequent generations acquired a novel means of expanding the host range through acquiring a wider temperature range for lysis by exchanging gene37. The method developed in this work offers a quick way to change or expand the host range of a phage. Future clinical applications for screening phages against a given clinical isolate could be achieved after acquiring more suitable homologous sequences.IMPORTANCE T4-like phages have been established as safe in numerous phage therapy applications. The primary drawbacks to the use of phages as therapeutic agents include their highly specific host range. Thus, changing or expanding the host range of T4-like phages is beneficial for selecting phages for phage therapy. In this study, the host range of one T4-like phage WG01 was expanded using genetic manipulation. The WG01 derivatives acquired a novel means

  5. In vitro comparison of self-expanding versus balloon-expandable stents in a human ex vivo model.

    PubMed

    Grenacher, Lars; Rohde, Stefan; Gänger, Ellen; Deutsch, Jochen; Kauffmann, Günter W; Richter, Götz M

    2006-01-01

    The objective was to compare the radial strength and expansile precision of self-expanding stents and balloon-expandable stents in a human cadaver bifurcation model. Seven different self-expanding (LUMINEXX, JOSTENT SelfX, JOSTENT SelfX hrf, Sinus-Repo, Sinus SuperFlex, Easy Wallstent, SMART) and four different balloon-expandable stent models (Palmaz, Sinus Stent, SAXX Medium, JOSTENT peripheral), each type 10 stents (total n = 110 stents) were implanted into the common iliac arteries of human cadaver corpses. The maximum stent diameter was 10 mm for all models. After stent implantation, the specimens were filled with silicone caoutchouc. After 24 h, the vascular walls including the stents were removed from the hardened casts. Diameters were taken and the weight of the cast cylinders was measured in air and in purified water to calculate the volume of the bodies (according to Archimedes Law) as a relative but precise degree for the radial strength of the implanted stents. The cylindrical casts of the self-expanding stents showed lower mean diameters (8.2 +/- 1.0 mm) and mean volumes (0.60 +/- 0.14 ml/cm) than in the balloon-expandable stent group (10.1 +/- 0.3 mm and 0.71 +/- 0.04 ml/cm, respectively; p < 0.01). The nominal maximum diameter of 10 mm was not achieved in any of the self-expanding stents, but this was achieved in more than 70% (29/40) of the balloon-expandable stent specimens (p < 0.05). The variation between achieved volumes was significantly larger in self-expanding (range: 0.23-0.78 ml/cm) than in balloon-expandable stents (range: 0.66-0.81 ml/cm; p < 0.05). Self-expanding stents presented considerably lower radial expansion force and lower degree of precision than balloon-expandable stents.

  6. In Vitro Comparison of Self-Expanding Versus Balloon-Expandable Stents in a Human Ex Vivo Model

    SciTech Connect

    Grenacher, Lars Rohde, Stefan Gaenger, Ellen; Deutsch, Jochen; Kauffmann, Guenter W.; Richter, Goetz M.

    2006-04-15

    The objective was to compare the radial strength and expansile precision of self-expanding stents and balloon-expandable stents in a human cadaver bifurcation model. Seven different self-expanding (LUMINEXX, JOSTENT SelfX, JOSTENT SelfX hrf, Sinus-Repo, Sinus SuperFlex, Easy Wallstent, SMART) and four different balloon-expandable stent models (Palmaz, Sinus Stent, SAXX Medium, JOSTENT peripheral), each type 10 stents (total n = 110 stents) were implanted into the common iliac arteries of human cadaver corpses. The maximum stent diameter was 10 mm for all models. After stent implantation, the specimens were filled with silicone caoutchouc. After 24 h, the vascular walls including the stents were removed from the hardened casts. Diameters were taken and the weight of the cast cylinders was measured in air and in purified water to calculate the volume of the bodies (according to Archimedes Law) as a relative but precise degree for the radial strength of the implanted stents. The cylindrical casts of the self-expanding stents showed lower mean diameters (8.2 {+-} 1.0 mm) and mean volumes (0.60 {+-} 0.14 ml/cm) than in the balloon-expandable stent group (10.1 {+-} 0.3 mm and 0.71 {+-} 0.04 ml/cm, respectively; p < 0.01). The nominal maximum diameter of 10 mm was not achieved in any of the self-expanding stents, but this was achieved in more than 70% (29/40) of the balloon-expandable stent specimens (p < 0.05). The variation between achieved volumes was significantly larger in self-expanding (range: 0.23-0.78 ml/cm) than in balloon-expandable stents (range: 0.66-0.81 ml/cm; p < 0.05). Self-expanding stents presented considerably lower radial expansion force and lower degree of precision than balloon-expandable stents.

  7. Comparison of latest generation transfemoral self-expandable and balloon-expandable transcatheter heart valves.

    PubMed

    Schaefer, Andreas; Linder, Matthias; Seiffert, Moritz; Schoen, Gerhard; Deuschl, Florian; Schofer, Niklas; Schneeberger, Yvonne; Blankenberg, Stefan; Reichenspurner, Hermann; Schaefer, Ulrich; Conradi, Lenard

    2017-06-26

    We herein aimed to compare acute 30-day outcomes of latest-generation self-expandable and balloon-expandable transcatheter heart valves. From 2012 through 2016, 104 consecutive patients (study group, 69.2% female, 81.7 ± 5.5 years, logEuroSCORE I 15.9 ± 9.3%) received transfemoral transcatheter aortic valve implantation using the Symetis ACURATE neo ® transcatheter heart valve. A control group of patients after transfemoral transcatheter aortic valve implantation with the Edwards Sapien 3™ transcatheter heart valve was retrieved from our database and matched to the study group. Data were retrospectively analysed according to updated Valve Academic Research Consortium definitions. Device success was 94.2% (98 of 104) and 98.1% (102 of 104) in study and control groups, respectively ( P  = 0.157). All-cause 30-day mortality was 3.9 (4 of 104) vs 0.9% (1 of 104) ( P =  0.317). Resultant transvalvular peak/mean gradients and effective orifice area were 14.2 ± 5.7 vs 22.6 ± 6.8 mmHg ( P  < 0.001)/7.3 ± 2.8 vs 11.8 ± 3.5 mmHg ( P  < 0.001) and 2.0 ± 0.4 vs 1.7 ± 0.4 cm 2 ( P =  0.063). Paravalvular leakage ≥moderate was observed in 4.8% (5 of 104) and 1.9% (2 of 104) ( P =  0.257). Rate of permanent pacemaker implantation was 10.6% (11 of 104) vs 16.4% (17 of 104) ( P =  0.239). Next-generation self-expandable transcatheter heart valves preserve superiority in terms of post-interventional haemodynamics without presenting former drawbacks: rate of postoperative permanent pacemaker implantation and severity of residual paravalvular leakage were similar to balloon-expandable transcatheter heart valves.

  8. Vietnam seeks help expanding voluntary surgical contraception.

    PubMed

    Piet-pelon, N J; Sukop, S

    1992-07-01

    Recent surveys by the Vietnamese Ministry of Health suggest that 60% of married women desire no more children. Yet only 2% of currently married women and less than 1/2 of 1% of their partners use sterilization. Underscoring the high unmet need for effective family planning, over 1 million abortions (legal in Vietnam for the past 20 years) are performed annually. This rate corresponds to 1 abortion for every live birth. The Ministry of Health has recently welcomed a variety of organizations, including AVSC, whose assistance can help expand the country's family planning programs. Sorely lacking in supplies, equipment, and trained personnel, Vietnam has merited priority status--2nd only to China and India--from the UNFPA, which has committed $36 million over the next 4 years. Other organizations currently working in Vietnam include the Population Council, the Population Crisis Committee, and the International Planned Parenthood Federation. Despite enormous casualties during the war years, and a decrease since the 1970s in average family size from 6 to 4 children, the population of Vietnam has continued to grow rapidly, far outpacing economic growth. Currently 67 million, the population is expected to reach 80 million by the year 2000. The average Vietnamese annual income is only $195, among the lowest in the world. Doi moi, the process of economic reform begun in 1986, coupled with new government incentives for families who have no more than 2 children, is changing the face of family planning in Vietnam. Newly opened pharmacies sell imported birth control pills and condoms (to those who can afford them), while government hospitals and health clinics provide mainly IUDs, in addition to limited supplies of pills and condoms. Throughout the country, some 8000 community-level health centers are staffed by nurse-midwives trained in family planning. Voluntary sterilization is available at the district, provincial, and national hospitals. All married women may obtain family

  9. Expanding the scope of lamellar keratoplasty.

    PubMed Central

    Rich, L F

    1999-01-01

    PURPOSE: To investigate whether applications of current technology, such as cryolathe and excimer laser, might improve outcomes and increase use of lamellar keratoplasty. METHODS: Six studies were performed, beginning with animals and progressing to human subjects. The first study compared cryolathed with hand-dissected rabbit corneas to ascertain which created a smoother donor interface. The second animal pilot study was done to determine whether thickness of donor cornea resection could be accurately predicted with the cryolathe. A prospective animal trial was then undertaken to compare lamellar keratoplasty outcomes using cryolathed versus hand-dissected tissue. The fourth work extrapolated previous animal findings to lamellar keratoplasty in human disease. Finally, two ongoing studies are described. The first explores the possibility of sutureless lamellar keratoplasty. The second utilizes the excimer laser to dissect the recipient stromal bed. RESULTS: The initial animal pilot study demonstrated a clearer stromal surface in cryolathed versus hand-dissected corneal tissue. The second pilot showed that plano-powered donor tissue could be generated to predetermined thickness. The prospective animal trial revealed that clear grafts of intended thickness could be obtained with cryolathing. Human studies suggested that lamellar keratoplasty using cryolathe-prepared donor tissue may offer superior results to free-hand dissection. Finally, one ongoing study indicates that sutureless lamellar keratoplasty is untenable, and the other shows that clear grafts can be obtained by combining cryolathed donor tissue with recipient photoablation. CONCLUSION: This body of work demonstrates that use of new lamellar keratoplasty technology may offer expanded scope and better outcomes than traditional lamellar keratoplasty techniques. Images FIGURE 1 FIGURE 3 FIGURE 4A FIGURE 4B FIGURE 8A FIGURE 8B FIGURE 9 FIGURE 10 FIGURE 10B FIGURE 11A FIGURE 11B FIGURE 12A FIGURE 12B FIGURE 13

  10. Expanding policy options for educating teenagers.

    PubMed

    Stern, David

    2009-01-01

    David Stern argues that some basic features of the American high school must be modified if it is to serve all students successfully. He notes, for example, that only three-quarters of U.S. high school students graduate four years after beginning ninth grade and that the National Assessment of Educational Progress found no improvement in reading or mathematics for seventeen-year-olds between 1971 and 2004. The nation's system for educating teenagers, says Stern, seems to be stuck, despite the constant efforts of teachers and repeated waves of reform. Citing two widely accepted public purposes of educating teenagers-preparation for civic participation and for economic self-sufficiency-Stern proposes four new strategies to achieve those goals. He draws on empirical evidence suggesting that these are promising directions for research and policy, but acknowledges that existing studies provide only limited guidance. First, he says, schools should continue the current trend toward integrating educational options to provide young people with skills and experiences that pave the way to both college and careers. Second, states and districts should tie education funding not simply to the number of students attending school, but also to what young people learn, whether they graduate, and whether they find jobs or enroll in postsecondary education. Such a move, he argues, would encourage teaching and learning formats that use students' time more effectively. Third, more adults in addition to classroom teachers should be involved in educating teenagers. Other adults acting as academic advisers, learning coaches, student advocates, internship supervisors, mentors, and college counselors could help guide the education of teenagers inside and outside of school and provide some relief for the chronic shortage of teachers. Fourth, schools should expand the options for educating teenagers outside of geographically fixed schools. Combining improved Internet-based curriculum with

  11. GeneCards Version 3: the human gene integrator

    PubMed Central

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73 000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards’ unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene’s functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite

  12. Study and design of beam expander with wide aperture

    NASA Astrophysics Data System (ADS)

    Guo, Ming; Jin, Guangyong; Cai, Jixing; Zhang, Wei; Wei, Zhi

    2014-12-01

    In order to improve the capacity of beam collimation for laser beam expander, it is necessary to design a more reasonable and feasible structure of beam expander system. Laser beam expander is used to compress the laser divergence angle, in order to reduce the energy losing in long distance scanning acquisition system. This paper introduces the working principle and design idea of the laser beam expander, the collimating multiplying power focal length and the collimated magnification formula of expander main, secondary mirror. According to the third-order aberration theory, Considering the spherical aberration, sine difference and divergence angle, the reasonable analysis of optical path, ZEMAX optical design software was used to design large-diameter laser beam expander and analysis and optimize, And given the actual design data and results. Display the maximum optical path difference is +/-0.01λ of the main light ray and each light ray. To combination the rear- group objective lens of Galileo and Kepler beam expander, a large-diameter(1.475m) laser beam expander was designed with 0.2m in the diameter, 1/2m in the relative caliber. In the objective lens System, a high-order aspherical was used to the aberration of extra-axial point. we can see that the image quality is close to the diffraction limit from the curves of wavefront. In addition to improve image quality effectively, the system has the characteristics of simple structure, less costly and less design difficulty to compare with the other beam expanding system. And make the output beam's divergence angle smaller, energy density higher, and the beam quality has been greatly improved. The results show that the beam expander is fully meet the design requirements, the use effect is good. Design and research of laser beam expanding system not only improves the quality of the laser beam in the laser system, but also enlarge the application field of laser technology in photoelectric system.

  13. Supporting Student Success: The Promise of Expanded Learning Opportunities

    ERIC Educational Resources Information Center

    NGA Center for Best Practices, 2010

    2010-01-01

    Expanded learning opportunities (ELOs) support state education goals by providing safe, structured learning environments for students outside the regular school day. ELOs include after-school and summer learning programs, as well as before-school, evening, and weekend programs. Although research demonstrates that high-quality expanded learning…

  14. New York: Expanding Time, Increasing Opportunities for Achievement

    ERIC Educational Resources Information Center

    Miller, Tiffany D.

    2014-01-01

    New York is poised to take an important step to improve student achievement by expanding learning time for students attending high-poverty, low-performing schools. Recent district- and state-level investments in expanded learning time--a promising strategy to close achievement and opportunity gaps--will give students more time to learn core…

  15. Still Not Equal: Expanding Educational Opportunity in Society

    ERIC Educational Resources Information Center

    Brown, M. Christopher, II, Ed.

    2007-01-01

    "Still Not Equal: Expanding Educational Opportunity in Society" addresses the successes and failures of "Brown v. Board of Education" and the Civil Rights Act of 1964, as well as the continuing challenge of expanding educational opportunity in the United States and across the Black diaspora. The educational, political, and social influence…

  16. Still Not Equal: Expanding Educational Opportunity in Society

    ERIC Educational Resources Information Center

    Brown, M. Christopher, II, Ed.

    2007-01-01

    "Still Not Equal: Expanding Educational Opportunity in Society" addresses the successes and failures of "Brown v. Board of Education" and the Civil Rights Act of 1964, as well as the continuing challenge of expanding educational opportunity in the United States and across the Black diaspora. The educational, political, and social influence…

  17. The helical screw expander evaluation project. [for geothermal wells

    NASA Technical Reports Server (NTRS)

    Mckay, R. A.

    1977-01-01

    A positive-displacement helical-screw expander of the Lysholm type has been adapted for geothermal service and successfully demonstrated in a 50 kW prototype power system. Evaluation of the expander by tests of a new model in a 1 MW power system under wellhead conditions in selected liquid-dominated geothermal fields is proposed. The objectives are to determine the performance characteristics of the expander and power system over a broad range of operating conditions and also to examine the concept of wellhead power plants. Throttling and fractionation of the fluids from the test wells is planned to simulate a wide range of wellhead pressures and steam fractions. Variation in the expander exhaust pressure is also planned. The investigation will include expander efficiency, corrosion, erosion, scale formation and control, and endurance testing. Interaction studies with the wells and an electric grid are also proposed.

  18. The helical screw expander evaluation project. [for geothermal wells

    NASA Technical Reports Server (NTRS)

    Mckay, R. A.

    1977-01-01

    A positive-displacement helical-screw expander of the Lysholm type has been adapted for geothermal service and successfully demonstrated in a 50 kW prototype power system. Evaluation of the expander by tests of a new model in a 1 MW power system under wellhead conditions in selected liquid-dominated geothermal fields is proposed. The objectives are to determine the performance characteristics of the expander and power system over a broad range of operating conditions and also to examine the concept of wellhead power plants. Throttling and fractionation of the fluids from the test wells is planned to simulate a wide range of wellhead pressures and steam fractions. Variation in the expander exhaust pressure is also planned. The investigation will include expander efficiency, corrosion, erosion, scale formation and control, and endurance testing. Interaction studies with the wells and an electric grid are also proposed.

  19. Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells

    PubMed Central

    Najm, Fadi J.; Lager, Angela M.; Zaremba, Anita; Wyatt, Krysta; Caprariello, Andrew V.; Factor, Daniel C.; Karl, Robert T.; Maeda, Tadao; Miller, Robert H.; Tesar, Paul J.

    2013-01-01

    Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to “induced” oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies. PMID:23584611

  20. Genitopatellar syndrome: expanding the phenotype and excluding mutations in LMX1B and TBX4.

    PubMed

    Abdul-Rahman, Omar A; La, Trang H; Kwan, Andrea; Schlaubitz, Silke; Barsh, Greg S; Enns, Gregory M; Hudgins, Louanne

    2006-07-15

    Genitopatellar syndrome is a newly described disorder characterized by absent/hypoplastic patellae, lower extremity contractures, urogenital anomalies, dysmorphic features, skeletal anomalies, and agenesis of the corpus callosum. More recently, cardiac anomalies and ectodermal dysplasia have been suggested as additional features of this syndrome. We report on two additional patients with genitopatellar syndrome and expand the spectrum of anomalies to include radio-ulnar synostosis. Since there exists significant overlap in the skeletal phenotype between genitopatellar syndrome and both the nail-patella and short patella syndromes, mutation screening of their causative genes, LMX1B and TBX4, was performed. Although there still does not appear to be an identifiable molecular etiology in genitopatellar syndrome, mutations in these two candidate genes have been excluded in our patients. Since both LMX1B and TBX4 are involved in a common molecular pathway, it is likely that the causative gene of genitopatellar syndrome functions within the same developmental process.

  1. The expanding family of hypophosphatemic syndromes.

    PubMed

    Carpenter, Thomas O

    2012-01-01

    Investigation of X-linked hypophosphatemia (XLH) has led to the identification of a novel phosphate-regulating homeostatic system. Initially considered vitamin D-refractory rickets, renal phosphate wasting was identified as the cardinal biochemical feature of XLH and several related disorders. Current therapy employs calcitriol and phosphate, which usually improves, but does not completely heal deformities and short stature. Later complications of XLH include development of osteophytes, entheses, and osteoarthritis. The mutated gene in XLH, PHEX, is expressed in osteocytes, but its role in the pathogenesis of phosphate wasting is poorly understood. Many hypophosphatemic disorders are mediated by FGF23, a unique fibroblast growth factor with endocrine properties. Renal action of FGF23 leads to reduced expression of type II sodium-phosphate co-transporters, as well as reduced expression of CYP27B1, which encodes vitamin D 1α-hydroxylase. FGF23-mediated hypophosphatemia is characterized by inappropriately normal circulating 1,25-dihydroxyvitamin D together with renal phosphate wasting. The FGF23 system serves as a novel mechanism by which the mineralizing skeleton can communicate phosphate supply to the kidney and thereby mediate excretion or conservation of this important skeletal component. Other forms of FGF23-mediated hypophosphatemia represent various aberrations in this axis. Secretion of excess FGF23 (as in tumor-induced osteomalacia), and mutations preventing proteolytic cleavage of FGF23 result in similar clinical features. Other hypophosphatemic disorders are discussed.

  2. Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

    PubMed Central

    Tian, Xia; Liang, Wen-Chen; Feng, Yanming; Wang, Jing; Zhang, Victor Wei; Chou, Chih-Hung; Huang, Hsien-Da; Lam, Ching Wan; Hsu, Ya-Yun; Lin, Thy-Sheng; Chen, Wan-Tzu

    2015-01-01

    Objective: To establish and evaluate the effectiveness of a comprehensive next-generation sequencing (NGS) approach to simultaneously analyze all genes known to be responsible for the most clinically and genetically heterogeneous neuromuscular diseases (NMDs) involving spinal motoneurons, neuromuscular junctions, nerves, and muscles. Methods: All coding exons and at least 20 bp of flanking intronic sequences of 236 genes causing NMDs were enriched by using SeqCap EZ solution-based capture and enrichment method followed by massively parallel sequencing on Illumina HiSeq2000. Results: The target gene capture/deep sequencing provides an average coverage of ∼1,000× per nucleotide. Thirty-five unrelated NMD families (38 patients) with clinical and/or muscle pathologic diagnoses but without identified causative genetic defects were analyzed. Deleterious mutations were found in 29 families (83%). Definitive causative mutations were identified in 21 families (60%) and likely diagnoses were established in 8 families (23%). Six families were left without diagnosis due to uncertainty in phenotype/genotype correlation and/or unidentified causative genes. Using this comprehensive panel, we not only identified mutations in expected genes but also expanded phenotype/genotype among different subcategories of NMDs. Conclusions: Target gene capture/deep sequencing approach can greatly improve the genetic diagnosis of NMDs. This study demonstrated the power of NGS in confirming and expanding clinical phenotypes/genotypes of the extremely heterogeneous NMDs. Confirmed molecular diagnoses of NMDs can assist in genetic counseling and carrier detection as well as guide therapeutic options for treatable disorders. PMID:27066551

  3. More and Better Learning: Year Three Report on the National Demonstration of ExpandED Schools. A TASC Report

    ERIC Educational Resources Information Center

    Traill, Saskia; Brohawn, Katie

    2015-01-01

    In the 2013-14 school year, TASC entered the third year of its national demonstration of ExpandED Schools. Ten elementary and middle schools in New York City, Baltimore and New Orleans continued their partnerships with youth-serving community organizations, such as settlement houses or community development corporations. Together, principals,…

  4. Distant Supernovae Indicate Ever-Expanding Universe

    NASA Astrophysics Data System (ADS)

    1998-12-01

    ESO Astronomers Contribute towards Resolution of Cosmic Puzzle Since the discovery of the expansion of the Universe by American astronomer Edwin Hubble in the 1920's, by measurement of galaxy velocities, astronomers have tried to learn how this expansion changes with time. Until now, most scientists have been considering two possibilities: the expansion rate is slowing down and will ultimately either come to a halt - whereafter the Universe would start to contract, or it will continue to expand forever. However, new studies by two independent research teams, based on observations of exploding stars ( supernovae ) by ESO astronomers [1] with astronomical telescopes at the La Silla Observatory as well as those of their colleagues at other institutions, appear to show that the expansion of the Universe is accelerating . The results take the discovery of the cosmological expansion one step further and challenge recent models of the Universe. If the new measurements are indeed correct, they show that the elusive "cosmological constant" , as proposed by Albert Einstein , contributes significantly to the evolution of the Universe. The existence of a non-zero cosmological constant implies that a repulsive force, counter-acting gravity, currently dominates the universal expansion , and consequently leads to an ever-expanding Universe. This new research is being named as the "Breakthrough of the Year" by the renowned US science journal Science in the December 18, 1998, issue. A Press Release is published by the journal on this occasion. "Fundamental Parameters" of the Universe Three fundamental parameters govern all cosmological models based on the theory of General Relativity. They are 1. the current expansion rate as described by Hubble's constant , i.e. the proportionality factor between expansion velocity and distance 2. the average matter density in the Universe, and 3. the amount of "other energy" present in space. From the measured values of these fundamental

  5. Expandable light tablet tool (XLTT): an expandable digital light tablet tool

    NASA Astrophysics Data System (ADS)

    Gruber, Michael; Walcher, Wolfgang

    1994-08-01

    The importance of digital images has increased and the need for hard- and software tools for creating, archiving, and managing digital images as well for image manipulation and image mensuration. The XLTT software (expandable light tablet tool) is designed to access medium sized digital images (usually 10 to 50 Megapixels each) and allow image coordinate mensuration with subpixel accuracy. Great efforts were spent on the design of the graphical user interface, which gives access to multiple images at a time and allows simultaneous coordinate mensuration of identical points. XLTT is modeled as a digitizer for convenient image mensuration. Additional functions, like image enhancement, geometric transformation of images, stereo mensuration of image pairs, and image correlation are also available. XLTT was developed using IDL+R) and C and is implemented on silicon graphics workstations.

  6. Comparison of Outcomes of Balloon-Expandable Versus Self-Expandable Transcatheter Heart Valves for Severe Aortic Stenosis.

    PubMed

    Wijeysundera, Harindra C; Qiu, Feng; Koh, Maria; Prasad, Treesa J; Cantor, Warren J; Cheema, Asim; Chu, Michael W A; Czarnecki, Andrew; Feindel, Christopher; Fremes, Stephen E; Kingsbury, Kori J; Natarajan, Madhu K; Peterson, Mark; Ruel, Marc; Strauss, Bradley; Ko, Dennis T

    2017-04-01

    Transcatheter aortic valve implantation (TAVI) is the treatment of choice for inoperable and high-risk patients with severe aortic stenosis. Our objectives were to elucidate potential differences in clinical outcomes and safety between balloon-expandable versus self-expandable transcatheter heart valves (THV). We performed a retrospective cohort study of all transfemoral TAVI procedures in Ontario, Canada, from 2007 to 2013. Patients were categorized into either balloon-expandable or self-expandable THV groups. The primary outcomes were 30-day and 1-year death, with secondary outcomes of all-cause readmission. Safety outcomes included bleeding, permanent pacemaker implantation, need for a second THV device, postprocedural paravalvular aortic regurgitation, stroke, vascular access complication, and intensive care unit length of stay. Inverse probability of treatment-weighted regression analyses using a propensity score were used to account for differences in baseline confounders. Our cohort consisted of 714 patients, of whom 397 received a self-expandable THV, whereas 317 had a balloon-expandable THV system. There were no differences in death or all-cause readmission. In terms of safety, the self-expandable group was associated with significantly higher rates of inhospital stroke (p value <0.05), need for a second THV device (5.3% vs 2.7%; p value = 0.013), and permanent pacemaker (22.6% vs 8.9%; p value <0.001), whereas the balloon-expandable group had more vascular access site complications (23.1% vs 16.7%; p value = 0.002). Thus, we found similar clinical outcomes of death or readmission for patients who underwent transfemoral TAVI with either balloon-expandable or self-expandable THV systems. However, there were important differences in their safety profiles.

  7. Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family.

    PubMed

    Amador, Claudia; Mathews, Anne M; Del Carmen Montoya, Maria; Laughridge, Mary E; Everman, David B; Holden, Kenton R

    2008-08-01

    We report a 4-generation Hispanic family with oculodentodigital dysplasia whose members were found to have typical phenotypic characteristics of this disorder, as well as a variable expression of neurologic manifestations in multiple generations ranging from a mild spastic gait to moderate to severe spastic tetraparesis/quadriplegia with epilepsy and an abnormal brain and spinal cord magnetic resonance imaging result. Gene testing documented a previously reported missense mutation in GJA1 (connexin 43) exon 2 (c.389T>C;p.I130T). Our evaluation not only expands the phenotypes associated with GJA1 gene mutations but also demonstrates that a great degree of variability in neurological defects can exist within a single family without evidence of genetic anticipation. A genotype-phenotype correlation between the p.I130T mutation and neurologic dysfunction appears more likely with the addition of this report's neurologic and GJA1 gene mutation findings. These findings expand the neurologic phenotype and prognosis and underscore the importance of counseling families with oculodentodigital dysplasia about the possibility of neurologic involvement.

  8. Improved expanding ring technique for determining dynamic material properties.

    PubMed

    Liang, M Z; Li, X Y; Qin, J G; Lu, F Y

    2013-06-01

    An improved expanding ring experimental technique has been described to determine dynamic material properties under conditions approximating uniform one-dimensional tensile loading. There are mainly explosive expanding ring technique and electromagnetic expanding ring technique currently, for which exist many limitations in practical applications. The work reported herein is an attempt to overcome this difficulty by lateral efficiency loading produced by projectile, made of low-density material, impacting the same material filling. The lateral efficiency loading is a convenient and effective method, which allows materials to be in uniform uniaxial stress conditions at a high stress rate. The procedure is illustrated by experiments performed on 1100-0 aluminum rings.

  9. Balloon-expandable Metallic Stents for Airway Diseases.

    PubMed

    Ohki, Takashi; Sugimoto, Seiichiro; Kurosaki, Takeshi; Otani, Shinji; Miyoshi, Kentaroh; Yamane, Masaomi; Miyoshi, Shinichiro; Oto, Takahiro

    2016-10-01

    Stent placement is an essential treatment for airway diseases. Although self-expandable metallic stents and silicone stents are commonly applied for the treatment of airway diseases, these stents are unsuitable for the treatment of small airway diseases encountered in pediatric patients and lung transplant recipients with airway complications. Currently, only vascular balloon-expandable metallic stents are available for the treatment of small airway diseases; however, little research has been conducted on the use of these stents in this field. We have launched a prospective feasibility study to clarify the safety and efficacy of balloon-expandable metallic stents for the treatment of airway diseases.

  10. Preparative chromatography of xylanase using expanded bed adsorption.

    PubMed

    Silvino, DosSantosEveraldo; Guirardello, Reginaldo; Teixeira, Franco Telma

    2002-01-25

    Expanded bed adsorption was used to purify a marketable xylanase often used in the kraft pulp bleaching process. Experiments in packed and expanded beds were carried out mainly to study the adsorption of xylanase on to a cationic adsorbent (Streamline SP) in the presence of cells. In order to study the presence of cells, a Bacillus pumilus mass (5% wet mass) was mixed with the enzyme extract and submitted to an expanded bed adsorption system. One xylanase was purified to homogeneity in the packed bed. However, the 5% cell content hampered purification.

  11. Expandable Total Humeral Replacement in a Child with Osteosarcoma

    PubMed Central

    Henderson, Eric R.; Gao, Jidi; Groundland, John; Letson, G. Douglas

    2015-01-01

    Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient's success indicates that expandable total humeral replacement is a viable option. PMID:26090254

  12. [Research of pressure of skin soft tissue expander].

    PubMed

    Xu, Kunming; Li, Hongmian; Luo, Zhijun; Li, Qingfeng

    2013-03-01

    To investigate the change law of the intracapsular pressure in vitro without outside force and the pressure of the expander upon the skin soft tissue in vivo during clinical routine expansion so as to provide some references for the safe application of the expander. The rectangle expanders of 50, 80, 100, 150, 200, 250, 300, and 400 mL were used for in vitro expansion at room temperature to 400% volume of the expander capacity. The pressures before and after saline injection were recorded. Twelve patients who needed scar plastic surgery were enrolled; 17 rectangle expanders were implanted in 5 areas (cheek, trunk, forehead and temporal, limb, and head) and expanded routinely. The pressures before and after saline injection were recorded. The pressure of the expander upon the skin soft tissue was calculated and the values of the pressure at 50%, 100%, 150%, and 200% volume of 5 areas were chosen and analyzed statistically. The intracapsular pressure of the expanders at different volumes in vitro without outside force during routine expansion before and after saline injection was beyond 0 mm Hg (1 mm Hg=0.133 kPa) at around 100% volume, increased rapidly from 100% to 250% volume, and kept stable from 250% to 400% volume. In vivo, 16 expanders within 200% volume had the maximum pressure before saline injection, 15 had the maximum pressure after saline injection. Before saline injection, the pressure of the expander upon the skin soft tissue was lowest in the cheek, showing significant difference when compared with those of the forehead and temporal and head (P < 0.05); the pressure in the trunk was significantly lower than that in the head (P < 0.05); and there was no significant difference between the other body sites (P > 0.05). After saline injection, the pressure of the expander upon the skin soft tissue was lowest in the cheek, and showed an increasing trend in the trunk, the limb, the forehead and temporal, and the head; no significant difference was found

  13. Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular localization and toxicity of polyQ disease protein via exportin-1.

    PubMed

    Chan, Wing Man; Tsoi, Ho; Wu, Chi Chung; Wong, Chi Hang; Cheng, Tat Cheung; Li, Hoi Yeung; Lau, Kwok Fai; Shaw, Pang Chui; Perrimon, Norbert; Chan, Ho Yin Edwin

    2011-05-01

    Polyglutamine (polyQ) diseases are a group of late-onset, progressive neurodegenerative disorders caused by CAG trinucleotide repeat expansion in the coding region of disease genes. The cell nucleus is an important site of pathology in polyQ diseases, and transcriptional dysregulation is one of the pathologic hallmarks observed. In this study, we showed that exportin-1 (Xpo1) regulates the nucleocytoplasmic distribution of expanded polyQ protein. We found that expanded polyQ protein, but not its unexpanded form, possesses nuclear export activity and interacts with Xpo1. Genetic manipulation of Xpo1 expression levels in transgenic Drosophila models of polyQ disease confirmed the specific nuclear export role of Xpo1 on expanded polyQ protein. Upon Xpo1 knockdown, the expanded polyQ protein was retained in the nucleus. The nuclear disease protein enhanced polyQ toxicity by binding to heat shock protein (hsp) gene promoter and abolished hsp gene induction. Further, we uncovered a developmental decline of Xpo1 protein levels in vivo that contributes to the accumulation of expanded polyQ protein in the nucleus of symptomatic polyQ transgenic mice. Taken together, we first showed that Xpo1 is a nuclear export receptor for expanded polyQ domain, and our findings establish a direct link between protein nuclear export and the progressive nature of polyQ neurodegeneration.

  14. Massive expanding hematoma of the chin following blunt trauma

    PubMed Central

    Niazi, K. Thanvir Mohamed; Raja, Dharmesh Kumar; Prakash, R.; Balaji, V. R.; Manikandan, D.; Ulaganathan, G.; Yoganandha, R.

    2016-01-01

    Posttraumatic hematoma of the face is common and usually self-limiting in nature. We report an unusual massive expanding hematoma of the chin within 9 h following a blunt trauma with no associated injuries or fracture. PMID:27829776

  15. Environmental assessment, expanded Ponnequin wind energy project, Weld County, Colorado

    SciTech Connect

    1999-02-01

    The US Department of Energy (DOE) has considered a proposal from the State of Colorado, Office of Energy Conservation (OEC), for funding construction of the Expanded Ponnequin Wind Project in Weld County, Colorado. OEC plans to enter into a contracting arrangement with Public Service Company of Colorado (PSCo) for the completion of these activities. PSCo, along with its subcontractors and business partners, are jointly developing the Expanded Ponnequin Wind Project. The purpose of this Final Environmental Assessment (EA) is to provide DOE and the public with information on potential environmental impacts associated with the Expanded Ponnequin Wind Energy Project. This EA, and public comments received on it, were used in DOE`s deliberations on whether to release funding for the expanded project under the Commercialization Ventures Program.

  16. Nitrogen expander cycles for large capacity liquefaction of natural gas

    SciTech Connect

    Chang, Ho-Myung; Park, Jae Hoon; Gwak, Kyung Hyun; Choe, Kun Hyung

    2014-01-29

    Thermodynamic study is performed on nitrogen expander cycles for large capacity liquefaction of natural gas. In order to substantially increase the capacity, a Brayton refrigeration cycle with nitrogen expander was recently added to the cold end of the reputable propane pre-cooled mixed-refrigerant (C3-MR) process. Similar modifications with a nitrogen expander cycle are extensively investigated on a variety of cycle configurations. The existing and modified cycles are simulated with commercial process software (Aspen HYSYS) based on selected specifications. The results are compared in terms of thermodynamic efficiency, liquefaction capacity, and estimated size of heat exchangers. The combination of C3-MR with partial regeneration and pre-cooling of nitrogen expander cycle is recommended to have a great potential for high efficiency and large capacity.

  17. Complementary and Alternative Medicine (CAM): Expanding Horizons of Health Care

    MedlinePlus

    ... Past Issues Special Section CAM Expanding Horizons of Health Care Past Issues / Winter 2009 Table of Contents For ... and why it is important to tell your health care providers about your use of CAM. We hope ...

  18. The Rate of Expanded Inner Speech During Spontaneous Sentence Productions.

    PubMed

    Netsell, Ronald; Kleinsasser, Steven; Daniel, Todd

    2016-10-01

    The rate of expanded inner speech and speech aloud was compared in 20 typical adults (3 males, 17 females; M age = 24 years, SD = 4). Participants generated and timed spontaneous sentences with both expanded inner speech and speech aloud following the instruction to say "the first thing that comes to mind." The rate of expanded inner speech was slightly, but significantly, faster than the rate of speech aloud. The findings supported the hypothesis that expanded inner speech was faster than speech aloud because of the time required to move the articulators in the latter. Physical measures of speaking rate are needed to validate self-timed measures. Limitations of the study and directions for research are discussed. © The Author(s) 2016.

  19. Massive expanding hematoma of the chin following blunt trauma.

    PubMed

    Niazi, K Thanvir Mohamed; Raja, Dharmesh Kumar; Prakash, R; Balaji, V R; Manikandan, D; Ulaganathan, G; Yoganandha, R

    2016-10-01

    Posttraumatic hematoma of the face is common and usually self-limiting in nature. We report an unusual massive expanding hematoma of the chin within 9 h following a blunt trauma with no associated injuries or fracture.

  20. Building an expanded learning time and opportunities school: principals' perspectives.

    PubMed

    Malone, Helen Janc

    2011-01-01

    Four principals from New York City, Los Angeles, and Houston share their schools' journeys of how they expanded learning time and opportunities to best meet their students' academic and developmental needs. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

  1. The use of a self-expandable stent with a self-expandable stent graft in a Fontan baffle.

    PubMed

    Choi, Eun Young; Lee, Kyung Suk; Song, Jin-young

    2013-02-01

    Intravascular or intracardiac stenosis occurs in various congenital heart diseases or after surgical repair. Although balloon angioplasty is the first option for relieving stenosis, frequently restenosis occurs because of elastic recoil or kingking component. The use of a self-expandable stent and covered stent in congenital heart disease has been reported for selected cases. In general, they have been performed for coarctation of the aorta or aortic aneurysm. We now report successful implantation of a self-expandable stent with a self-expandable covered stent graft in a case of lateral tunnel dehiscence with stenosis after a Fontan operation.

  2. Analytic Solution of the Boltzmann Equation in an Expanding System.

    PubMed

    Bazow, D; Denicol, G S; Heinz, U; Martinez, M; Noronha, J

    2016-01-15

    For a massless gas with a constant cross section in a homogeneous, isotropically expanding spacetime we reformulate the relativistic Boltzmann equation as a set of nonlinear coupled moment equations. For a particular initial condition this set can be solved exactly, yielding the first analytical solution of the Boltzmann equation for an expanding system. The nonequilibrium behavior of this relativistic gas can be mapped onto that of a homogeneous, static nonrelativistic gas of Maxwell molecules.

  3. Self-Expanding, Tough Biodegradable Elastomers for Wound Stasis

    DTIC Science & Technology

    2015-08-06

    the civilian setting, with no effective therapies available at point of injury. We previously reported that a self- expanding polyurethane foam...setting, with no effective therapies available at point of injury. We previously reported that a self-expanding polyurethane foam significantly...externalized percutaneously. Routine abdominal fascial closure was performed using #1 Nylon suture (Ethicon). Retraction of the cutting wire in a sawing

  4. Expanding the Scope of High-Performance Computing Facilities

    SciTech Connect

    Uram, Thomas D.; Papka, Michael E.

    2016-05-01

    The high-performance computing centers of the future will expand their roles as service providers, and as the machines scale up, so should the sizes of the communities they serve. National facilities must cultivate their users as much as they focus on operating machines reliably. The authors present five interrelated topic areas that are essential to expanding the value provided to those performing computational science.

  5. Experimental and Analytical Study of a Steam Vane Expander

    DTIC Science & Technology

    1977-02-01

    expander. Additionally, friction and to a lesser extent leakage , have been modeled in vane air compressors and in the Rovac machine utilizing techniques...Schematic Diagram of Vane Expander Model .. ......... ... 27 8. Vane Free Body Diagram ...... ................. .... 29 9. Leakage Paths for a...capability to predict transient pressure effects. 3 Peterson and McGahan [3] developed a thermodynamic model of an oil flooded sliding vane air

  6. Free-piston reciprocating cryogenic expander utilizing phase controller

    NASA Astrophysics Data System (ADS)

    Cha, Jeongmin; Park, Jiho; Kim, Kyungjoong; Jeong, Sangkwon

    2017-02-01

    In a free-piston expander which eliminates mechanical linkages, a prescribed behaviour of the free-piston movement is the key to an expander performance. In this paper, we have proposed an idea of reducing complexity of the free-piston expander. It is to replace both multiple solenoid valves and reservoirs that are indispensable in a previous machine with a combination of a single orifice-reservoir assembly. It functions as a phase controller like that of a pulse tube refrigerator so that it generates time-delay of pressure variation between the warm-end and the reservoir resulting in the intended expansion of the cold-end volume down to the pre-set reservoir pressure. The modeling of this unique free-piston reciprocating expander utilizing phase controller is developed to understand and predict the performance of the new-type expander. Additionally, the operating parameters are analysed at the specified conditions to enable one to develop a more efficient free-piston type cryogenic expander.

  7. Regulation of expanded polyglutamine protein aggregation and nuclear localization by the glucocorticoid receptor.

    PubMed

    Diamond, M I; Robinson, M R; Yamamoto, K R

    2000-01-18

    Spinobulbar muscular atrophy and Huntington's disease are caused by polyglutamine expansion in the androgen receptor and huntingtin, respectively, and their pathogenesis has been associated with abnormal nuclear localization and aggregation of truncated forms of these proteins. Here we show, in diverse cell types, that glucocorticoids can up- or down-modulate aggregation and nuclear localization of expanded polyglutamine polypeptides derived from the androgen receptor and huntingtin through specific regulation of gene expression. Wild-type glucocorticoid receptor (GR), as well as C-terminal deletion derivatives, suppressed the aggregation and nuclear localization of these polypeptides, whereas mutations within the DNA binding domain and N terminus of GR abolished this activity. Surprisingly, deletion of a transcriptional regulatory domain within the GR N terminus markedly increased aggregation and nuclear localization of the expanded polyglutamine proteins. Thus, aggregation and nuclear localization of expanded polyglutamine proteins are regulated cellular processes that can be modulated by a well-characterized transcriptional regulator, the GR. Our findings suggest approaches to study the molecular pathogenesis and selective neuronal degeneration of polyglutamine expansion diseases.

  8. Regulation of expanded polyglutamine protein aggregation and nuclear localization by the glucocorticoid receptor

    PubMed Central

    Diamond, Marc I.; Robinson, Melissa R.; Yamamoto, Keith R.

    2000-01-01

    Spinobulbar muscular atrophy and Huntington's disease are caused by polyglutamine expansion in the androgen receptor and huntingtin, respectively, and their pathogenesis has been associated with abnormal nuclear localization and aggregation of truncated forms of these proteins. Here we show, in diverse cell types, that glucocorticoids can up- or down-modulate aggregation and nuclear localization of expanded polyglutamine polypeptides derived from the androgen receptor and huntingtin through specific regulation of gene expression. Wild-type glucocorticoid receptor (GR), as well as C-terminal deletion derivatives, suppressed the aggregation and nuclear localization of these polypeptides, whereas mutations within the DNA binding domain and N terminus of GR abolished this activity. Surprisingly, deletion of a transcriptional regulatory domain within the GR N terminus markedly increased aggregation and nuclear localization of the expanded polyglutamine proteins. Thus, aggregation and nuclear localization of expanded polyglutamine proteins are regulated cellular processes that can be modulated by a well-characterized transcriptional regulator, the GR. Our findings suggest approaches to study the molecular pathogenesis and selective neuronal degeneration of polyglutamine expansion diseases. PMID:10639135

  9. Clonal CD8+ TCR-Vbeta expanded populations with effector memory phenotype in Churg Strauss syndrome.

    PubMed

    Guida, Giuseppe; Vallario, Antonella; Stella, Stefania; Boita, Monica; Circosta, Paola; Mariani, Sara; Prato, Giuseppina; Heffler, Enrico; Bergia, Roberta; Sottile, Antonino; Rolla, Giovanni; Cignetti, Alessandro

    2008-07-01

    Churg Strauss Syndrome (CSS) is a systemic vasculitis in which oligoclonal T cell expansions might be involved in the pathogenesis. Combined analysis of TCR-Vbeta expression profile by flow cytometry and of TCR gene rearrangement by heteroduplex PCR was used to detect and characterize T cell expansions in 8 CSS patients, 10 asthmatics and 42 healthy subjects. In all CSS patients one or two Vbeta families were expanded among CD8+ cells, with an effector memory phenotype apt to populate tissues and inflammatory sites. Heteroduplex PCR showed the presence of one or more clonal TCR rearrangements, which reveals monoclonal or oligoclonal T cells subpopulations. After purification with a Vbeta specific monoclonal antibody, each CD8+/Vbeta+ expanded family showed a single TCR rearrangement, clearly suggestive of monoclonality. All CD8+ expansions were detectable throughout the disease course. TCR-Vbeta expanded or deleted populations were not observed in asthmatic patients. Clonal CD8+/Vbeta+ T cell expansions might be useful as a disease marker.

  10. The expanding genomic landscape of autism: discovering the ‘forest’ beyond the ‘trees’

    PubMed Central

    Hu, Valerie W

    2013-01-01

    Autism spectrum disorders are neurodevelopmental disorders characterized by significant deficits in reciprocal social interactions, impaired communication and restricted, repetitive behaviors. As autism spectrum disorders are among the most heritable of neuropsychiatric disorders, much of autism research has focused on the search for genetic variants in protein-coding genes (i.e., the ‘trees’). However, no single gene can account for more than 1% of the cases of autism spectrum disorders. Yet, genome-wide association studies have often identified statistically significant associations of genetic variations in regions of DNA that do not code for proteins (i.e., intergenic regions). There is increasing evidence that such noncoding regions are actively transcribed and may participate in the regulation of genes, including genes on different chromosomes. This article summarizes evidence that suggests that the research spotlight needs to be expanded to encompass far-reaching gene-regulatory mechanisms that include a variety of epigenetic modifications, as well as noncoding RNA (i.e., the ‘forest’). Given that noncoding RNA represents over 90% of the transcripts in most cells, we may be observing just the ‘tip of the iceberg’ or the ‘edge of the forest’ in the genomic landscape of autism. PMID:23637569

  11. Creating new knowledge for ruminant reproduction from rapidly expanding and evolving scientific databases.

    PubMed

    Bauersachs, S; Blum, H; Krebs, S; Fröhlich, T; Arnold, G J; Wolf, E

    2010-01-01

    Declining fertility is a major problem for the dairy industry. Recent developments of Omics-technologies facilitate a comprehensive analysis of molecular patters in gametes, embryos and tissues of the reproductive tract which may help to identify the reasons for impaired fertility. Large Omics-datasets require appropriate bioinformatics analysis in the context of rapidly expanding and evolving scientific databases. This overview summarizes the current status of ruminant genome projects, describes currently existing resources for ruminant genomics, transcriptomics and proteomics as well as databases and tools for the interpretation and exploitation of transcriptomics and proteomics datasets. Gene set enrichment analysis (GSEA) and transcription factor binding site (TFBS) analyses are strategies for the identification of regulatory genes. In general, the comprehensive analysis of molecular traits by Omics-technologies can enhance the interpretation of genome-wide association studies, providing insights into the biological pathways linking genotype and phenotype, and their modulation by endogenous and environmental factors.

  12. The expanded octarepeat domain selectively binds prions and disrupts homomeric prion protein interactions.

    PubMed

    Leliveld, Sirik Rutger; Dame, Remus Thei; Wuite, Gijs J L; Stitz, Lothar; Korth, Carsten

    2006-02-10

    Insertion of additional octarepeats into the prion protein gene has been genetically linked to familial Creutzfeldt Jakob disease and hence to de novo generation of infectious prions. The pivotal event during prion formation is the conversion of the normal prion protein (PrPC) into the pathogenic conformer PrPSc, which subsequently induces further conversion in an autocatalytic manner. Apparently, an expanded octarepeat domain directs folding of PrP toward the PrPSc conformation and initiates a self-replicating conversion process. Here, based on three main observations, we have provided a model on how altered molecular interactions between wild-type and mutant PrP set the stage for familial Creutzfeldt Jakob disease with octarepeat insertions. First, we showed that wild-type octarepeat domains interact in a copper-dependent and reversible manner, a "copper switch." This interaction becomes irreversible upon domain expansion, possibly reflecting a loss of function. Second, expanded octarepeat domains of increasing length gradually form homogenous globular multimers of 11-21 nm in the absence of copper ions when expressed as soluble glutathione S-transferase fusion proteins. Third, octarepeat domain expansion causes a gain of function with at least 10 repeats selectively binding PrPSc in a denaturant-resistant complex in the absence of copper ions. Thus, the combination of both a loss and gain of function profoundly influences homomeric interaction behavior of PrP with an expanded octarepeat domain. A multimeric cluster of prion proteins carrying expanded octarepeat domains may therefore capture and incorporate spontaneously arising short-lived PrPSc-like conformers, thereby providing a matrix for their conversion.

  13. Search area Expanding Strategy and Dynamic Priority Setting Method in the Improved 2-opt Method

    NASA Astrophysics Data System (ADS)

    Matayoshi, Mitsukuni; Nakamura, Morikazu; Miyagi, Hayao

    We propose a new 2-opt base method in a Memetic algorithm, that is, Genetic Algorithms(GAs) with a local search. The basic idea is from the fast 2-opt(1) method and the improved 2-opt method(20). Our new search method uses the “Priority" employed in the improved 2-opt method. The “Priority" represents the contribution level in exchange of genes. Matayoshi's method exchanges genes based on previous contribution to the fitness value improvement. We propose a new search method by using the concept of the Priority. We call our method the search area expanding strategy method in the improved 2-opt method. Our method escalates the search area by using “Priority". In computer experiment, it is shown that the computation time to find exact solution depends on the value of the Priority. If our method does not set an appropriate priority beforehand, then we propose the method to adapt to suitable value. If improvement does not achieved for certain generations, our dynamic priority method tries to modify the priority by the mutation operation. Experimental results show that the search area expanding strategy method embedded with the dynamic priority setting method can find the exact solution at earlier generation than other methods for comparison.

  14. Testing the Expanding-Contracting Polar Cap Paradigm

    NASA Astrophysics Data System (ADS)

    Sotirelis, T.; Keller, M. R.; Smith, D.; Barnes, R. J.; Talaat, E. R.; Newell, P. T.; Baker, J. B.

    2013-12-01

    The expanding-contracting polar cap (ECPC) paradigm is tested. Under the ECPC paradigm ionospheric convection in the polar cap is driven by the combined effects of dayside merging and nightside reconnection, as opposed to being mapped down from higher altitudes. The ECPC paradigm is tested by separately examining convection when the polar cap is expanding versus contracting. The open magnetic flux is estimated from SuperDARN observations of the convection reversal boundary (CRB) made simultaneously at different local times. (Sotirelis et al. [2005] established the CRB as a proxy for the Open-Closed Boundary (OCB).) The correlation of the ionospheric convection potential with solar wind/IMF driving is indeed found to depend on whether the polar cap is expanding or contracting. Specifically, when the polar cap is expanding, ionospheric convection correlates best (0.86) with the most recent 10 minutes of solar wind/IMF driving (versus 0.57 for contracting). When contracting, convection correlates best (0.87) with 90-minute averages of solar wind/IMF driving (versus 0.51 for expanding). This is consistent with ECPC expectations.

  15. Theoretical investigation of flash vaporisation in a screw expander

    NASA Astrophysics Data System (ADS)

    Vasuthevan, Hanushan; Brümmer, Andreas

    2017-08-01

    In the present study flash vaporisation of liquid injection in a twin screw expander for a Trilateral Flash Cycle (TFC) is examined theoretically. The TFC process comprises a pressure increase in the working fluid, followed by heating the liquid close to boiling point. The hot liquid is injected into the working chamber of a screw expander. During this process the pressure of the liquid drops below the saturation pressure, while the temperature of the liquid remains virtually constant. Hence the liquid is superheated and in a metastable state. The liquid jet seeks to achieve a stable state in thermodynamic equilibrium and is therefore partially vaporised. This effect is referred to as flash vaporisation. Accordingly, a two-phase mixture, consisting of vapour and liquid, exists in the working chamber. Thermodynamic simulations were carried out using water as the working fluid for representative screw expander geometry. The simulations presented are performed from two different aspects during the filling process of a screw expander. The first case is the vaporisation of the injected liquid in a state of thermodynamic equilibrium, whereby the two-phase mixture is treated entirely as a compressible and homogeneous gas. The second case considers flashing efficiency. It describes the quantity of flashed vapour and consists of a liquid and vapour domain. Both models are compared and analysed with respect to the operational behaviour of a screw expander.

  16. Slow Magnetoacoustic Wave Oscillation of an Expanding Coronal Loop

    NASA Astrophysics Data System (ADS)

    Schmidt, J. M.; Ofman, L.

    2011-10-01

    We simulated an expanding loop or slow coronal mass ejection (CME) in the solar corona dimensioned with size parameters taken from real coronal expanding loops observed with the STEREO spacecraft. We find that the loop expands to Sun's size within about one hour, consistent with slow CME observations. At the top of the loop, plasma is being blown off the loop, enabled with the reconnection between the loop's flux rope magnetic field and the radial magnetic field of the Sun, thus yielding feeding material for the formation of the slow solar wind. This mechanism is in accordance with the observed blob formation of the slow solar wind. We find wave packets traveling with local sound speed downward toward the footpoints of the loop, already seen in coronal seismology observations and simulations of stationary coronal loops. Here, we generalize these results for an expanding medium. We also find a reflection of the wave packets, identified as slow magnetoacoustic waves, at the footpoints of the loop. This confirms the formation of standing waves within the coronal loop. In particular, the reflected waves can partly escape the loop top and contribute to the heating of the solar wind. The present study improves our understanding on how loop material can emerge to form blobs, major ingredients of slow CMEs, and how the release of the wave energy stored in slow magnetoacoustic waves, and transported away from the Sun within expanding loops, contributes to the acceleration and formation of the slow solar wind.

  17. Self-expanding/shrinking structures by 4D printing

    NASA Astrophysics Data System (ADS)

    Bodaghi, M.; Damanpack, A. R.; Liao, W. H.

    2016-10-01

    The aim of this paper is to create adaptive structures capable of self-expanding and self-shrinking by means of four-dimensional printing technology. An actuator unit is designed and fabricated directly by printing fibers of shape memory polymers (SMPs) in flexible beams with different arrangements. Experiments are conducted to determine thermo-mechanical material properties of the fabricated part revealing that the printing process introduced a strong anisotropy into the printed parts. The feasibility of the actuator unit with self-expanding and self-shrinking features is demonstrated experimentally. A phenomenological constitutive model together with analytical closed-form solutions are developed to replicate thermo-mechanical behaviors of SMPs. Governing equations of equilibrium are developed for printed structures based on the non-linear Green-Lagrange strain tensor and solved implementing a finite element method along with an iterative incremental Newton-Raphson scheme. The material-structural model is then applied to digitally design and print SMP adaptive lattices in planar and tubular shapes comprising a periodic arrangement of SMP actuator units that expand and then recover their original shape automatically. Numerical and experimental results reveal that the proposed planar lattice as meta-materials can be employed for plane actuators with self-expanding/shrinking features or as structural switches providing two different dynamic characteristics. It is also shown that the proposed tubular lattice with a self-expanding/shrinking mechanism can serve as tubular stents and grippers for bio-medical or piping applications.

  18. Oligomeric and polymeric aggregates formed by proteins containing expanded polyglutamine

    PubMed Central

    Iuchi, S.; Hoffner, G.; Verbeke, P.; Djian, P.; Green, H.

    2003-01-01

    Neurological diseases resulting from proteins containing expanded polyglutamine (polyQ) are characteristically associated with insoluble neuronal inclusions, usually intranuclear, and neuronal death. We describe here oligomeric and polymeric aggregates formed in cells by expanded polyQ. These aggregates are not dissociated by concentrated formic acid, an extremely effective solvent for otherwise insoluble proteins. Perinuclear inclusions formed in cultured cells by expanded polyQ can be completely dissolved in concentrated formic acid, but a soluble protein oligomer containing the expanded polyQ and released by the formic acid is not dissociated to monomer. In Huntington's disease, a formic acid-resistant oligomer is present in cerebral cortex, but not in cerebellum. Cortical nuclei contain a polymeric aggregate of expanded polyQ that is insoluble in formic acid, does not enter polyacrylamide gels, but is retained on filters. This finding shows that the process of polymerization is more advanced in the cerebral cortex than in cultured cells. The resistance of oligomer and polymer to formic acid suggests the participation of covalent bonds in their stabilization. PMID:12591956

  19. Numerical simulation of a twin screw expander for performance prediction

    NASA Astrophysics Data System (ADS)

    Papes, Iva; Degroote, Joris; Vierendeels, Jan

    2015-08-01

    With the increasing use of twin screw expanders in waste heat recovery applications, the performance prediction of these machines plays an important role. This paper presents a mathematical model for calculating the performance of a twin screw expander. From the mass and energy conservation laws, differential equations are derived which are then solved together with the appropriate Equation of State in the instantaneous control volumes. Different flow processes that occur inside the screw expander such as filling (accompanied by a substantial pressure loss) and leakage flows through the clearances are accounted for in the model. The mathematical model employs all geometrical parameters such as chamber volume, suction and leakage areas. With R245fa as working fluid, the Aungier Redlich-Kwong Equation of State has been used in order to include real gas effects. To calculate the mass flow rates through the leakage paths formed inside the screw expander, flow coefficients are considered as constant and they are derived from 3D Computational Fluid Dynamic calculations at given working conditions and applied to all other working conditions. The outcome of the mathematical model is the P-V indicator diagram which is compared to CFD results of the same twin screw expander. Since CFD calculations require significant computational time, developed mathematical model can be used for the faster performance prediction.

  20. Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin-Releasing Hormone Deficiency

    PubMed Central

    Choi, Jin-Ho; Balasubramanian, Ravikumar; Lee, Phil H.; Shaw, Natalie D.; Hall, Janet E.; Plummer, Lacey; Buck, Cassandra L.; Kottler, Marie-Laure; Jarzabek, Katarzyna; Wołczynski, Sławomir; Quinton, Richard; Latronico, Ana Claudia; Dode, Catherine; Ogata, Tsutomu; Kim, Hyung-Goo; Layman, Lawrence C.; Gusella, James F.

    2015-01-01

    Context: Loss of function (LoF) mutations in more than 20 genes are now known to cause isolated GnRH deficiency (IGD) in humans. Most causal IGD mutations are typically private, ie, limited to a single individual/pedigree. However, somewhat paradoxically, four IGD genes (GNRH1, TAC3, PROKR2, and GNRHR) have been shown to harbor LoF founder mutations that are shared by multiple unrelated individuals. It is not known whether similar founder mutations occur in other IGD genes. Objective: The objective of the study was to determine whether shared deleterious mutations in IGD-associated genes represent founder alleles. Setting: This study was an international collaboration among academic medical centers. Methods: IGD patients with shared mutations, defined as those documented in three or more unrelated probands in 14 IGD-associated genes, were identified from various academic institutions, the Human Gene Mutation Database, and literature reports by other international investigators. Haplotypes of single-nucleotide polymorphisms and short tandem repeats surrounding the mutations were constructed to assess genetic ancestry. Results: A total of eight founder mutations in five genes, GNRHR (Q106R, R262Q, R139H), TACR3 (W275X), PROKR2 (R85H), FGFR1 (R250Q, G687R), and HS6ST1 (R382W) were identified. Most founder alleles were present at low frequency in the general population. The estimated age of these mutant alleles ranged from 1925 to 5600 years and corresponded to the time of rapid human population expansion. Conclusions: We have expanded the spectrum of founder alleles associated with IGD to a total of eight founder mutations. In contrast to the approximately 9000-year-old PROKR2 founder allele that may confer a heterozygote advantage, the rest of the founder alleles are relatively more recent in origin, in keeping with the timing of recent human population expansion and any selective heterozygote advantage of these alleles requires further evaluation. PMID:26207952