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Sample records for acts genetically downstream

  1. The Genetic Privacy Act and commentary

    SciTech Connect

    Annas, G.J.; Glantz, L.H.; Roche, P.A.

    1995-02-28

    The Genetic Privacy Act is a proposal for federal legislation. The Act is based on the premise that genetic information is different from other types of personal information in ways that require special protection. Therefore, to effectively protect genetic privacy unauthorized collection and analysis of individually identifiable DNA must be prohibited. As a result, the premise of the Act is that no stranger should have or control identifiable DNA samples or genetic information about an individual unless that individual specifically authorizes the collection of DNA samples for the purpose of genetic analysis, authorized the creation of that private information, and has access to and control over the dissemination of that information.

  2. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.

    PubMed

    Brunner, E; Peter, O; Schweizer, L; Basler, K

    1997-02-27

    Members of the Wnt/Wingless (Wg) family of signalling proteins organize many aspects of animal development by regulating the expression of particular target genes in responding cells. Recent biochemical studies indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta-catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway. However, these studies do not address whether the endogenous Lef/Tcf family members are required in vivo to transduce Wnt signals. Using genetic methods in Drosophila, we define a new segment polarity gene, pangolin (pan), and show that its product is required in vivo for Wg signal transduction in embryos and in developing adult tissues. In addition, we show that pan encodes a Lef/Tcf homologue and provide evidence that its protein product binds to the beta-catenin homologue Armadillo in vivo. Finally, we demonstrate that Pan functions downstream of Arm to transduce the Wg signal. Thus, our results indicate that Pan is an essential component of the Wg transduction pathway and suggest that it acts directly to regulate gene transcription in response to Wg signalling.

  3. The Genetic Privacy Act and commentary

    SciTech Connect

    Annas, G.J.; Glantz, L.H.; Roche, P.A.

    1995-02-28

    The Genetic Privacy Act is a proposal for federal legislation. The Act is based on the premise that genetic information is different from other types of personal information in ways that require special protection. The DNA molecule holds an extensive amount of currently indecipherable information. The major goal of the Human Genome Project is to decipher this code so that the information it contains is accessible. The privacy question is, accessible to whom? The highly personal nature of the information contained in DNA can be illustrated by thinking of DNA as containing an individual`s {open_quotes}future diary.{close_quotes} A diary is perhaps the most personal and private document a person can create. It contains a person`s innermost thoughts and perceptions, and is usually hidden and locked to assure its secrecy. Diaries describe the past. The information in one`s genetic code can be thought of as a coded probabilistic future diary because it describes an important part of a unique and personal future. This document presents an introduction to the proposal for federal legislation `the Genetic Privacy Act`; a copy of the proposed act; and comment.

  4. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

    PubMed

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. PMID:26371509

  5. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma

    PubMed Central

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. DOI: http://dx.doi.org/10.7554/eLife.07068.001 PMID:26371509

  6. Examination of a genetic algorithm for the application in high-throughput downstream process development.

    PubMed

    Treier, Katrin; Berg, Annette; Diederich, Patrick; Lang, Katharina; Osberghaus, Anna; Dismer, Florian; Hubbuch, Jürgen

    2012-10-01

    Compared to traditional strategies, application of high-throughput experiments combined with optimization methods can potentially speed up downstream process development and increase our understanding of processes. In contrast to the method of Design of Experiments in combination with response surface analysis (RSA), optimization approaches like genetic algorithms (GAs) can be applied to identify optimal parameter settings in multidimensional optimizations tasks. In this article the performance of a GA was investigated applying parameters applicable in high-throughput downstream process development. The influence of population size, the design of the initial generation and selection pressure on the optimization results was studied. To mimic typical experimental data, four mathematical functions were used for an in silico evaluation. The influence of GA parameters was minor on landscapes with only one optimum. On landscapes with several optima, parameters had a significant impact on GA performance and success in finding the global optimum. Premature convergence increased as the number of parameters and noise increased. RSA was shown to be comparable or superior for simple systems and low to moderate noise. For complex systems or high noise levels, RSA failed, while GA optimization represented a robust tool for process optimization. Finally, the effect of different objective functions is shown exemplarily for a refolding optimization of lysozyme.

  7. Genetic Information Nondiscrimination Act. Final rule.

    PubMed

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act of 2008 as they relate to employer-sponsored wellness programs. This rule addresses the extent to which an employer may offer an inducement to an employee for the employee's spouse to provide information about the spouse's manifestation of disease or disorder as part of a health risk assessment (HRA) administered in connection with an employer-sponsored wellness program. Several technical changes to the existing regulations are included. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) that addresses the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations.

  8. Genetic Information Nondiscrimination Act. Final rule.

    PubMed

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act of 2008 as they relate to employer-sponsored wellness programs. This rule addresses the extent to which an employer may offer an inducement to an employee for the employee's spouse to provide information about the spouse's manifestation of disease or disorder as part of a health risk assessment (HRA) administered in connection with an employer-sponsored wellness program. Several technical changes to the existing regulations are included. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) that addresses the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. PMID:27192741

  9. Strigolactone acts downstream of auxin to regulate bud outgrowth in pea and Arabidopsis.

    PubMed

    Brewer, Philip B; Dun, Elizabeth A; Ferguson, Brett J; Rameau, Catherine; Beveridge, Christine A

    2009-05-01

    During the last century, two key hypotheses have been proposed to explain apical dominance in plants: auxin promotes the production of a second messenger that moves up into buds to repress their outgrowth, and auxin saturation in the stem inhibits auxin transport from buds, thereby inhibiting bud outgrowth. The recent discovery of strigolactone as the novel shoot-branching inhibitor allowed us to test its mode of action in relation to these hypotheses. We found that exogenously applied strigolactone inhibited bud outgrowth in pea (Pisum sativum) even when auxin was depleted after decapitation. We also found that strigolactone application reduced branching in Arabidopsis (Arabidopsis thaliana) auxin response mutants, suggesting that auxin may act through strigolactones to facilitate apical dominance. Moreover, strigolactone application to tiny buds of mutant or decapitated pea plants rapidly stopped outgrowth, in contrast to applying N-1-naphthylphthalamic acid (NPA), an auxin transport inhibitor, which significantly slowed growth only after several days. Whereas strigolactone or NPA applied to growing buds reduced bud length, only NPA blocked auxin transport in the bud. Wild-type and strigolactone biosynthesis mutant pea and Arabidopsis shoots were capable of instantly transporting additional amounts of auxin in excess of endogenous levels, contrary to predictions of auxin transport models. These data suggest that strigolactone does not act primarily by affecting auxin transport from buds. Rather, the primary repressor of bud outgrowth appears to be the auxin-dependent production of strigolactones. PMID:19321710

  10. The Genetic Information Nondiscrimination Act (GINA): A Civil Rights Victory

    ERIC Educational Resources Information Center

    Petruniak, Mark; Krokosky, Alyson; Terry, Sharon F.

    2011-01-01

    This article discusses the Genetic Information Nondiscrimination Act (GINA) which President George W. Bush officially signed in 2008. The law prohibits employers from making adverse employment decisions based on a person's genetic information, including family health history. It also forbids insurance companies from discriminating against…

  11. Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure

    PubMed Central

    Ray, Heather J.; Niswander, Lee A.

    2016-01-01

    The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. PMID:26903501

  12. The Osr1 and Osr2 genes act in the pronephric anlage downstream of retinoic acid signaling and upstream of Wnt2b to maintain pectoral fin development.

    PubMed

    Neto, Ana; Mercader, Nadia; Gómez-Skarmeta, José Luis

    2012-01-01

    Vertebrate odd-skipped related genes (Osr) have an essential function during the formation of the intermediate mesoderm (IM) and the kidney structures derived from it. Here, we show that these genes are also crucial for limb bud formation in the adjacent lateral plate mesoderm (LPM). Reduction of zebrafish Osr function impairs fin development by the failure of tbx5a maintenance in the developing pectoral fin bud. Osr morphant embryos show reduced wnt2b expression, and increasing Wnt signaling in Osr morphant embryos partially rescues tbx5a expression. Thus, Osr genes control limb bud development in a non-cell-autonomous manner, probably through the activation of Wnt2b. Finally, we demonstrate that Osr genes are downstream targets of retinoic acid (RA) signaling. Therefore, Osr genes act as a relay within the genetic cascade of fin bud formation: by controlling the expression of the signaling molecule Wnt2ba in the IM they play an essential function transmitting the RA signaling originated in the somites to the LPM.

  13. LIMITING OCCUPATIONAL MEDICAL EVALUATIONS UNDER THE AMERICANS WITH DISABILITIES ACT AND THE GENETIC INFORMATION NONDISCRIMINATION ACT.

    PubMed

    Rothstein, Mark A; Roberts, Jessica; Guidotti, Tee L

    2015-01-01

    Although medical care delivery by one's personal physician is the paradigmatic American healthcare arrangement, in the workplace setting, many Americans undergo medical evaluations to assess their fitness for duty or degree of impairment. This Article explores the complex and evolving legal status of occupational medical evaluations. Beginning with the legal and ethical frameworks of occupational medical practice, the Article then examines the effects of increasingly detailed legal regulation under the Americans with Disabilities Act and the Genetic Information Nondiscrimination Act on employees, employers, and physicians. PMID:26863849

  14. PUNCTATE VASCULAR EXPRESSION1 Is a Novel Maize Gene Required for Leaf Pattern Formation That Functions Downstream of the Trans-Acting Small Interfering RNA Pathway1[C][W][OA

    PubMed Central

    Zhang, Xiaolan; Douglas, Ryan N.; Strable, Josh; Lee, Michelle; Buckner, Brent; Janick-Buckner, Diane; Schnable, Patrick S.; Timmermans, Marja C.P.; Scanlon, Michael J.

    2012-01-01

    The maize (Zea mays) gene RAGGED SEEDLING2-R (RGD2-R) encodes an ARGONAUTE7-like protein required for the biogenesis of trans-acting small interfering RNA, which regulates the accumulation of AUXIN RESPONSE FACTOR3A transcripts in shoots. Although dorsiventral polarity is established in the narrow and cylindrical leaves of rgd2-R mutant plants, swapping of adaxial/abaxial epidermal identity occurs and suggests a model wherein RGD2 is required to coordinate dorsiventral and mediolateral patterning in maize leaves. Laser microdissection-microarray analyses of the rgd2-R mutant shoot apical meristem identified a novel gene, PUNCTATE VASCULAR EXPRESSION1 (PVE1), that is down-regulated in rgd2-R mutant apices. Transcripts of PVE1 provide an early molecular marker for vascular morphogenesis. Reverse genetic analyses suggest that PVE1 functions during vascular development and in mediolateral and dorsiventral patterning of maize leaves. Molecular genetic analyses of PVE1 and of rgd2-R;pve1-M2 double mutants suggest a model wherein PVE1 functions downstream of RGD2 in a pathway that intersects and interacts with the trans-acting small interfering RNA pathway. PMID:22669891

  15. Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors.

    PubMed

    Baik, Song; Sekai, Miho; Hamazaki, Yoko; Jenkinson, William E; Anderson, Graham

    2016-04-01

    Thymic epithelial cells (TECs) provide essential signals for αβT-cell development, and medullary TECs (mTECs) control T-cell tolerance through both negative selection and Foxp3(+) regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK-RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK(+) TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA-1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA-1(+) mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb(-/-) mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK(+) mTEC progenitors. Collectively, our work defines stage-specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and provides new information on mechanisms controlling mTEC specification. PMID:26806881

  16. Human sperm liver receptor homolog-1 (LRH-1) acts as a downstream target of the estrogen signaling pathway.

    PubMed

    Montanaro, Daniela; Santoro, Marta; Carpino, Amalia; Perrotta, Ida; De Amicis, Francesca; Sirianni, Rosa; Rago, Vittoria; Gervasi, Serena; Aquila, Saveria

    2015-10-01

    In the last decade, the study of human sperm anatomy, at molecular level, has revealed the presence of several nuclear protein receptors. In this work, we examined the expression profile and the ultrastructural localization of liver receptor homolog-1 (LRH-1) in human spermatozoa. We evidenced the presence of the receptor by Western blotting and real time-RT-PCR. Furthermore, we used immunogold electron microscopy to investigate the sperm anatomical regions containing LRH-1. The receptor was mainly located in the sperm head, whereas its expression was reduced in the neck and across the tail. Interestingly, we observed the presence of LRH-1 in different stages of testicular germ cell development by immunohistochemistry. In somatic cells, it has been suggested that the LRH-1 pathway is tightly linked with estrogen signaling and the important role of estradiol has been widely studied in sperm cells. To assess the significance of LRH-1 in male gametes and to deepen understanding of the role of estrogens in these cells, we investigated important sperm features such as motility, survival and capacitation. Spermatozoa were treated with 10 nm estradiol and the inhibition of LRH-1 reversed the estradiol stimulatory action. From our data, we discovered that human spermatozoa can be considered a new site of expression for LRH-1, evidencing its role in sperm motility, survival and cholesterol efflux. Furthermore, we may presume that in spermatozoa the LRH-1 effects are closely integrated with the estrogen signaling, supporting LRH-1 as a downstream effector of the estradiol pathway on some sperm functions.

  17. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis

    PubMed Central

    Xu, Jingyue; Liu, Han; Park, Joo-Seop; Lan, Yu; Jiang, Rulang

    2014-01-01

    Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-directed commitment is not well understood, however. We report here that Six2 is required to maintain expression of Osr1, a homolog of the Drosophila odd-skipped zinc-finger transcription factor, in the undifferentiated cap mesenchyme. Tissue-specific inactivation of Osr1 in the cap mesenchyme caused premature depletion of nephron progenitor cells and severe renal hypoplasia. We show that Osr1 and Six2 act synergistically to prevent premature differentiation of the cap mesenchyme. Furthermore, although both Six2 and Osr1 could form protein interaction complexes with TCF proteins, Osr1, but not Six2, enhances TCF interaction with the Groucho family transcriptional co-repressors. Moreover, we demonstrate that loss of Osr1 results in β-catenin/TCF-mediated ectopic activation of Wnt4 enhancer-driven reporter gene expression in the undifferentiated nephron progenitor cells in vivo. Together, these data indicate that Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by stabilizing TCF-Groucho transcriptional repressor complexes to antagonize Wnt-directed nephrogenic differentiation. PMID:24598167

  18. Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis.

    PubMed

    Xu, Jingyue; Liu, Han; Park, Joo-Seop; Lan, Yu; Jiang, Rulang

    2014-04-01

    Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains the nephron progenitor cells against Wnt-directed commitment is not well understood, however. We report here that Six2 is required to maintain expression of Osr1, a homolog of the Drosophila odd-skipped zinc-finger transcription factor, in the undifferentiated cap mesenchyme. Tissue-specific inactivation of Osr1 in the cap mesenchyme caused premature depletion of nephron progenitor cells and severe renal hypoplasia. We show that Osr1 and Six2 act synergistically to prevent premature differentiation of the cap mesenchyme. Furthermore, although both Six2 and Osr1 could form protein interaction complexes with TCF proteins, Osr1, but not Six2, enhances TCF interaction with the Groucho family transcriptional co-repressors. Moreover, we demonstrate that loss of Osr1 results in β-catenin/TCF-mediated ectopic activation of Wnt4 enhancer-driven reporter gene expression in the undifferentiated nephron progenitor cells in vivo. Together, these data indicate that Osr1 plays crucial roles in Six2-dependent maintenance of nephron progenitors during mammalian nephrogenesis by stabilizing TCF-Groucho transcriptional repressor complexes to antagonize Wnt-directed nephrogenic differentiation.

  19. Different Pathways Act Downstream of the CEP Peptide Receptor CRA2 to Regulate Lateral Root and Nodule Development.

    PubMed

    Mohd-Radzman, Nadiatul A; Laffont, Carole; Ivanovici, Ariel; Patel, Neha; Reid, Dugald; Stougaard, Jens; Frugier, Florian; Imin, Nijat; Djordjevic, Michael A

    2016-08-01

    C-TERMINALLY ENCODED PEPTIDEs (CEPs) control root system architecture in a non-cell-autonomous manner. In Medicago truncatula, MtCEP1 affects root development by increasing nodule formation and inhibiting lateral root emergence by unknown pathways. Here, we show that the MtCEP1 peptide-dependent increase in nodulation requires the symbiotic signaling pathway and ETHYLENE INSENSITIVE2 (EIN2)/SICKLE (SKL), but acts independently of SUPER NUMERIC NODULES. MtCEP1-dependent inhibition of lateral root development acts through an EIN2-independent mechanism. MtCEP1 increases nodulation by promoting rhizobial infections, the developmental competency of roots for nodulation, the formation of fused nodules, and an increase in frequency of nodule development that initiates at proto-phloem poles. These phenotypes are similar to those of the ein2/skl mutant and support that MtCEP1 modulates EIN2-dependent symbiotic responses. Accordingly, MtCEP1 counteracts the reduction in nodulation induced by increasing ethylene precursor concentrations, and an ethylene synthesis inhibitor treatment antagonizes MtCEP1 root phenotypes. MtCEP1 also inhibits the development of EIN2-dependent pseudonodule formation. Finally, mutants affecting the COMPACT ROOT ARCHITECTURE2 (CRA2) receptor, which is closely related to the Arabidopsis CEP Receptor1, are unresponsive to MtCEP1 effects on lateral root and nodule formation, suggesting that CRA2 is a CEP peptide receptor mediating both organogenesis programs. In addition, an ethylene inhibitor treatment counteracts the cra2 nodulation phenotype. These results indicate that MtCEP1 and its likely receptor, CRA2, mediate nodulation and lateral root development through different pathways. PMID:27342310

  20. Different Pathways Act Downstream of the CEP Peptide Receptor CRA2 to Regulate Lateral Root and Nodule Development1[OPEN

    PubMed Central

    Mohd-Radzman, Nadiatul A.; Ivanovici, Ariel; Frugier, Florian; Djordjevic, Michael A.

    2016-01-01

    C-TERMINALLY ENCODED PEPTIDEs (CEPs) control root system architecture in a non-cell-autonomous manner. In Medicago truncatula, MtCEP1 affects root development by increasing nodule formation and inhibiting lateral root emergence by unknown pathways. Here, we show that the MtCEP1 peptide-dependent increase in nodulation requires the symbiotic signaling pathway and ETHYLENE INSENSITIVE2 (EIN2)/SICKLE (SKL), but acts independently of SUPER NUMERIC NODULES. MtCEP1-dependent inhibition of lateral root development acts through an EIN2-independent mechanism. MtCEP1 increases nodulation by promoting rhizobial infections, the developmental competency of roots for nodulation, the formation of fused nodules, and an increase in frequency of nodule development that initiates at proto-phloem poles. These phenotypes are similar to those of the ein2/skl mutant and support that MtCEP1 modulates EIN2-dependent symbiotic responses. Accordingly, MtCEP1 counteracts the reduction in nodulation induced by increasing ethylene precursor concentrations, and an ethylene synthesis inhibitor treatment antagonizes MtCEP1 root phenotypes. MtCEP1 also inhibits the development of EIN2-dependent pseudonodule formation. Finally, mutants affecting the COMPACT ROOT ARCHITECTURE2 (CRA2) receptor, which is closely related to the Arabidopsis CEP Receptor1, are unresponsive to MtCEP1 effects on lateral root and nodule formation, suggesting that CRA2 is a CEP peptide receptor mediating both organogenesis programs. In addition, an ethylene inhibitor treatment counteracts the cra2 nodulation phenotype. These results indicate that MtCEP1 and its likely receptor, CRA2, mediate nodulation and lateral root development through different pathways. PMID:27342310

  1. NDRG2 acts as a negative regulator downstream of androgen receptor and inhibits the growth of androgen-dependent and castration-resistant prostate cancer.

    PubMed

    Yu, Chuigong; Wu, Guojun; Li, Ruixiao; Gao, Lei; Yang, Fan; Zhao, Yi; Zhang, Jian; Zhang, Rui; Zhang, Jing; Yao, Libo; Yuan, Jianlin; Li, Xia

    2015-01-01

    Castration resistance is a major issue during castration therapy for prostate cancer and thus more effective treatment are needed for castration-resistant prostate cancer (CRPC). NDRG2 (N-Myc downstream regulated gene 2), a recently identified tumor suppressor, was previously shown to inhibit the proliferation and invasion of prostate cancer, but whether NDRG2 is involved in CRPC remains to be known. Because androgen receptor (AR) axis plays an important role in castration resistance, we evaluate the role of NDRG2 in AR signaling and CRPC. Immunohistochemistry examination of prostate cancer tissues demonstrated that the expression of NDRG2 is negatively correlated with that of AR and c-Myc. Furthermore, AR negatively regulates NDRG2, as well as alters levels of c-Myc and prostate specific antigen (PSA). Forced expression of NDRG2 significantly inhibits the in vitro growth of androgen-dependent and castration-resistant prostate cancer cells; this was accompanied by alterations in PSA, but not by those of AR and c-Myc. Finally, by mimicking castration therapy in a xenograft mouse model, we showed that lentivirus-mediated NDRG2 overexpression efficiently overcomes castration resistance. Thus, by acting as a negative regulator downstream of AR, NDRG2 may emerge as a potential therapy molecule for CRPC.

  2. The transcriptional repressor Blimp-1 acts downstream of BMP signaling to generate primordial germ cells in the cricket Gryllus bimaculatus.

    PubMed

    Nakamura, Taro; Extavour, Cassandra G

    2016-01-15

    Segregation of the germ line from the soma is an essential event for transmission of genetic information across generations in all sexually reproducing animals. Although some well-studied systems such as Drosophila and Xenopus use maternally inherited germ determinants to specify germ cells, most animals, including mice, appear to utilize zygotic inductive cell signals to specify germ cells during later embryogenesis. Such inductive germ cell specification is thought to be an ancestral trait of Bilateria, but major questions remain as to the nature of an ancestral mechanism to induce germ cells, and how that mechanism evolved. We previously reported that BMP signaling-based germ cell induction is conserved in both the mouse Mus musculus and the cricket Gryllus bimaculatus, which is an emerging model organism for functional studies of induction-based germ cell formation. In order to gain further insight into the functional evolution of germ cell specification, here we examined the Gryllus ortholog of the transcription factor Blimp-1 (also known as Prdm1), which is a widely conserved bilaterian gene known to play a crucial role in the specification of germ cells in mice. Our functional analyses of the Gryllus Blimp-1 ortholog revealed that it is essential for Gryllus primordial germ cell development, and is regulated by upstream input from the BMP signaling pathway. This functional conservation of the epistatic relationship between BMP signaling and Blimp-1 in inductive germ cell specification between mouse and cricket supports the hypothesis that this molecular mechanism regulated primordial germ cell specification in a last common bilaterian ancestor.

  3. Regulations Under the Americans With Disabilities Act; Genetic Information Nondiscrimination Act. Final rule.

    PubMed

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing its final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) to provide guidance on the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. This rule applies to all wellness programs that include disability-related inquiries and/or medical examinations whether they are offered only to employees enrolled in an employer-sponsored group health plan, offered to all employees regardless of whether they are enrolled in such a plan, or offered as a benefit of employment by employers that do not sponsor a group health plan or group health insurance. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act (GINA) that addresses the extent to which employers may offer incentives for an employee's spouse to participate in a wellness program. PMID:27192736

  4. Regulations Under the Americans With Disabilities Act; Genetic Information Nondiscrimination Act. Final rule.

    PubMed

    2016-05-17

    The Equal Employment Opportunity Commission (EEOC or Commission) is issuing its final rule to amend the regulations and interpretive guidance implementing Title I of the Americans with Disabilities Act (ADA) to provide guidance on the extent to which employers may use incentives to encourage employees to participate in wellness programs that ask them to respond to disability-related inquiries and/or undergo medical examinations. This rule applies to all wellness programs that include disability-related inquiries and/or medical examinations whether they are offered only to employees enrolled in an employer-sponsored group health plan, offered to all employees regardless of whether they are enrolled in such a plan, or offered as a benefit of employment by employers that do not sponsor a group health plan or group health insurance. Published elsewhere in this issue of the Federal Register, the EEOC also issued a final rule to amend the regulations implementing Title II of the Genetic Information Nondiscrimination Act (GINA) that addresses the extent to which employers may offer incentives for an employee's spouse to participate in a wellness program.

  5. Transcriptional activation of the herpes simplex virus type 1 UL38 promoter conferred by the cis-acting downstream activation sequence is mediated by a cellular transcription factor.

    PubMed Central

    Guzowski, J F; Singh, J; Wagner, E K

    1994-01-01

    The herpes simplex virus (HSV) type 1 strict late (gamma) UL38 promoter contains three cis-acting transcriptional elements: a TATA box, a specific initiator element, and the downstream activation sequence (DAS). DAS is located between positions +20 and +33 within the 5' untranslated leader region and strongly influences transcript levels during productive infection. In this communication, we further characterize DAS and investigate its mechanism of action. DAS function has a strict spacing requirement, and DAS contains an essential 6-bp core element. A similarly positioned element from the gamma gC gene (UL44) has partial DAS function within the UL38 promoter context, and the promoter controlling expression of the gamma US11 transcript contains an identically located element with functional and sequence similarity to UL38 DAS. These data suggest that downstream elements are a common feature of many HSV gamma promoters. Results with recombinant viruses containing modifications of the TATA box or initiator element of the UL38 promoter suggest that DAS functions to increase transcription initiation and not the efficiency of transcription elongation. In vitro transcription assays using uninfected HeLa nuclear extracts show that, as in productive infection with recombinant viruses, the deletion of DAS from the UL38 promoter dramatically decreases RNA expression. Finally, electrophoretic mobility shift assays and UV cross-linking experiments show that DAS DNA forms a specific, stable complex with a cellular protein (the DAS-binding factor) of approximately 35 kDa. These data strongly suggest that the interaction of cellular DAS-binding factor with DAS is required for efficient expression of UL38 and other HSV late genes. Images PMID:7966567

  6. What's in a name: the Vermont Genetically Engineered Food Labeling Act

    PubMed Central

    McPherson, Malia J.

    2014-01-01

    On May 8, 2014, Vermont passed the Vermont Genetically Engineered Food Labeling Act (Act) requiring labels on certain genetically engineered foods. Once the bill takes effect July 1, 2016, all Vermont-retailed foods with more than 0.9% of their total weight in genetically modified ingredients must be labeled with language stating, “may be partially produced with genetic engineering.” As genetically engineered food are considered scientifically equivalent to their traditional counterparts and are not subject to federal labeling by the FDA, the Act presents several legal questions. Several of the legal questions have been raised in a recent lawsuit filed by the Grocery Manufactures Association that claims the Act violates the First Amendment, Supremacy Clause, and Commerce Clause. This paper will discuss why the Second Circuit could strike down the Act as unconstitutional as to each claim. PMID:27774175

  7. N-terminal domains of native multidomain proteins have the potential to assist de novo folding of their downstream domains in vivo by acting as solubility enhancers

    PubMed Central

    Kim, Chul Woo; Han, Kyoung Sim; Ryu, Ki-Sun; Kim, Byung Hee; Kim, Kyun-Hwan; Choi, Seong Il; Seong, Baik L.

    2007-01-01

    The fusion of soluble partner to the N terminus of aggregation-prone polypeptide has been popularly used to overcome the formation of inclusion bodies in the E. coli cytosol. The chaperone-like functions of the upstream fusion partner in the artificial multidomain proteins could occur in de novo folding of native multidomain proteins. Here, we show that the N-terminal domains of three E. coli multidomain proteins such as lysyl-tRNA synthetase, threonyl-tRNA synthetase, and aconitase are potent solubility enhancers for various C-terminal heterologous proteins. The results suggest that the N-terminal domains could act as solubility enhancers for the folding of their authentic C-terminal domains in vivo. Tandem repeat of N-terminal domain or insertion of aspartic residues at the C terminus of the N-terminal domain also increased the solubility of fusion proteins, suggesting that the solubilizing ability correlates with the size and charge of N-terminal domains. The solubilizing ability of N-terminal domains would contribute to the autonomous folding of multidomain proteins in vivo, and based on these results, we propose a model of how N-terminal domains solubilize their downstream domains. PMID:17384228

  8. The conservation genetics juggling act: Integrating genetics and ecology, science and policy

    USGS Publications Warehouse

    Haig, Susan M.; Miller, Mark P.; Bellinger, Renee; Draheim, Hope M.; Mercer, Dacey; Mullins, Tom

    2016-01-01

    The field of conservation genetics, when properly implemented, is a constant juggling act integrating molecular genetics, ecology, and demography with applied aspects concerning managing declining species or implementing conservation laws and policies. This young field has grown substantially since the 1980’s following development of the polymerase chain reaction and now into the genomics era. Our lab has “grown up” with the field, having worked on these issues for over three decades. Our multi-disciplinary approach entails understanding the behavior and ecology of species as well as the underlying processes that contribute to genetic viability. Taking this holistic approach provides a comprehensive understanding of factors that influence species persistence and evolutionary potential while considering annual challenges that occur throughout their life cycle. As a federal lab, we are often addressing the needs of the U.S. Fish and Wildlife Service in their efforts to list, de-list or recover species. Nevertheless, there remains an overall communication gap between research geneticists and biologists who are charged with implementing their results. Therefore, we outline the need for a National Center for Small Population Biology to ameliorate this problem and provide organizations charged with making status decisions firmer ground from which to make their critical decisions. 

  9. The conservation genetics juggling act: integrating genetics and ecology, science and policy.

    PubMed

    Haig, Susan M; Miller, Mark P; Bellinger, Renee; Draheim, Hope M; Mercer, Dacey M; Mullins, Thomas D

    2016-01-01

    The field of conservation genetics, when properly implemented, is a constant juggling act integrating molecular genetics, ecology, and demography with applied aspects concerning managing declining species or implementing conservation laws and policies. This young field has grown substantially since the 1980s following the development of polymerase chain reaction and now into the genomics era. Our laboratory has 'grown up' with the field, having worked on these issues for over three decades. Our multidisciplinary approach entails understanding the behavior and ecology of species as well as the underlying processes that contribute to genetic viability. Taking this holistic approach provides a comprehensive understanding of factors that influence species persistence and evolutionary potential while considering annual challenges that occur throughout their life cycle. As a federal laboratory, we are often addressing the needs of the U.S. Fish and Wildlife Service in their efforts to list, de-list, or recover species. Nevertheless, there remains an overall communication gap between research geneticists and biologists who are charged with implementing their results. Therefore, we outline the need for a National Center for Small Population Biology to ameliorate this problem and provide organizations charged with making status decisions firmer ground from which to make their critical decisions.

  10. The conservation genetics juggling act: integrating genetics and ecology, science and policy.

    PubMed

    Haig, Susan M; Miller, Mark P; Bellinger, Renee; Draheim, Hope M; Mercer, Dacey M; Mullins, Thomas D

    2016-01-01

    The field of conservation genetics, when properly implemented, is a constant juggling act integrating molecular genetics, ecology, and demography with applied aspects concerning managing declining species or implementing conservation laws and policies. This young field has grown substantially since the 1980s following the development of polymerase chain reaction and now into the genomics era. Our laboratory has 'grown up' with the field, having worked on these issues for over three decades. Our multidisciplinary approach entails understanding the behavior and ecology of species as well as the underlying processes that contribute to genetic viability. Taking this holistic approach provides a comprehensive understanding of factors that influence species persistence and evolutionary potential while considering annual challenges that occur throughout their life cycle. As a federal laboratory, we are often addressing the needs of the U.S. Fish and Wildlife Service in their efforts to list, de-list, or recover species. Nevertheless, there remains an overall communication gap between research geneticists and biologists who are charged with implementing their results. Therefore, we outline the need for a National Center for Small Population Biology to ameliorate this problem and provide organizations charged with making status decisions firmer ground from which to make their critical decisions. PMID:27087847

  11. Lateral Organ Boundaries Domain16 and 18 Act Downstream of the AUXIN1 and LIKE-AUXIN3 Auxin Influx Carriers to Control Lateral Root Development in Arabidopsis1

    PubMed Central

    Lee, Han Woo; Cho, Chuloh; Kim, Jungmook

    2015-01-01

    Several members of the Lateral Organ Boundaries Domain (LBD)/Asymmetric Leaves2-Like (ASL) gene family have been identified to play important roles in Arabidopsis (Arabidopsis thaliana) lateral root (LR) development during auxin response, but their functional relationship with auxin transporters has not been established yet. Here, we show that the AUXIN1 (AUX1) and LIKE-AUXIN3 (LAX3) auxin influx carriers are required for auxin signaling that activates LBD16/ASL18 and LBD18/ASL20 to control LR development. The lax3 mutant phenotype was not significantly enhanced when combined with lbd16 or lbd18. However, LBD18 overexpression could rescue the defects in LR emergence in lax3 with concomitant expression of the LBD18 target genes. Genetic and gene expression analyses indicated that LBD16 and LBD18 act with AUX1 to regulate LR initiation and LR primordium development, and that AUX1 and LAX3 are needed for auxin-responsive expression of LBD16 and LBD18. LBD18:SUPERMAN REPRESSIVE DOMAIN X in the lbd18 mutant inhibited LR initiation and LR primordium development in response to a gravitropic stimulus and suppressed promoter activities of the cell cycle genes Cyclin-Dependent Kinase A1;1 and CYCLINB1;1. Taken together, these results suggest that LBD16 and LBD18 are important regulators of LR initiation and development downstream of AUX1 and LAX3. PMID:26059335

  12. The Nuclear Hormone Receptor NHR-40 Acts Downstream of the Sulfatase EUD-1 as Part of a Developmental Plasticity Switch in Pristionchus.

    PubMed

    Kieninger, Manuela R; Ivers, Nicholas A; Rödelsperger, Christian; Markov, Gabriel V; Sommer, Ralf J; Ragsdale, Erik J

    2016-08-22

    Developmental plasticity, the ability of one genotype to produce distinct phenotypes in different environments, has been suggested to facilitate phenotypic diversification, and several examples in plants and animals support its macroevolutionary potential [1-8]. However, little is known about associated molecular mechanisms, because environmental effects on development are difficult to study by laboratory approaches. One promising system is the mouth dimorphism of the nematode Pristionchus pacificus [9-12]. Following an irreversible decision in larval development, these nematodes form moveable teeth that occur in either of two discrete morphs. The "eurystomatous" (Eu) form has a wide mouth and two teeth, allowing predatory feeding on other nematodes. In contrast, the alternative ("stenostomatous"; St) form has diminutive mouthparts that largely constrain its diet to microbes. The sulfatase EUD-1 was previously discovered to execute a polyphenism switch based on dosage of functional alleles [13] and confirmed a prediction of evolutionary theory about how developmental switches control plasticity [1, 3]. However, the genetic context of this single gene, and hence the molecular complexity of switch mechanisms, was previously unknown. Here we use a suppressor screen to identify factors downstream of eud-1 in mouth-form regulation. We isolated three dominant, X-linked mutants in the nuclear hormone receptor gene nhr-40 that are haploinsufficient. Both eud-1 nhr-40 double and nhr-40 single mutants are all Eu, whereas transgenic overexpression of nhr-40 does not restore the wild-type phenotype but instead results in nearly all-St lines. Thus, NHR-40 is part of a developmental switch, suggesting that switch mechanisms controlling plasticity consist of multi-component hormonal signaling systems. PMID:27451902

  13. The Genetic Privacy Act: an analysis of privacy and research concerns.

    PubMed

    Troy, E S

    1997-01-01

    Author argues that the Genetic Privacy Act fails to protect nucleic acid-based information as it relates to individual privacy, yet overburdens medical and scientific research with vague consent standards.

  14. Genetic discrimination and the public entities and public accommodations titles of the americans with disabilities act

    SciTech Connect

    Alper, J.S. ); Natowicz, M.R. Shriver Center for Mental Retardation, Waltham, MA )

    1993-07-01

    The introduction of newly developed medical genetic diagnostic tests has been accompanied by social problems involving privacy issues and genetic discrimination. Previous studies of genetic discrimination have focused on the areas of employment and insurance. In this paper, the authors provide six hypothetical illustrative cases of genetic discrimination involving access to public entities and to private entities considered to be public accommodations. They argue that many of these forms of genetic discrimination that arise in both the public and private sectors should be prohibited by Titles II and III, respectively, of the Americans with Disabilities Act of 1990.

  15. Genetic discrimination and the public entities and public accommodations Titles of the Americans with Disabilities Act.

    PubMed

    Alper, J S; Natowicz, M R

    1993-07-01

    The introduction of newly developed medical genetic diagnostic tests has been accompanied by social problems involving privacy issues and genetic discrimination. Previous studies of genetic discrimination have focused on the areas of employment and insurance. In this paper, we provide six hypothetical illustrative cases of genetic discrimination involving access to public entities and to private entities considered to be public accommodations. We argue that many of these forms of genetic discrimination that arise in both the public and private sectors should be prohibited by Titles II and III, respectively, of the Americans with Disabilities Act of 1990.

  16. A hub for ABA signaling to the nucleus: significance of a cytosolic and nuclear dual-localized PPR protein SOAR1 acting downstream of Mg-chelatase H subunit.

    PubMed

    Jiang, Shang-Chuan; Mei, Chao; Wang, Xiao-Fang; Zhang, Da-Peng

    2014-01-01

    SOAR1 is a cytosol-nucleus dual-localized pentatricopeptide repeat (PPR) protein, which we indentified recently as a crucial regulator in the CHLH/ABAR (Mg-chelatase H subunit /putative ABA receptor)-mediated signaling pathway, acting downstream of CHLH/ABAR and upstream of a nuclear ABA-responsive bZIP transcription factor ABI5. Downregulation and upregulation of SOAR1 expression alter dramatically both ABA sensitivity and expression of a subset of key, nuclear ABA-responsive genes, suggesting that SOAR1 is a hub for ABA signaling to the nucleus, and CHLH/ABAR mediates a central signaling pathway to regulate downstream gene expression through SOAR1.

  17. BMX acts downstream of PI3K to promote colorectal cancer cell survival and pathway inhibition sensitizes to the BH3 mimetic ABT-737.

    PubMed

    Potter, Danielle S; Kelly, Paul; Denneny, Olive; Juvin, Veronique; Stephens, Len R; Dive, Caroline; Morrow, Christopher J

    2014-02-01

    Evasion of apoptosis is a hallmark of cancer, and reversing this process by inhibition of survival signaling pathways is a potential therapeutic strategy. Phosphoinositide 3-kinase (PI3K) signaling can promote cell survival and is upregulated in solid tumor types, including colorectal cancer (CRC), although these effects are context dependent. The role of PI3K in tumorigenesis combined with their amenability to specific inhibition makes them attractive drug targets. However, we observed that inhibition of PI3K in HCT116, DLD-1, and SW620 CRC cells did not induce apoptotic cell death. Moreover, these cells were relatively resistant to the Bcl-2 homology domain 3 (BH3) mimetic ABT-737, which directly targets the Bcl-2 family of apoptosis regulators. To test the hypothesis that PI3K inhibition lowers the apoptotic threshold without causing apoptosis per se, PI3K inhibitors were combined with ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis by 2.3- to 4.5-fold and reduced expression levels of MCL-1, the resistance biomarker for ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis a further 1.4- to 2.4-fold in CRC cells with small interfering RNA-depleted MCL-1, indicative of additional sensitizing mechanisms. The observation that ABT-737-induced apoptosis was unaffected by inhibition of PI3K downstream effectors AKT and mTOR, implicated a novel PI3K-dependant pathway. To elucidate this, an RNA interference (RNAi) screen of potential downstream effectors of PI3K signaling was conducted, which demonstrated that knockdown of the TEC kinase BMX sensitized to ABT-737. This suggests that BMX is an antiapoptotic downstream effector of PI3K, independent of AKT. PMID:24709422

  18. LATERAL ROOT PRIMORDIA 1 of maize acts as a transcriptional activator in auxin signalling downstream of the Aux/IAA gene rootless with undetectable meristem 1.

    PubMed

    Zhang, Yanxiang; von Behrens, Inga; Zimmermann, Roman; Ludwig, Yvonne; Hey, Stefan; Hochholdinger, Frank

    2015-07-01

    Only little is known about target genes of auxin signalling downstream of the Aux/IAA-ARF module. In the present study, it has been demonstrated that maize lateral root primordia 1 (lrp1) encodes a transcriptional activator that is directly regulated by the Aux/IAA protein ROOTLESS WITH UNDETECTABLE MERISTEM 1 (RUM1). Expression of lrp1 is confined to early root primordia and meristems and is auxin-inducible. Based on its primary protein structure, LRP1 is predicted to be a transcription factor. This notion is supported by exclusive LRP1 localization in the nucleus and its ability to activate downstream gene activity. Based on the observation that lrp1 transcription is completely repressed in the semi-dominant gain of function mutant rum1, it was demonstrated that the lrp1 promoter is a direct target of RUM1 proteins. Subsequently, promoter activation assays indicated that RUM1 represses the expression of a GFP reporter fused to the native promoter of lrp1. Constitutive repression of lrp1 in rum1 mutants is a consequence of the stability of mutated rum1 proteins which cannot be degraded by the proteasome and thus constitutively bind to the lrp1 promoter and repress transcription. Taken together, the repression of the transcriptional activator lrp1 by direct binding of RUM1 to its promoter, together with specific expression of lrp1 in root meristems, suggests a function in maize root development via the RUM1-dependent auxin signalling pathway. PMID:25911745

  19. Rho kinase acts as a downstream molecule to participate in protein kinase Cε regulation of vascular reactivity after hemorrhagic shock in rats.

    PubMed

    Li, Tao; Zhu, Yu; Zang, Jia-tao; Peng, Xiao-yong; Lan, Dan; Yang, Guang-ming; Xu, Jing; Liu, Liang-ming

    2014-09-01

    Our previous study demonstrated that Rho kinase and protein kinase C (PKC) played important parts in the regulation of vascular reactivity after shock. Using superior mesenteric arteries (SMAs) from hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cells (VSMCs), relationship of PKCε regulation of vascular reactivity to Rho kinase, as well as the signal transduction after shock, was investigated. The results showed that inhibition of Rho kinase with the Rho kinase-specific inhibitor Y-27632 antagonized the PKCε-specific agonist carbachol and highly expressed PKCε-induced increase of vascular reactivity in SMAs and VSMCs, whereas inhibition of PKCε with its specific inhibitory peptide did not antagonize the Rho kinase agonist (U-46619)-induced increase of vascular reactivity in SMAs and VSMCs. Activation of PKCε or highly expressed PKCε upregulated the activity of Rho kinase and the phosphorylation of PKC-dependent phosphatase inhibitor 17 (CPI-17), zipper interacting protein kinase (ZIPK), and integrin-linked kinase (ILK), whereas activation of Rho kinase increased only CPI-17 phosphorylation. The specific neutralization antibodies of ZIPK and ILK antagonized PKCε-induced increases in the activity of Rho kinase, but CPI-17 neutralization antibody did not antagonize this effect. These results suggested that Rho kinase takes part in the regulation of PKCε on vascular reactivity after shock. Rho kinase is downstream of PKCε. Protein kinase Cε activates Rho kinase via ZIPK and ILK; CPI-17 is downstream of Rho kinase.

  20. cis-acting sequences located downstream of the human immunodeficiency virus type 1 promoter affect its chromatin structure and transcriptional activity.

    PubMed

    el Kharroubi, A; Martin, M A

    1996-06-01

    We have examined the roles of AP-1, AP-3-like, DBF1, and Sp1 binding sites, which are located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter, in regulating basal transcriptional activity directed by the integrated viral long terminal repeat (LTR). Point mutations affecting all four of these elements functionally inactivated the HIV-1 LTR when it was constrained in a chromatin configuration. Analyses of the chromatin structures of the transcriptionally active wild-type and inactive mutated HIV-1 promoters revealed several differences. In the active promoter, the 3' half of the U3 region, including the basal promoter, the enhancer, and the putative upstream regulatory sequences are situated within a nuclease-hypersensitive region. However, the far upstream U3 region appears to be packaged into a nuclease-resistant nucleosomal structure, whereas the R, U5, and gag leader sequences are associated with a region of altered chromatin that is sensitive to restriction endonucleases. In the inactive template, only the basal promoter and enhancer element remain sensitive to nucleases, and the adjacent upstream and downstream regions are incorporated into nuclease-resistant nucleosomal structures. Taken together, these results indicate that the chromatin structure of the integrated HIV-1 LTR plays a critical role in modulating basal transcriptional activity. PMID:8649407

  1. The need to be aware and beware of the genetic information nondiscrimination act.

    PubMed

    Steck, Mary Beth; Eggert, Julia A

    2011-06-01

    Genetic advancements have presented numerous discrimination predicaments to individuals, the healthcare community, and legislators at state and federal levels. Oncology nurses should be knowledgeable about the Genetic Information Nondiscrimination Act of 2008 (GINA) and its applications to clinical practice. GINA is the first federal law passed to protect U.S. citizens with inherited disorders from being treated unfairly because of their genetic makeup. Understanding the legislation known as GINA, including how it modifies existing federal laws governing health insurance coverage and employment discrimination, can assist oncology nurses in providing important education and advocating for patients and their extended families. Federal agencies that govern and enforce GINA's provisions are identified. Case situations are included to demonstrate how to apply information concerning GINA to patients with cancer and their families who are considering or have already completed genetic testing. Privacy of genetic information is a timely issue but difficult to understand; therefore, provisions of GINA should be addressed and evaluated carefully.

  2. NK cell cytotoxicity mediated by 2B4 and NTB-A is dependent on SAP acting downstream of receptor phosphorylation.

    PubMed

    Meinke, Stephan; Watzl, Carsten

    2013-01-01

    2B4 (CD244) and NK-T-B-antigen (NTB-A, CD352) are activating receptors on human natural killer (NK) cells and belong to the family of signaling lymphocyte activation molecule (SLAM)-related receptors (SRR). Engagement of these receptors leads to phosphorylation of their cytoplasmic tails and recruitment of the adapter proteins SLAM-associated protein (SAP) and Ewing's sarcoma-activated transcript-2 (EAT-2). X-linked lymphoproliferative syndrome (XLP) is a severe immunodeficiency that results from mutations in the SAP gene. 2B4 and NTB-A-mediated cytotoxicity are abrogated in XLP NK cells. To elucidate the molecular basis for this defect we analyzed early signaling events in SAP knockdown cells. Similar to XLP NK cells, knockdown of SAP in primary human NK cells leads to a reduction of 2B4 and NTB-A-mediated cytotoxicity. We found that early signaling events such as raft recruitment and receptor phosphorylation are not affected by the absence of SAP, indicating the defect in the absence of SAP is downstream of these events. In addition, knockdown of EAT-2 does not impair 2B4 or NTB-A-mediated cytotoxicity. Surprisingly, EAT-2 recruitment to both receptors is abrogated in the absence of SAP, revealing a novel cooperativity between these adapters.

  3. Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

    PubMed

    Liang, Xiao-Huan; Deng, Wen-Bo; Li, Ming; Zhao, Zhen-Ao; Wang, Tong-Song; Feng, Xu-Hui; Cao, Yu-Jing; Duan, En-Kui; Yang, Zeng-Ming

    2014-08-22

    Embryo implantation is a highly synchronized process between an activated blastocyst and a receptive uterus. Successful implantation relies on the dynamic interplay of estrogen and progesterone, but the key mediators underlying embryo implantation are not fully understood. Here we show that transcription factor early growth response 1 (Egr1) is regulated by estrogen as a downstream target through leukemia inhibitory factor (LIF) signal transducer and activator of transcription 3 (STAT3) pathway in mouse uterus. Egr1 is localized in the subluminal stromal cells surrounding the implanting embryo on day 5 of pregnancy. Estrogen rapidly, markedly, and transiently enhances Egr1 expression in uterine stromal cells, which fails in estrogen receptor α knock-out mouse uteri. STAT3 is phosphorylated by LIF and subsequently recruited on Egr1 promoter to induce its expression. Our results of Egr1 expression under induced decidualization in vivo and in vitro show that Egr1 is rapidly induced after deciduogenic stimulus. Egr1 knockdown can inhibit in vitro decidualization of cultured uterine stromal cells. Chromatin immunoprecipitation data show that Egr1 is recruited to the promoter of wingless-related murine mammary tumor virus integration site 4 (Wnt4). Collectively, our study presents for the first time that estrogen regulates Egr1 expression through LIF-STAT3 signaling pathway in mouse uterus, and Egr1 functions as a critical mediator of stromal cell decidualization by regulating Wnt4. PMID:25012664

  4. Hydrogen sulfide acts as a downstream signal molecule in salicylic acid-induced heat tolerance in maize (Zea mays L.) seedlings.

    PubMed

    Li, Zhong-Guang; Xie, Lin-Run; Li, Xiao-Juan

    2015-04-01

    Salicylic acid (SA), 2-hydroxy benzoic acid, is a small phenolic compound with multifunction that is involved in plant growth, development, and the acquisition of stress tolerance. In recent years, hydrogen sulfide (H2S) has been found to have similar functions, but cross talk between SA and H2S in the acquisition of heat tolerance is not clear. In this study, pretreatment of maize seedlings with SA improved the survival percentage of seedlings under heat stress, indicating that SA pretreatment could improve the heat tolerance of maize seedlings. In addition, treatment with SA enhanced the activity of L-cysteine desulfhydrase (L-DES), a key enzyme in H2S biosynthesis, which in turn induced accumulation of endogenous H2S. Interestingly, SA-induced heat tolerance was enhanced by addition of NaHS, a H2S donor, but weakened by specific inhibitors of H2S biosynthesis DL-propargylglycine (PAG) and its scavenger hydroxylamine (HT). Furthermore, pretreatment with paclobutrazol (PAC) and 2-aminoindan-2-phosphonic acid (AIP), inhibitors of SA biosynthesis, had no significant effect on NaHS-induced heat tolerance of maize seedlings. Similarly, significant change in the activities of phenylalanine ammonia lyase (PAL) and benzoic-acid-2-hydroxylase (BA2H), the key enzymes in SA biosynthesis, and the content of endogenous SA, was not observed in maize seedlings by NaHS treatment. All of the above-mentioned results suggest that SA pretreatment could improve the heat tolerance of maize seedlings, and H2S might be a novel downstream signal molecule in SA-induced heat tolerance.

  5. Crumbs and stardust act in a genetic pathway that controls the organization of epithelia in Drosophila melanogaster.

    PubMed

    Tepass, U; Knust, E

    1993-09-01

    We provide evidence that the genes crumbs (crb) and stardust (sdt) encode critical components of a pathway that acts at the apical pole of epithelial cells to control the cytoarchitecture of ectodermally derived epithelia of the Drosophila embryo. We describe the developmental defects caused by sdt mutations, which are very similar to those associated with mutations in crb. In both mutants the epithelial structure of ectodermal cells breaks down during early organogenesis, leading to the formation of irregular clusters of cells and cell death in some epithelia. Certain cells can, however, compensate for the loss of crb or sdt function in a tissue-specific manner, later reassuming an epithelial cell shape and forming small epithelial vesicles, suggesting that, besides crb and sdt, other tissue-specific components are involved in this process. The crb protein (CRB) is continuously expressed in wild-type embryos in cells of the ectoderm and ectodermally derived epithelia. In sdt mutant embryos CRB is present only during gastrulation, but becomes undetectable during germ band extension; the protein is again visible during early organogenesis, at the time when the sdt mutant phenotype becomes apparent. In sdt mutant embryos, CRB is associated with the apical membrane only in well-differentiated epithelial cells, but it is expressed diffusely in the cytoplasm of cells which have lost epithelial morphology. Our results suggest that time- and tissue-specific control mechanisms exist to establish and maintain epithelial cell structure. Mosaic experiments suggest that sdt is required cell autonomously, in contrast to crb, the requirement of which appears to be non-cell-autonomous. Double mutant combinations of crb and sdt suggest that these genes are part of a common genetic pathway (crb/sdt pathway), in which sdt acts downstream of crb and is activated by the latter.

  6. U.S. Senate Bill 422: the Genetic Confidentiality and Nondiscrimination Act of 1997.

    PubMed

    Berman, J J; Moore, G W; Hutchins, G M

    1998-08-01

    On March 11, 1997, Senator Pete Domenici introduced U.S. Senate Bill 422, the Genetic Confidentiality and Non-Discrimination Act of 1997. The bill specifies that "existing legal protections for genetic information are inadequate to ensure genetic privacy and to prevent genetic discrimination." The first stated purpose of the bill is "to define the circumstances under which DNA samples may be collected, stored, and analyzed and genetic information may be collected, stored, analyzed, and disclosed." The bill reinforces statutes already passed in 19 states that guarantee patients certain rights of control over their own personal genetic information (Congressional Record, S2141). This bill fundamentally changes the mechanism whereby molecular biologists acquire tissue, and defines new obligations between researchers and human subjects. Even if this bill is not passed in its present form, it appears inevitable that legislation with a similar intent will soon emerge. Any such legislation will carry the full weight and penalties of law. Because many current research practices may violate these proposed new regulations, researchers should understand the provisions of S. 422. Furthermore, it is crucial that researchers understand the bill now, before it becomes law, because this may be their last opportunity to lobby for any modifications of the bill.

  7. Family physicians' awareness and knowledge of the Genetic Information Non-Discrimination Act (GINA).

    PubMed

    Laedtke, Amanda L; O'Neill, Suzanne M; Rubinstein, Wendy S; Vogel, Kristen J

    2012-04-01

    Historically, physicians have expressed concern about their patients' risk of genetic discrimination, which has acted as a barrier to uptake of genetic services. The Genetic Information Nondiscrimination Act of 2008 (GINA) is intended to protect patients against employer and health insurance discrimination. Physicians' awareness and knowledge of GINA has yet to be evaluated. In 2009, we mailed surveys to 1500 randomly selected members of the American Academy of Family Physicians. Questions measured physicians' current knowledge of GINA and their level of concern for genetic discrimination. In total, 401 physicians completed the survey (response rate 26.9%). Approximately half (54.5%) of physicians had no awareness of GINA. Of physicians who reported basic knowledge of GINA, the majority were aware of the protections offered for group health insurance (92.7%), private health insurance (82.9%), and employment (70.7%). Fewer physicians were aware of GINA's limitations regarding life insurance (53.7%) and long-term care insurance (58.8%). Physicians demonstrated highest levels of concern for health insurance, life insurance, and long-term care insurance discrimination, with less concern for employer and family/social discrimination. Level of concern for the risk of genetic discrimination did not correlate significantly with awareness of GINA. Approximately 17 months after GINA was signed into federal law, physicians' knowledge remained limited regarding the existence of this legislation and relevant details. Physicians who are aware of GINA continue to have significant concerns regarding the risk of genetic discrimination. This study reveals the need to further educate physicians about the existence of GINA and the protections offered.

  8. FANC Pathway Promotes UV-Induced Stalled Replication Forks Recovery by Acting Both Upstream and Downstream Polη and Rev1

    PubMed Central

    Renaud, Emilie; Rosselli, Filippo

    2013-01-01

    To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1. PMID:23365640

  9. FANC pathway promotes UV-induced stalled replication forks recovery by acting both upstream and downstream Polη and Rev1.

    PubMed

    Renaud, Emilie; Rosselli, Filippo

    2013-01-01

    To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1.

  10. Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act.

    PubMed

    Allain, Dawn C; Friedman, Sue; Senter, Leigha

    2012-12-01

    To examine the awareness and attitudes about the Genetic Information Nondiscrimination Act in individuals who made contact with a Hereditary Breast and Ovarian Cancer Syndrome advocacy group. This is a descriptive study of individuals (n = 1,699) who were invited via email and advertisements to complete an online questionnaire available from August 2009 through December 2010. Response distributions of relevant subgroups were compared using cross tabulation and Chi-squared tests were used. The majority of respondents (69.2 %) had undergone genetic testing (n = 1,156) and 30.2 % had not. Of those who did not undergo genetic testing, the most common reason given for declining testing was cost (28.8 %), followed by concerns about insurance discrimination (19.5 %). More than half (60.5 %) were worried about health insurance discrimination when they first considered genetic testing and 28.6 % were worried about employment discrimination. Slightly more individuals were worried about health insurance discrimination if they had no prior knowledge of GINA. While "cost" was cited most frequently as the reason not to test, "fear of insurance discrimination" was the second most common reason. Knowledge of GINA among consumers is still limited and public education may help promote reduction in fear.

  11. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance.

    PubMed

    Forsberg, Simon K G; Andreatta, Matthew E; Huang, Xin-Yuan; Danku, John; Salt, David E; Carlborg, Örjan

    2015-11-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or "missing heritability". Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations.

  12. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

    PubMed Central

    Forsberg, Simon K. G.; Andreatta, Matthew E.; Huang, Xin-Yuan; Danku, John; Salt, David E.; Carlborg, Örjan

    2015-01-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or “missing heritability”. Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations. PMID:26599497

  13. Invadolysin acts genetically via the SAGA complex to modulate chromosome structure

    PubMed Central

    Rao, Shubha Gururaja; Janiszewski, Michal M.; Duca, Edward; Nelson, Bryce; Abhinav, Kanishk; Panagakou, Ioanna; Vass, Sharron; Heck, Margarete M.S.

    2015-01-01

    Identification of components essential to chromosome structure and behaviour remains a vibrant area of study. We have previously shown that invadolysin is essential in Drosophila, with roles in cell division and cell migration. Mitotic chromosomes are hypercondensed in length, but display an aberrant fuzzy appearance. We additionally demonstrated that in human cells, invadolysin is localized on the surface of lipid droplets, organelles that store not only triglycerides and sterols but also free histones H2A, H2Av and H2B. Is there a link between the storage of histones in lipid droplets and the aberrantly structured chromosomes of invadolysin mutants? We have identified a genetic interaction between invadolysin and nonstop, the de-ubiquitinating protease component of the SAGA (Spt-Ada-Gcn5-acetyltransferase) chromatin-remodelling complex. invadolysin and nonstop mutants exhibit phenotypic similarities in terms of chromosome structure in both diploid and polyploid cells. Furthermore, IX-141/not1 transheterozygous animals accumulate mono-ubiquitinated histone H2B (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount immunostaining of IX-141/not1 transheterozygous salivary glands revealed that ubH2B accumulates surprisingly in the cytoplasm, rather than the nucleus. Over-expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating either the invadolysin or nonstop genes. Intriguingly, nonstop and mutants of other SAGA subunits (gcn5, ada2b and sgf11) all suppress an invadolysin-induced rough eye phenotype. We conclude that the abnormal chromosome phenotype of invadolysin mutants is likely the result of disrupting the histone modification cycle, as accumulation of ubH2B and H3K4me3 is observed. We further suggest that the mislocalization of ubH2B to the cytoplasm has additional consequences on downstream components essential for chromosome behaviour. We therefore propose that invadolysin plays a crucial role in chromosome organization

  14. Genetic counselors and health literacy: the role of genetic counselors in developing a web-based resource about the Affordable Care Act.

    PubMed

    Mann, Sylvia; Mui, Pauline; Boomsma, Jennifer; Hasegawa, Lianne

    2015-06-01

    The Western States Genetic Services Collaborative (WSGSC) recognized the need for clear and understandable information about the Affordable Care Act (ACA) for families throughout the life course. The genetic counselors working in the WSGSC developed, tested, and implemented a web resource ( http://www.westernstatesgenetics.org/ACA_home.htm ) to help families navigate information about the ACA tailored to their life situation. The training and experience of genetic counselors provide the skills needed to translate complicated information, like that of the ACA, into formats that the general public can comprehend. The website went public in October 2013, and it has been positively received. The development of this website is a good case study in how genetic counseling skills can be applied to public health education and improving health literacy. PMID:25502406

  15. AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo.

    PubMed

    Wang, Xiaowen; Li, Kai; Liu, Ling; Shi, Qiong; Song, Pu; Jian, Zhe; Guo, Sen; Wang, Gang; Li, Chunying; Gao, Tianwen

    2015-09-15

    Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR -129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that -129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with -129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than -129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo.

  16. AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo

    PubMed Central

    Wang, Xiaowen; Li, Kai; Liu, Ling; Shi, Qiong; Song, Pu; Jian, Zhe; Guo, Sen; Wang, Gang; Li, Chunying; Gao, Tianwen

    2015-01-01

    Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR −129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that −129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with −129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than −129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo. PMID:26370050

  17. Genetic Barrier to Direct Acting Antivirals in HCV Sequences Deposited in the European Databank

    PubMed Central

    Tovo, Cristiane Valle; Gorini da Veiga, Ana Beatriz; Machado, André Luiz; West, John

    2016-01-01

    Background & Aims Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs. Methods The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzeds 789 NS3 sequences, 708 sequences and 536 NS5B sequences deposited in the European Hepatitis C Virus Database, in the following resistance-associated positions: NS3: F43/I/L/S/V, Q80K/R, R155K/G, A156G/S/T and D168A/C/E/G/H/N/T/V/Y; NS5A: L/M28A/T/V, Q30E/H/R, L31F/I/M/V, H58D or P58S and Y93C/F/H/N/S; NS5B: S282P/R/T, C316H/N/Y, S368T, Y448C/H, S556G/R, D559R. Results Variants that require only one transversion in NS3 were found in 4 positions and include F43S, R80K, R155K/G and A156T. The genetic barrier to resistance shows subtypic differences at position 155 of the NS3 gene where a single transition is necessary in subtype 1a. In the NS5A gene, 5 positions where only one nucleotide change can confer resistance were found, such as L31M which requires one transversion in all subtypes, except in 0.28% of 1b sequences; and R30H, generated by a single transition, which was found in 10.25% of the sequences of genotype 1b. Other subtypic differences were observed at position 58, where resistance is less likely in genotype 1a because a transversion is required to create the variant 58S. For the NS5B inhibitors, the genetic barrier at positions conferring resistance was nearly identical in subtypes 1a and 1b, and single transitions or transversions were necessary in 5 positions to generate a drug-resistant variant of HCV. The positions C316Y and S556D required only one transition in all genotypes, Y448H and S

  18. The Genetic Information Nondiscrimination Act (GINA): public policy and medical practice in the age of personalized medicine.

    PubMed

    Feldman, Eric A

    2012-06-01

    Survey data suggest that many people fear genetic discrimination by health insurers or employers. In fact, such discrimination has not yet been a significant problem. This article examines the fear and reality of genetic discrimination in the United States, describes how Congress sought to prohibit such discrimination by passing the Genetic Information Nondiscrimination Act of 2008 (GINA), and explores the implications of GINA for general internists and their institutions. It concludes that medical providers and health care institutions must be familiar with the general intent and specific terms of GINA, and should continue to collect genetic information that can contribute to the high quality provision of medical treatment. Not doing so violates their medical mission and diminishes the quality of care patients deserve.

  19. A systematic review of factors that act as barriers to patient referral to genetic services

    PubMed Central

    Delikurt, Türem; Williamson, Graham R; Anastasiadou, Violetta; Skirton, Heather

    2015-01-01

    Patients who might benefit from genetic services may be denied access through failure to be referred. To investigate the evidence on barriers to referral to genetic services, we conducted a systematic review of empirical evidence on this topic. Nine studies were included in the review. Barriers related to non-genetic healthcare professionals were: lack of awareness of patient risk factors, failure to obtain adequate family history, lack of knowledge of genetics and genetic conditions, lack of awareness of genetic services, inadequate coordination of referral and lack of genetics workforce. Those related to individuals affected by or at risk of a genetic condition were: lack of awareness of personal risk, lack of knowledge and/or awareness of medical history of family members and lack of knowledge of genetic services. Research on access to genetic services is heterogeneous; stronger empirical evidence is needed on factors that are barriers, and further research is needed to develop ‘targeted interventions' for equitable access to genetic services in a range of populations. PMID:25205405

  20. Thailand's downstream projects proliferate

    SciTech Connect

    Not Available

    1991-06-03

    Thailand continues to press expansion and modernization of its downstream sector. Among recent developments: Construction of an olefins unit at Thailand's second major petrochemical complex and a worldscale aromatics unit in Thailand is threatened by rising costs. Thailand's National Petrochemical Corp (NPC) let a 9 billion yen contract to Mitsui Engineering and Shipbuilding Co. and C. Itoh and Co. for a dual fuel cogeneration power plant at its Mab Ta Phud, Rayong province, petrochemical complex. Financing is in place to flash a green light for a $530 million Belgian-Thai joint venture sponsoring a worldscale polyvinyl chloride/vinyl chloride monomer plant in Thailand. Work is more than 50% complete on the $345 million second phase expansion of Thai Oil's Sri Racha refinery in Chon Buri province. Petroleum Authority of Thailand (PTT) endorsed a plan to install two more natural gas processing plants in Thailand to meet rapidly growing domestic demand for petroleum gas.

  1. Could refuge theory and rivers acting as barriers explain the genetic variability distribution in the Atlantic Forest?

    PubMed

    Cazé, Ana Luiza R; Mäder, Geraldo; Nunes, Teonildes S; Queiroz, Luciano P; de Oliveira, Guilherme; Diniz-Filho, José Alexandre F; Bonatto, Sandro L; Freitas, Loreta B

    2016-08-01

    The Atlantic Forest is one of the most species-rich ecoregions in the world. The historical origins of this richness and the evolutionary processes that produced diversification and promoted speciation in this ecosystem remain poorly understood. In this context, focusing on Passiflora contracta, an endemic species from the Atlantic Forest distributed exclusively at sea level along forest edges, this study aimed to characterize the patterns of genetic variability and explore two hypotheses that attempt to explain the possible causes of the genetic diversity in this region: the refuge and riverine barrier theories. We employed Bayesian methods combined with niche modeling to identify genetically homogeneous groups, to determine the diversification age, and identify long-term climate stability areas to species survival. The analyses were performed using molecular markers from nuclear and plastid genomes, with samples collected throughout the entire geographic distribution of the species, and comparisons with congeners species. The results indicated that populations were genetically structured and provided evidence of demographic stability. The molecular markers indicated the existence of a clear structure and the presence of five homogeneous groups. Interestingly, the separation of the groups coincides with the geographical locations of local rivers, corroborating the hypothesis of rivers acting as barriers to gene flow in this species. The highest levels of genetic diversity and the areas identified as having long-term climate stability were found in the same region reported for other species as a possible refuge area during the climatic changes of the Quaternary. PMID:27188539

  2. Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification rules under the Health Information Technology for Economic and Clinical Health Act and the Genetic Information Nondiscrimination Act; other modifications to the HIPAA rules.

    PubMed

    2013-01-25

    The Department of Health and Human Services (HHS or ``the Department'') is issuing this final rule to: Modify the Health Insurance Portability and Accountability Act (HIPAA) Privacy, Security, and Enforcement Rules to implement statutory amendments under the Health Information Technology for Economic and Clinical Health Act (``the HITECH Act'' or ``the Act'') to strengthen the privacy and security protection for individuals' health information; modify the rule for Breach Notification for Unsecured Protected Health Information (Breach Notification Rule) under the HITECH Act to address public comment received on the interim final rule; modify the HIPAA Privacy Rule to strengthen the privacy protections for genetic information by implementing section 105 of Title I of the Genetic Information Nondiscrimination Act of 2008 (GINA); and make certain other modifications to the HIPAA Privacy, Security, Breach Notification, and Enforcement Rules (the HIPAA Rules) to improve their workability and effectiveness and to increase flexibility for and decrease burden on the regulated entities.

  3. Disclosure of genetic information to at-risk relatives: recent amendments to the Privacy Act 1988 (Cwlth).

    PubMed

    Otlowski, Margaret F A

    2007-10-01

    The federal Privacy Act 1988 (Cwlth) has recently been amended to permit the disclosure of genetic information to an at-risk relative when there is a serious (although not necessarily imminent) threat to that person's life, health, or safety. This represents a significant exception to the statutory obligations to maintain the privacy of a patient's health information. However, its scope of operation is limited in that it applies only to doctors and other health professionals working in the private sector, and does not cover those working in State public hospitals or for Commonwealth Government agencies. PMID:17908004

  4. Downstream in Mawrth Valles

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site]

    The THEMIS VIS camera is capable of capturing color images of the Martian surface using five different color filters. In this mode of operation, the spatial resolution and coverage of the image must be reduced to accommodate the additional data volume produced from using multiple filters. To make a color image, three of the five filter images (each in grayscale) are selected. Each is contrast enhanced and then converted to a red, green, or blue intensity image. These three images are then combined to produce a full color, single image. Because the THEMIS color filters don't span the full range of colors seen by the human eye, a color THEMIS image does not represent true color. Also, because each single-filter image is contrast enhanced before inclusion in the three-color image, the apparent color variation of the scene is exaggerated. Nevertheless, the color variation that does appear is representative of some change in color, however subtle, in the actual scene. Note that the long edges of THEMIS color images typically contain color artifacts that do not represent surface variation.

    This false color image is from further downstream in Mawrth Valles than yesterday's image. The channel here is at the end of the vallis. This image was collected during the Northern Spring season.

    Image information: VIS instrument. Latitude 26.7, Longitude 340.2 East (19.8 West). 37 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages

  5. The application of genetic information for regulatory standard setting under the clean air act: a decision-analytic approach.

    PubMed

    Cullen, Alison C; Corrales, Mark A; Kramer, C Bradley; Faustman, Elaine M

    2008-08-01

    In 2002, the U.S. Environmental Protection Agency (EPA) released an "Interim Policy on Genomics," stating a commitment to developing guidance on the inclusion of genetic information in regulatory decision making. This statement was followed in 2004 by a document exploring the potential implications. Genetic information can play a key role in understanding and quantifying human susceptibility, an essential step in many of the risk assessments used to shape policy. For example, the federal Clean Air Act (CAA) requires EPA to set National Ambient Air Quality Standards (NAAQS) for criteria pollutants at levels to protect even sensitive populations from adverse health effects with an adequate margin of safety. Asthmatics are generally regarded as a sensitive population, yet substantial research gaps in understanding genetic susceptibility and disease have hindered quantitative risk analysis. This case study assesses the potential role of genomic information regarding susceptible populations in the NAAQS process for fine particulate matter (PM(2.5)) under the CAA. In this initial assessment, we model the contribution of a single polymorphism to asthma risk and mortality risk; however, multiple polymorphisms and interactions (gene-gene and gene-environment) are known to play key roles in the disease process. We show that the impact of new information about susceptibility on estimates of population risk or average risk derived from large epidemiological studies depends on the circumstances. We also suggest that analysis of a single polymorphism, or other risk factor such as health status, may or may not change estimates of individual risk enough to alter a particular regulatory decision, but this depends on specific characteristics of the decision and risk information. We also show how new information about susceptibility in the context of the NAAQS for PM(2.5) could have a large impact on the estimated distribution of individual risk. This would occur if a group were

  6. A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

    PubMed

    Read, Timothy; Richmond, Phillip A; Dowell, Robin D

    2016-01-01

    Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.

  7. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  8. The genetic signatures of pediatric high-grade glioma: no longer a one-act play.

    PubMed

    Diaz, Alexander K; Baker, Suzanne J

    2014-10-01

    Advances in understanding pediatric high-grade glioma (pHGG) genetics have revealed key differences between pHGG and adult HGG and have uncovered unique molecular drivers among subgroups within pHGG. The 3 core adult HGG pathways, the receptor tyrosine kinase-Ras-phosphatidylinositide 3-kinase, p53, and retinoblastoma networks, are also disrupted in pHGG, but they exhibit a different spectrum of effectors targeted by mutation. There are also similarities and differences in the genomic landscape of diffuse intrinsic pontine glioma (DIPG) and pediatric nonbrainstem (pNBS)-HGG. In 2012, histone H3 mutations were identified in nearly 80% of DIPGs and ~35% of pNBS-HGG. These were the first reports of histone mutations in human cancer, implicating novel biology in pediatric gliomagenesis. Additionally, DIPG and midline pNBS-HGG vary in the frequency and specific histone H3 amino acid substitution compared with pNBS-HGGs arising in the cerebral hemispheres, demonstrating a molecular difference among pHGG subgroups. The gene expression signatures as well as DNA methylation signatures of these tumors are also distinctive, reflecting a combination of the driving mutations and the developmental context from which they arise. These data collectively highlight unique selective pressures within the developing brainstem and solidify DIPG as a specific molecular and biological entity among pHGGs. Emerging studies continue to identify novel mutations that distinguish subgroups of pHGG. The molecular heterogeneity among pHGGs will undoubtedly have clinical implications moving forward. The discovery of unique oncogenic drivers is a critical first step in providing patients with appropriate, targeted therapies. Despite these insights, our vantage point has been largely limited to an in-depth analysis of protein coding sequences. Given the clear importance of histone mutations in pHGG, it will be interesting to see how aberrant epigenetic regulation contributes to tumorigenesis in the

  9. The genetic signatures of pediatric high-grade glioma: no longer a one-act play

    PubMed Central

    Diaz, Alexander K.; Baker, Suzanne J.

    2014-01-01

    Advances in understanding pediatric high-grade glioma (pHGG) genetics have revealed key differences between pediatric and adult high-grade gliomas (aHGGs), and have uncovered unique molecular drivers among subgroups within pHGG. The three core aHGG pathways, the receptor tyrosine kinase(RTK)/Ras/Phosphatidylinositide 3-kinase (PI3K), p53, and retinoblastoma (RB) networks, are also disrupted in pHGG, but they exhibit a different spectrum of effectors targeted by mutation. There are also similarities and differences in the genomic landscape of diffuse intrinsic pontine glioma (DIPG) and pediatric non-brainstem high-grade glioma (pNBS-HGG). In 2012, histone H3 mutations were identified in nearly 80% of DIPGs and ∼35% of pNBS-HGG. These were the first reports of histone mutations in human cancer, implicating novel biology in pediatric gliomagenesis. Additionally, DIPG and midline pNBS-HGG vary in the frequency and specific histone H3 amino acid substitution compared to pNBS-HGGs arising in the cerebral hemispheres, demonstrating a molecular difference among pHGG subgroups. The gene expression signatures as well as DNA methylation signatures of these tumors also carry distinctive signatures, reflecting a combination of the driving mutations and the developmental context from which they arise. These data collectively highlight unique selective pressures within the developing brainstem and solidify DIPG as a specific molecular and biological entity among pHGGs. Emerging studies continue to identify novel mutations that distinguish subgroups of pHGG. The molecular heterogeneity among pHGGs will undoubtedly have clinical implications moving forward. The discovery of unique oncogenic drivers is a critical first step in providing patients with appropriate, targeted therapies. Despite these insights, our vantage point has been largely limited to an in-depth analysis of protein coding sequences. Given the clear importance of histone mutations in pHGG, it will be interesting

  10. Cis- and trans-acting genetic factors contribute to heterogeneity in the rate of crossing over between the Drosophila simulans clade species.

    PubMed

    Cattani, M V; Kingan, S B; Presgraves, D C

    2012-10-01

    In the genus Drosophila, variation in recombination rates has been found within and between species. Genetic variation for both cis- and trans-acting factors has been shown to affect recombination rates within species, but little is known about the genetic factors that affect differences between species. Here, we estimate rates of crossing over for seven segments that tile across the euchromatic length of the X chromosome in the genetic backgrounds of three closely related Drosophila species. We first generated a set of Drosophila mauritiana lines each having two semidominant visible markers on the X chromosome and then introgressed these doubly marked segments into the genetic backgrounds of its sibling species, Drosophila simulans and Drosophila sechellia. Using these 21 lines (seven segments, three genetic backgrounds), we tested whether recombination rates within the doubly marked intervals differed depending on genetic background. We find significant heterogeneity among intervals and among species backgrounds. Our results suggest that a combination of both cis- and trans-acting factors have evolved among the three D. simulans clade species and interact to affect recombination rate.

  11. Unravelling fears of genetic discrimination: an exploratory study of Dutch HCM families in an era of genetic non-discrimination acts.

    PubMed

    Geelen, Els; Horstman, Klasien; Marcelis, Carlo L M; Doevendans, Pieter A; Van Hoyweghen, Ine

    2012-10-01

    Since the 1990s, many countries in Europe and the United States have enacted genetic non-discrimination legislation to prevent people from deferring genetic tests for fear that insurers or employers would discriminate against them based on that information. Although evidence for genetic discrimination exists, little is known about the origins and backgrounds of fears of discrimination and how it affects decisions for uptake of genetic testing. The aim of this article is to gain a better understanding of these fears and its possible impact on the uptake of testing by studying the case of hypertrophic cardiomyopathy (HCM). In a qualitative study, we followed six Dutch extended families involved in genetic testing for HCM for three-and-a-half years. Semi-structured interviews were conducted with 57 members of these families. Based on the narratives of the families, we suggest that fears of discrimination have to be situated in the broader social and life-course context of family and kin. We describe the processes in which families developed meaningful interpretations of genetic discrimination and how these interpretations affected family members' decisions to undergo genetic testing. Our findings show that fears of genetic discrimination do not so much stem from the opportunity of genetic testing but much more from earlier experiences of discrimination of diseased family members. These results help identify the possible limitations of genetic non-discrimination regulations and provide direction to clinicians supporting their clients as they confront issues of genetic testing and genetic discrimination.

  12. Chemical downstream etching of tungsten

    SciTech Connect

    Blain, M.G.; Jarecki, R.L.; Simonson, R.J.

    1998-07-01

    The downstream etching of tungsten and tungsten oxide has been investigated. Etching of chemical vapor deposited tungsten and e-beam deposited tungsten oxide samples was performed using atomic fluorine generated by a microwave discharge of argon and NF{sub 3}. Etching was found to be highly activated with activation energies approximated to be 6.0{plus_minus}0.5thinspkcal/mol and 5.4{plus_minus}0.4thinspkcal/mol for W and WO{sub 3}, respectively. In the case of F etching of tungsten, the addition of undischarged nitric oxide (NO) directly into the reaction chamber results in the competing effects of catalytic etch rate enhancement and the formation of a nearly stoichiometric WO{sub 3} passivating tungsten oxide film, which ultimately stops the etching process. For F etching of tungsten oxide, the introduction of downstream NO reduces the etch rate. {copyright} {ital 1998 American Vacuum Society.}

  13. Continuous downstream processing of biopharmaceuticals.

    PubMed

    Jungbauer, Alois

    2013-08-01

    Continuous manufacturing has been applied in many different industries but has been pursued reluctantly in biotechnology where the batchwise process is still the standard. A shift to continuous operation can improve productivity of a process and substantially reduce the footprint. Continuous operation also allows robust purification of labile biomolecules. A full set of unit operations is available to design continuous downstream processing of biopharmaceuticals. Chromatography, the central unit operation, is most advanced in respect to continuous operation. Here, the problem of 'batch' definition has been solved. This has also paved the way for implementation of continuous downstream processing from a regulatory viewpoint. Economic pressure, flexibility, and parametric release considerations will be the driving force to implement continuous manufacturing strategies in future.

  14. Continuous downstream processing of biopharmaceuticals.

    PubMed

    Jungbauer, Alois

    2013-08-01

    Continuous manufacturing has been applied in many different industries but has been pursued reluctantly in biotechnology where the batchwise process is still the standard. A shift to continuous operation can improve productivity of a process and substantially reduce the footprint. Continuous operation also allows robust purification of labile biomolecules. A full set of unit operations is available to design continuous downstream processing of biopharmaceuticals. Chromatography, the central unit operation, is most advanced in respect to continuous operation. Here, the problem of 'batch' definition has been solved. This has also paved the way for implementation of continuous downstream processing from a regulatory viewpoint. Economic pressure, flexibility, and parametric release considerations will be the driving force to implement continuous manufacturing strategies in future. PMID:23849674

  15. Genetically Engineered Safety Act

    THOMAS, 112th Congress

    Rep. Kucinich, Dennis J. [D-OH-10

    2011-12-02

    12/19/2011 Referred to the Subcommittee on Rural Development, Research, Biotechnology, and Foreign Agriculture. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  16. Using chromatography in downstream processing.

    PubMed

    Becker, C

    1989-01-01

    This article concludes the series on the use of chromatography for downstream processing. Although it has only scratched the surface when considering the number of parameters involved in process chromatography, it does give a broad overview including the choice of components through process standards. Pharmacia LKB Biotechnology has had more than 15 years experience in the design development and running of large scale chromatographic processes. During this time the company has gathered a vast amount of experience and information on the key points to successful product purification. Pharmacia LKB can advise on the choice of techniques and the development of a separation process up to full production scale.

  17. A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left-right asymmetry downstream or in parallel to nodal flow.

    PubMed

    Ellertsdottir, Elin; Ganz, Julia; Dürr, Katrin; Loges, Niki; Biemar, Frederic; Seifert, Franziska; Ettl, Anne-Katrin; Kramer-Zucker, Albrecht K; Nitschke, Roland; Driever, Wolfgang

    2006-07-01

    While there is a good conceptual framework of dorsoventral and anterioposterior axes formation in most vertebrate groups, understanding of left-right axis initiation is fragmentary. Diverse mechanisms have been implied to contribute to the earliest steps of left-right asymmetry, including small molecule signals, gap junctional communication, membrane potential, and directional flow of extracellular liquid generated by monocilia in the node region. Here we demonstrate that a mutation in the zebrafish Na,K-ATPase subunit atp1a1a causes left-right defects including isomerism of internal organs at the anatomical level. The normally left-sided Nodal signal spaw as well as its inhibitor lefty are expressed bilaterally, while pitx2 may appear random or bilateral. Monocilia movement and fluid circulation in Kupffer's vesicle are normal in atp1a1a(m883) mutant embryos. Therefore, the Na,K-ATPase is required downstream or in parallel to monocilia function during initiation of left-right asymmetry in zebrafish. PMID:16628609

  18. Genetic and biochemical studies of poliovirus cis-acting replication element cre in relation to VPg uridylylation.

    PubMed

    Rieder, E; Paul, A V; Kim, D W; van Boom, J H; Wimmer, E

    2000-11-01

    In addition to highly conserved stem-loop structures located in the 5'- and 3'-nontranslated regions, genome replication of picornaviruses requires cis-acting RNA elements located in the coding region (termed cre) (K. L. McKnight and S. M. Lemon, J. Virol. 70:1941-1952, 1996; P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560-11565, 1999; I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590-4600, 2000). cre elements appear to be essential for minus-strand RNA synthesis by an as-yet-unknown mechanism. We have discovered that the cre element of poliovirus (mapping to the 2C coding region of poliovirus type 1; nucleotides 4444 to 4505 in 2C), which is homologous to the cre element of poliovirus type 3, is preferentially used as a template for the in vitro uridylylation of VPg catalyzed by 3D(pol) in a reaction that is greatly stimulated by 3CD(pro) (A. V. Paul, E. Rieder, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74:10359-10370, 2000). Here we report a direct correlation between mutations that eliminate, or severely reduce, the in vitro VPg-uridylylation reaction and produce replication phenotypes in vivo. None of the genetic changes significantly influenced translation or polyprotein processing. A substitution mapping to the first A (A4472C) of a conserved AAACA sequence in the loop of PV-cre(2C) eliminated the ability of the cre RNA to serve as template for VPg uridylylation and abolished RNA infectivity. Mutagenesis of the second A (A4473C; AAACA) severely reduced the yield of VPgpUpU and RNA infectivity was restored only after reversion to the wild-type sequence. The effect of substitution of the third A (A4474G; AAACA) was less severe but reduced both VPg uridylylation and virus yield. Disruption of base pairing within the upper stem region of PV-cre(2C) also affected uridylylation of VPg. Virus derived from transcripts containing mutations in the stem

  19. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  20. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  1. A Downstream voyage with mercury

    USGS Publications Warehouse

    Heinz, Gary

    2016-01-01

    Retrospective essay for the Bulletin of Environmental Contamination and Toxicology.As I look back on my paper, “Effects of Low Dietary Levels of Methyl Mercury on Mallard Reproduction,” published in 1974 in the Bulletin of Environmental Contamination and Toxicology, a thought sticks in my mind. I realize just how much my mercury research was not unlike a leaf in a stream, carried this way and that, sometimes stalled in an eddy, restarted, and carried downstream at a pace and path that was not completely under my control. I was hired in 1969 by the Patuxent Wildlife Research Center to study the effects of environmental pollutants on the behavior of wildlife. A colleague was conducting a study on the reproductive effects of methylmercury on mallards (Anas platyrhynchos), and he offered to give me some of the ducklings. I conducted a pilot study, testing how readily ducklings approached a tape-recorded maternal call. Sample sizes were small, but the results suggested that ducklings from mercury-treated parents behaved differently than controls. That’s how I got into mercury research—pretty much by chance.

  2. A downstream voyage with mercury

    USGS Publications Warehouse

    Heinz, Gary

    2016-01-01

    Retrospective essay for the Bulletin of Environmental Contamination and Toxicology.As I look back on my paper, “Effects of Low Dietary Levels of Methyl Mercury on Mallard Reproduction,” published in 1974 in the Bulletin of Environmental Contamination and Toxicology, a thought sticks in my mind. I realize just how much my mercury research was not unlike a leaf in a stream, carried this way and that, sometimes stalled in an eddy, restarted, and carried downstream at a pace and path that was not completely under my control. I was hired in 1969 by the Patuxent Wildlife Research Center to study the effects of environmental pollutants on the behavior of wildlife. A colleague was conducting a study on the reproductive effects of methylmercury on mallards (Anas platyrhynchos), and he offered to give me some of the ducklings. I conducted a pilot study, testing how readily ducklings approached a tape-recorded maternal call. Sample sizes were small, but the results suggested that ducklings from mercury-treated parents behaved differently than controls. That’s how I got into mercury research—pretty much by chance.

  3. Canine adenovirus downstream processing protocol.

    PubMed

    Puig, Meritxell; Piedra, Jose; Miravet, Susana; Segura, María Mercedes

    2014-01-01

    Adenovirus vectors are efficient gene delivery tools. A major caveat with vectors derived from common human adenovirus serotypes is that most adults are likely to have been exposed to the wild-type virus and exhibit active immunity against the vectors. This preexisting immunity limits their clinical success. Strategies to circumvent this problem include the use of nonhuman adenovirus vectors. Vectors derived from canine adenovirus type 2 (CAV-2) are among the best-studied representatives. CAV-2 vectors are particularly attractive for the treatment of neurodegenerative disorders. In addition, CAV-2 vectors have shown great promise as oncolytic agents in virotherapy approaches and as vectors for recombinant vaccines. The rising interest in CAV-2 vectors calls for the development of scalable GMP compliant production and purification strategies. A detailed protocol describing a complete scalable downstream processing strategy for CAV-2 vectors is reported here. Clarification of CAV-2 particles is achieved by microfiltration. CAV-2 particles are subsequently concentrated and partially purified by ultrafiltration-diafiltration. A Benzonase(®) digestion step is carried out between ultrafiltration and diafiltration operations to eliminate contaminating nucleic acids. Chromatography purification is accomplished in two consecutive steps. CAV-2 particles are first captured and concentrated on a propyl hydrophobic interaction chromatography column followed by a polishing step using DEAE anion exchange monoliths. Using this protocol, high-quality CAV-2 vector preparations containing low levels of contamination with empty viral capsids and other inactive vector forms are typically obtained. The complete process yield was estimated to be 38-45 %. PMID:24132487

  4. [Utilization of complex technologies of molecular genetics for forensic expert identification of unidentified remains of victims of terrorist acts in Moscow in 1999].

    PubMed

    Ivanov, P L; Zharov, V V; Frolova, S A; Ryseva, E V; Kolmakova, M A; Trusova, G R; Tomilin, V V

    2002-01-01

    This paper presents the first experience gained in Russia in expert identification practice with complex utilization of technologies of molecular genetic individualization of biological objects for solving identification tasks requiring the maximum complete armory of mutually supplementing means. This is particularly important for forensic expert personality identification in cases with many deaths, when indirect identification has to be resorted to, consisting in the use of biological samples from relatives of the victims as the identifying objects. Methodological approaches and concepts of expert studies, used for identification of the remains of people who died in terroristic acts committed in Moscow in September, 1999, are discussed. The results of this study and methodological experience notably extend the potentialities of expert evaluation as regards forensic medical identification of victims of overall disasters, terroristic acts, and war conflicts.

  5. The Role of Headwater Streams in Downstream Water Quality.

    PubMed

    Alexander, Richard B; Boyer, Elizabeth W; Smith, Richard A; Schwarz, Gregory E; Moore, Richard B

    2007-02-01

    Knowledge of headwater influences on the water-quality and flow conditions of downstream waters is essential to water-resource management at all governmental levels; this includes recent court decisions on the jurisdiction of the Federal Clean Water Act (CWA) over upland areas that contribute to larger downstream water bodies. We review current watershed research and use a water-quality model to investigate headwater influences on downstream receiving waters. Our evaluations demonstrate the intrinsic connections of headwaters to landscape processes and downstream waters through their influence on the supply, transport, and fate of water and solutes in watersheds. Hydrological processes in headwater catchments control the recharge of subsurface water stores, flow paths, and residence times of water throughout landscapes. The dynamic coupling of hydrological and biogeochemical processes in upland streams further controls the chemical form, timing, and longitudinal distances of solute transport to downstream waters. We apply the spatially explicit, mass-balance watershed model SPARROW to consider transport and transformations of water and nutrients throughout stream networks in the northeastern United States. We simulate fluxes of nitrogen, a primary nutrient that is a water-quality concern for acidification of streams and lakes and eutrophication of coastal waters, and refine the model structure to include literature observations of nitrogen removal in streams and lakes. We quantify nitrogen transport from headwaters to downstream navigable waters, where headwaters are defined within the model as first-order, perennial streams that include flow and nitrogen contributions from smaller, intermittent and ephemeral streams. We find that first-order headwaters contribute approximately 70% of the mean-annual water volume and 65% of the nitrogen flux in second-order streams. Their contributions to mean water volume and nitrogen flux decline only marginally to about 55% and

  6. The Role of Headwater Streams in Downstream Water Quality1

    PubMed Central

    Alexander, Richard B; Boyer, Elizabeth W; Smith, Richard A; Schwarz, Gregory E; Moore, Richard B

    2007-01-01

    Knowledge of headwater influences on the water-quality and flow conditions of downstream waters is essential to water-resource management at all governmental levels; this includes recent court decisions on the jurisdiction of the Federal Clean Water Act (CWA) over upland areas that contribute to larger downstream water bodies. We review current watershed research and use a water-quality model to investigate headwater influences on downstream receiving waters. Our evaluations demonstrate the intrinsic connections of headwaters to landscape processes and downstream waters through their influence on the supply, transport, and fate of water and solutes in watersheds. Hydrological processes in headwater catchments control the recharge of subsurface water stores, flow paths, and residence times of water throughout landscapes. The dynamic coupling of hydrological and biogeochemical processes in upland streams further controls the chemical form, timing, and longitudinal distances of solute transport to downstream waters. We apply the spatially explicit, mass-balance watershed model SPARROW to consider transport and transformations of water and nutrients throughout stream networks in the northeastern United States. We simulate fluxes of nitrogen, a primary nutrient that is a water-quality concern for acidification of streams and lakes and eutrophication of coastal waters, and refine the model structure to include literature observations of nitrogen removal in streams and lakes. We quantify nitrogen transport from headwaters to downstream navigable waters, where headwaters are defined within the model as first-order, perennial streams that include flow and nitrogen contributions from smaller, intermittent and ephemeral streams. We find that first-order headwaters contribute approximately 70% of the mean-annual water volume and 65% of the nitrogen flux in second-order streams. Their contributions to mean water volume and nitrogen flux decline only marginally to about 55% and

  7. The role of headwater streams in downstream water quality

    USGS Publications Warehouse

    Alexander, R.B.; Boyer, E.W.; Smith, R.A.; Schwarz, G.E.; Moore, R.B.

    2007-01-01

    Knowledge of headwater influences on the water-quality and flow conditions of downstream waters is essential to water-resource management at all governmental levels; this includes recent court decisions on the jurisdiction of the Federal Clean Water Act (CWA) over upland areas that contribute to larger downstream water bodies. We review current watershed research and use a water-quality model to investigate headwater influences on downstream receiving waters. Our evaluations demonstrate the intrinsic connections of headwaters to landscape processes and downstream waters through their influence on the supply, transport, and fate of water and solutes in watersheds. Hydrological processes in headwater catchments control the recharge of subsurface water stores, flow paths, and residence times of water throughout landscapes. The dynamic coupling of hydrological and biogeochemical processes in upland streams further controls the chemical form, timing, and longitudinal distances of solute transport to downstream waters. We apply the spatially explicit, mass-balance watershed model SPARROW to consider transport and transformations of water and nutrients throughout stream networks in the northeastern United States. We simulate fluxes of nitrogen, a primary nutrient that is a water-quality concern for acidification of streams and lakes and eutrophication of coastal waters, and refine the model structure to include literature observations of nitrogen removal in streams and lakes. We quantify nitrogen transport from headwaters to downstream navigable waters, where headwaters are defined within the model as first-order, perennial streams that include flow and nitrogen contributions from smaller, intermittent and ephemeral streams. We find that first-order headwaters contribute approximately 70% of the mean-annual water volume and 65% of the nitrogen flux in second-order streams. Their contributions to mean water volume and nitrogen flux decline only marginally to about 55% and

  8. Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

    PubMed Central

    dos Reis, Sávio Pinho; Lima, Aline Medeiros; de Souza, Cláudia Regina Batista

    2012-01-01

    Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops. PMID:22942725

  9. Transcriptional Derepression Uncovers Cryptic Higher-Order Genetic Interactions

    PubMed Central

    Taylor, Matthew B.; Ehrenreich, Ian M.

    2015-01-01

    Disruption of certain genes can reveal cryptic genetic variants that do not typically show phenotypic effects. Because this phenomenon, which is referred to as ‘phenotypic capacitance’, is a potential source of trait variation and disease risk, it is important to understand how it arises at the genetic and molecular levels. Here, we use a cryptic colony morphology trait that segregates in a yeast cross to explore the mechanisms underlying phenotypic capacitance. We find that the colony trait is expressed when a mutation in IRA2, a negative regulator of the Ras pathway, co-occurs with specific combinations of cryptic variants in six genes. Four of these genes encode transcription factors that act downstream of the Ras pathway, indicating that the phenotype involves genetically complex changes in the transcriptional regulation of Ras targets. We provide evidence that the IRA2 mutation reveals the phenotypic effects of the cryptic variants by disrupting the transcriptional silencing of one or more genes that contribute to the trait. Supporting this role for the IRA2 mutation, deletion of SFL1, a repressor that acts downstream of the Ras pathway, also reveals the phenotype, largely due to the same cryptic variants that were detected in the IRA2 mutant cross. Our results illustrate how higher-order genetic interactions among mutations and cryptic variants can result in phenotypic capacitance in specific genetic backgrounds, and suggests these interactions might reflect genetically complex changes in gene expression that are usually suppressed by negative regulation. PMID:26484664

  10. Comprehensive genetic analyses reveal evolutionary distinction of a mouse (Zapus hudsonius preblei) proposed for delisting from the US Endangered Species Act

    USGS Publications Warehouse

    King, T.L.; Switzer, J.F.; Morrison, C.L.; Eackles, M.S.; Young, C.C.; Lubinski, B.A.; Cryan, P.

    2006-01-01

    Zapus hudsonius preblei, listed as threatened under the US Endangered Species Act (ESA), is one of 12 recognized subspecies of meadow jumping mice found in North America. Recent morphometric and phylogenetic comparisons among Z. h. preblei and neighbouring conspecifics questioned the taxonomic status of selected subspecies, resulting in a proposal to delist the Z. h. preblei from the ESA. We present additional analyses of the phylogeographic structure within Z. hudsonius that calls into question previously published data (and conclusions) and confirms the original taxonomic designations. A survey of 21 microsatellite DNA loci and 1380 base pairs from two mitochondrial DNA (mtDNA) regions (control region and cytochrome b) revealed that each Z. hudsonius subspecies is genetically distinct. These data do not support the null hypothesis of a homogeneous gene pool among the five subspecies found within the southwestern portion of the species' range. The magnitude of the observed differentiation was considerable and supported by significant findings for nearly every statistical comparison made, regardless of the genome or the taxa under consideration. Structuring of nuclear multilocus genotypes and subspecies-specific mtDNA haplotypes corresponded directly with the disjunct distributions of the subspecies investigated. Given the level of correspondence between the observed genetic population structure and previously proposed taxonomic classification of subspecies (based on the geographic separation and surveys of morphological variation), we conclude that the nominal subspecies surveyed in this study do not warrant synonymy, as has been proposed for Z. h. preblei, Z. h. campestris, and Z. h. intermedius. ?? 2006 The Authors.

  11. Philippines' downstream sector poised for growth

    SciTech Connect

    Not Available

    1992-05-11

    This paper reports that the Philippines' downstream sector is poised for sharp growth. Despite a slip in refined products demand in recent years, Philippines products demand will rebound sharply by 2000, East-West Center (EWC), Honolulu, predicts. Philippines planned refinery expansions are expected to meet that added demand, EWC Director Fereidun Fesharaki says. Like the rest of the Asia-Pacific region, product specifications are changing, but major refiners in the area expect to meet the changes without major case outlays. At the same time, Fesharaki says, push toward deregulation will further bolster the outlook for the Philippines downstream sector.

  12. Genetic interactions between an essential 3' cis-acting RNA pseudoknot, replicase gene products, and the extreme 3' end of the mouse coronavirus genome.

    PubMed

    Züst, Roland; Miller, Timothy B; Goebel, Scott J; Thiel, Volker; Masters, Paul S

    2008-02-01

    The upstream end of the 3' untranslated region (UTR) of the mouse hepatitis virus genome contains two essential and overlapping RNA secondary structures, a bulged stem-loop and a pseudoknot, which have been proposed to be elements of a molecular switch that is critical for viral RNA synthesis. It has previously been shown that a particular six-base insertion in loop 1 of the pseudoknot is extremely deleterious to the virus. We have now isolated multiple independent second-site revertants of the loop 1 insertion mutant, and we used reverse-genetics methods to confirm the identities of suppressor mutations that could compensate for the original insertion. The suppressors were localized to two separate regions of the genome. Members of one class of suppressor were mapped to the portions of gene 1 that encode nsp8 and nsp9, thereby providing the first evidence for specific interactions between coronavirus replicase gene products and a cis-acting genomic RNA element. The second class of suppressor was mapped to the extreme 3' end of the genome, a result which pointed to the existence of a direct base-pairing interaction between loop 1 of the pseudoknot and the genomic terminus. The latter finding was strongly supported by phylogenetic evidence and by the construction of a deletion mutant that reduced the 3' UTR to its minimal essential elements. Taken together, the interactions revealed by the two classes of suppressors suggest a model for the initiation of coronavirus negative-strand RNA synthesis.

  13. Downstream Sediment Sorting as a Fractionation Process

    NASA Astrophysics Data System (ADS)

    Paola, C.; Fedele, J. J.

    2007-12-01

    Downstream size segregation in net depositional systems can be thought of as a fractination process in which a well mixed, heterogeneous input is unmixed based on its relative mobility. Although we are accustomed to thinking of the segregation process as hydraulically driven and rather complex, we argue that at large time and length scales size segregation can be substantially simplified. The main controls are the downstream distribution of sediment extraction, which is typically controlled externally (e.g. by subsidence) and the size distribution of the sediment supply. Hydraulics plays a secondary role because of the tendency for river channels to self organize to a shape that maintains a limited range of dimensionless shear stress on the channel bed. The end result of this line of reasoning is a simple method for calculating downstream size segregation in depositional systems that is in good agreement with the limited data available. In terms of local dynamics, we introduce evidence that topographic roughness plays an important role. This is not explicitly incorporated in our analysis, and the best ways to characterize roughness for this purpose are yet to be determined. Finally, to estimate the importance of abrasion effects at large scales, we re-introduce a dimensionless parameter to describe the relative importance of abrasion, which sorts material by durability, and selective transport, which sorts by transportability.

  14. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

    PubMed

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-09-01

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  15. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance

    PubMed Central

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-01-01

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1–6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%–0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  16. Flow downstream of the heliospheric terminal shock - Magnetic field kinematics

    NASA Technical Reports Server (NTRS)

    Nerney, S.; Suess, S. T.; Schmahl, E. J.

    1991-01-01

    A kinematic model of the interplanetary magnetic field in the heliosheath beyond the solar wind terminal shock is presented in order to evaluate the possible importance of MHD effects in that region of space. The need for this evaluation arises because the interplanetary magnetic field is compressed across the terminal shock and further amplified by the decreasing flow speed beyond the shock. Streamlines which approach the stagnation point before turning in the downstream direction lead to the strongest effects due to the extreme slowing of the solar wind and consequent compression of the embedded magnetic field. The magnetic volume force therefore cannot be neglected on streamlines that approach the heliopause in the upstream direction, where the volume containing them is a large fraction of the overall of the heliosheath in the upstream direction. The increase in the magnetic pressure may act to bring the upstream terminal shock significantly closer to the sun, potentially reconciling a conflict between models and observations.

  17. LLM-Domain B-GATA Transcription Factors Promote Stomatal Development Downstream of Light Signaling Pathways in Arabidopsis thaliana Hypocotyls.

    PubMed

    Klermund, Carina; Ranftl, Quirin L; Diener, Julia; Bastakis, Emmanouil; Richter, René; Schwechheimer, Claus

    2016-03-01

    Stomata are pores that regulate the gas and water exchange between the environment and aboveground plant tissues, including hypocotyls, leaves, and stems. Here, we show that mutants of Arabidopsis thaliana LLM-domain B-GATA genes are defective in stomata formation in hypocotyls. Conversely, stomata formation is strongly promoted by overexpression of various LLM-domain B-class GATA genes, most strikingly in hypocotyls but also in cotyledons. Genetic analyses indicate that these B-GATAs act upstream of the stomata formation regulators SPEECHLESS(SPCH), MUTE, and SCREAM/SCREAM2 and downstream or independent of the patterning regulators TOO MANY MOUTHS and STOMATAL DENSITY AND DISTRIBUTION1 The effects of the GATAs on stomata formation are light dependent but can be induced in dark-grown seedlings by red, far-red, or blue light treatments. PHYTOCHROME INTERACTING FACTOR(PIF) mutants form stomata in the dark, and in this genetic background, GATA expression is sufficient to induce stomata formation in the dark. Since the expression of the LLM-domain B-GATAs GNC(GATA, NITRATE-INDUCIBLE, CARBON METABOLISM-INVOLVED) and GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR1 as well as that of SPCH is red light induced but the induction of SPCH is compromised in a GATA gene mutant background, we hypothesize that PIF- and light-regulated stomata formation in hypocotyls is critically dependent on LLM-domain B-GATA genes. PMID:26917680

  18. miR-326 is downstream of Sonic hedgehog signaling and regulates the expression of Gli2 and smoothened.

    PubMed

    Jiang, Zhihua; Cushing, Leah; Ai, Xingbin; Lü, Jining

    2014-08-01

    Sonic hedgehog (Shh) is expressed and secreted from the embryonic lung epithelium and acts on the adjacent mesenchymal cells via its receptor Patched (Ptch)/Smoothened (Smo) and transcriptional effectors Gli proteins. Genetic studies showed that the Shh pathway plays critical roles in mouse lung development. However, little is known about microRNAs (miRNAs) downstream of Shh in embryonic lungs. Here we profiled miRNAs in embryonic lung cultures treated with cyclopamine, a specific Smo antagonist or with Smo agonist by next-generation of sequencing. We then performed functional screening to examine whether some of these miRNAs can modulate the induction of Gli-responsive luciferase by Shh treatment. These analyses revealed that expression of miR-326 and its host gene, Arrestin β1, is selectively enriched in embryonic lung mesenchymal cells and is specifically influenced by Shh activity. Furthermore, functional analyses showed that miR-326 acts as a negative modulator for Shh signaling by directly targeting Smo and Gli2. Together, these findings suggest a novel miR-326-negative feedback loop in regulating the activity of Shh signaling.

  19. Turbocharger with downstream pressure-gain combustor

    SciTech Connect

    Sherikar, S.V.

    1991-05-14

    This patent describes a turbocharger. It comprises: an internal combustion engine; a compressor located upstream of the internal combustion engine for increasing the inlet pressure of the internal combustion engine; a turbine located down stream of the internal combustion engine and mechanically coupled to the compressor for driving the compressor; and a pressure-gain combustor located downstream of the turbine for decreasing the outlet pressure of the internal combustion engineer and thus increasing the turbine power output and improving the starting characteristics of the turbocharger.

  20. Plasma waves downstream of weak collisionless shocks

    NASA Technical Reports Server (NTRS)

    Coroniti, F. V.; Greenstadt, E. W.; Moses, S. L.; Smith, E. J.; Tsurutani, B. T.

    1993-01-01

    In September 1983 the International Sun Earth Explorer 3 (ISEE 3) International Cometary Explorer (ICE) spacecraft made a long traversal of the distant dawnside flank region of the Earth's magnetosphere and had many encounters with the low Mach number bow shock. These weak shocks excite plasma wave electric field turbulence with amplitudes comparable to those detected in the much stronger bow shock near the nose region. Downstream of quasi-perpendicular (quasi-parallel) shocks, the E field spectra exhibit a strong peak (plateau) at midfrequencies (1 - 3 kHz); the plateau shape is produced by a low-frequency (100 - 300 Hz) emission which is more intense behind downstream of two quasi-perpendicular shocks show that the low frequency signals are polarized parallel to the magnetic field, whereas the midfrequency emissions are unpolarized or only weakly polarized. A new high frequency (10 - 30 kHz) emission which is above the maximum Doppler shift exhibit a distinct peak at high frequencies; this peak is often blurred by the large amplitude fluctuations of the midfrequency waves. The high-frequency component is strongly polarized along the magnetic field and varies independently of the lower-frequency waves.

  1. Headwater Influences on Downstream Water Quality

    PubMed Central

    Oakes, Robert M.

    2007-01-01

    We investigated the influence of riparian and whole watershed land use as a function of stream size on surface water chemistry and assessed regional variation in these relationships. Sixty-eight watersheds in four level III U.S. EPA ecoregions in eastern Kansas were selected as study sites. Riparian land cover and watershed land use were quantified for the entire watershed, and by Strahler order. Multiple regression analyses using riparian land cover classifications as independent variables explained among-site variation in water chemistry parameters, particularly total nitrogen (41%), nitrate (61%), and total phosphorus (63%) concentrations. Whole watershed land use explained slightly less variance, but riparian and whole watershed land use were so tightly correlated that it was difficult to separate their effects. Water chemistry parameters sampled in downstream reaches were most closely correlated with riparian land cover adjacent to the smallest (first-order) streams of watersheds or land use in the entire watershed, with riparian zones immediately upstream of sampling sites offering less explanatory power as stream size increased. Interestingly, headwater effects were evident even at times when these small streams were unlikely to be flowing. Relationships were similar among ecoregions, indicating that land use characteristics were most responsible for water quality variation among watersheds. These findings suggest that nonpoint pollution control strategies should consider the influence of small upland streams and protection of downstream riparian zones alone is not sufficient to protect water quality. PMID:17999108

  2. 9. VIEW WEST TOWARD DOWNSTREAM SIDE OF SPILLWAY FROM NORTH ...

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

    9. VIEW WEST TOWARD DOWNSTREAM SIDE OF SPILLWAY FROM NORTH SIDE OF DOWNSTREAM BANK OF DAM - Upper Doughty Dam, 200 feet west of Garden State Parkway, 1.7 miles west of Absecon, Egg Harbor City, Atlantic County, NJ

  3. Unit 4, downstream from Johns Street Bridge Johnstown Local ...

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

    Unit 4, downstream from Johns Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  4. Unit 6, downstream from Ferndale Bridge Johnstown Local Flood ...

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

    Unit 6, downstream from Ferndale Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  5. Unit 3, downstream from Point Park Johnstown Local Flood ...

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

    Unit 3, downstream from Point Park - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  6. Unit 3, downstream from Fourth Avenue Bridge Johnstown Local ...

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

    Unit 3, downstream from Fourth Avenue Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  7. Unit 1, downstream from Laurel Run Johnstown Local Flood ...

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

    Unit 1, downstream from Laurel Run - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  8. Unit 5, downstream from Haynes Street Bridge Johnstown Local ...

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

    Unit 5, downstream from Haynes Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  9. Unit 6, downstream from Horner Street Bridge Johnstown Local ...

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

    Unit 6, downstream from Horner Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  10. Unit 4, downstream from First Street Bridge Johnstown Local ...

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

    Unit 4, downstream from First Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  11. Unit 5, downstream from Hickory Street Bridge Johnstown Local ...

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

    Unit 5, downstream from Hickory Street Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  12. Unit 2, downstream from Coppersdale Bridge Johnstown Local Flood ...

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

    Unit 2, downstream from Coppersdale Bridge - Johnstown Local Flood Protection Project, Beginning on Conemaugh River approx 3.8 miles downstream from confluence of Little Conemaugh & Stony Creek Rivers at Johnstown, Johnstown, Cambria County, PA

  13. 7. VIEW DOWNSTREAM FROM THE NEWHALEM INTAKE WITH NO WATER ...

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

    7. VIEW DOWNSTREAM FROM THE NEWHALEM INTAKE WITH NO WATER BEING DIVERTED TO THE POWER TUNNEL, 1989. - Skagit Power Development, Newhalem Powerhouse & Dam, On Skagit River, 0.3 mile downstream from Newhalem, Newhalem, Whatcom County, WA

  14. Turbulence decay downstream of an active grid

    NASA Astrophysics Data System (ADS)

    Bewley, Gregory; Bodenschatz, Eberhard

    2015-11-01

    A grid in a wind tunnel stirs up turbulence that has a certain large-scale structure. The moving parts in a so-called ``active grid'' can be programmed to produce different structures. We use a special active grid in which each of 129 paddles on the grid has its own position-controlled servomotor that can move independently of the others. We observe among other things that the anisotropy in the amplitude of the velocity fluctuations and in the correlation lengths can be set and varied with an algorithm that oscillates the paddles in a specified way. The variation in the anisotropies that we observe can be explained by our earlier analysis of anisotropic ``soccer ball'' turbulence (Bewley, Chang and Bodenschatz 2012, Phys. Fluids). We define the influence of this variation in structure on the downstream evolution of the turbulence. with Eberhard Bodenschatz and others.

  15. Channel changes downstream from a dam

    USGS Publications Warehouse

    Hadley, R.F.; Emmett, W.W.

    1998-01-01

    A flood-control dam was completed during 1979 on Bear Creek, a small tributary stream to the South Platte River in the Denver, Colorado, area. Before and after dam closure, repetitive surveys between 1977 and 1992 at five cross sections downstream of the dam documented changes in channel morphology. During this 15-year period, channel width increased slightly, but channel depth increased by more than 40 percent. Within the study reach, stream gradient decreased and median bed material sizes coarsened from sand in the pools and fine gravel on the riffle to a median coarse gravel throughout the reach. The most striking visual change was from a sparse growth of streamside grasses to a dense growth of riparian woody vegetation.

  16. Downstream process options for the ABE fermentation.

    PubMed

    Friedl, Anton

    2016-05-01

    Butanol is a very interesting substance both for the chemical industry and as a biofuel. The classical distillation process for the removal of butanol is far too energy demanding, at a factor of 220% of the energy content of butanol. Alternative separation processes studied are hybrid processes of gas-stripping, liquid-liquid extraction and pervaporation with distillation and a novel adsorption/drying/desorption hybrid process. Compared with the energy content of butanol, the resulting energy demand for butanol separation and concentration of optimized hybrid processes is 11%-22% for pervaporation/distillation and 11%-17% for liquid-liquid extraction/distillation. For a novel adsorption/drying/desorption process, the energy demand is 9.4%. But all downstream process options need further proof of industrial applicability. PMID:27020411

  17. Widespread Inducible Transcription Downstream of Human Genes

    PubMed Central

    Vilborg, Anna; Passarelli, Maria C.; Yario, Therese A.; Tycowski, Kazimierz T.; Steitz, Joan A.

    2015-01-01

    Summary Pervasive transcription of the human genome generates RNAs whose mode of formation and functions are largely uncharacterized. Here, we combine RNA-Seq with detailed mechanistic studies to describe a transcript type derived from protein-coding genes. The resulting RNAs, which we call DoGs for downstream of gene containing transcripts, possess long non-coding regions (often >45 kb) and remain chromatin bound. DoGs are inducible by osmotic stress through an IP3 receptor signaling-dependent pathway, indicating active regulation. DoG levels are increased by decreased termination of the upstream transcript, a previously undescribed mechanism for rapid transcript induction. Relative depletion of polyA signals in DoG regions correlates with increased levels of DoGs after osmotic stress. We detect DoG transcription in several human cell lines and provide evidence for thousands of DoGs genome-wide. PMID:26190259

  18. Ammonia downstream from HH 80 North

    NASA Technical Reports Server (NTRS)

    Girart, Jose M.; Rodriguez, Luis F.; Anglada, Guillem; Estalella, Robert; Torrelles, Jose, M.; Marti, Josep; Pena, Miriam; Ayala, Sandra; Curiel, Salvador; Noriega-Crespo, Alberto

    1994-01-01

    HH 80-81 are two optically visible Herbig-Haro (HH) objects located about 5 minutes south of their exciting source IRAS 18162-2048. Displaced symmetrically to the north of this luminous IRAS source, a possible HH counterpart was recently detected as a radio continuum source with the very large array (VLA). This radio source, HH 80 North, has been proposed to be a member of the Herbig-Haro class since its centimeter flux density, angular size, spectral index, and morphology are all similar to those of HH 80. However, no object has been detected at optical wavelengths at the position of HH 80 North, possibly because of high extinction, and the confirmation of the radio continuum source as an HH object has not been possible. In the prototypical Herbig-Haro objects HH 1 and 2, ammonia emission has been detected downstream of the flow in both objects. This detection has been intepreted as a result of an enhancement in the ammonia emission produced by the radiation field of the shock associated with the HH object. In this Letter we report the detection of the (1,1) and (2,2) inversion transitions of ammonia downstream HH 80 North. This detection gives strong suppport to the interpretation of HH 80 North as a heavily obscured HH object. In addition, we suggest that ammonia emission may be a tracer of embedded Herbig-Haro objects in other regions of star formation. A 60 micrometer IRAS source could be associated with HH 80 North and with the ammonia condensation. A tentative explanation for the far-infrared emission as arising in dust heated by their optical and UV radiation of the HH object is presented.

  19. Detection of cis- and trans-acting Factors in DNA Structure-Induced Genetic Instability Using In silico and Cellular Approaches

    PubMed Central

    Wang, Guliang; Zhao, Junhua; Vasquez, Karen M.

    2016-01-01

    Sequences that can adopt alternative DNA structures (i.e., non-B DNA) are very abundant in mammalian genomes, and recent studies have revealed many important biological functions of non-B DNA structures in chromatin remodeling, DNA replication, transcription, and genetic instability. Here, we provide results from an in silico web-based search engine coupled with cell-based experiments to characterize the roles of non-B DNA conformations in genetic instability in eukaryotes. The purpose of this article is to illustrate strategies that can be used to identify and interrogate the biological roles of non-B DNA structures, particularly on genetic instability. We have included unpublished data using a short H-DNA-forming sequence from the human c-MYC promoter region as an example, and identified two different mechanisms of H-DNA-induced genetic instability in yeast and mammalian cells: a DNA replication-related model of mutagenesis; and a replication-independent cleavage model. Further, we identified candidate proteins involved in H-DNA-induced genetic instability by using a yeast genetic screen. A combination of in silico and cellular methods, as described here, should provide further insight into the contributions of non-B DNA structures in biological functions, genetic evolution, and disease development. PMID:27532010

  20. Detection of cis- and trans-acting Factors in DNA Structure-Induced Genetic Instability Using In silico and Cellular Approaches.

    PubMed

    Wang, Guliang; Zhao, Junhua; Vasquez, Karen M

    2016-01-01

    Sequences that can adopt alternative DNA structures (i.e., non-B DNA) are very abundant in mammalian genomes, and recent studies have revealed many important biological functions of non-B DNA structures in chromatin remodeling, DNA replication, transcription, and genetic instability. Here, we provide results from an in silico web-based search engine coupled with cell-based experiments to characterize the roles of non-B DNA conformations in genetic instability in eukaryotes. The purpose of this article is to illustrate strategies that can be used to identify and interrogate the biological roles of non-B DNA structures, particularly on genetic instability. We have included unpublished data using a short H-DNA-forming sequence from the human c-MYC promoter region as an example, and identified two different mechanisms of H-DNA-induced genetic instability in yeast and mammalian cells: a DNA replication-related model of mutagenesis; and a replication-independent cleavage model. Further, we identified candidate proteins involved in H-DNA-induced genetic instability by using a yeast genetic screen. A combination of in silico and cellular methods, as described here, should provide further insight into the contributions of non-B DNA structures in biological functions, genetic evolution, and disease development. PMID:27532010

  1. Detection of cis- and trans-acting Factors in DNA Structure-Induced Genetic Instability Using In silico and Cellular Approaches.

    PubMed

    Wang, Guliang; Zhao, Junhua; Vasquez, Karen M

    2016-01-01

    Sequences that can adopt alternative DNA structures (i.e., non-B DNA) are very abundant in mammalian genomes, and recent studies have revealed many important biological functions of non-B DNA structures in chromatin remodeling, DNA replication, transcription, and genetic instability. Here, we provide results from an in silico web-based search engine coupled with cell-based experiments to characterize the roles of non-B DNA conformations in genetic instability in eukaryotes. The purpose of this article is to illustrate strategies that can be used to identify and interrogate the biological roles of non-B DNA structures, particularly on genetic instability. We have included unpublished data using a short H-DNA-forming sequence from the human c-MYC promoter region as an example, and identified two different mechanisms of H-DNA-induced genetic instability in yeast and mammalian cells: a DNA replication-related model of mutagenesis; and a replication-independent cleavage model. Further, we identified candidate proteins involved in H-DNA-induced genetic instability by using a yeast genetic screen. A combination of in silico and cellular methods, as described here, should provide further insight into the contributions of non-B DNA structures in biological functions, genetic evolution, and disease development.

  2. Genetic variation in insulin-induced kinase signaling

    PubMed Central

    Wang, Isabel Xiaorong; Ramrattan, Girish; Cheung, Vivian G

    2015-01-01

    Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance. PMID:26202599

  3. Downstream Processing of Synechocystis for Biofuel Production

    NASA Astrophysics Data System (ADS)

    Sheng, Jie

    Lipids and free fatty acids (FFA) from cyanobacterium Synechocystis can be used for biofuel (e.g. biodiesel or renewable diesel) production. In order to utilize and scale up this technique, downstream processes including culturing and harvest, cell disruption, and extraction were studied. Several solvents/solvent systems were screened for lipid extraction from Synechocystis. Chloroform + methanol-based Folch and Bligh & Dyer methods were proved to be "gold standard" for small-scale analysis due to their highest lipid recoveries that were confirmed by their penetration of the cell membranes, higher polarity, and stronger interaction with hydrogen bonds. Less toxic solvents, such as methanol and MTBE, or direct transesterification of biomass (without preextraction step) gave only slightly lower lipid-extraction yields and can be considered for large-scale application. Sustained exposure to high and low temperature extremes severely lowered the biomass and lipid productivity. Temperature stress also triggered changes of lipid quality such as the degree of unsaturation; thus, it affected the productivities and quality of Synechocystis-derived biofuel. Pulsed electric field (PEF) was evaluated for cell disruption prior to lipid extraction. A treatment intensity > 35 kWh/m3 caused significant damage to the plasma membrane, cell wall, and thylakoid membrane, and it even led to complete disruption of some cells into fragments. Treatment by PEF enhanced the potential for the low-toxicity solvent isopropanol to access lipid molecules during subsequent solvent extraction, leading to lower usage of isopropanol for the same extraction efficiency. Other cell-disruption methods also were tested. Distinct disruption effects to the cell envelope, plasma membrane, and thylakoid membranes were observed that were related to extraction efficiency. Microwave and ultrasound had significant enhancement of lipid extraction. Autoclaving, ultrasound, and French press caused significant

  4. Microbial production of scleroglucan and downstream processing.

    PubMed

    Castillo, Natalia A; Valdez, Alejandra L; Fariña, Julia I

    2015-01-01

    Synthetic petroleum-based polymers and natural plant polymers have the disadvantage of restricted sources, in addition to the non-biodegradability of the former ones. In contrast, eco-sustainable microbial polysaccharides, of low-cost and standardized production, represent an alternative to address this situation. With a strong global market, they attracted worldwide attention because of their novel and unique physico-chemical properties as well as varied industrial applications, and many of them are promptly becoming economically competitive. Scleroglucan, a β-1,3-β-1,6-glucan secreted by Sclerotium fungi, exhibits high potential for commercialization and may show different branching frequency, side-chain length, and/or molecular weight depending on the producing strain or culture conditions. Water-solubility, viscosifying ability and wide stability over temperature, pH and salinity make scleroglucan useful for different biotechnological (enhanced oil recovery, food additives, drug delivery, cosmetic and pharmaceutical products, biocompatible materials, etc.), and biomedical (immunoceutical, antitumor, etc.) applications. It can be copiously produced at bioreactor scale under standardized conditions, where a high exopolysaccharide concentration normally governs the process optimization. Operative and nutritional conditions, as well as the incidence of scleroglucan downstream processing will be discussed in this chapter. The relevance of using standardized inocula from selected strains and experiences concerning the intricate scleroglucan scaling-up will be also herein outlined. PMID:26528259

  5. Upstream/downstream: Issues in environmental ethics

    SciTech Connect

    Scherer, D.

    1991-01-01

    Upstream/Downstream reminds us that there are four issues that are more or less distinctive to environmental ethics. First, and most distinctively, environmental issues involve the standing of nonhuman living things and systems. Thus, environmental politics is only partly a clash among the interest of the parties involved; it often involves actions on behalf of the existence rights of nonhuman life forms. Second, environmental ethics concern the intergenerational distribution of benefits more explicitly than do most other ethical issues, which brings out serious weaknesses in legal frameworks that rely on claims for damages. Third, the complexity and indirectness of many environmental impacts introduces a high degree of uncertainty and thus technical as well as ethical issues of prudent behavior. Specifically, where science may not fully reveal environmental risks, should development proceed; should analysis proceed if it is known to have a Pollyanna bias Fourth, insofar as environmental damage is typically done to common property, and thus its regulation is generally a matter for governmental regulation, the obligations of private actors to make sacrifices beyond what government requires is at issue - an issue that one would expect to be taken up at length in the other volumes.

  6. Microbial production of scleroglucan and downstream processing

    PubMed Central

    Castillo, Natalia A.; Valdez, Alejandra L.; Fariña, Julia I.

    2015-01-01

    Synthetic petroleum-based polymers and natural plant polymers have the disadvantage of restricted sources, in addition to the non-biodegradability of the former ones. In contrast, eco-sustainable microbial polysaccharides, of low-cost and standardized production, represent an alternative to address this situation. With a strong global market, they attracted worldwide attention because of their novel and unique physico-chemical properties as well as varied industrial applications, and many of them are promptly becoming economically competitive. Scleroglucan, a β-1,3-β-1,6-glucan secreted by Sclerotium fungi, exhibits high potential for commercialization and may show different branching frequency, side-chain length, and/or molecular weight depending on the producing strain or culture conditions. Water-solubility, viscosifying ability and wide stability over temperature, pH and salinity make scleroglucan useful for different biotechnological (enhanced oil recovery, food additives, drug delivery, cosmetic and pharmaceutical products, biocompatible materials, etc.), and biomedical (immunoceutical, antitumor, etc.) applications. It can be copiously produced at bioreactor scale under standardized conditions, where a high exopolysaccharide concentration normally governs the process optimization. Operative and nutritional conditions, as well as the incidence of scleroglucan downstream processing will be discussed in this chapter. The relevance of using standardized inocula from selected strains and experiences concerning the intricate scleroglucan scaling-up will be also herein outlined. PMID:26528259

  7. Hydroeconomic optimization of reservoir management under downstream water quality constraints

    NASA Astrophysics Data System (ADS)

    Davidsen, Claus; Liu, Suxia; Mo, Xingguo; Holm, Peter E.; Trapp, Stefan; Rosbjerg, Dan; Bauer-Gottwein, Peter

    2015-10-01

    A hydroeconomic optimization approach is used to guide water management in a Chinese river basin with the objectives of meeting water quantity and water quality constraints, in line with the China 2011 No. 1 Policy Document and 2015 Ten-point Water Plan. The proposed modeling framework couples water quantity and water quality management and minimizes the total costs over a planning period assuming stochastic future runoff. The outcome includes cost-optimal reservoir releases, groundwater pumping, water allocation, wastewater treatments and water curtailments. The optimization model uses a variant of stochastic dynamic programming known as the water value method. Nonlinearity arising from the water quality constraints is handled with an effective hybrid method combining genetic algorithms and linear programming. Untreated pollutant loads are represented by biochemical oxygen demand (BOD), and the resulting minimum dissolved oxygen (DO) concentration is computed with the Streeter-Phelps equation and constrained to match Chinese water quality targets. The baseline water scarcity and operational costs are estimated to 15.6 billion CNY/year. Compliance to water quality grade III causes a relatively low increase to 16.4 billion CNY/year. Dilution plays an important role and increases the share of surface water allocations to users situated furthest downstream in the system. The modeling framework generates decision rules that result in the economically efficient strategy for complying with both water quantity and water quality constraints.

  8. Olfactory Processing and Behavior Downstream from Highly Selective Receptor Neurons

    PubMed Central

    Schlief, Michelle L.; Wilson, Rachel I.

    2010-01-01

    In either the vertebrate nose or the insect antenna, most olfactory receptor neurons (ORNs) respond to multiple odors. However, some ORNs respond to just a single odor, or at most to a few highly related odors. It has been hypothesized that narrowly-tuned ORNs project to narrowly-tuned neurons in the brain, and that these dedicated circuits mediate innate behavioral responses to a particular ligand. Here we have investigated neural activity and behavior downstream from two narrowly-tuned ORN types in Drosophila. We found that genetically ablating either of these ORN types impairs innate behavioral attraction to their cognate ligand. Neurons in the antennal lobe postsynaptic to one of these ORN types are, like their presynaptic ORNs, narrowly tuned to a pheromone. However, neurons postsynaptic to the second ORN type are broadly tuned. These results demonstrate that some narrowly-tuned ORNs project to dedicated central circuits, ensuring a tight connection between stimulus and behavior, whereas others project to central neurons which participate in the ensemble representations of many odors. PMID:17417635

  9. gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum

    PubMed Central

    Zhang, Ting; Xu, Yue; Liu, Yanfen; Ye, Yihong

    2015-01-01

    Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER) via a conserved process termed ER-associated degradation (ERAD). Central regulators of the ERAD system are membrane-bound ubiquitin ligases, which are thought to channel misfolded proteins through the ER membrane during retrotranslocation. Hrd1 and gp78 are mammalian ubiquitin ligases homologous to Hrd1p, an ubiquitin ligase essential for ERAD in Saccharomyces cerevisiae. However, the functional relevance of these proteins to Hrd1p is unclear. In this paper, we characterize the gp78-containing ubiquitin ligase complex and define its functional interplay with Hrd1 using biochemical and recently developed CRISPR-based genetic tools. Our data show that transient inactivation of the gp78 complex by short hairpin RNA–mediated gene silencing causes significant stabilization of both luminal and membrane ERAD substrates, but unlike Hrd1, which plays an essential role in retrotranslocation and ubiquitination of these ERAD substrates, knockdown of gp78 does not affect either of these processes. Instead, gp78 appears to act downstream of Hrd1 to promote ERAD via cooperation with the BAG6 chaperone complex. We conclude that the Hrd1 complex forms an essential retrotranslocation module that is evolutionarily conserved, but the mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during retrotranslocation. PMID:26424800

  10. AERIAL VIEW FACING NORTH. DOWNSTREAM VIEW OF FABRIC BUILDING, STRUCTURAL ...

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

    AERIAL VIEW FACING NORTH. DOWNSTREAM VIEW OF FABRIC BUILDING, STRUCTURAL WAREHOUSE, RAIL MILL, & OPEN HEARTH COMPLEX. - Pittsburgh Steel Company, Monessen Works, Donner Avenue, Monessen, Westmoreland County, PA

  11. 7. STONE PIER OF ORIGINAL WATERWHEEL INSTALLATION DOWNSTREAM FROM MILL ...

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

    7. STONE PIER OF ORIGINAL WATERWHEEL INSTALLATION DOWNSTREAM FROM MILL William E. Barrett, photographer, 1973 (copy negative) - Thomas Shepherd's Grist Mill, High Street Vicinity, Shepherdstown, Jefferson County, WV

  12. 5. DOWNSTREAM ELEVATION OF BRIDGE AND SUBSTRUCTURE (with graduated meter ...

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

    5. DOWNSTREAM ELEVATION OF BRIDGE AND SUBSTRUCTURE (with graduated meter pole); VIEW TO NORTH-NORTHEAST. - Auwaiakeakua Bridge, Spanning Auwaiakekua Gulch at Mamalahoa Highway, Waikoloa, Hawaii County, HI

  13. 1. VIEW OF DOWNSTREAM SIDE OF DIVERSION DAM ON THE ...

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

    1. VIEW OF DOWNSTREAM SIDE OF DIVERSION DAM ON THE SNAKE RIVER, LOOKING NORTHEAST. NOTE HEADGATE STRUCTURE ON NORTH BANK, SPILLWAY ON LEFT SIDE OF DAM, AND SPLASH LOGS ON DOWNSTREAM SIDE OF DAM. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

  14. 11. VIEW NORTH ALONG DOWNSTREAM BANK OF DAM FROM SOUTH ...

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

    11. VIEW NORTH ALONG DOWNSTREAM BANK OF DAM FROM SOUTH SIDE OF CHANNEL ON DOWNSTREAM SIDE OF RESERVOIR - Upper Doughty Dam, 200 feet west of Garden State Parkway, 1.7 miles west of Absecon, Egg Harbor City, Atlantic County, NJ

  15. Arabidopsis NAC1 transduces auxin signal downstream of TIR1 to promote lateral root development.

    PubMed

    Xie, Q; Frugis, G; Colgan, D; Chua, N H

    2000-12-01

    Auxin plays a key role in lateral root formation, but the signaling pathway for this process is poorly understood. We show here that NAC1, a new member of the NAC family, is induced by auxin and mediates auxin signaling to promote lateral root development. NAC1 is a transcription activator consisting of an N-terminal conserved NAC-domain that binds to DNA and a C-terminal activation domain. This factor activates the expression of two downstream auxin-responsive genes, DBP and AIR3. Transgenic plants expressing sense or antisense NAC1 cDNA show an increase or reduction of lateral roots, respectively. Finally, TIR1-induced lateral root development is blocked by expression of antisense NAC1 cDNA, and NAC1 overexpression can restore lateral root formation in the auxin-response mutant tir1, indicating that NAC1 acts downstream of TIR1.

  16. Genetic control of Drosophila nerve cord development

    NASA Technical Reports Server (NTRS)

    Skeath, James B.; Thor, Stefan

    2003-01-01

    The Drosophila ventral nerve cord has been a central model system for studying the molecular genetic mechanisms that control CNS development. Studies show that the generation of neural diversity is a multistep process initiated by the patterning and segmentation of the neuroectoderm. These events act together with the process of lateral inhibition to generate precursor cells (neuroblasts) with specific identities, distinguished by the expression of unique combinations of regulatory genes. The expression of these genes in a given neuroblast restricts the fate of its progeny, by activating specific combinations of downstream genes. These genes in turn specify the identity of any given postmitotic cell, which is evident by its cellular morphology and choice of neurotransmitter.

  17. ACT: Acting Out Central Theme.

    ERIC Educational Resources Information Center

    Kise, Joan Duff

    1982-01-01

    The author describes ACT (Acting Out Central Theme), a method for dealing with psychomotor, cognitive, and affective domains in slow readers. The ACT approach involves three sessions which focus on discussion of a theme such as friendship, presentaton of the theme as a skit, and assignment of topics to individual students. (SW)

  18. 3. VIEW OF DIABLO CANYON LOOKING DOWNSTREAM FROM THE VALVE ...

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

    3. VIEW OF DIABLO CANYON LOOKING DOWNSTREAM FROM THE VALVE HOUSE AT ELEVATION 1044, 1989. - Skagit Power Development, Diablo Dam, On Skagit River, 6.9 miles upstream from Newhalem, Newhalem, Whatcom County, WA

  19. 7. VIEW OF MAIN CANAL, LOOKING SOUTH, IMMEDIATELY DOWNSTREAM FROM ...

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

    7. VIEW OF MAIN CANAL, LOOKING SOUTH, IMMEDIATELY DOWNSTREAM FROM THE SNAKE RIVER VALLEY IRRIGATION DISTRICT, SECTION 34, T2N, R37E - Woodville Canal Company, West side of Snake River (River Mile 796), Woodville, Bingham County, ID

  20. 5. VIEW SHOWING THE DOWNSTREAM SIDE OF SWAN FALLS DAM ...

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

    5. VIEW SHOWING THE DOWNSTREAM SIDE OF SWAN FALLS DAM AND POWER HOUSE, LOOKING UPSTREAM TO SOUTH FROM THE A MOUND OF DEBRIS ABOUT THIRTY TO FORTY FEET ABOVE THE RIVER - Swan Falls Dam, Snake River, Kuna, Ada County, ID

  1. 14. INSIDE VIEW OF FLUME, LOOKING DOWNSTREAM TOWARD SETTLING BASIN, ...

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

    14. INSIDE VIEW OF FLUME, LOOKING DOWNSTREAM TOWARD SETTLING BASIN, SHOWING RIGHT FORK TO BYPASS, LEFT FORK TO BASIN - Electron Hydroelectric Project, Along Puyallup River, Electron, Pierce County, WA

  2. 15. INSIDE VIEW OF FLUME, LOOKING DOWNSTREAM, LEFT FORK TO ...

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

    15. INSIDE VIEW OF FLUME, LOOKING DOWNSTREAM, LEFT FORK TO SETTLING BASIN, SHOWING RIGHT FORK WITH GATE IN PLACE AND A FEW NEEDLES IN PLACE - Electron Hydroelectric Project, Along Puyallup River, Electron, Pierce County, WA

  3. 3. EASTERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON ...

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

    3. EASTERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON DAM SHOWING THE SOUTHEAST END OF THE DAM, AND THE HOLLOW BAYS. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  4. 29. VIEW OF STONE BUILDING, ABOUT ONE MILE DOWNSTREAM OF ...

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

    29. VIEW OF STONE BUILDING, ABOUT ONE MILE DOWNSTREAM OF DAM, USED TO STORE EXPLOSIVES DURING THE CONSTRUCTION OF HORSE MESA - Horse Mesa Dam, Salt River, 65 miles East of Phoenix, Phoenix, Maricopa County, AZ

  5. Wave and particle evolution downstream of quasi-perpendicular shocks

    NASA Technical Reports Server (NTRS)

    Mckean, M. E.; Omidi, N.; Krauss-Varban, D.; Karimabadi, H.

    1995-01-01

    Distributions of ions heated in quasi-perpendicular bow shocks have large perpendicular temperature anisotropies that provide free energy for the growth of Alfven ion cyclotron (AIC) and mirror waves. These modes are often obsreved in the Earth's magnetosheath. Using two-dimensional hybrid simulations, we show that these waves are produced near the shock front and convected downstream rather than being produced locally downstream. The wave activity reduces the proton anisotropy to magnetosheath levels within a few tens of gyroradii of the shock but takes significantly longer to reduce the anisotropy of He(++) ions. The waves are primarily driven by proton anisotropy and the dynamics of the helium ions is controlled by the proton waves. Downstream of high Mach number shocks, mirror waves compete effectively with AIC waves. Downstream of low Mach number shocks, AIC waves dominate.

  6. 10. VIEW WEST TOWARD DOWNSTREAM SIDE OF SPILLWAY FROM UNDERSIDE ...

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

    10. VIEW WEST TOWARD DOWNSTREAM SIDE OF SPILLWAY FROM UNDERSIDE OF GARDEN STATE PARKWAY ABUTMENT - Upper Doughty Dam, 200 feet west of Garden State Parkway, 1.7 miles west of Absecon, Egg Harbor City, Atlantic County, NJ

  7. COMPLETED STRUCTURE. View is eastsoutheast of downstream side of bridge, ...

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

    COMPLETED STRUCTURE. View is east-southeast of downstream side of bridge, from beyond confluence of Trinity and South Fork Trinity Rivers - South Fork Trinity River Bridge, State Highway 299 spanning South Fork Trinity River, Salyer, Trinity County, CA

  8. 7. View to southeast. View of downstream side of bridge ...

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

    7. View to southeast. View of downstream side of bridge from confluence of Trinity and South Fork Trinity Rivers. (90mm Lens) - South Fork Trinity River Bridge, State Highway 299 spanning South Fork Trinity River, Salyer, Trinity County, CA

  9. LOOKING EASTSOUTHEAST. Showing downstream side of completed bridge, from confluence ...

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

    LOOKING EAST-SOUTHEAST. Showing downstream side of completed bridge, from confluence of Trinity and South Fork Trinity Rivers - South Fork Trinity River Bridge, State Highway 299 spanning South Fork Trinity River, Salyer, Trinity County, CA

  10. 10. Downstream face of Mormon Flat Dam under construction. Cement ...

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

    10. Downstream face of Mormon Flat Dam under construction. Cement storage shed is at center right. Photographer unknown, September 1924. Source: Salt River Project. - Mormon Flat Dam, On Salt River, Eastern Maricopa County, east of Phoenix, Phoenix, Maricopa County, AZ

  11. 27. DETAIL VIEW OF CONCRETE MONOLITH CONSTRUCTION AT DOWNSTREAM END ...

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

    27. DETAIL VIEW OF CONCRETE MONOLITH CONSTRUCTION AT DOWNSTREAM END OF WEST MAIN LOCK WALL, LOOKiNG SOUTHEAST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam 26R, Alton, Madison County, IL

  12. 32. Otter Lake Dam. View from downstream show how the ...

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

    32. Otter Lake Dam. View from downstream show how the dam blends into its environment. Looking east-northeast. - Blue Ridge Parkway, Between Shenandoah National Park & Great Smoky Mountains, Asheville, Buncombe County, NC

  13. 5. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, LOOKING ...

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

    5. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, LOOKING SOUTHWEST - High Mountain Dams in Upalco Unit, Kidney Lake Dam, Ashley National Forest, 4.7 miles North of Miners Gulch Campground, Mountain Home, Duchesne County, UT

  14. 6. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, LOOKING ...

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

    6. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, LOOKING SOUTHWEST - High Mountain Dams in Upalco Unit, Kidney Lake Dam, Ashley National Forest, 4.7 miles North of Miners Gulch Campground, Mountain Home, Duchesne County, UT

  15. 9. DETAIL EXTERIOR VIEW LOOKING SOUTHEAST, SHOWING DOWNSTREAM MITER GATES ...

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

    9. DETAIL EXTERIOR VIEW LOOKING SOUTHEAST, SHOWING DOWNSTREAM MITER GATES FOR NAVIGATION LOCK #1. - Bonneville Project, Navigation Lock No. 1, Oregon shore of Columbia River near first Powerhouse, Bonneville, Multnomah County, OR

  16. 2. GENERAL EXTERIOR VIEW LOOKING WEST, SHOWING CHANNEL DOWNSTREAM FROM ...

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

    2. GENERAL EXTERIOR VIEW LOOKING WEST, SHOWING CHANNEL DOWNSTREAM FROM NAVIGATION LOCK #1; MOVABLE BRIDGE IS VISIBLE IN LEFT FOREGROUND. - Bonneville Project, Navigation Lock No. 1, Oregon shore of Columbia River near first Powerhouse, Bonneville, Multnomah County, OR

  17. 40. Reservoir behind Pleasant Dam, looking downstream, spillway is at ...

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

    40. Reservoir behind Pleasant Dam, looking downstream, spillway is at right. Photographer unknown, c. late 1920s. Source: MWD. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  18. 54. Downstream face of Agua Fria project's diversion dam showing ...

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

    54. Downstream face of Agua Fria project's diversion dam showing initial masonry construction and poured concrete capping. Photographer Mark Durben, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  19. 57. Downstream side of left section of diversion dam. Photographer ...

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

    57. Downstream side of left section of diversion dam. Photographer Mark Durben, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  20. 55. Downstream face of diversion dam looking northwest. Photographer Mark ...

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

    55. Downstream face of diversion dam looking northwest. Photographer Mark Durben, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  1. 28. View of construction shops looking west and downstream. Photographer ...

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

    28. View of construction shops looking west and downstream. Photographer unknown, October 29, 1926. Source: MWD. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  2. 70. Downstream view of Waddell Dam spillway and taintor gates. ...

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

    70. Downstream view of Waddell Dam spillway and taintor gates. Photographer Mark Durben. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  3. 42. View of emergency spillway excavation looking downstream from spillway. ...

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

    42. View of emergency spillway excavation looking downstream from spillway. Photographer unknown, 1929. Source: ADWR. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  4. 69. View of downstream face from west or right abutment. ...

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

    69. View of downstream face from west or right abutment. Photographer Mark Durben. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  5. 49. Downstream face of Humbug Creek Diversion Dam with sluice ...

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

    49. Downstream face of Humbug Creek Diversion Dam with sluice opening at center. Photographer James Eastwood, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  6. 51. Downstream end of diversion tunnel around east end of ...

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

    51. Downstream end of diversion tunnel around east end of Humbug Creek Diversion Dam. Photographer James Eastwood, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  7. 65. Close up view of downstream face of arch, buttress ...

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

    65. Close up view of downstream face of arch, buttress ties and roadway support work. Photographer Mark Durben. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  8. 27. Evening view of downstream face of Pleasant Dam under ...

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

    27. Evening view of downstream face of Pleasant Dam under construction. Part of construction camp housing is visible in foreground. Photographer unknown, 1927. Source: MWD. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  9. 2. NORTHERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON ...

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

    2. NORTHERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON DAM SHOWING THE NORTHWEST END OF THE DAM, THE CONTROL HOUSE, AND SPILLWAY CHUTE. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  10. 9. VIEW, LOOKING SOUTH OF DOWNSTREAM SIDES OF ALL THREE ...

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

    9. VIEW, LOOKING SOUTH OF DOWNSTREAM SIDES OF ALL THREE BRIDGES, SHOWING PROXIMITY OF BRIDGE TO ONE ANOTHER - Van Duzen River Bridge, Spanning Van Duzen River at CA State Highway 101, Alton, Humboldt County, CA

  11. 7. Contextual view to eastnortheast showing downstream (west) side of ...

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

    7. Contextual view to east-northeast showing downstream (west) side of bridge in setting, depicting dense riparian nature of area. - Stanislaus River Bridge, Atchison, Topeka & Santa Fe Railway at Stanislaus River, Riverbank, Stanislaus County, CA

  12. MAIN CANAL HEADWORKS, FROM DOWNSTREAM (TO RIGHT), NOTE SAND AND ...

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

    MAIN CANAL HEADWORKS, FROM DOWNSTREAM (TO RIGHT), NOTE SAND AND SILT SLUICE GATE FOR DIVERSION DAM ON LEFT, VIEW TO NORTHWEST - Salmon Creek Diversion Dam, Main Canal Headworks, Salmon Creek, Okanogan, Okanogan County, WA

  13. 2. OVERALL VIEW OF DAM, SHOWING CREST AND DOWNSTREAM FACE, ...

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

    2. OVERALL VIEW OF DAM, SHOWING CREST AND DOWNSTREAM FACE, WITH CONCRETE EXTENSION IN FOREGROUND, LOOKING NORTH - High Mountain Dams in Bonneville Unit, Fire Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  14. 2. DOWNSTREAM VIEW OF THE SOUTH CHANNEL DAM, LOOKING WEST. ...

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

    2. DOWNSTREAM VIEW OF THE SOUTH CHANNEL DAM, LOOKING WEST. - Washington Water Power Company Post Falls Power Plant, South Channel Dam, West of intersection of Spokane & Fourth Streets, Post Falls, Kootenai County, ID

  15. 4. DETAIL VIEW OF CCCBUILT RIVERCOBBLE WING WALL ON DOWNSTREAM ...

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

    4. DETAIL VIEW OF CCC-BUILT RIVER-COBBLE WING WALL ON DOWNSTREAM SIDE OF OUTLET WORKS AT DAM 87, LOOKING WEST - Upper Souris National Wildlife Refuge, Dam 87, Souris River Basin, Foxholm, Surrey (England), ND

  16. 15. WAIKOLU STREAM CROSSING NO. 1, VIEW DOWNSTREAM ACROSS TOP ...

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

    15. WAIKOLU STREAM CROSSING NO. 1, VIEW DOWNSTREAM ACROSS TOP OF STRUCTURE. LINE IS BURIED BEYOND. - Kalaupapa Water Supply System, Waikolu Valley to Kalaupapa Settlement, Island of Molokai, Kalaupapa, Kalawao County, HI

  17. 14. WAIKOLU STREAM CROSSING NO. 1, VIEW DOWNSTREAM WITH PALI ...

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

    14. WAIKOLU STREAM CROSSING NO. 1, VIEW DOWNSTREAM WITH PALI SEEN IN BACKGROUND. AQUEDUCT CROSSES AT RIGHT. - Kalaupapa Water Supply System, Waikolu Valley to Kalaupapa Settlement, Island of Molokai, Kalaupapa, Kalawao County, HI

  18. DOWNSTREAM LOCK GATE DETAIL VIEW WITH DOG HOUSE. NOTE CONTROL ...

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

    DOWNSTREAM LOCK GATE DETAIL VIEW WITH DOG HOUSE. NOTE CONTROL ARM AND GEAR FOR GATE. LOOKING NORTHWEST. - Illinois Waterway, Dresden Island Lock and Dam , 7521 North Lock Road, Channahon, Will County, IL

  19. 10. OBLIQUE VIEW OF BRIDGE, LOOKING EAST OF DOWNSTREAM SIDE ...

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

    10. OBLIQUE VIEW OF BRIDGE, LOOKING EAST OF DOWNSTREAM SIDE OF BRIDGE FROM YOLO COUNTY SIDE OF THE SACRAMENTO RIVER - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  20. 8. EMPTY LOCK CHAMBER FROM DOWNSTREAM (WEST) END, WITH VISITORS ...

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

    8. EMPTY LOCK CHAMBER FROM DOWNSTREAM (WEST) END, WITH VISITORS CENTER (LEFT) AND LOCKMASTER'S HOUSE ON NORTH BANK. VIEW TO NORTHEAST. - Starved Rock Locks & Dam, Illinois Waterway River mile 231, Peru, La Salle County, IL

  1. 6. DOWNSTREAM SIDE OF LOWER MITER GATES WITH FULL LOCK ...

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

    6. DOWNSTREAM SIDE OF LOWER MITER GATES WITH FULL LOCK CHAMBER, VISITORS, AND LOCKMASTER'S HOUSE IN BACKGROUND. VIEW TO NORTHEAST. - Starved Rock Locks & Dam, Illinois Waterway River mile 231, Peru, La Salle County, IL

  2. EVALUATING THE EFFECT OF UPSTREAM WATERSHED ACTIVITIES TO DOWNSTREAM STREAMFLOW

    EPA Science Inventory

    Linking the impacts of upstream activities such as urban development to changes in downstream streamflow is critical to achieving a balance between economic development and environmental protection as a basis for sustainable watershed development. This paper presents a modeling a...

  3. View of downstream debris field at the Merry Generator House, ...

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

    View of downstream debris field at the Merry Generator House, showing possible concrete generator seats, looking south - Arthur Holmes Merry Generator House, Signal Lake North of Range Road, Fort Gordon, Richmond County, GA

  4. 18. GENERAL VIEW OF THE OUTLET STRUCTURE LOOKING DOWNSTREAM AT ...

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

    18. GENERAL VIEW OF THE OUTLET STRUCTURE LOOKING DOWNSTREAM AT WEST ABUTMENT.... Volume XVI, No. 13, July 26, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  5. 16. DOWNSTREAM VIEW OF OUTLET STRUCTURE AND OUTLET CHANNEL, FROM ...

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

    16. DOWNSTREAM VIEW OF OUTLET STRUCTURE AND OUTLET CHANNEL, FROM WEST END OF EMBANKMENT. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  6. 23. DOWNSTREAM VIEW OF COMPLETED OUTLET CONTROL STRUCTURE.... Volume XIX, ...

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

    23. DOWNSTREAM VIEW OF COMPLETED OUTLET CONTROL STRUCTURE.... Volume XIX, No. 8, April 12, 1940. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  7. 28. DOWNSTREAM VIEW OF ROCK PAVING OPERATIONS ON LEFT BANK ...

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

    28. DOWNSTREAM VIEW OF ROCK PAVING OPERATIONS ON LEFT BANK OF OUTLET CHANNEL.... Volume XVI, No. 18, September 29, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  8. 14. Credit PED. Downstream elevation, near completion, showing tail race ...

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

    14. Credit PED. Downstream elevation, near completion, showing tail race and trestle used to carry excavated rock and construction materials across tail race. Photo c. 1909. - Dam No. 4 Hydroelectric Plant, Potomac River, Martinsburg, Berkeley County, WV

  9. 8. VIEW OF DOWNSTREAM OUTLET CULVERT AND WING RETAINING WALLS, ...

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

    8. VIEW OF DOWNSTREAM OUTLET CULVERT AND WING RETAINING WALLS, LOOKING NORTHWEST - High Mountain Dams in Upalco Unit, Twin Pots Dam, Ashley National Forest, 10.1 miles North of Mountain Home, Mountain Home, Duchesne County, UT

  10. 34. DOWNSTREAM VIEW OF COOLIDGE DAM COMPLETED. POWER HOUSE, INTAKE ...

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

    34. DOWNSTREAM VIEW OF COOLIDGE DAM COMPLETED. POWER HOUSE, INTAKE TOWERS, WEST SPILLWAY CHANNEL AND DECORATIVE EAGLES ALL CLEARLY VISIBLE, c. 1928 - Coolidge Dam, Gila River, Peridot, Gila County, AZ

  11. 14. VIEW OF DAM SITE, LOOKING SOUTH (DOWNSTREAM). MIXING PLANT ...

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

    14. VIEW OF DAM SITE, LOOKING SOUTH (DOWNSTREAM). MIXING PLANT IS VISIBLE AT RIGHT, COFFER DAM IS UPSTREAM OF PLACING TOWER. EAST DOME IS VISIBLE AT LEFT OF TOWER, c. 1927 - Coolidge Dam, Gila River, Peridot, Gila County, AZ

  12. Genetic discrimination in the workplace.

    PubMed

    Miller, P S

    1998-01-01

    Author argues that the Americans with Disabilities Act prohibits discrimination against workers based on their genetic makeup. He also examines state legislation and recently proposed federal legislation prohibiting genetic discrimination.

  13. Downstream influence scaling of turbulent flow past expansion corners

    NASA Technical Reports Server (NTRS)

    Lu, Frank K.; Chung, Kung-Ming

    1992-01-01

    Previous studies of the high-speed viscous inviscid interaction between a turbulent boundary layer and an expansion at a convex corner have noted that surface pressure decreases toward the downstream inviscid value yielded by a Prandtl-Meyer expansion. A downstream influence on the corner is presently identified which is based on the mean surface pressure distribution; a scaling law is proposed for this distance.

  14. Modeling Neutral Densities Downstream of a Gridded Ion Thruster

    NASA Technical Reports Server (NTRS)

    Soulas, George C.

    2010-01-01

    The details of a model for determining the neutral density downstream of a gridded ion thruster are presented. An investigation of the possible sources of neutrals emanating from and surrounding a NEXT ion thruster determined that the most significant contributors to the downstream neutral density include discharge chamber neutrals escaping through the perforated grids, neutrals escaping from the neutralizer, and vacuum facility background neutrals. For the neutral flux through the grids, near- and far-field equations are presented for rigorously determining the neutral density downstream of a cylindrical aperture. These equations are integrated into a spherically-domed convex grid geometry with a hexagonal array of apertures for determining neutral densities downstream of the ion thruster grids. The neutrals escaping from an off-center neutralizer are also modeled assuming diffuse neutral emission from the neutralizer keeper orifice. Finally, the effect of the surrounding vacuum facility neutrals is included and assumed to be constant. The model is used to predict the neutral density downstream of a NEXT ion thruster with and without neutralizer flow and a vacuum facility background pressure. The impacts of past simplifying assumptions for predicting downstream neutral densities are also examined for a NEXT ion thruster.

  15. Juggling Act

    ERIC Educational Resources Information Center

    Rudalevige, Andrew

    2009-01-01

    Two education bills from George W. Bush's first term are long overdue for reauthorization. One, of course, is the No Child Left Behind Act (NCLB), passed in late 2001. The other is the Education Sciences Reform Act (ESRA), which in November 2002 replaced the Office of Educational Research and Improvement (OERI) with a new Institute of Education…

  16. DNA Source Selection for Downstream Applications Based on DNA Quality Indicators Analysis

    PubMed Central

    Lucena-Aguilar, Gema; Sánchez-López, Ana María; Barberán-Aceituno, Cristina; Carrillo-Ávila, José Antonio; López-Guerrero, José Antonio

    2016-01-01

    High-quality human DNA samples and associated information of individuals are necessary for biomedical research. Biobanks act as a support infrastructure for the scientific community by providing a large number of high-quality biological samples for specific downstream applications. For this purpose, biobank methods for sample preparation must ensure the usefulness and long-term functionality of the products obtained. Quality indicators are the tool to measure these parameters, the purity and integrity determination being those specifically used for DNA. This study analyzes the quality indicators in DNA samples derived from 118 frozen human tissues in optimal cutting temperature (OCT) reactive, 68 formalin-fixed paraffin-embedded (FFPE) tissues, 119 frozen blood samples, and 26 saliva samples. The results obtained for DNA quality are discussed in association with the usefulness for downstream applications and availability of the DNA source in the target study. In brief, if any material is valid, blood is the most approachable option of prospective collection of samples providing high-quality DNA. However, if diseased tissue is a requisite or samples are available, the recommended source of DNA would be frozen tissue. These conclusions will determine the best source of DNA, according to the planned downstream application. Furthermore our results support the conclusion that a complete procedure of DNA quantification and qualification is necessary to guarantee the appropriate management of the samples, avoiding low confidence results, high costs, and a waste of samples. PMID:27158753

  17. DNA Source Selection for Downstream Applications Based on DNA Quality Indicators Analysis.

    PubMed

    Lucena-Aguilar, Gema; Sánchez-López, Ana María; Barberán-Aceituno, Cristina; Carrillo-Ávila, José Antonio; López-Guerrero, José Antonio; Aguilar-Quesada, Rocío

    2016-08-01

    High-quality human DNA samples and associated information of individuals are necessary for biomedical research. Biobanks act as a support infrastructure for the scientific community by providing a large number of high-quality biological samples for specific downstream applications. For this purpose, biobank methods for sample preparation must ensure the usefulness and long-term functionality of the products obtained. Quality indicators are the tool to measure these parameters, the purity and integrity determination being those specifically used for DNA. This study analyzes the quality indicators in DNA samples derived from 118 frozen human tissues in optimal cutting temperature (OCT) reactive, 68 formalin-fixed paraffin-embedded (FFPE) tissues, 119 frozen blood samples, and 26 saliva samples. The results obtained for DNA quality are discussed in association with the usefulness for downstream applications and availability of the DNA source in the target study. In brief, if any material is valid, blood is the most approachable option of prospective collection of samples providing high-quality DNA. However, if diseased tissue is a requisite or samples are available, the recommended source of DNA would be frozen tissue. These conclusions will determine the best source of DNA, according to the planned downstream application. Furthermore our results support the conclusion that a complete procedure of DNA quantification and qualification is necessary to guarantee the appropriate management of the samples, avoiding low confidence results, high costs, and a waste of samples. PMID:27158753

  18. The effect of CD4 receptor downregulation and its downstream signaling molecules on HIV-1 latency

    SciTech Connect

    Kim, Kyung-Chang; Kim, Hyeon Guk; Roh, Tae-Young; Park, Jihwan; Jung, Kyung-Min; Lee, Joo-Shil; Choi, Sang-Yun; Kim, Sung Soon; Choi, Byeong-Sun

    2011-01-14

    Research highlights: {yields} CD4 receptors were downregulated on the surface of HIV-1 latently infected cells. {yields} CD4 downstream signaling molecules were suppressed in HIV-1 latently infected cells. {yields} HIV-1 progeny can be reactivated by induction of T-cell activation signal molecules. {yields} H3K4me3 and H3K9ac were highly enriched in CD4 downstream signaling molecules. {yields} HIV-1 latency can be maintained by the reduction of downstream signaling molecules. -- Abstract: HIV-1 can establish a latent infection in memory CD4 + T cells to evade the host immune response. CD4 molecules can act not only as the HIV-1 receptor for entry but also as the trigger in an intracellular signaling cascade for T-cell activation and proliferation via protein tyrosine kinases. Novel chronic HIV-1-infected A3.01-derived (NCHA) cells were used to examine the involvement of CD4 downstream signaling in HIV-1 latency. CD4 receptors in NCHA cells were dramatically downregulated on its surface but were slightly decreased in whole-cell lysates. The expression levels of CD4 downstream signaling molecules, including P56{sup Lck}, ZAP-70, LAT, and c-Jun, were sharply decreased in NCHA cells. The lowered histone modifications of H3K4me3 and H3K9ac correlated with the downregulation of P56{sup Lck}, ZAP-70, and LAT in NCHA cells. AP-1 binding activity was also reduced in NCHA cells. LAT and c-Jun suppressed in NCHA cells were highly induced after PMA treatment. In epigenetic analysis, other signal transduction molecules which are associated with active and/or latent HIV-1 infection showed normal states in HIV-1 latently infected cells compared to A3.01 cells. In conclusion, we demonstrated that the HIV-1 latent state is sustained by the reduction of downstream signaling molecules via the downregulation of CD4 and the attenuated activity of transcription factor as AP-1. The HIV-1 latency model via T-cell deactivation may provide some clues for the development of the new

  19. Downstream approaches to phosphorus management in agricultural landscapes: regional applicability and use.

    PubMed

    Kröger, R; Dunne, E J; Novak, J; King, K W; McLellan, E; Smith, D R; Strock, J; Boomer, K; Tomer, M; Noe, G B

    2013-01-01

    This review provides a critical overview of conservation practices that are aimed at improving water quality by retaining phosphorus (P) downstream of runoff genesis. The review is structured around specific downstream practices that are prevalent in various parts of the United States. Specific practices that we discuss include the use of controlled drainage, chemical treatment of waters and soils, receiving ditch management, and wetlands. The review also focuses on the specific hydrology and biogeochemistry associated with each of those practices. The practices are structured sequentially along flowpaths as you move through the landscape, from the edge-of-field, to adjacent aquatic systems, and ultimately to downstream P retention. Often practices are region specific based on geology, cropping practices, and specific P related problems and thus require a right practice, and right place mentality to management. Each practice has fundamental P transport and retention processes by systems that can be optimized by management with the goal of reducing downstream P loading after P has left agricultural fields. The management of P requires a system-wide assessment of the stability of P in different biogeochemical forms (particulate vs. dissolved, organic vs. inorganic), in different storage pools (soil, sediment, streams etc.), and under varying biogeochemical and hydrological conditions that act to convert P from one form to another and promote its retention in or transport out of different landscape components. There is significant potential of hierarchically placing practices in the agricultural landscape and enhancing the associated P mitigation. But an understanding is needed of short- and long-term P retention mechanisms within a certain practice and incorporating maintenance schedules if necessary to improve P retention times and minimize exceeding retention capacity.

  20. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  1. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  2. Gas phase oxidation downstream of a catalytic combustor

    NASA Technical Reports Server (NTRS)

    Tien, J. S.; Anderson, D. N.

    1979-01-01

    Effect of the length available for gas-phase reactions downstream of the catalytic reactor on the emission of CO and unburned hydrocarbons was investigated. A premixed, prevaporized propane/air feed to a 12/cm/diameter catalytic/reactor test section was used. The catalytic reactor was made of four 2.5 cm long monolithic catalyst elements. Four water cooled gas sampling probes were located at positions between 0 and 22 cm downstream of the catalytic reactor. Measurements of unburned hydrocarbon, CO, and CO2 were made. Tests were performed with an inlet air temperature of 800 K, a reference velocity of 10 m/s, pressures of 3 and 600,000 Pa, and fuel air equivalence ratios of 0.14 to 0.24. For very lean mixtures, hydrocarbon emissions were high and CO continued to be formed downstream of the catalytic reactor. At the highest equivalence ratios tested, hydrocarbon levels were much lower and CO was oxidized to CO2 in the gas phase downstream. To achieve acceptable emissions, a downstream region several times longer than the catalytic reactor could be required.

  3. Downstream Yangtze River levels impacted by Three Gorges Dam

    NASA Astrophysics Data System (ADS)

    Wang, Jida; Sheng, Yongwei; Gleason, Colin J.; Wada, Yoshihide

    2013-12-01

    Changes in the Yangtze River level induced by large-scale human water regulation have profound implications on the inundation dynamics of surrounding lakes/wetlands and the integrity of related ecosystems. Using in situ measurements and hydrological simulation, this study reveals an altered Yangtze level regime downstream from the Three Gorges Dam (TGD) to the Yangtze estuary in the East China Sea as a combined result of (i) TGD’s flow regulation and (ii) Yangtze channel erosion due to reduced sediment load. During the average annual cycle of TGD’s regular flow control in 2009-2012, downstream Yangtze level variations were estimated to have been reduced by 3.9-13.5% at 15 studied gauging stations, manifested as evident level decrease in fall and increase in winter and spring. The impacts on Yangtze levels generally diminished in a longitudinal direction from the TGD to the estuary, with a total time lag of ˜9-12 days. Chronic Yangtze channel erosion since the TGD closure has lowered water levels in relation to flows at most downstream stations, which in turn counteracts the anticipated level increase by nearly or over 50% in winter and spring while reinforcing the anticipated level decrease by over 20% in fall. Continuous downstream channel erosion in the near future may further counteract the benefit of increased Yangtze levels during TGD’s water supplement in winter and accelerate the receding of inundation areas/levels of downstream lakes in fall.

  4. Modeling downstream fining in sand-bed rivers. I: Formulation

    USGS Publications Warehouse

    Wright, S.; Parker, G.

    2005-01-01

    In this paper a numerical modeling formulation is presented for simulation of the development of the longitudinal profile and bed sediment distribution in sand-bed rivers. The objective of the model application, which is presented in the companion paper (Wright and Parker, 2005), is to study the development of two characteristics of large, low-slope, sand-bed rivers: (1) a downstream decrease in bed slope (i.e. concave upward longitudinal profile) and (2) a downstream decrease in characteristic bed sediment diameter (e.g. the median bed surface size D50). Three mechanisms that lead to an upward concave profile and downstream fining are included in the modeling formulation: (1) a delta prograding into standing water at the downstream boundary, (2) sea-level rise, and (3) tectonic subsidence. In the companion paper (Wright and Parker, 2005) the model is applied to simulate the development of the longitudinal profile and downstream fining in sand-bed rivers flowing into the ocean during the past 5000 years of relatively slow sea-level rise. ?? 2005 International Association of Hydraulic Engineering and Research.

  5. Mortality of zebra mussel, Dreissena polymorpha, veligers during downstream transport

    USGS Publications Warehouse

    Horvath, T.G.; Lamberti, G.A.

    1999-01-01

    1. Streams flowing from lakes which contain zebra mussels, Dreissena polymorpha, provide apparently suitable habitats for mussel colonization and downstream range expansion, yet most such streams contain few adult mussels. We postulated that mussel veligers experience high mortality during dispersal via downstream transport. They tested this hypothesis in Christiana Creek, a lake-outlet stream in south-western Michigan, U.S.A., in which adult mussel density declined exponentially with distance downstream. 2. A staining technique using neutral red was developed and tested to distinguish quickly live and dead veligers. Live and dead veligers were distinguishable after an exposure of fresh samples to 13.3 mg L-1 of neutral red for 3 h. 3. Neutral red was used to determine the proportion of live veligers in samples taken longitudinally along Christiana Creek. The proportion of live veligers (mean ?? SE) declined from 90 ?? 3% at the lake outlet to 40 ?? 8% 18 km downstream. 4. Veligers appear to be highly susceptible to damage by physical forces (e.g. shear), and therefore, mortality in turbulent streams could be an important mechanism limiting zebra mussel dispersal to downstream reaches. Predictions of zebra mussel spread and population growth should consider lake-stream linkages and high mortality in running waters.

  6. Rotor wake mixing effects downstream of a compressor rotor

    NASA Technical Reports Server (NTRS)

    Ravindranath, A.; Lakshminarayana, B.

    1981-01-01

    An experimental study of rotor wake was conducted in the trailing-edge and near-wake regions of a moderately loaded compressor rotor blade using a rotating triaxial hot-wire probe in a rotating frame of reference. The flow-field was surveyed very close to the trailing-edge as well as inside the annulus- and hub-wall boundary layers. The large amount of data acquired during this program has been analyzed to discern the decay effects as well as the spanwise variation of three components of velocity, three components of intensities and three components of shear stresses. The data set also include extensive information on the variation of the flow properties downstream. The other derived quantities include wake momentum thickness and deviation angles at various spanwise and downstream locations. These data are presented and interpreted, with emphasis on the downstream mixing as well as endwall-wake interaction effects.

  7. Experimental investigation of unsteady fan flow interaction with downstream struts

    NASA Technical Reports Server (NTRS)

    Ng, W. F.; Obrien, W. F.; Olsen, T. L.

    1986-01-01

    In the present study of the unsteady pressure field produced on fan rotor blades by interaction with downstream struts, a single stage, low speed axial-flow fan was instrumented with blade-mounted high frequency pressure transducers. In addition, stationary pressure problems were used to map out the flowfield. Fluctuating pressure measurements are presented for blade midspan and 85-percent span on both the suction and pressure surfaces of the rotor blades at several positions of the downstream struts, and for two different flow coefficients. The strut is found to produce an effect on the unsteady pressure field on the rotor blades; this effect exceeds that due to the stator at design rotor-stator-strut spacing, but it rapidly declines as the struts are moved downstream.

  8. Critical effects of downstream boundary conditions on vortex breakdown

    NASA Technical Reports Server (NTRS)

    Kandil, Osama; Kandil, Hamdy A.; Liu, C. H.

    1992-01-01

    The unsteady, compressible, full Navier-Stokes (NS) equations are used to study the critical effects of the downstream boundary conditions on the supersonic vortex breakdown. The present study is applied to two supersonic vortex breakdown cases. In the first case, quasi-axisymmetric supersonic swirling flow is considered in a configured circular duct, and in the second case, quasi-axisymmetric supersonic swirling jet, that is issued from a nozzle into a supersonic jet of lower Mach number, is considered. For the configured duct flow, four different types of downstream boundary conditions are used, and for the swirling jet flow from the nozzle, two types of downstream boundary conditions are used. The solutions are time accurate which are obtained using an implicit, upwind, flux-difference splitting, finite-volume scheme.

  9. An Upstream By-product from Ester Activation via NHC-Catalysis Catalyzes Downstream Sulfonyl Migration Reaction.

    PubMed

    Han, Runfeng; He, Liwenze; Liu, Lin; Xie, Xingang; She, Xuegong

    2016-01-01

    A sequential reaction combining N-heterocyclic carbene (NHC) and N-hydroxyphthalimide (NHPI) catalysis allowed for the upstream by-product NHPI, which was generated in the NHC-catalyzed cycloaddition reaction, to act as the catalyst for a downstream nitrogen-to-carbon sulfonyl migration reaction. Enantiomeric excess of the major product in the cycloaddition reaction remained intact in the follow-up sulfonyl migration reaction.

  10. Interaction of fan rotor flow with downstream struts

    NASA Technical Reports Server (NTRS)

    Obrien, W. F., Jr.; Reimers, S. L.; Richardson, S. W.

    1983-01-01

    The detailed unsteady pressure field produced on the rotor blades of an axial-flow fan by interaction with downstream struts was investigated. The experimental arrangement was similar to that found in the fan casings of turbofan aircraft engines. Acoustically significant pressure fluctuations were measured on both thy suction and pressure sides of the rotor blades for several positions of the downstream struts. The level of the observed interaction decreased with increased spacing of the struts behind the rotor. An inviscid flow analysis for the disturbance level is compared with trends of the measured results.

  11. Transition duct with divided upstream and downstream portions

    SciTech Connect

    McMahan, Kevin Weston; LeBegue, Jeffrey Scott; Maldonado, Jaime Javier; Dillard, Daniel Jackson; Flanagan, James Scott

    2015-07-14

    Turbine systems are provided. In one embodiment, a turbine system includes a transition duct comprising an inlet, an outlet, and a duct passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The duct passage includes an upstream portion extending from the inlet and a downstream portion extending from the outlet. The turbine system further includes a rib extending from an outer surface of the duct passage, the rib dividing the upstream portion and the downstream portion.

  12. Van Gogh and Frizzled act redundantly in the Drosophila sensory organ precursor cell to orient its asymmetric division.

    PubMed

    Gomes, José-Eduardo; Corado, Maria; Schweisguth, François

    2009-01-01

    Drosophila sensory organ precursor cells (SOPs) divide asymmetrically along the anterior-posterior (a-p) body axis to generate two different daughter cells. Planar Cell Polarity (PCP) regulates the a-p orientation of the SOP division. The localization of the PCP proteins Van Gogh (Vang) and Frizzled (Fz) define anterior and posterior apical membrane domains prior to SOP division. Here, we investigate the relative contributions of Vang, Fz and Dishevelled (Dsh), a membrane-associated protein acting downstream of Fz, in orienting SOP polarity. Genetic and live imaging analyses suggest that Dsh restricts the localization of a centrosome-attracting activity to the anterior cortex and that Vang is a target of Dsh in this process. Using a clone border assay, we provide evidence that the Vang and fz genes act redundantly in SOPs to orient its polarity axis in response to extrinsic local PCP cues. Additionally, we find that the activity of Vang is dispensable for the non-autonomous polarizing activity of fz. These observations indicate that both Vang and Fz act as cues for downstream effectors orienting the planar polarity axis of dividing SOPs.

  13. 3. VIEW ALONG FLUME TOWARD DOWNSTREAM SIDE OF BRIDGE AND ...

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

    3. VIEW ALONG FLUME TOWARD DOWNSTREAM SIDE OF BRIDGE AND POWERHOUSE. FLUME IS FED FROM AFTERBAY OF POWERHOUSE. LOOKING NEAST-NORTHEAST. 90mm lens - Tule River Hydroelectric Complex, Tule River Bridge, Spanning North Fork of Middle Fork of Tule River, Springville, Tulare County, CA

  14. 5. AERATOR VIEW FROM DOWNSTREAM. FLUSH VALVE AT RIGHT OPENS ...

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

    5. AERATOR VIEW FROM DOWNSTREAM. FLUSH VALVE AT RIGHT OPENS TO CLEAR THE SYSTEM ABOVE THE SILT AND DEBRIS AND TO STOP THE FLOW OF WATER INTO THE SYSTEM DOWN LINE. BOX FLUME CONTINUES DOWN LINE TO SEDIMENTATION CHAMBER. - Kalaupapa Water Supply System, Waikolu Valley to Kalaupapa Settlement, Island of Molokai, Kalaupapa, Kalawao County, HI

  15. Modeling downstream fining in sand-bed rivers. II: Application

    USGS Publications Warehouse

    Wright, S.; Parker, G.

    2005-01-01

    In this paper the model presented in the companion paper, Wright and Parker (2005) is applied to a generic river reach typical of a large, sand-bed river flowing into the ocean in order to investigate the mechanisms controlling longitudinal profile development and downstream fining. Three mechanisms which drive downstream fining are studied: a delta prograding into standing water, sea-level rise, and tectonic subsidence. Various rates of sea-level rise (typical of the late Holocene) and tectonic subsidence are modeled in order to quantify their effects on the degree of profile concavity and downstream fining. Also, several other physical mechanisms which may affect fining are studied, including the relative importance of the suspended versus bed load, the effect of the loss of sediment overbank, and the influence of the delta bottom slope. Finally, sensitivity analysis is used to show that the grain-size distribution at the interface between the active layer and substrate has a significant effect on downstream fining. ?? 2005 International Association of Hydraulic Engineering and Research.

  16. 8. NORTHERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON ...

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

    8. NORTHERLY VIEW OF THE DOWNSTREAM ELEVATION OF BIG DALTON DAM SHOWING THE HOLLOW BAYS 2, 3, 4, 5, AND 6 AND THE PLUNGE POOL IN THE FOREGROUND. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  17. 1. LOOKING DOWNSTREAM (NORTHEAST) ALONG WINTER'S RUN TOWARD THE MITCHELL'S ...

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

    1. LOOKING DOWNSTREAM (NORTHEAST) ALONG WINTER'S RUN TOWARD THE MITCHELL'S MILL BRIDGE, SHOWING THE SETTING OF THE BRIDGE. CARRS MILL ROAD APPROACHES THE BRIDGE FROM THE SOUTH, ON THE RIGHT. - Mitchell's Mill Bridge, Spanning Winter's Run on Carrs Mill Road, west of Bel Air, Bel Air, Harford County, MD

  18. 8. Detail view of downstream side, looking south. Buttresses, struttie ...

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

    8. Detail view of downstream side, looking south. Buttresses, strut-tie beams, and arch-rings are shown. The white discoloration on the concrete is the result of efflorescence. - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  19. LOOKING DOWNSTREAM FROM KACHESS DAM CREST, 1910 RIVER CUTOFF CHANNEL ...

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

    LOOKING DOWNSTREAM FROM KACHESS DAM CREST, 1910 RIVER CUTOFF CHANNEL WITH CRIB STRUCTURE IN CENTER. BRIDGE FOOTING CRIB STRUCTURE AT RIGHT (Upstream face of Kachess Dam in foreground) - Kachess Dam, Cutoff Channel and Crib Structures, Kachess River, 1.5 miles north of Interstate 90, Easton, Kittitas County, WA

  20. 16. Detail, lower chord connection point on downstream side at ...

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

    16. Detail, lower chord connection point on downstream side at end panel showing lower chord eye bars, vertical tension eye bar, original and supplemental floor beams, turnbuckled lower laterals. View to northwest. - Dry Creek Bridge, Spanning Dry Creek at Cook Road, Ione, Amador County, CA

  1. STEEL ERECTION. View of downstream of bridge, looking southeast from ...

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

    STEEL ERECTION. View of downstream of bridge, looking southeast from confluence of Trinity and South Fork Trinity rivers. The old suspension bridge is in background - South Fork Trinity River Bridge, State Highway 299 spanning South Fork Trinity River, Salyer, Trinity County, CA

  2. 1. CONTEXTUAL VIEW FROM DOWNSTREAM OF BRIDGE IN ITS SETTING, ...

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

    1. CONTEXTUAL VIEW FROM DOWNSTREAM OF BRIDGE IN ITS SETTING, LOOKING NORTH-NORTHEAST FROM PIONEER BRIDGE (BUSINESS ROUTE 80). CAPITOL BANK OF COMMERCE BUILDING IS AT EXTREME RIGHT. - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  3. 13. VIEW OF DOWNSTREAM ELEVATION SHOWING CONSTRUCTION OF THE ARCH ...

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

    13. VIEW OF DOWNSTREAM ELEVATION SHOWING CONSTRUCTION OF THE ARCH NEAR THE TOP AND THE SPILLWAY OF BIG TUJUNGA DAM, TAKEN ON APRIL 22, 1931, (PHOTOGRAPHER UNKNOWN). PICTURE WAS DEVELOPED FROM COPY NEGATIVES WHICH WERE TAKEN ON JUNE 5, 1973, BY PHOTOGRAPHER GATSON OF L.A. COUNTY PUBLIC WORKS. - Big Tujunga Dam, 809 West Big Tujunga Road, Sunland, Los Angeles County, CA

  4. 8. Chandler Falls, looking downstream, and downhill from the edge ...

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

    8. Chandler Falls, looking downstream, and downhill from the edge of the mesa (from south). Penstock and foundation of the hydropower plant visible on left. Photographer: Mark Durben, February 1989. Source: SRPA - Tempe Canal, South Side Salt River in Tempe, Mesa & Phoenix, Tempe, Maricopa County, AZ

  5. 2. View from the Minnesota bank looking downstream (northnorthwest) at ...

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

    2. View from the Minnesota bank looking downstream (north-northwest) at bridge's southwest elevation; the bridge approach is missing - Enloe Bridge No. 90021, Spanning Red River of North between Minnesota & North Dakota on County State Aid Highway 28, Wolverton, Wilkin County, MN

  6. 1. GENERAL EXTERIOR VIEW LOOKING SOUTHWEST, SHOWING DOWNSTREAM END OF ...

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

    1. GENERAL EXTERIOR VIEW LOOKING SOUTHWEST, SHOWING DOWNSTREAM END OF NAVIGATION LOCK #1 WITH CHAMBER FILLED; THE CONTROL HOUSE IS ON RIGHT; VIEW IS TAKEN FROM ROOF OF POWERHOUSE #1. - Bonneville Project, Navigation Lock No. 1, Oregon shore of Columbia River near first Powerhouse, Bonneville, Multnomah County, OR

  7. 51. Photocopy of photograph, October 16, 1942. VIEW, LOOKING DOWNSTREAM, ...

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

    51. Photocopy of photograph, October 16, 1942. VIEW, LOOKING DOWNSTREAM, OF POWER HOUSE DURING FLOOD. (Courtesy of the Potomac Edison Company Library (Hagerstown, MD), Historical Data Files, Dam NO. 5 listing) - Dam No. 5 Hydroelectric Plant, On Potomac River, Hedgesville, Berkeley County, WV

  8. 5. DETAIL OF THE DOWNSTREAM SIDE OF THE GATES SHOWING ...

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

    5. DETAIL OF THE DOWNSTREAM SIDE OF THE GATES SHOWING REINFORCEMENT AND THE TOP EDGE OF THE UPSTREAM MASONRY WALL OF THE HISTORIC OUTLET WORKS TAKEN FROM THE SOUTHERN EMBANKMENT. VIEW LOOKING NORTH. - Twin Lakes Dam & Outlet Works, Beneath Twin Lakes Reservoir, T11S, R80W, S22, Twin Lakes, Lake County, CO

  9. 4. DOWNSTREAM VIEW OF HISTORIC OUTLET WORKS TAKEN FROM THE ...

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

    4. DOWNSTREAM VIEW OF HISTORIC OUTLET WORKS TAKEN FROM THE NORTH BANK OF THE CHANNEL BETWEEN THE OLD WORKS AND TWIN LAKES DAM. VIEW LOOKING WEST. - Twin Lakes Dam & Outlet Works, Beneath Twin Lakes Reservoir, T11S, R80W, S22, Twin Lakes, Lake County, CO

  10. 6. DETAIL VIEW OF THE MASONRY FACING ON THE DOWNSTREAM ...

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

    6. DETAIL VIEW OF THE MASONRY FACING ON THE DOWNSTREAM SIDE OF THE HISTORIC OUTLET WORKS. VIEW LOOKING NORTHEAST. - Twin Lakes Dam & Outlet Works, Beneath Twin Lakes Reservoir, T11S, R80W, S22, Twin Lakes, Lake County, CO

  11. 3. DOWNSTREAM VIEW OF HISTORIC OUTLET WORKS TAKEN FROM THE ...

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

    3. DOWNSTREAM VIEW OF HISTORIC OUTLET WORKS TAKEN FROM THE SOUTH SIDE OF THE CHANNEL BETWEEN THE OLD WORKS AND TWIN LAKES DAM. VIEW LOOKING NORTHWEST - Twin Lakes Dam & Outlet Works, Beneath Twin Lakes Reservoir, T11S, R80W, S22, Twin Lakes, Lake County, CO

  12. 53. Humbug Creek looking downstream from Humbug Diversion Dam. Retaining ...

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

    53. Humbug Creek looking downstream from Humbug Diversion Dam. Retaining wall for canal is visible beginning at left center. Photographer James Eastwood, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  13. 71. Close up view of downstream view of four large ...

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

    71. Close up view of downstream view of four large taintor gates and section for sector gate (now removed). Photographer Mark Durben. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  14. 59. Downstream view of Waddell Dam showing buttress ties, crane, ...

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

    59. Downstream view of Waddell Dam showing buttress ties, crane, housing over penstock outlet (left) and storage building (right). Photographer Mark Durben, 1986. Source: Salt River Project. - Waddell Dam, On Agua Fria River, 35 miles northwest of Phoenix, Phoenix, Maricopa County, AZ

  15. 10. EASTERLY VIEW OF THE ACCESS ROAD TO THE DOWNSTREAM ...

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

    10. EASTERLY VIEW OF THE ACCESS ROAD TO THE DOWNSTREAM SIDE OF BIG DALTON DAM EXTENDING FROM THE FOOTBRIDGE TO THE GAGING STATION. BIG DALTON DAM IN BACKGROUND. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  16. 13. VIEW OF DOWNSTREAM ELEVATION OF BIG DALTON DAM SHOWING ...

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

    13. VIEW OF DOWNSTREAM ELEVATION OF BIG DALTON DAM SHOWING CONSTRUCTION OF THE ARCHES AND ARCH WALLS TAKEN IN 1928-1929 (PHOTOGRAPHER UNKNOWN). PICTURE WAS DEVELOPED FROM COPY NEGATIVES WHICH WERE TAKEN ON 2-15-1973 BY PHOTOGRAPHER D. MEIER OF L.A. COUNTY PUBLIC WORKS. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  17. 2. VIEW OF DOWNSTREAM END OF SPILLWAY CHUTE FROM SOUTH ...

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

    2. VIEW OF DOWNSTREAM END OF SPILLWAY CHUTE FROM SOUTH SIDE OF PLUNGE POOL, FACING NORTHWEST. CUTOFF WALL AND RETAINING WALL (ON EAST SIDE OF CHUTE) VISIBLE ABOVE WATER LEVEL - Cushman No. 1 Hydroelectric Power Plant, Spillway, North Fork of Skokomish River, 5 miles West of Hood Canal, Hoodsport, Mason County, WA

  18. 19. Downstream elevation of bridge. Original photograph published in The ...

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

    19. Downstream elevation of bridge. Original photograph published in The Architect and Engineer, July 1920, p.90, photographer unknown. Note width of channel, and compare to CA-126-5 and CA-126-7. - Salt River Bridge, Spanning Salt River at Dillon Road, Ferndale, Humboldt County, CA

  19. 12. Close up view of construction on the downstream face. ...

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

    12. Close up view of construction on the downstream face. Track at lower center conveyed aggregate from the stream bed to the mixing plant. Photographer unknown, October 15, 1924. Source: Salt River Project. - Mormon Flat Dam, On Salt River, Eastern Maricopa County, east of Phoenix, Phoenix, Maricopa County, AZ

  20. VIEW OF DOWNSTREAM SIDE OF CHECK DAM, CONCRETE SPILLWAY WITH ...

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

    VIEW OF DOWNSTREAM SIDE OF CHECK DAM, CONCRETE SPILLWAY WITH MORTARED ROCK WALLS, AND CIPPOLETTI WEIR ON TUMALO RESERVOIR FEED CANAL NEAR COLLINS ROAD (IN BACKGROUND). LOOKING NORTHEAST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  1. 60. PANORAMIC VIEW OF DOWNSTREAM FACE. No date, but believed ...

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

    60. PANORAMIC VIEW OF DOWNSTREAM FACE. No date, but believed to be just subsequent to construction. Photograph by C.G. Duffey, Long Beach, California. (38' x 11' framed print). - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  2. 9. OBLIQUE OF DOWNSTREAM SIDE OF BRIDGE, LOOKING EAST FROM ...

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

    9. OBLIQUE OF DOWNSTREAM SIDE OF BRIDGE, LOOKING EAST FROM YOLO COUNTY SIDE OF THE SACRAMENTO RIVER. VESSEL MOORED AT RIGHT IS DELTA KING, WHICH HAS SINCE BEEN REFURBISHED AND MOVED UPSTREAM OF BRIDGE TO PERMANENT MOORING. CAPITOL BANK OF COMMERCE BUILDING IS BEHIND VESSEL. - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

  3. 13. OVERALL VIEW OF DOWNSTREAM FACE OF LIFT GATE SECTION ...

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

    13. OVERALL VIEW OF DOWNSTREAM FACE OF LIFT GATE SECTION (FROM EDGE OF COFFERDAM) WITH BOILERHOUSE AND TAINTER GATE SECTION IN BACKGROUND TO THE RIGHT. VIEW TO SOUTHEAST. - Starved Rock Locks & Dam, Illinois Waterway River mile 231, Peru, La Salle County, IL

  4. 1. Contextual view of bridge in setting, from downstream, view ...

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

    1. Contextual view of bridge in setting, from downstream, view to south from edge of bluff east of Rawson Road. Bridge visible among trees at left center. - Red Bank Creek Bridge, Spanning Red Bank Creek at Rawson Road, Red Bluff, Tehama County, CA

  5. 20. VIEW FROM DOWNSTREAM SIDE OF DAM SHOWING BUTTS OF ...

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

    20. VIEW FROM DOWNSTREAM SIDE OF DAM SHOWING BUTTS OF LOGS PROJECTING BETWEEN CROSS LOGS. FREQUENTLY WHOLE TREES WERE USED IN CONSTRUCTING THESE DAMS. THE BRANCHES WERE PLACED UPSTREAM AND COVERED WITH EARTH AND STONE TO ANCHOR THEM. Photographed November 6, 1935. - Forge Creek Dam-John Cable Mill, Townsend, Blount County, TN

  6. 8. View of gabeon west wall added downstream from the ...

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

    8. View of gabeon west wall added downstream from the lower dam. Photograph taken from east side of Millstone Creek. VIEW SOUTH - Loleta Recreation Area, Lower Dam, 6 miles Southeast of interesection of State Route 24041 & State Route 66, Loleta, Elk County, PA

  7. 9. SOUTHERLY VIEW OF THE ACCESS ROAD TO THE DOWNSTREAM ...

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

    9. SOUTHERLY VIEW OF THE ACCESS ROAD TO THE DOWNSTREAM SIDE OF BIG DALTON DAM EXTENDING FROM THE DAM TO THE FOOTBRIDGE. VIEW FROM BIG DALTON DAM SHOWING THE TOE WEIR IN FOREGROUND AND FOOTBRIDGE IN BACKGROUND. - Big Dalton Dam, 2600 Big Dalton Canyon Road, Glendora, Los Angeles County, CA

  8. 23. The Salt River, downstream, from atop Mormon Flat Dam. ...

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

    23. The Salt River, downstream, from atop Mormon Flat Dam. HEFU generator deck is at center bottom. Photographer Mark Durben, 1988. Source: Salt River Project. - Mormon Flat Dam, On Salt River, Eastern Maricopa County, east of Phoenix, Phoenix, Maricopa County, AZ

  9. 5. Downstream elevation, view to southeast. Dark stains on side ...

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

    5. Downstream elevation, view to southeast. Dark stains on side of main girder are from deck drain scuppers, marking deck level within the girders. Compare this view and CA-126-7 to CA-126-19 for indication of severity of siltation of Salt River channel has silted. - Salt River Bridge, Spanning Salt River at Dillon Road, Ferndale, Humboldt County, CA

  10. 1. CONTEXTUAL VIEW OF THE POST FALLS POWERHOUSE LOOKING DOWNSTREAM. ...

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

    1. CONTEXTUAL VIEW OF THE POST FALLS POWERHOUSE LOOKING DOWNSTREAM. POWER PLANT AND INTAKE GATES ARE IN THE LEFT FOREGROUND, AND THE ATTACHED 'OLD SWITCHING BUILDING' (NOW ABANDONED) IS IN THE RIGHT BACKGROUND, LOOKING NORTHWEST. - Washington Water Power Company Post Falls Power Plant, Middle Channel Powerhouse & Dam, West of intersection of Spokane & Fourth Streets, Post Falls, Kootenai County, ID

  11. 1. CONTEXTUAL VIEW, LOOKING DOWNSTREAM (NORTHERLY) OF THE CONCRETE ARCH ...

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

    1. CONTEXTUAL VIEW, LOOKING DOWNSTREAM (NORTHERLY) OF THE CONCRETE ARCH ('ONE-WAY BRIDGE') THAT PROVIDES PRIVATE (WWP) ACCESS TO THE MIDDLE CHANNEL OF THE POST FALLS POWER PLANT. - Washington Water Power Company Post Falls Power Plant, Concrete Arch Bridge, West of intersection of Spokane & Fourth Streets, Post Falls, Kootenai County, ID

  12. 3. DOWNSTREAM AERIAL VIEW OF THE DIVERSION CHANNEL AND CONTROL ...

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

    3. DOWNSTREAM AERIAL VIEW OF THE DIVERSION CHANNEL AND CONTROL WORKS. THE OUTLET CONTROL TOWER AND THE PIER FOR THE SERVICE BRIDGE ARE SHOWN COMPLETED.... Volume XVIII, No. 11, January 18, 1940. - Prado Dam, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  13. 20. DOWNSTREAM VIEW OF THE INTAKE STRUCTURE, SHOWING THE SLIDE ...

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

    20. DOWNSTREAM VIEW OF THE INTAKE STRUCTURE, SHOWING THE SLIDE GATES FOR THE CONTROLLED OUTLET, IN POSITION FOR INSTALLATION.... Volume XVII, No. 15, November 13, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  14. 27. A DOWNSTREAM VIEW FROM THE LOWER END OF THE ...

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

    27. A DOWNSTREAM VIEW FROM THE LOWER END OF THE OUTLET CONDUIT, SHOWING STILLING BASIN BAFFLE PIERS.... Volume XVII, No. 17, November 29, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  15. 17. VIEW EASTERLY ALONG DOWNSTREAM END OF THE SPILLWAY, SHOWING ...

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

    17. VIEW EASTERLY ALONG DOWNSTREAM END OF THE SPILLWAY, SHOWING CELL WALL CONSTRUCTION IN THE CRIB CUTOFF.... Volume XX, No. 4, August 3, 1940. - Prado Dam, Spillway, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  16. 7. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, WITH ...

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

    7. VIEW SHOWING DOWNSTREAM FACE AND TOE OF DAM, WITH OUTLET CULVERT AND WING RETAINING WALLS, LOOKING NORTH - High Mountain Dams in Upalco Unit, Twin Pots Dam, Ashley National Forest, 10.1 miles North of Mountain Home, Mountain Home, Duchesne County, UT

  17. 2. EXTERIOR VIEW OF DOWNSTREAM SIDE OF COTTAGE 191 TAKEN ...

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

    2. EXTERIOR VIEW OF DOWNSTREAM SIDE OF COTTAGE 191 TAKEN FROM ROOF OF GARAGE 393. CAMERA FACING SOUTHEAST. COTTAGE 181 AND CHILDREN'S PLAY AREA VISIBLE ON EITHER SIDE OF ROOF. GRAPE ARBOR IN FOREGROUND. - Swan Falls Village, Cottage 191, Snake River, Kuna, Ada County, ID

  18. 3. View of Potomac River looking downstream from the Great ...

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

    3. View of Potomac River looking downstream from the Great Falls of the Potomac. Reduction of stream in width during low water, is clearly shown by exposed beach on left side and indisputable normal water height markings shown on right side of photograph. Mr. Horyduzak, photographer, 1943. - Potowmack Company: Great Falls Canal & Locks, Great Falls, Fairfax County, VA

  19. View of Flume Bridge #5 from FS 502 looking downstream ...

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

    View of Flume Bridge #5 from FS 502 looking downstream (south). Bridge is on the left side of the photograph. This is similar to other flume bridges in the system and is the only photograph representing these features. - Childs-Irving Hydroelectric Project, Childs System, Flume Bridge No. 5, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  20. Methylation of Hg downstream from the Bonanza Hg mine, Oregon

    USGS Publications Warehouse

    Gray, John E.; Hines, Mark E.; Krabbenhoft, David P.; Thoms, Bryn

    2012-01-01

    Speciation of Hg and conversion to methyl-Hg were evaluated in stream sediment, stream water, and aquatic snails collected downstream from the Bonanza Hg mine, Oregon. Total production from the Bonanza mine was >1360t of Hg, during mining from the late 1800s to 1960, ranking it as an intermediate sized Hg mine on an international scale. The primary objective of this study was to evaluate the distribution, transport, and methylation of Hg downstream from a Hg mine in a coastal temperate climatic zone. Data shown here for methyl-Hg, a neurotoxin hazardous to humans, are the first reported for sediment and water from this area. Stream sediment collected from Foster Creek flowing downstream from the Bonanza mine contained elevated Hg concentrations that ranged from 590 to 71,000ng/g, all of which (except the most distal sample) exceeded the probable effect concentration (PEC) of 1060ng/g, the Hg concentration above which harmful effects are likely to be observed in sediment-dwelling organisms. Concentrations of methyl-Hg in stream sediment collected from Foster Creek varied from 11 to 62ng/g and were highly elevated compared to regional baseline concentrations (0.11-0.82ng/g) established in this study. Methyl-Hg concentrations in stream sediment collected in this study showed a significant correlation with total organic C (TOC, R2=0.62), generally indicating increased methyl-Hg formation with increasing TOC in sediment. Isotopic-tracer methods indicated that several samples of Foster Creek sediment exhibited high rates of Hg-methylation. Concentrations of Hg in water collected downstream from the mine varied from 17 to 270ng/L and were also elevated compared to baselines, but all were below the 770ng/L Hg standard recommended by the USEPA to protect against chronic effects to aquatic wildlife. Concentrations of methyl-Hg in the water collected from Foster Creek ranged from 0.17 to 1.8ng/L, which were elevated compared to regional baseline sites upstream and downstream

  1. Downstream-migrating fluvial point bars in the rock record

    NASA Astrophysics Data System (ADS)

    Ghinassi, Massimiliano; Ielpi, Alessandro; Aldinucci, Mauro; Fustic, Milovan

    2016-04-01

    Classical models developed for ancient fluvial point bars are based on the assumption that meander bends invariably increase their radius as meander-bend apices migrate in a direction transverse to the channel-belt axis (i.e., meander bend expansion). However, many modern meandering rivers are also characterized by down-valley migration of the bend apex, a mechanism that takes place without a significant change in meander radius and wavelength. Downstream-migrating fluvial point bars (DMFPB) are the dominant architectural element of these types of meander belts. Yet they are poorly known from ancient fluvial-channel belts, since their disambiguation from expansional point bars often requires fully-3D perspectives. This study aims to review DMFPB deposits spanning in age from Devonian to Holocene, and to discuss their main architectural and sedimentological features from published outcrop, borehole and 3D-seismic datasets. Fluvial successions hosting DMFPB mainly accumulated in low accommodation conditions, where channel belts were affected by different degrees of morphological (e.g., valleys) or tectonic (e.g., axial drainage of shortening basins) confinement. In confined settings, bends migrate downstream along the erosion-resistant valley flanks and little or no floodplain deposits are preserved. Progressive floor aggradation (e.g., valley filling) allow meander belts with DMFPB to decrease their degree of confinement. In less confined settings, meander bends migrate downstream mainly after impinging against older, erosion-resistant channel fill mud. By contrast, tectonic confinement is commonly associated with uplifted alluvial plains that prevented meander-bend expansion, in turn triggering downstream translation. At the scale of individual point bars, translational morphodynamics promote the preservation of downstream-bar deposits, whereas the coarser-grained upstream and central beds are less frequently preserved. However, enhanced preservation of upstream

  2. A novel virtual hub approach for multisource downstream service integration

    NASA Astrophysics Data System (ADS)

    Previtali, Mattia; Cuca, Branka; Barazzetti, Luigi

    2016-08-01

    A large development of downstream services is expected to be stimulated starting from earth observations (EO) datasets acquired by Copernicus satellites. An important challenge connected with the availability of downstream services is the possibility for their integration in order to create innovative applications with added values for users of different categories level. At the moment, the world of geo-information (GI) is extremely heterogeneous in terms of standards and formats used, thus preventing a facilitated access and integration of downstream services. Indeed, different users and data providers have also different requirements in terms of communication protocols and technology advancement. In recent years, many important programs and initiatives have tried to address this issue even on trans-regional and international level (e.g. INSPIRE Directive, GEOSS, Eye on Earth and SEIS). However, a lack of interoperability between systems and services still exists. In order to facilitate the interaction between different downstream services, a new architectural approach (developed within the European project ENERGIC OD) is proposed in this paper. The brokering-oriented architecture introduces a new mediation layer (the Virtual Hub) which works as an intermediary to bridge the gaps linked to interoperability issues. This intermediation layer de-couples the server and the client allowing a facilitated access to multiple downstream services and also Open Data provided by national and local SDIs. In particular, in this paper an application is presented integrating four services on the topic of agriculture: (i) the service given by Space4Agri (providing services based on MODIS and Landsat data); (ii) Gicarus Lab (providing sample services based on Landsat datasets) and (iii) FRESHMON (providing sample services for water quality) and services from a several regional SDIs.

  3. Nonsense-Mediated Decay in Genetic Disease: Friend or Foe?

    PubMed Central

    Miller, Jake N.; Pearce, David A.

    2014-01-01

    Eukaryotic cells utilize various RNA quality control mechanisms to ensure high fidelity of gene expression, thus protecting against the accumulation of nonfunctional RNA and the subsequent production of abnormal peptides. Messenger RNAs (mRNAs) are largely responsible for protein production, and mRNA quality control is particularly important for protecting the cell against the downstream effects of genetic mutations. Nonsense-mediated decay (NMD) is an evolutionarily conserved mRNA quality control system in all eukaryotes that degrades transcripts containing premature termination codons (PTCs). By degrading these aberrant transcripts, NMD acts to prevent the production of truncated proteins that could otherwise harm the cell through various insults, such as dominant negative effects or the ER stress response. Although NMD functions to protect the cell against the deleterious effects of aberrant mRNA, there is a growing body of evidence that mutation-, codon-, gene-, cell-, and tissue-specific differences in NMD efficiency can alter the underlying pathology of genetic disease. In addition, the protective role that NMD plays in genetic disease can undermine current therapeutic strategies aimed at increasing the production of full-length functional protein from genes harboring nonsense mutations. Here, we review the normal function of this RNA surveillance pathway and how it is regulated, provide current evidence for the role that it plays in modulating genetic disease phenotypes, and how NMD can be used as a therapeutic target. PMID:25485595

  4. Nonsense-mediated decay in genetic disease: friend or foe?

    PubMed

    Miller, Jake N; Pearce, David A

    2014-01-01

    Eukaryotic cells utilize various RNA quality control mechanisms to ensure high fidelity of gene expression, thus protecting against the accumulation of nonfunctional RNA and the subsequent production of abnormal peptides. Messenger RNAs (mRNAs) are largely responsible for protein production, and mRNA quality control is particularly important for protecting the cell against the downstream effects of genetic mutations. Nonsense-mediated decay (NMD) is an evolutionarily conserved mRNA quality control system in all eukaryotes that degrades transcripts containing premature termination codons (PTCs). By degrading these aberrant transcripts, NMD acts to prevent the production of truncated proteins that could otherwise harm the cell through various insults, such as dominant negative effects or the ER stress response. Although NMD functions to protect the cell against the deleterious effects of aberrant mRNA, there is a growing body of evidence that mutation-, codon-, gene-, cell-, and tissue-specific differences in NMD efficiency can alter the underlying pathology of genetic disease. In addition, the protective role that NMD plays in genetic disease can undermine current therapeutic strategies aimed at increasing the production of full-length functional protein from genes harboring nonsense mutations. Here, we review the normal function of this RNA surveillance pathway and how it is regulated, provide current evidence for the role that it plays in modulating genetic disease phenotypes, and how NMD can be used as a therapeutic target.

  5. Assessing the cumulative effect of the weather variability on wetlands and the hydrological connection between wetlands and downstream waters

    NASA Astrophysics Data System (ADS)

    Yeo, I. Y.; Lang, M. W.; Lee, S.; Mccarty, G.; Peng, Y.; Huang, C.

    2014-12-01

    Wetlands are crucial ecosystem features that provide important ecological benefits to improve water quality and reduce the climate change impact. This ecosystem functioning of wetlands is largely dependent upon their hydrological characteristics and linkage to the downstream waters. However, the cumulative impacts of the climate on wetlands and the hydrological connection between wetlands and downstream waters have been rarely quantified at the landscape scale. This study reports findings from time series satellite observation that can illustrate the changes in extent of wetland inundation at a high spatial resolution (30-m) over the period 1985-2010. This remote sensing based observation provides crucial information to gain insights onto inter-annual variability of inundation dynamics, and we analyze this product with the drought indices, streamflows, the USFS NWI-hydrologic modifier. This study focuses on natural palustrine wetlands, densely distributed in the coastal plain of the Chesapeake Bay Watershed (CBW). We observe inundation patterns change in response to the weather variability, and it is proportionally related to the downstream flow discharge. While those wetlands with a longer hydro-period (i.e., permanently ponded wetlands during the growing season) show the strongest relationship with stream discharge (including baseflow, contributed from the shallow groundwater), inundation patterns of headwater/isolated wetlands are also strongly related to stream discharge. It shows the strong relationship between wetlands and downstream water regardless of geographic isolation and their mutual reliance on groundwater. The study provides the support for the conservation of wetlands through section 404 of the Clean Water Act.

  6. Optimizing turbine withdrawal from a tropical reservoir for improved water quality in downstream wetlands

    NASA Astrophysics Data System (ADS)

    Kunz, Manuel J.; Senn, David B.; Wehrli, Bernhard; Mwelwa, Elenestina M.; Wüest, Alfred

    2013-09-01

    Large reservoirs in the tropics act as efficient nutrient traps and often develop hypoxic conditions in the hypolimnion. Both effects may have severe implications for aquatic ecosystems, such as limited primary production in downstream riparian agriculture and in natural wetlands due to reduced nutrient loads, and, if hypolimnetic waters are withdrawn, hypoxic conditions that pose toxic risks in downstream rivers. This study using Itezhi-Tezhi Reservoir (Zambia) as a model system aims at defining optimized turbine withdrawal to prevent hypoxia and to relieve low-nutrient conditions in the downstream Kafue Flats floodplain. A biogeochemical 1-D model simulating reservoir-internal processes and water quality in the outflow was used for estimating dissolved oxygen (DO) concentrations and inorganic nitrogen and phosphorus loads in the outflow. The water depth of turbine withdrawals was varied in a set of simulations to optimize outflow water quality. Releasing hypolimnetic water was shown to result in lower average outflow DO concentrations of 4.1-6.8 mg l-1 compared to the current 7.6 mg l-1. More importantly, the outflow will remain hypoxic during up to 189 days. Meanwhile, withdrawing nutrient-rich hypolimnetic water compensated effectively for nutrient losses to the reservoir sediment. Both outflow DO concentrations and nutrient output could be optimized in the scenario with 50% epilimnetic turbine discharge originating from ˜13 m depth. In this optimal scenario, hypoxia was prevented permanently, and average DO concentrations decreased moderately to 5.2 mg l-1. Additionally, five-times higher dissolved inorganic N and dissolved inorganic P loads resulted in comparison to the current dam operation.

  7. Vaccinia virus inhibits NF-κB-dependent gene expression downstream of p65 translocation.

    PubMed

    Sumner, Rebecca P; Maluquer de Motes, Carlos; Veyer, David L; Smith, Geoffrey L

    2014-03-01

    The transcription factor nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) plays a critical role in host defense against viral infection by inducing the production of proinflammatory mediators and type I interferon. Consequently, viruses have evolved many mechanisms to block its activation. The poxvirus vaccinia virus (VACV) encodes numerous inhibitors of NF-κB activation that target multiple points in the signaling pathway. A derivative of VACV strain Copenhagen, called vv811, lacking 55 open reading frames in the left and right terminal regions of the genome was reported to still inhibit NF-κB activation downstream of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), suggesting the presence of one or more additional inhibitors. In this study, we constructed a recombinant vv811 lacking the recently described NF-κB inhibitor A49 (vv811ΔA49), yielding a virus that lacked all currently described inhibitors downstream of TNF-α and IL-1β. Unlike vv811, vv811ΔA49 no longer inhibited degradation of the phosphorylated inhibitor of κBα and p65 translocated into the nucleus. However, despite this translocation, vv811ΔA49 still inhibited TNF-α- and IL-1β-induced NF-κB-dependent reporter gene expression and the transcription and production of cytokines induced by these agonists. This inhibition did not require late viral gene expression. These findings indicate the presence of another inhibitor of NF-κB that is expressed early during infection and acts by a novel mechanism downstream of p65 translocation into the nucleus.

  8. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.

    PubMed

    Franzén, Oscar; Ermel, Raili; Cohain, Ariella; Akers, Nicholas K; Di Narzo, Antonio; Talukdar, Husain A; Foroughi-Asl, Hassan; Giambartolomei, Claudia; Fullard, John F; Sukhavasi, Katyayani; Köks, Sulev; Gan, Li-Ming; Giannarelli, Chiara; Kovacic, Jason C; Betsholtz, Christer; Losic, Bojan; Michoel, Tom; Hao, Ke; Roussos, Panos; Skogsberg, Josefin; Ruusalepp, Arno; Schadt, Eric E; Björkegren, Johan L M

    2016-08-19

    Genome-wide association studies (GWAS) have identified hundreds of cardiometabolic disease (CMD) risk loci. However, they contribute little to genetic variance, and most downstream gene-regulatory mechanisms are unknown. We genotyped and RNA-sequenced vascular and metabolic tissues from 600 coronary artery disease patients in the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task study (STARNET). Gene expression traits associated with CMD risk single-nucleotide polymorphism (SNPs) identified by GWAS were more extensively found in STARNET than in tissue- and disease-unspecific gene-tissue expression studies, indicating sharing of downstream cis-/trans-gene regulation across tissues and CMDs. In contrast, the regulatory effects of other GWAS risk SNPs were tissue-specific; abdominal fat emerged as an important gene-regulatory site for blood lipids, such as for the low-density lipoprotein cholesterol and coronary artery disease risk gene PCSK9 STARNET provides insights into gene-regulatory mechanisms for CMD risk loci, facilitating their translation into opportunities for diagnosis, therapy, and prevention. PMID:27540175

  9. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases.

    PubMed

    Franzén, Oscar; Ermel, Raili; Cohain, Ariella; Akers, Nicholas K; Di Narzo, Antonio; Talukdar, Husain A; Foroughi-Asl, Hassan; Giambartolomei, Claudia; Fullard, John F; Sukhavasi, Katyayani; Köks, Sulev; Gan, Li-Ming; Giannarelli, Chiara; Kovacic, Jason C; Betsholtz, Christer; Losic, Bojan; Michoel, Tom; Hao, Ke; Roussos, Panos; Skogsberg, Josefin; Ruusalepp, Arno; Schadt, Eric E; Björkegren, Johan L M

    2016-08-19

    Genome-wide association studies (GWAS) have identified hundreds of cardiometabolic disease (CMD) risk loci. However, they contribute little to genetic variance, and most downstream gene-regulatory mechanisms are unknown. We genotyped and RNA-sequenced vascular and metabolic tissues from 600 coronary artery disease patients in the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task study (STARNET). Gene expression traits associated with CMD risk single-nucleotide polymorphism (SNPs) identified by GWAS were more extensively found in STARNET than in tissue- and disease-unspecific gene-tissue expression studies, indicating sharing of downstream cis-/trans-gene regulation across tissues and CMDs. In contrast, the regulatory effects of other GWAS risk SNPs were tissue-specific; abdominal fat emerged as an important gene-regulatory site for blood lipids, such as for the low-density lipoprotein cholesterol and coronary artery disease risk gene PCSK9 STARNET provides insights into gene-regulatory mechanisms for CMD risk loci, facilitating their translation into opportunities for diagnosis, therapy, and prevention.

  10. Spatial Response of Epilithic Diatom Communities to Downstream Nutrient Increases.

    PubMed

    Schuch, Marilia; Oliveira, Maria Angelica; Lobo, Eduardo A

    2015-06-01

    To monitor water quality and investigate relationships between downstream nutrient increases and diatom communities in the Pardo River Basin, Brazil, water and diatom samples were collected between 2005 and 2009. There were significant differences in diatom community composition among all river zones, with the greatest differences found between the upper and lower reaches. Significant changes were detected in relative abundances of diatom species and spatial structuring was evident. Dissolved oxygen, phosphates, turbidity, Eicherichia coli, and total dissolved solids were the most important variables shaping diatom communities, characterizing an organic pollution and eutrophication gradient. However, the hypothesis of sensitive species prevailing upstream and their gradual downstream replacement for more tolerant species was not confirmed because shifts in relative abundances of the same group of species in both the upper and lower reaches of the rivers were identified. PMID:26459823

  11. Effects of bursty protein production on the noisy oscillatory properties of downstream pathways

    PubMed Central

    Toner, D. L. K.; Grima, R.

    2013-01-01

    Experiments show that proteins are translated in sharp bursts; similar bursty phenomena have been observed for protein import into compartments. Here we investigate the effect of burstiness in protein expression and import on the stochastic properties of downstream pathways. We consider two identical pathways with equal mean input rates, except in one pathway proteins are input one at a time and in the other proteins are input in bursts. Deterministically the dynamics of these two pathways are indistinguishable. However the stochastic behavior falls in three categories: (i) both pathways display or do not display noise-induced oscillations; (ii) the non-bursty input pathway displays noise-induced oscillations whereas the bursty one does not; (iii) the reverse of (ii). We derive necessary conditions for these three cases to classify systems involving autocatalysis, trimerization and genetic feedback loops. Our results suggest that single cell rhythms can be controlled by regulation of burstiness in protein production. PMID:23942456

  12. Dynamics of wakes downstream of wind turbine towers

    NASA Technical Reports Server (NTRS)

    Snyder, M. H.; Wentz, W. H., Jr.

    1981-01-01

    The near field wakes downstream of circular cylinders and of 12 sided cylinders were surveyed in a wind tunnel. Local velocity and velocity deficit diagrams are presented. The variation of turbulence in the wake was surveyed and the frequency of the periodic component of wake motion was determined. Differences between wakes of circular cylinders and of 12 sided cylinders are discussed. Also effects of strakes, orientation of the 12 sided cylinders, and rounding of the corners are noted.

  13. 15. Detail, lower chord connection point on downstream side, showing ...

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

    15. Detail, lower chord connection point on downstream side, showing pinned connection of lower chord eye bars, laced vertical compression member, diagonal eye bar tension members, turnbuckled diagonal counters, and floor beam. Note also timber floor stringers supported by floor beam, and exposed ends of timber deck members visible at left above lower chord eye bar. View to northwest. - Dry Creek Bridge, Spanning Dry Creek at Cook Road, Ione, Amador County, CA

  14. Results from modeling and simulation of chemical downstream etch systems

    SciTech Connect

    Meeks, E.; Vosen, S.R.; Shon, J.W.; Larson, R.S.; Fox, C.A.; Buchenauer

    1996-05-01

    This report summarizes modeling work performed at Sandia in support of Chemical Downstream Etch (CDE) benchmark and tool development programs under a Cooperative Research and Development Agreement (CRADA) with SEMATECH. The Chemical Downstream Etch (CDE) Modeling Project supports SEMATECH Joint Development Projects (JDPs) with Matrix Integrated Systems, Applied Materials, and Astex Corporation in the development of new CDE reactors for wafer cleaning and stripping processes. These dry-etch reactors replace wet-etch steps in microelectronics fabrication, enabling compatibility with other process steps and reducing the use of hazardous chemicals. Models were developed at Sandia to simulate the gas flow, chemistry and transport in CDE reactors. These models address the essential components of the CDE system: a microwave source, a transport tube, a showerhead/gas inlet, and a downstream etch chamber. The models have been used in tandem to determine the evolution of reactive species throughout the system, and to make recommendations for process and tool optimization. A significant part of this task has been in the assembly of a reasonable set of chemical rate constants and species data necessary for successful use of the models. Often the kinetic parameters were uncertain or unknown. For this reason, a significant effort was placed on model validation to obtain industry confidence in the model predictions. Data for model validation were obtained from the Sandia Molecular Beam Mass Spectrometry (MBMS) experiments, from the literature, from the CDE Benchmark Project (also part of the Sandia/SEMATECH CRADA), and from the JDP partners. The validated models were used to evaluate process behavior as a function of microwave-source operating parameters, transport-tube geometry, system pressure, and downstream chamber geometry. In addition, quantitative correlations were developed between CDE tool performance and operation set points.

  15. "No. 172. General view of the dam, looking downstream from ...

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

    "No. 172. General view of the dam, looking downstream from the east end. F.E.D. June, 1916." Compare this historic image, taken upon dam completion (1916), with current-condition photograph HAER CO-90-1. The dam retains a remarkable degree of integrity of design and setting - Grand Valley Diversion Dam, Half a mile north of intersection of I-70 & Colorado State Route 65, Cameo, Mesa County, CO

  16. Influence of sediment storage on downstream delivery of contaminated sediment

    USGS Publications Warehouse

    Malmon, D.V.; Reneau, S.L.; Dunne, T.; Katzman, D.; Drakos, P.G.

    2005-01-01

    Sediment storage in alluvial valleys can strongly modulate the downstream migration of sediment and associated contaminants through landscapes. Traditional methods for routing contaminated sediment through valleys focus on in-channel sediment transport but ignore the influence of sediment exchanges with temporary sediment storage reservoirs outside the channel, such as floodplains. In theory, probabilistic analysis of particle trajectories through valleys offers a useful strategy for quantifying the influence of sediment storage on the downstream movement of contaminated sediment. This paper describes a field application and test of this theory, using 137Cs as a sediment tracer over 45 years (1952-1997), downstream of a historical effluent outfall at the Los Alamos National Laboratory (LANL), New Mexico. The theory is parameterized using a sediment budget based on field data and an estimate of the 137Cs release history at the upstream boundary. The uncalibrated model reasonably replicates the approximate magnitude and spatial distribution of channel- and floodplain-stored 137Cs measured in an independent field study. Model runs quantify the role of sediment storage in the long-term migration of a pulse of contaminated sediment, quantify the downstream impact of upstream mitigation, and mathematically decompose the future 137Cs flux near the LANL property boundary to evaluate the relative contributions of various upstream contaminant sources. The fate of many sediment-bound contaminants is determined by the relative timescales of contaminant degradation and particle residence time in different types of sedimentary environments. The theory provides a viable approach for quantifying the long-term movement of contaminated sediment through valleys. Copyright 2005 by the American Geophysical Union.

  17. Heavy metals in sediments of Ganga River: up- and downstream urban influences

    NASA Astrophysics Data System (ADS)

    Pandey, Jitendra; Singh, Rachna

    2015-09-01

    Bottom sediment in a river often acts as a sink and indicator of changes in water column and magnitude of anthropogenic influences through air and watersheds. Heavy metal concentration in sediments of Ganga River was studied along a 37-km stretch to assess whether there is a significant difference between sites situated upstream and downstream of Varanasi urban core. Metal concentration increased consistently along the study gradient, indicating the influence of urban sources. Concentration in the river sediment was found highest for Fe followed by Mn, Zn, Cr, Cu, Ni, Pb, and Cd. Mann-Kendall trend analysis showed marked seasonality in the concentration with values being highest in summer and lowest in rainy season. Enrichment factor revealed severe enrichment of Cd and Pb at downstream sites, and principal component analysis segregated sites into four distinct groups indicating source relationships. Concentrations of Cd, Pb, Ni, Cu, and Cr did exceed WHO standards. The study has relevance designing control measures and action plans for reducing sediment contamination in anthropogenic impacted rivers.

  18. Localized electron heating and density peaking in downstream helicon plasma

    NASA Astrophysics Data System (ADS)

    Ghosh, Soumen; Barada, K. K.; Chattopadhyay, P. K.; Ghosh, J.; Bora, D.

    2015-06-01

    Localized electron temperature and density peaking at different axial locations in the downstream helicon plasma have been observed in a linear helicon device with both geometrical and magnetic expansion. The discharge is produced with an m=+1 right helical antenna powered by a RF source operating at 13.56 MHz. Axial wave field measurement shows the presence of damped helicon waves with standing wave character folded into it even at low densities (˜ {{10}16} m-3 ). The measured helicon wavelength is just about twice the antenna length and the phase velocity ≤ft({{v}p}\\right) is almost the speed required for electron impact ionization. These experimental observations strongly advocate the Landau damping heating and density production by the helicon waves, particularly in low density plasma such as ours. The electron temperature maximizes at 35-45 cm away from the antenna center in our experiments indicating a local source of heating at those locations. Different mechanisms responsible for this additional heating at a particular spatial location have been discussed for their possible roles. Further downstream from the location of the maximum electron temperature, a density peak located 55-65 cm away from the antenna is observed. This downstream density peaking can be explained through pressure balance in the system.

  19. Alfven waves and associated energetic ions downstream from Uranus

    NASA Astrophysics Data System (ADS)

    Zhang, M.; Belcher, J. W.; Richardson, J. D.; Smith, C. W.

    1991-02-01

    Low-frequency waves have been observed in the solar wind downstream from Uranus. These waves are observed by the Voyager spacecraft for more than 2 weeks after the encounter with Uranus and are present during this period whenever the interplanetary magnetic field is oriented such that field lines intersect the Uranian bow shock. The magnetic field and velocity components transverse to the background field are strongly correlated, consistent with the interpretation that these waves are Alfvenic and/or fast-mode waves. The waves appear to propagate along the magnetic field lines outward from Uranus and are right-hand polarized. Theory suggests that these waves are generated in the upstream region by a resonant instability with a proton beam streaming along the magnetic field lines. The solar wind subsequently carries these waves downstream to the spacecraft location. These waves are associated with the presence of energetic ions observed by the low-energy charged particle instrument. These ions appear two days after the start of the wave activity and occur thereafter whenever the Alfven waves occur, increasing in intensity away from Uranus. The ions are argued to originate in the Uranian magnetosphere, but pitch-angle scattering in the upstream region is required to bring them downstream to the spacecraft location.

  20. Mammalian TBX1 preferentially binds and regulates downstream targets via a tandem T-site repeat.

    PubMed

    Castellanos, Raquel; Xie, Qing; Zheng, Deyou; Cvekl, Ales; Morrow, Bernice E

    2014-01-01

    Haploinsufficiency or mutation of TBX1 is largely responsible for the etiology of physical malformations in individuals with velo-cardio-facial/DiGeorge syndrome (VCFS/DGS/22q11.2 deletion syndrome). TBX1 encodes a transcription factor protein that contains an evolutionarily conserved DNA binding domain termed the T-box that is shared with other family members. All T-box proteins, examined so far, bind to similar but not identical consensus DNA sequences, indicating that they have specific binding preferences. To identify the TBX1 specific consensus sequence, Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was performed. In contrast to other TBX family members recognizing palindrome sequences, we found that TBX1 preferentially binds to a tandem repeat of 5'-AGGTGTGAAGGTGTGA-3'. We also identified a second consensus sequence comprised of a tandem repeat with a degenerated downstream site. We show that three known human disease-causing TBX1 missense mutations (F148Y, H194Q and G310S) do not alter nuclear localization, or disrupt binding to the tandem repeat consensus sequences, but they reduce transcriptional activity in cell culture reporter assays. To identify Tbx1-downstream genes, we performed an in silico genome wide analysis of potential cis-acting elements in DNA and found strong enrichment of genes required for developmental processes and transcriptional regulation. We found that TBX1 binds to 19 different loci in vitro, which may correspond to putative cis-acting binding sites. In situ hybridization coupled with luciferase gene reporter assays on three gene loci, Fgf8, Bmper, Otog-MyoD, show that these motifs are directly regulated by TBX1 in vitro. Collectively, the present studies establish new insights into molecular aspects of TBX1 binding to DNA. This work lays the groundwork for future in vivo studies, including chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) to further elucidate the molecular

  1. SS1 (NAL1)- and SS2-Mediated Genetic Networks Underlying Source-Sink and Yield Traits in Rice (Oryza sativa L.).

    PubMed

    Xu, Jian-Long; Wang, Yun; Zhang, Fan; Wu, Yuan; Zheng, Tian-Qing; Wang, Yong-Hong; Zhao, Xiu-Qin; Cui, Yan-Ru; Chen, Kai; Zhang, Qiang; Lin, Hong-Xuan; Li, Jia-Yang; Li, Zhi-Kang

    2015-01-01

    Source leaf/sink capacity (SS) traits are important determinants of grain yield (GY) of rice. To understand the genetic basis of the SS relationship in rice, five SS and GY traits of rice were genetically dissected using two reciprocal introgression populations. Seventy-three QTL affecting the SS and GY traits were identified, most of which were detected in one of the parental genetic backgrounds (GBs). Two major QTL at bins 4.7 (SS1) and 3.12 (SS2) were associated consistently with all measured SS and yield traits in both GBs across two contrasting environments. Strong interactions between SS1/SS2 and the detected QTL led us to the discovery of genetic networks affecting the SS and GY traits. The SS1 acted as a regulator controlling two groups of downstream QTL affecting the source leaf width and grain number per panicle (GNP). SS2 functioned as a regulator positively regulating different groups of downstream QTL affecting the source leaf length, GNP, grain weight, and GY. Map-based cloning of SS1 indicates that SS1 is NAL1 involved in polar auxin/IAA transport. Different alleles at NAL1 were apparently able to qualitatively and/or quantitatively control the IAA transport from the apical meristem to different plant tissues and thus regulate those downstream loci/pathways controlling different SS traits of rice. There was a functional allele and a non-functional mutation in the parents at each of the QTL downstream of SS1 or SS2, which were detectable only in the presence of the functional allele of SS1 or SS2. Our results provided direct evidence that SS and yield traits in rice are controlled by complex signaling pathways and suggest further improvement of rice yield potential with enhanced and balanced SS relationships can be achieved by accurately manipulating allelic combinations at loci in the SS1 and SS2 mediated pathways.

  2. National Newborn Screening and Genetics Resource Center

    MedlinePlus

    ... GENERAL INFORMATION Conditions Screened by US Programs General Resources Genetics Birth Defects Hearing Screening FOR PROFESSIONALS ACT Sheets(ACMG) General Resources Newborn Screening Genetics Birth Defects FOR FAMILIES FAQs ...

  3. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist. PMID:27067213

  4. Alfven waves and associated energetic ions downstream from Uranus

    SciTech Connect

    Zhang, Ming; Belcher, J.W.; Richardson, J.D. ); Smith, C.W. )

    1991-02-01

    The authors report the observation of low-frequency waves in the solar wind downstream from Uranus. These waves are observed by the Voyager spacecraft for more than 2 weeks after the encounter with Uranus and are present during this period whenever the interplanetary magnetic field is oriented such that the field lines intersect the Uranian bow shock. The magnetic field and velocity components transverse to the background field are strongly correlated, consistent with the interpretation that these waves are Alfvenic and/or fast-mode waves. The waves have a spacecraft frame frequency of about 10{sup {minus}3} Hz, and when first observed near the bow shock have an amplitude comparable to the background field. As the spacecraft moves farther from Uranus, the amplitude decays. The waves appear to propagate along the magnetic field lines outward from Uranus and are right-hand polarized. Theory suggests that these waves are generated in the upstream region by a resonant instability with a proton beam streaming along the magnetic field lines. The solar wind subsequently carries these waves downstream to the spacecraft location. These waves are associated with the presence of energetic (> 28 keV) ions observed by the low-energy charged particle instrument. These ions appear two days after the start of the wave activity and occur thereafter whenever the Alfven waves occur, increasing in intensity away from Uranus. The ions are argued to originate in the Uranian magnetosphere, but pitch-angle scattering in the upstream region is required to bring them downstream to the spacecraft location.

  5. Growth Characteristics Downstream of a Shallow Bump: Computation and Experiment

    NASA Technical Reports Server (NTRS)

    Joslin, Ronald D.; Grosch, Chester E.

    1996-01-01

    Measurements of the velocity field created by a shallow bump on a wall revealed that an energy peak in the spanwise spectrum associated with the driver decays and an initially small-amplitude secondary mode rapidly grows with distance downstream of the bump. Linear theories could not provide an explanation for this growing mode. The present Navier-Stokes simulation replicates and confirms the experimental results. Insight into the structure of the flow was obtained from a study of the results of the calculations and is presented.

  6. Downstream System for the Second Axis of the DARHT Facility

    SciTech Connect

    Chen, Y-J; Bertolini, L; Caporaso, G J; Chambers, F W; Cook, E G; Falabella, S; Goldin, F J; Guethlein, G; Ho, D D-M; McCarrick, J F; Nelson, S D; Neurath, R; Paul, A C; Pincosy, P A; Poole, B R; Richardson, R A; Sampayan, S; Wang, L-F; Watson, J A; Westenskow, G A; Weir, J T

    2002-07-15

    This paper presents the physics design of the DARHT-II downstream system, which consists of a diagnostic beam stop, a fast, high-precision kicker system and the x-ray converter target assembly. The beamline configuration, the transverse resistive wall instability and the ion hose instability modeling are presented. They also discuss elimination of spot size dilution during kicker switching and implementation of the foil-barrier scheme to minimize the backstreaming ion focusing effects. Finally, they present the target converter's configuration, and the simulated DARHT-II x-ray spot sizes and doses. Some experimental results, which support the physics design, are also presented.

  7. Act resilient.

    PubMed

    Joseph, Genie; Bice-Stephens, Wynona

    2014-01-01

    Attendees have reported changing from being fearful to serene, from listless to energized, from disengaged to connected, and becoming markedly less anxious in a few weeks. Anecdotally, self-reported stress levels have been reduced by over 50% after just one class. Attendees learn not to be afraid of their feelings by working with emotions in a playful manner. When a person can act angry, but separate himself from his personal story, the emotional energy exists in a separate form that is not attached to specific events, and can be more easily dealt with and neutralized. Attendees are taught to "take out the emotional trash" through expressive comedy. They become less intimated by their own emotional intensity and triggers as they learn how even metaphorical buckets of anger, shame, guilt and hurt can be emotionally emptied. The added benefit is that this is accomplished without the disclosure of personal information of the requirement to reexperience past pain which can trigger its own cascade of stress. PMID:24706248

  8. Drosophila Fascin is a novel downstream target of prostaglandin signaling during actin remodeling.

    PubMed

    Groen, Christopher M; Spracklen, Andrew J; Fagan, Tiffany N; Tootle, Tina L

    2012-12-01

    Although prostaglandins (PGs)-lipid signals produced downstream of cyclooxygenase (COX) enzymes-regulate actin cytoskeletal dynamics, their mechanisms of action are unknown. We previously established Drosophila oogenesis, in particular nurse cell dumping, as a new model to determine how PGs regulate actin remodeling. PGs, and thus the Drosophila COX-like enzyme Pxt, are required for both the parallel actin filament bundle formation and the cortical actin strengthening required for dumping. Here we provide the first link between Fascin (Drosophila Singed, Sn), an actin-bundling protein, and PGs. Loss of either pxt or fascin results in similar actin defects. Fascin interacts, both pharmacologically and genetically, with PGs, as reduced Fascin levels enhance the effects of COX inhibition and synergize with reduced Pxt levels to cause both parallel bundle and cortical actin defects. Conversely, overexpression of Fascin in the germline suppresses the effects of COX inhibition and genetic loss of Pxt. These data lead to the conclusion that PGs regulate Fascin to control actin remodeling. This novel interaction has implications beyond Drosophila, as both PGs and Fascin-1, in mammalian systems, contribute to cancer cell migration and invasion.

  9. Initial PVO Evidence of Electron Depletion Signatures Downstream of Venus

    NASA Technical Reports Server (NTRS)

    Intriligator, D. S.; Hartle, R. E.; Perez-de-Tejada, H.; Siscoe, G. L.

    1993-01-01

    This first analysis of Pioneer Venus Orbiter (PVO) plasma analyzer electron measurements obtained in early 1992 during the PVO entry phase of the mission indicates the presence downstream from the terminator of a depletion or "bite out" of energetic ionosheath electrons similar to that observed on Mariner 10. There is more than one possible explanation for this energetic electron depletion. If it is due to atmospheric scattering, the electrons traveling along draped magnetic flux tubes that thread through the Venus neutral atmosphere would lose energy from impact ionization with oxygen. The cross-section for such electron impact ionization of oxygen has a peak near 100 eV, and it remains high above this energy, so atmospheric loss could provide a natural process for electrons at these energies to be selectively removed. In this case, our results are consistent with the Kar et al. (1994) study of PVO atmospheric entry ion mass spectrometer data which indicates that electron impact plays a significant role in maintaining the nightside ionosphere. Although it is appealing to interpret the energetic electron depletion in terms of direct atmospheric scattering, alternatively it could result from strong draping which connects the depletion region magnetically to the weak downstream bow shock and thereby reduces the electron source strength.

  10. Initial PVO evidence of electron depletion signatures downstream of Venus

    NASA Technical Reports Server (NTRS)

    Intriligator, D. S.; Hartle, R. E.; Perez-De-tejada, H.; Siscoe, G. L.

    1993-01-01

    This first analysis of Pioneer Venus Orbiter (PVO) plasma analyzer electron measurements obtained in early 1992 during teh PVO entry phase of the mission indicates the presence downstream from the terminator of a depletion or 'bite out' of energetic ionosheath electrons similar to that observed on Mariner 10. There is more than one possible explanation for this energetic electron depletion. If it is due to atmospheric scattering, the electrons traveling along draped magnetic flux tubes that thread through the Venus neutral atmosphere would lose energy from impact ionization with oxygen. The cross-section for such electron impact ionization of oxygen has a peak near 100 eV, and it remains high above this energy, so atmospheric loss could provde a natural process for electrons at these energies to be selectively removed. In this case, our results are consistent with the Kar et al. (1994) study of PVO atmospheric entry ion mass spectrometer data, which indicates that electron impact plays a significant role in maintaining the nightside ionosphere. Although it is appealing to interpret the energetic electron depletion in terms of direct atmospheric scattering, alternatively it could result from strong draping which connects the depletion region magnetically to the weak downstream bow shock and thereby reduces the electron source strength.

  11. Volumetric Velocity Fields Downstream of a 2-Bladed Turbine

    NASA Astrophysics Data System (ADS)

    Troolin, Daniel

    2013-11-01

    Tip vortices of axial-flow turbines are important in understanding the mean and turbulent characteristics of the wake. Volumetric 3-component velocimetry (V3V) was used to examine the flow downstream of a model two-bladed turbine in air. The turbine had a diameter of 177.8 mm and was powered by a motor operating at approximately 150 rpm. The measurement volume (50 × 50 × 20 mm) was positioned approximately 5 mm downstream of the blade tip, in order to examine the tip vortex structure. The V3V system utilized three 4MP cameras with 85 mm lenses positioned in a fixed triangular frame located at a distance of 450 mm from the back of the measurement volume. The illumination source was a 200 mJ dual-head pulsed Nd:YAG laser operating at 7.25 Hz and illuminating 1 micron olive oil droplets as tracer particles. The particle images were then analyzed to produce volumetric vector fields. The focus was placed on visualizing the complex interaction between the turbine tip vortices. Insights on the tip vortex dynamics and three dimensional characteristics of the wake flow will be discussed.

  12. Flow downstream of the heliospheric terminal shock. I - Irrotational flow

    NASA Technical Reports Server (NTRS)

    Suess, Steven T.; Nerney, Steven

    1990-01-01

    Recent reports of remote detection of the heliospheric terminal shock place it near 50 AU. These conflict with standard models which, when combined with current data on the local interstellar medium, place the shock beyod 100 AU. Resolution of this discrepancy has led to hypotheses that invoke cosmic ray pressure, momentum exchange with interstellar neutrals, and magnetic field effects between the shock and the contact discontinuity dividing the solar wind from interstellar plasma. These hypotheses depend not only on properties of the interstellar medium, but also on the downstream three-dimensional flow between the shock and the contact discontinuity, in the region called the 'heliosheath'. The downstream flow field in the absence of magnetic fields is examined here under the assumptions that the flow everywhere outside the shock can be approximated as irrotational and incompressible. It is found, in particular, that the distance between the terminal shock and the contact discontinuity is less than the heliocentric distance to the terminal shock, effectively eliminating magnetic field effects in the heliosheath as being dynamically important.

  13. Downstream processing of biopharmaceutical proteins produced in plants

    PubMed Central

    Buyel, Johannes Felix; Fischer, Rainer

    2014-01-01

    All biological platforms for the manufacture of biopharmaceutical proteins produce an initially turbid extract that must be clarified to avoid fouling sensitive media such as chromatography resins. Clarification is more challenging if the feed stream contains large amounts of dispersed particles, because these rapidly clog the filter media typically used to remove suspended solids. Charged polymers (flocculants) can increase the apparent size of the dispersed particles by aggregation, facilitating the separation of solids and liquids, and thus reducing process costs. However, many different factors can affect the behavior of flocculants, including the pH and conductivity of the medium, the size and charge distribution of the particulates, and the charge density and molecular mass of the polymer. Importantly, these properties can also affect the recovery of the target protein and the overall safety profile of the process. We therefore used a design of experiments approach to establish reliable predictive models that characterize the impact of flocculants during the downstream processing of biopharmaceutical proteins. We highlight strategies for the selection of flocculants during process optimization. These strategies will contribute to the quality by design aspects of process development and facilitate the development of safe and efficient downstream processes for plant-derived pharmaceutical proteins. PMID:24637706

  14. Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors

    PubMed Central

    Karlsson, Hannah; Svensson, Emma; Gigg, Camilla; Jarvius, Malin; Olsson-Strömberg, Ulla; Savoldo, Barbara; Dotti, Gianpietro; Loskog, Angelica

    2015-01-01

    CD19-targeting CAR T cells have shown potency in clinical trials targeting B cell leukemia. Although mainly second generation (2G) CARs carrying CD28 or 4-1BB have been investigated in patients, preclinical studies suggest that third generation (3G) CARs with both CD28 and 4-1BB have enhanced capacity. However, little is known about the intracellular signaling pathways downstream of CARs. In the present work, we have analyzed the signaling capacity post antigen stimulation in both 2G and 3G CARs. 3G CAR T cells expanded better than 2G CAR T cells upon repeated stimulation with IL-2 and autologous B cells. An antigen-driven accumulation of CAR+ cells was evident post antigen stimulation. The cytotoxicity of both 2G and 3G CAR T cells was maintained by repeated stimulation. The phosphorylation status of intracellular signaling proteins post antigen stimulation showed that 3G CAR T cells had a higher activation status than 2G. Several proteins involved in signaling downstream the TCR were activated, as were proteins involved in the cell cycle, cell adhesion and exocytosis. In conclusion, 3G CAR T cells had a higher degree of intracellular signaling activity than 2G CARs which may explain the increased proliferative capacity seen in 3G CAR T cells. The study also indicates that there may be other signaling pathways to consider when designing or evaluating new generations of CARs. PMID:26700307

  15. Ferric chloride based downstream process for microalgae based biodiesel production.

    PubMed

    Seo, Yeong Hwan; Sung, Mina; Kim, Bohwa; Oh, You-Kwan; Kim, Dong Yeon; Han, Jong-In

    2015-04-01

    In this study, ferric chloride (FeCl3) was used to integrate downstream processes (harvesting, lipid extraction, and esterification). At concentration of 200 mg/L and at pH 3, FeCl3 exhibited an expected degree of coagulation and an increase in cell density of ten times (170 mg/10 mL). An iron-mediated oxidation reaction, Fenton-like reaction, was used to extract lipid from the harvested biomass, and efficiency of 80% was obtained with 0.5% H2O2 at 90 °C. The iron compound was also employed in the esterification step, and converted free fatty acids to fatty acid methyl esters under acidic conditions; thus, the fatal problem of saponification during esterification with alkaline catalysts was avoided, and esterification efficiency over 90% was obtained. This study clearly showed that FeCl3 in the harvesting process is beneficial in all downstream steps and have a potential to greatly reduce the production cost of microalgae-originated biodiesel.

  16. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  17. Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways.

    PubMed

    Meyers, J L; Salling, M C; Almli, L M; Ratanatharathorn, A; Uddin, M; Galea, S; Wildman, D E; Aiello, A E; Bradley, B; Ressler, K; Koenen, K C

    2015-01-01

    Rodent models implicate metabotropic glutamate receptors (mGluRs) and downstream signaling pathways in addictive behaviors through metaplasticity. One way mGluRs can influence synaptic plasticity is by regulating the local translation of AMPA receptor trafficking proteins via eukaryotic elongation factor 2 (eEF2). However, genetic variation in this pathway has not been examined with human alcohol use phenotypes. Among a sample of adults living in Detroit, Michigan (Detroit Neighborhood Health Study; n = 788; 83% African American), 206 genetic variants across the mGluR-eEF2-AMPAR pathway (including GRM1, GRM5, HOMER1, HOMER2, EEF2K, MTOR, EIF4E, EEF2, CAMK2A, ARC, GRIA1 and GRIA4) were found to predict number of drinking days per month (corrected P-value < 0.01) when considered as a set (set-based linear regression conducted in PLINK). In addition, a CpG site located in the 3'-untranslated region on the north shore of EEF2 (cg12255298) was hypermethylated in those who drank more frequently (P < 0.05). Importantly, the association between several genetic variants within the mGluR-eEF2-AMPAR pathway and alcohol use behavior (i.e., consumption and alcohol-related problems) replicated in the Grady Trauma Project (GTP), an independent sample of adults living in Atlanta, Georgia (n = 1034; 95% African American), including individual variants in GRM1, GRM5, EEF2, MTOR, GRIA1, GRIA4 and HOMER2 (P < 0.05). Gene-based analyses conducted in the GTP indicated that GRM1 (empirical P < 0.05) and EEF2 (empirical P < 0.01) withstood multiple test corrections and predicted increased alcohol consumption and related problems. In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR-eEF2-AMPAR pathway. PMID:26101849

  18. Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways

    PubMed Central

    Meyers, J L; Salling, M C; Almli, L M; Ratanatharathorn, A; Uddin, M; Galea, S; Wildman, D E; Aiello, A E; Bradley, B; Ressler, K; Koenen, K C

    2015-01-01

    Rodent models implicate metabotropic glutamate receptors (mGluRs) and downstream signaling pathways in addictive behaviors through metaplasticity. One way mGluRs can influence synaptic plasticity is by regulating the local translation of AMPA receptor trafficking proteins via eukaryotic elongation factor 2 (eEF2). However, genetic variation in this pathway has not been examined with human alcohol use phenotypes. Among a sample of adults living in Detroit, Michigan (Detroit Neighborhood Health Study; n=788; 83% African American), 206 genetic variants across the mGluR–eEF2–AMPAR pathway (including GRM1, GRM5, HOMER1, HOMER2, EEF2K, MTOR, EIF4E, EEF2, CAMK2A, ARC, GRIA1 and GRIA4) were found to predict number of drinking days per month (corrected P-value <0.01) when considered as a set (set-based linear regression conducted in PLINK). In addition, a CpG site located in the 3′-untranslated region on the north shore of EEF2 (cg12255298) was hypermethylated in those who drank more frequently (P<0.05). Importantly, the association between several genetic variants within the mGluR–eEF2–AMPAR pathway and alcohol use behavior (i.e., consumption and alcohol-related problems) replicated in the Grady Trauma Project (GTP), an independent sample of adults living in Atlanta, Georgia (n=1034; 95% African American), including individual variants in GRM1, GRM5, EEF2, MTOR, GRIA1, GRIA4 and HOMER2 (P<0.05). Gene-based analyses conducted in the GTP indicated that GRM1 (empirical P<0.05) and EEF2 (empirical P<0.01) withstood multiple test corrections and predicted increased alcohol consumption and related problems. In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR–eEF2–AMPAR pathway. PMID:26101849

  19. A simple feature construction method for predicting upstream/downstream signal flow in human protein-protein interaction networks

    PubMed Central

    Mei, Suyu; Zhu, Hao

    2015-01-01

    Signaling pathways play important roles in understanding the underlying mechanism of cell growth, cell apoptosis, organismal development and pathways-aberrant diseases. Protein-protein interaction (PPI) networks are commonly-used infrastructure to infer signaling pathways. However, PPI networks generally carry no information of upstream/downstream relationship between interacting proteins, which retards our inferring the signal flow of signaling pathways. In this work, we propose a simple feature construction method to train a SVM (support vector machine) classifier to predict PPI upstream/downstream relations. The domain based asymmetric feature representation naturally embodies domain-domain upstream/downstream relations, providing an unconventional avenue to predict the directionality between two objects. Moreover, we propose a semantically interpretable decision function and a macro bag-level performance metric to satisfy the need of two-instance depiction of an interacting protein pair. Experimental results show that the proposed method achieves satisfactory cross validation performance and independent test performance. Lastly, we use the trained model to predict the PPIs in HPRD, Reactome and IntAct. Some predictions have been validated against recent literature. PMID:26648121

  20. A Hydraulic Nexus between Geographically Isolated Wetlands and Downstream Water Bodies

    NASA Astrophysics Data System (ADS)

    Mclaughlin, D. L.; Kaplan, D. A.; Cohen, M. J.

    2014-12-01

    Geographic isolation does not imply hydrological isolation; indeed, local groundwater exchange between geographically isolated wetlands (GIWs) and surrounding uplands may yield important controls on regional hydrology. Differences in specific yield (Sy) between aquifers and inundated GIWs drive differences in water level responses to atmospheric fluxes, leading to frequent reversals in hydraulic gradients that cause GIWs to act as both groundwater sinks and sources. When distributed across the landscape, these reversals in local groundwater fluxes are predicted to collectively buffer the surficial aquifer and its regulation of baseflow delivery, a process we refer to as landscape hydrologic capacitance. To test this hypothesis, we integrated models of daily soil moisture, upland water table, and wetland stage dynamics to simulate hydrology of a low-relief landscape with GIWs. Simulations explored the influences of cumulative wetland area, individual wetland size, climate, and soil texture on water table and baseflow variation. Increasing cumulative wetland area and decreasing individual wetland size reduced water table variation and the frequency of extremely shallow and deep water tables. This buffering effect extended to baseflow deliveries, decreasing the standard deviation of daily baseflow by as much as 50%. For the same total wetland area, landscapes with fewer (i.e., larger) wetlands exhibited markedly lower hydrologic capacitance than those with more (i.e., smaller) wetlands, highlighting the important role of small GIWs in regulating regional hydrology. Recent U.S. Supreme Court rulings have limited federal protections for GIWs except where a "significant nexus" to a navigable water body is demonstrated. Our results suggest that GIWs regulate downstream baseflow, even where water in GIWs may never physically reach downstream systems, providing a significant "hydraulic" nexus to distant water bodies.

  1. 7. OBLIQUE VIEW OF NORTH PORTAL AND DOWNSTREAM SIDE OF ...

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

    7. OBLIQUE VIEW OF NORTH PORTAL AND DOWNSTREAM SIDE OF BRIDGE, LOOKING WEST. Lights and illuminated sign on portal bracing were elements of an overheight load warning system designed to eliminate accidents of the type which damaged the bridge. However, the system was in place only on the north side of the bridge, controlling trucks approaching from Oregon. In theory, trucks with overheight, overwidth, or overweight loads from California would be controlled by the State's permit system. In fact, it was a 'permit' load originating in California, being hauled without the requisite permit which struck and damaged the bridge. - Smith River Bridge, CA State Highway 199 Spanning Smith River, Crescent City, Del Norte County, CA

  2. Plasma turbulence in the downstream ionosheath of Venus

    NASA Technical Reports Server (NTRS)

    Intriligator, D. S.; Scarf, F. L.

    1982-01-01

    Observations made by the Pioneer Venus Orbiter plasma analyzer and the plasma wave instrument in the Venus ionosheath are compared. Large increases in plasma wave turbulence levels appear to be connected with changing plasma distributions and interpenetrating plasma beams. Some of these plasma waves are identified as Doppler - shifted ion acoustic waves due to beam/beam interactions, but it is noted that different forms of instabilities are probably also operative. The changes in the temperature, intensity and energy of the peak in the PVO plasma distributions are similar to those observed by Venera 10 closer to the planet and appear to be evidence for rarefaction and compression in the downstream ionosheath. Some of the changes in the PVO plasma distributions may be related to the presence of a second ion population or the acceleration of protons.

  3. Downstream properties of magnetic flux transfer events. [in magnetosphere

    NASA Technical Reports Server (NTRS)

    Sibeck, D. G.; Siscoe, G. L.

    1984-01-01

    Attention is given to the downstream evolution of the field line tubes known as 'flux transfer events' (FTEs), whose magnetic field and plasma properties are distinct from those of the nearby unmerged magnetosheath and magnetosphere field lines. After the FTE has moved 200 earth radii down the tail, its drained portion reaches 25 earth radii radially outward from the tail boundary. It is suggested that most multiple crossings of the tail boundary observed by spacecraft are encounters with tailward-moving FTEs, thereby explaining both the behavior of boundary normals during multiple crossings and how the sign of the IMF causes the observed dawn-dusk asymmetries in the thickness of the magnetotail boundary layer.

  4. Plasma fluctuations in the magnetosheath downstream from Uranus

    NASA Technical Reports Server (NTRS)

    Richardson, John D.; Zhang, Ming; Belcher, John W.; Siscoe, George L.

    1990-01-01

    The Voyager plasma experiment observed large-amplitude plasma fluctuations in the Uranian magnetosheat downstream from the planet. This is a region that has not been well sampled in the earth's magnetosphere. These waves have periods of tens of minutes, are characterized by an anticorrelation between the plasma density and temperature, and are associated with deflections in the flow angle of the plasma. These fluctuations are observed only in regions where the magnetic field is rapidly varying. These waves have time and distance scales placing them in the MHD regime, but their characteristics are not compatible with any known solution of the MHD equations. It is suggested that these fluctuations are produced by the solar wind interaction with the magnetosphere at the bow shock, but the physics governing the production and propagation of these fluctuations is not understood.

  5. Tone generation by rotor-downstream strut interaction

    NASA Technical Reports Server (NTRS)

    Woodward, R. P.; Balombin, J. R.

    1983-01-01

    A JT15D fan stage was acoustically tested in the NASA Lewis anechoic chamber as part of the joint Lewis-Langley Research Center investigation of flight simulation techniques and flight effects using the JT15D engine as a common test vehicle. Suspected rotor-downstream support strut interaction was confirmed through the use of simulated support struts which were tested at three axial rotor-strut spacings. Tests were also performed with the struts removed. Inlet boundary layer suction in conjuction with an inflow control device was also explored. The removal of the boundary layer reduced the fan fundamental tone levels suggesting that the mounting and mating of such a device to the nacelle requires careful attention. With the same inflow control device installed good acoustic agreement was shown between the engine on an outdoor test stand and the fan in the anechoic chamber.

  6. Tone generation by rotor-downstream strut interaction

    NASA Technical Reports Server (NTRS)

    Woodward, R. P.; Balombin, J. R.

    1983-01-01

    A JT15D fan stage was acoustically tested in the NASA Lewis anechoic chamber as part of the joint Lewis-Langley Research Center investigation of flight simulation techniques and flight effects using the JT15D engine as a common test vehicle. Suspected rotor-downstream support strut interaction was confirmed through the use of simulated support struts which were tested at three axial rotor-strut spacings. Tests were also performed with the struts removed. Inlet boundary layer suction in conjunction with an inflow control device was also explored. The removal of the boundary layer reduced the fan fundamental tone levels suggesting that the mounting and mating of such a device to the nacelle requires careful attention. With the same inflow control device installed good acoustic agreement was shown between the engine on an outdoor test stand and the fan in the anechoic chamber.

  7. Optical radiation from regions downstream of mercury bombardment thrusters

    NASA Technical Reports Server (NTRS)

    Milder, N. L.; Sovey, J. S.

    1972-01-01

    A 0.5 meter focal length, plane grating monochromator was used to measure the radiance of spectral radiation emanating from regions downstream of a mercury bombardment thruster. The wavelength range investigated was 2800 A. This radiation was due primarily to the radiative decay of excited mercury atoms exhausted from the thruster. Radiance values ranged from 10 to the minus 11th power to 10 to the minus 9th power W/sq cm sr, varying with wavelength. For resonant radiation, the spectral radiance may exceed 10 to the minus 8th power W/sq cm sr. From such radiance measurements, it was concluded that the thruster background radiation should not interfere with the control functions of a star tracker viewing through the thruster exhaust, provided that the tracker is designed to operate with a sufficiently small field of view.

  8. Plasma fluctuations in the magnetosheath downstream from Uranus

    NASA Astrophysics Data System (ADS)

    Richardson, J. D.; Zhang, M.; Belcher, J. W.; Siscoe, G. L.

    1990-05-01

    The Voyager plasma experiment observed large-amplitude plasma fluctuations in the Uranian magnetosheat downstream from the planet. This is a region that has not been well sampled in the earth's magnetosphere. These waves have periods of tens of minutes, are characterized by an anticorrelation between the plasma density and temperature, and are associated with deflections in the flow angle of the plasma. These fluctuations are observed only in regions where the magnetic field is rapidly varying. These waves have time and distance scales placing them in the MHD regime, but their characteristics are not compatible with any known solution of the MHD equations. It is suggested that these fluctuations are produced by the solar wind interaction with the magnetosphere at the bow shock, but the physics governing the production and propagation of these fluctuations is not understood.

  9. Ethiopia's Grand Renaissance Dam: Implications for Downstream Riparian Countries

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Block, P. J.; Hammond, M.; King, A.

    2013-12-01

    Ethiopia has begun seriously developing their significant hydropower potential by launching construction of the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile River to facilitate local and regional growth. Although this has required substantial planning on Ethiopia's part, no policy dictating the reservoir filling rate strategy has been publicly issued. This filling stage will have clear implications on downstream flows in Sudan and Egypt, complicated by evaporative losses, climate variability, and climate change. In this study, various filling policies and future climate states are simultaneously explored to infer potential streamflow reductions at Lake Nasser, providing regional decision-makers with a set of plausible, justifiable, and comparable outcomes. Schematic of the model framework Box plots of 2017-2032 percent change in annual average streamflow at Lake Nasser for each filling policy constructed from the 100 time-series and weighted precipitation changes. All values are relative to the no dam policy and no changes to future precipitation.

  10. Progesterone and its downstream molecules as blastocyst implantation essential factors.

    PubMed

    Yoshinaga, Koji

    2014-08-01

    This review is to update the previous review (Am J Reprod Immunol, 63, 2010 and 413) on the research on blastocyst implantation essential factors (BIEFs). Focus of the current review is on progesterone and its downstream molecules in the process of blastocyst implantation. To understand the process of implantation, we need to know where and when the BIEFs are expressed and what they do. Progress in this research area is rapid, and its update is indeed necessary. The basic concept of BIEFs is that they have dual functions, one physiological and the other immunological (J Reprod Dev, 58, 2012 and 196). As we are still exploring the mechanism of implantation, available data are incomplete and human data are few. Thus, I will use information obtained through research on animal models, in vitro studies, cell lines, and some human studies where available. The ultimate goal of the review is to understand human blastocyst implantation. PMID:24754263

  11. Continuous downstream processing for high value biological products: A Review.

    PubMed

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations. PMID:26153056

  12. Operating multireservoir hydropower systems for downstream water quality

    SciTech Connect

    Hayes, D.F.

    1990-01-01

    Hydropower reservoir operations often impact tailwater quality and water quality in the stream or river below the impoundment for many miles. Determining optimal operating strategies for a system of hydropower reservoirs involves solving a highly dimensional nonlinear, nonconvex optimization problem. This research adds the additional complexities of downstream water quality considerations within the optimization formulation to determine operating strategies for a system of hydropower reservoirs operating in series (tandem) or parallel. The formulation was used to determine operating strategies for six reservoirs of the upper Cumberland river basin in Tennessee and Kentucky. Significant dissolved oxygen (DO) violations occur just upstream of Nashville, Tennessee below Old Hickory dam during the months of August and September. Daily reservoir releases were determined for the period of June through September which would produce the maximum hydropower revenue while meeting downstream water quality objectives. Optimal releases for three operational strategies were compared to historical operations for the years 1985, 1986, and 1988. These strategies included: spilling as necessary to meet water quality criteria, near normal operation (minimal spills), and drawdown of reservoirs as necessary to meet criteria without spills. Optimization results showed an 8% to 15% hydropower loss may be necessary to meet water quality criteria through spills and a 2% to 9% improvement in DO below Old Hickory may be possible without significant spills. Results also showed that substantial increases in initial headwater elevations would be necessary to meet daily DO criteria and avoid spills. The optimal control theory algorithm used to solve the problem proved to be an efficient and robust solver of this large optimization problem.

  13. Serine-71 phosphorylation of Rac1 modulates downstream signaling.

    PubMed

    Schwarz, Janett; Proff, Julia; Hävemeier, Anika; Ladwein, Markus; Rottner, Klemens; Barlag, Britta; Pich, Andreas; Tatge, Helma; Just, Ingo; Gerhard, Ralf

    2012-01-01

    The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-71 phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1 and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to selected effector proteins. Binding of the constitutively active (Q61L) variants of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP, respectively, as well as to their common effector protein PAK was abrogated when Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly affected. This ambivalent behaviour was obvious in functional assays. In contrast to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF-kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at serine-71 represents a reversible mechanism to shift specificity of GTPase/effector coupling, and to preferentially address selected downstream pathways. PMID:22970203

  14. A Copernicus downstream service for surface displacement monitoring in Germany

    NASA Astrophysics Data System (ADS)

    Cahyadi Kalia, Andre; Frei, Michaela; Lege, Thomas

    2016-04-01

    SAR Interferometry is a powerful technique able to detect and monitor various surface displacements caused by e.g. gravitative mass movement, subrosion, groundwater extraction, fluid injection, natural gas extraction. These processes can e.g. cause damage to buildings, infrastructure, affect ecosystems, agriculture and the economic use of the geological underground by influencing the hydro(geo)logical setting. Advanced techniques of interferometric processing (Persistent Scatterer Interferometry, PSI) allow highly precise displacement measurements (mm precision) by analyzing stacks of SAR imagery. The PSI mapping coverage can be increased to entire nations by using several adjacent satellite tracks. In order to assist the operational use of this technique a German-wide, officially approved, PSI dataset is under development. The intention of this presentation is to show i) the concept of the Copernicus downstream service for surface displacement monitoring in Germany and ii) a pilot study to exemplarily demonstrate the workflow and potential products from the Copernicus downstream service. The pilot study is focusing on the built up of an officially approved wide-area PSI dataset. The study area covers an area of more than 30.000 km² and is located in the Northwest German Basin. Several natural processes (e.g. compaction of marine sediments, peat loss) and anthropogenic activities (e.g. natural gas extraction, rock salt mining) are causing surface displacements in the study area. The PSI analysis is based on six ERS-1/-2 data stacks covering the timespan from 1992 until 2001. Each data stack consists of 49 to 73 ERS-1/-2 SAR images. A comparison of the PSI results with thematic data (e.g. volume and location of extracted natural gas) strongly indicates that a part of the detected land subsidence is caused by natural gas extraction. Furthermore, land subsidence caused by e.g. fluid injection and rock salt mining were successfully detected by the PSI analysis.

  15. Downstream cumulative effects of land use on freshwater communities

    NASA Astrophysics Data System (ADS)

    Kuglerová, L.; Kielstra, B. W.; Moore, D.; Richardson, J. S.

    2015-12-01

    Many streams and rivers are subject to disturbance from intense land use such as urbanization and agriculture, and this is especially obvious for small headwaters. Streams are spatially organized into networks where headwaters represent the tributaries and provide water, nutrients, and organic material to the main stems. Therefore perturbations within the headwaters might be cumulatively carried on downstream. Although we know that the disturbance of headwaters in urban and agricultural landscapes poses threats to downstream river reaches, the magnitude and severity of these changes for ecological communities is less known. We studied stream networks along a gradient of disturbance connected to land use intensity, from urbanized watersheds to watersheds placed in agricultural settings in the Greater Toronto Area. Further, we compared the patterns and processes found in the modified watershed to a control watershed, situated in a forested, less impacted landscape. Preliminary results suggest that hydrological modifications (flash floods), habitat loss (drainage and sewer systems), and water quality issues of small streams in urbanized and agricultural watersheds represent major disturbances and threats for aquatic and riparian biota on local as well as larger spatial scales. For example, communities of riparian plants are dominated by species typical of the land use on adjacent uplands as well as the dominant land use on the upstream contributing area, instead of riparian obligates commonly found in forested watersheds. Further, riparian communities in disturbed environments are dominated by invasive species. The changes in riparian communities are vital for various functions of riparian vegetation. Bank erosion control is suppressed, leading to severe channel transformations and sediment loadings in urbanized watersheds. Food sources for instream biota and thermal regimes are also changed, which further triggers alterations of in-stream biological communities

  16. Evolutionary behavioral genetics

    PubMed Central

    Zietsch, Brendan P.; de Candia, Teresa R; Keller, Matthew C.

    2014-01-01

    We describe the scientific enterprise at the intersection of evolutionary psychology and behavioral genetics—a field that could be termed Evolutionary Behavioral Genetics—and how modern genetic data is revolutionizing our ability to test questions in this field. We first explain how genetically informative data and designs can be used to investigate questions about the evolution of human behavior, and describe some of the findings arising from these approaches. Second, we explain how evolutionary theory can be applied to the investigation of behavioral genetic variation. We give examples of how new data and methods provide insight into the genetic architecture of behavioral variation and what this tells us about the evolutionary processes that acted on the underlying causal genetic variants. PMID:25587556

  17. Efficient transcription from the rice tungro bacilliform virus promoter requires elements downstream of the transcription start site.

    PubMed Central

    Chen, G; Rothnie, H M; He, X; Hohn, T; Fütterer, J

    1996-01-01

    Elements downstream of the transcription start site enhance the activity of the rice tungro bacilliform virus (RTBV) promoter in protoplasts derived from cultured rice cells. This enhancer region was located to the first 90 nucleotides of the RTBV leader sequence. Within this region, at least two components which act together to enhance expression from the RTBV promoter could be identified. One is a position- and orientation-independent DNA element within a CT-rich region, and the other is a position-dependent element. Either element was found to be capable of acting independently on a heterologous promoter. The enhancer activity of the DNA element correlates with specific binding of nuclear proteins. Nuclear proteins also recognize an RNA transcript covering the first 90 nucleotides of the RTBV leader. PMID:8970962

  18. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  19. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  20. Nek7 is an essential mediator of NLRP3 activation downstream of potassium efflux

    PubMed Central

    He, Yuan; Zeng, Melody Y.; Yang, Dahai; Motro, Benny; Núñez, Gabriel

    2016-01-01

    Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases1. To date, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor ASC to activate caspase-1, leading to the secretion of mature IL-1β and IL-182,3. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases4,5 as well as Cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations6,7. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by multiple stimuli8,9. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. We report here the identification of Nek7, a member of the family of mammalian NIMA-related kinases (Neks)10, as an NLRP3-binding protein that acts downstream of potassium efflux to regulate NLRP3 oligomerization and activation. In the absence of Nek7, caspase-1 activation and IL-1β release were abrogated in response to signals that activate NLRP3, but not NLRC4 or AIM2 inflammasome. NLRP3-activating stimuli promoted the NLRP3-Nek7 interaction in a process dependent on potassium efflux. NLRP3 associated with the catalytic domain of Nek7, but the catalytic activity of Nek7 was dispensable for activation of the NLRP3 inflammasome. Activated macrophages formed a high-molecular-mass NLRP3-Nek7 complex, which along with ASC oligomerization and ASC speck formation were abrogated in the absence of Nek7. Nek7 was required for macrophages harboring the CAPS-associated NLRP3R258W activating mutation to activate caspase-1. Mouse chimeras reconstituted with wild-type, Nek7−/− or Nlrp3−/− hematopoietic cells revealed that Nek7 was required for NLRP3 inflammasome activation in vivo. These studies demonstrate that Nek7 is an essential protein that acts downstream of potassium efflux to mediate NLRP3 inflammasome

  1. Issue Backgrounder : Downstream Fish Migration : Improving the Odds of Survival.

    SciTech Connect

    United States. Bonneville Power Administration.

    1985-05-01

    Background information is given on the problems caused to anadromous fish migrations, especially salmon and steelhead trout, by the development of hydroelectric power dams on the Columbia River and its tributaries. Programs arising out of the Pacific Northwest Electric Power Planning and conservation Act of 1980 to remedy these problems and restore fish and wildlife populations are described. (ACR)

  2. Electron acceleration at nearly perpendicular collisionless shocks. 3: Downstream distributions

    NASA Technical Reports Server (NTRS)

    Krauss-Varban, D.

    1994-01-01

    Spacecraft observations at the Earth's bow shock and at interplanetary shocks have established that the largest fluxes of accelerated suprathermal electrons occur in so-called shock spike events immediately downstream of the shock ramp. Previous theoretical efforts have mainly focused on explaining upstream energetic electron beams. Here we investigate the general motion and acceleration of energetic electrons in a curved, nearly perpendicular shock by numerically integrating the orbits of solar wind halo electrons in shock fields generated by a hybrid simulation (core electron fluid and kinetic ions). Close to the angle Theta(sub Bn) = 90 degs between the upstream magnetic field and shock normal, the calculations result in a (perpendicular) temperature increase proportional to the magnetic field ratio and give the highest phase space densities in the overshoot. For a steep distribution, the temperature change can correspond to an enhancement of the distribution by several orders of magnitude. These results are in agreement with predictions from adiabatic mapping. With smaller angles Theta(sub Bn), the overshoot and downstream densities fall off quickly, because the adiabatic energy gain is less and fewer electrons transmit. The shock curvature also leads to an accumulation of electrons close to 90 degs. Without pitch angle scattering, energization is only significant within a few (approximately 5 to 10 degs) degrees of the point of tangency. However, shock spike events appear to be observed more easily and farther away from 90 degs. Given that over a region of several degrees around 90 degs the theory gives enhancements of up to approximately 4 orders of magnitude, such electrons could in principle account for the typically observed enhancements of 1 to 2 orders of magnitude, if they were distributed over Theta(sub Bn). To test the idea that scattering could efficiently redistribute the energetic electrons, we have conducted test particle simulations in which

  3. Corrosion impact of reductant on DWPF and downstream facilities

    SciTech Connect

    Mickalonis, J. I.; Imrich, K. J.; Jantzen, C. M.; Murphy, T. H.; Wilderman, J. E.

    2014-12-01

    Glycolic acid is being evaluated as an alternate reductant in the preparation of high level waste for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). During processing, the glycolic acid is not completely consumed and small quantities of the glycolate anion are carried forward to other high level waste (HLW) facilities. The impact of the glycolate anion on the corrosion of the materials of construction throughout the waste processing system has not been previously evaluated. A literature review had revealed that corrosion data in glycolate-bearing solution applicable to SRS systems were not available. Therefore, testing was recommended to evaluate the materials of construction of vessels, piping and components within DWPF and downstream facilities. The testing, conducted in non-radioactive simulants, consisted of both accelerated tests (electrochemical and hot-wall) with coupons in laboratory vessels and prototypical tests with coupons immersed in scale-up and mock-up test systems. Eight waste or process streams were identified in which the glycolate anion might impact the performance of the materials of construction. These streams were 70% glycolic acid (DWPF feed vessels and piping), SRAT/SME supernate (Chemical Processing Cell (CPC) vessels and piping), DWPF acidic recycle (DWPF condenser and recycle tanks and piping), basic concentrated recycle (HLW tanks, evaporators, and transfer lines), salt processing (ARP, MCU, and Saltstone tanks and piping), boric acid (MCU separators), and dilute waste (HLW evaporator condensate tanks and transfer line and ETF components). For each stream, high temperature limits and worst-case glycolate concentrations were identified for performing the recommended tests. Test solution chemistries were generally based on analytical results of actual waste samples taken from the various process facilities or of prototypical simulants produced in the laboratory. The materials of construction for most vessels

  4. New Genetics

    MedlinePlus

    ... human genome, behavioral genetics, pharmacogenetics, drug resistance, biofilms, computer modeling. » more Chapter 5: 21st-Century Genetics Covers systems biology, GFP, genetic testing, privacy concerns, DNA forensics, ...

  5. Genetic Counseling

    MedlinePlus

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  6. Genetic Counseling

    MedlinePlus

    ... Articles Genetic Counseling Information For... Media Policy Makers Genetic Counseling Language: English Español (Spanish) Recommend on Facebook ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  7. Wake Vortices and Tropical Cyclogenesis Downstream of Sumatra over the Indian Ocean

    NASA Astrophysics Data System (ADS)

    Fine, Caitlin Marie

    A myriad of processes acting singly or in concert may contribute to tropical cyclogenesis, including convectively coupled waves, breakdown of the inter-tropical convergence zone (ITCZ), or upper-level troughs. This thesis investigates the role that topographic effects from the island of Sumatra may play in initiating tropical cyclogenesis (TC genesis) in the eastern Indian Ocean. If easterly flow is split by the mountains of Sumatra, counter-rotating lee vortices may form downstream. Because Sumatra straddles the equator, though the wake vortices rotate in opposite directions, they will both be cyclonic when winds are easterly upon Sumatra, and may intensify further into tropical cyclones. The phenomenon of crossequatorial cyclone pairs, or "twin" tropical cyclones, in the Indian Ocean originating from Sumatra was first noted by Kuettner (1989). TC genesis appears to be particularly favored during the pre-onset phase of the Madden Julian Oscillation (MJO), when easterly flow encroaches upon Sumatra and the resulting cyclonic wake vortices encounter convectively coupled waves and enhanced moisture associated with the MJO in the Indian Ocean. Operational analysis data from the Year of Tropical Convection (YOTC) and Dynamics of the Madden Julian Oscillation (DYNAMO) campaigns were used to evaluate the impacts of Sumatra's topography upon the flow. The YOTC data encompass two years, from May 2008 to April 2010, while the special observing period of DYNAMO was conducted from October to December 2011. This research also presents three case studies of twin tropical cyclones west of Sumatra in the Indian Ocean, which were all determined to originate from Sumatran wake vortices and occurred between October and December of 2008, 2009, and 2011. Multiple cyclonic wake vortices and vorticity streamers were observed downstream of Sumatra during periods of easterly flow, most frequently between October and December. Froude numbers calculated for the region upstream of Sumatra

  8. Characterisation of turbulence downstream of a linear compressor cascade

    NASA Astrophysics Data System (ADS)

    di Mare, Luca; Jelly, Thomas; Day, Ivor

    2014-11-01

    Characterisation of turbulence in turbomachinery remains one of the most complex tasks in fluid mechanics. In addition, current closure models required for Reynolds-averaged Navier-Stokes computations do not accurately represent the action of turbulent forces against the mean flow. Therefore, the statistical properties of turbulence in turbomachinery are of significant interest. In the current work, single- and two-point hot-wire measurements have been acquired downstream of a linear compressor cascade in order to examine the properties of large-scale turbulent structures and to assess how they affect turbulent momentum and energy transfer in compressor passages. The cascade has seven controlled diffusion which are representative of high-pressure stator blades found in turbofan engines. Blade chord, thickness and camber are 0.1515 m, 9.3% and 42 degrees, respectively. Measurements were acquired at a chord Reynolds number of 6 . 92 ×105 . Single-point statistics highlight differences in turbulence structure when comparing mid-span and end-wall regions. Evaluation of two-point correlations and their corresponding spectra reveal the length-scales of the energy-bearing eddies in the cascade. Ultimately, these measurements can be used to calibrate future computational models. The authors gratefully acknowledge Rolls-Royce plc for funding this work and granting permission for its publication.

  9. Oxidative stress and its downstream signaling in aging eyes

    PubMed Central

    Pinazo-Durán, María Dolores; Gallego-Pinazo, Roberto; García-Medina, Jose Javier; Zanón-Moreno, Vicente; Nucci, Carlo; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Galbis-Estrada, Carmen; Marco-Ramírez, Carla; López-Gálvez, Maria Isabel; Galarreta, David J; Díaz-Llópis, Manuel

    2014-01-01

    Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases. PMID:24748782

  10. Downstream effects of a hydroelectric reservoir on aquatic plant assemblages.

    PubMed

    Bernez, Ivan; Haury, Jacques; Ferreira, Maria Teresa

    2002-03-16

    Macrophytes were studied downstream of the Rophémel hydroelectric dam on the River Rance (Côtes d'Armor Department, western France) to assess the effects of hydroelectric functioning on river macrophyte communities. We studied ten representative sections of the hydro-peaking channel on five occasions in 1995 and 1996, on a 15-km stretch of river. Floristic surveys were carried out on sections 50 m in length, and genera of macroalgae, species of bryophyta, hydrophytes, and emergent rhizophytes were identified. For the aquatic bryophytes and spermatophytes section of our study, we compared our results with 19th century floristic surveys, before the dam was built. During the vegetative growth period, the hydro-peaking frequency was low. The plant richness was highest near the dam. The macrophyte communities were highly modified according to the distance to the dam. The frequency and magnitude of hydro-peaking was related to the aquatic macrophyte richness in an Intermediate Disturbance Hypothesis position. However, the results of the eco-historical comparison with 19th century floristic surveys point to the original nature of the flora found at the site. Some floral patterns, seen during both periods and at an interval of 133 years, were indicative of the ubiquity of the aquatic flora and of the plants" adaptability. This demonstrates the importance of taking river basin history into account in such biological surveys.

  11. Upstream and Downstream: Anthropological Contributions to River Basin Development

    NASA Astrophysics Data System (ADS)

    Horowitz, M.

    2003-04-01

    It is now almost 30 years since Thayer Scudder and Elizabeth Colson first focused anthropological analysis on the consequences of forced relocation of peoples from the reservoir areas upstream from large dams. The rate of large dam construction has been enormous, more than 50,000 having been built since the mid-1930s, and the total number of persons forcibly relocated has reached the many millions. Inspired by their work, my colleagues and I at the Institute for Development Anthropology began focusing on the downstream consequences of dam construction, particularly on the Senegal River, invited by the Organisation pour la Mise en Valeur du Fleuve Senegal (OMVS). The work resulted not only in an analysis, but in a proposed alternative dam-management approach that would permit hydropower generation yet substantially reduce the costs of changed flow regimes borne by the riparian peoples. In this discussion, I would like to bring the situation up-to-date. What has happened to those recommendations, initially embraced by at least some of the players involved in the river's management?

  12. Synthetic Routes to Methylerythritol Phosphate Pathway Intermediates and Downstream Isoprenoids

    PubMed Central

    Jarchow-Choy, Sarah K; Koppisch, Andrew T; Fox, David T

    2014-01-01

    Isoprenoids constitute the largest class of natural products with greater than 55,000 identified members. They play essential roles in maintaining proper cellular function leading to maintenance of human health, plant defense mechanisms against predators, and are often exploited for their beneficial properties in the pharmaceutical and nutraceutical industries. Most impressively, all known isoprenoids are derived from one of two C5-precursors, isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). In order to study the enzyme transformations leading to the extensive structural diversity found within this class of compounds there must be access to the substrates. Sometimes, intermediates within a biological pathway can be isolated and used directly to study enzyme/pathway function. However, the primary route to most of the isoprenoid intermediates is through chemical catalysis. As such, this review provides the first exhaustive examination of synthetic routes to isoprenoid and isoprenoid precursors with particular emphasis on the syntheses of intermediates found as part of the 2C-methylerythritol 4-phosphate (MEP) pathway. In addition, representative syntheses are presented for the monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30) and tetraterpenes (C40). Finally, in some instances, the synthetic routes to substrate analogs found both within the MEP pathway and downstream isoprenoids are examined. PMID:25009443

  13. Downstream Processing, Formulation Development and Antithrombotic Evaluation of Microbial Nattokinase.

    PubMed

    Kapoor, Rohit; Harde, Harshad; Jain, Sanyog; Panda, Amulya Kumar; Panda, Bibhu Prasad

    2015-07-01

    The present research work describes the downstreaming of nattokinase (NK) produced by Bacillus subtilis under solid state fermentation; and the role of efficient oral formulation of purified NK in the management of thrombotic disorders. Molecular weight of purified NK was estimated to be 28 kDa with specific activity of 504.4 FU/mg. Acid stable nattokinase loaded chitosan nanoparticles (sNLCN) were fabricated for oral delivery of this enzyme. Box-Behnken design (BBD) was employed to investigate and validate the effect of process (independent) variables on the quality attributes (dependent variables) of nanoparticles. The integrity, conformational stability and preservation of fibrinolytic activity of NK (in both free and sNLCN forms) were established by SDS-PAGE, CD analysis and in vitro clot lytic examination, respectively. A 'tail thrombosis model' demonstrated significant decrease in frequency of thrombosis in Wistar rats upon peroral administration of sNLCN in comparison with negative control and free NK group. Furthermore, coagulation analysis, namely the measurement of prothrombin and activated partial thromboplastin time illustrated that sNLCN showed significantly (p < 0.001) higher anti-thrombotic potential in comparison to the free NK. Further, sNLCN showed anti-thrombotic profile similar to warfarin. This study signifies the potential of sNLCN in oral delivery of NK for the management of thrombotic disorders.

  14. Alternative downstream processes for production of antibodies and antibody fragments.

    PubMed

    Arakawa, Tsutomu; Tsumoto, Kouhei; Ejima, Daisuke

    2014-11-01

    Protein-A or Protein-L affinity chromatography and virus inactivation are key processes for the manufacturing of therapeutic antibodies and antibody fragments. These two processes often involve exposure of therapeutic proteins to denaturing low pH conditions. Antibodies have been shown to undergo conformational changes at low pH, which can lead to irreversible damages on the final product. Here, we review alternative downstream approaches that can reduce the degree of low pH exposure and consequently damaged product. We and others have been developing technologies that minimize or eliminate such low pH processes. We here cover facilitated elution of antibodies using arginine in Protein-A and Protein-G affinity chromatography, a more positively charged amidated Protein-A, two Protein-A mimetics (MEP and Mabsorbent), mixed-mode and steric exclusion chromatography, and finally enhanced virus inactivation by solvents containing arginine. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID:24859179

  15. An atypical bHLH transcription factor regulates early xylem development downstream of auxin.

    PubMed

    Ohashi-Ito, Kyoko; Matsukawa, Manami; Fukuda, Hiroo

    2013-03-01

    The vascular system in plants, which comprises xylem, phloem and vascular stem cells, originates from provascular cells and forms a continuous network throughout the plant body. Although various aspects of vascular development have been extensively studied, the early process of vascular development remains largely unknown. LONESOME HIGHWAY (LHW), which encodes an atypical basic helix-loop-helix (bHLH) transcription factor, plays an essential role in establishing vascular cells. Here, we report the analysis of LHW homologs in relation to vascular development. Three LHW homologs, LONESOME HIGHWAY LIKE 1-3 (LHL1-LHL3), were preferentially expressed in the plant vasculature. Genetic analysis indicated that, although the LHL3 loss-of-function mutant showed no obvious phenotype, the lhw lhl3 double mutant displayed more severe phenotypic defects in the vasculature of the cotyledons and roots than the lhw single mutant. Only one xylem vessel was formed at the metaxylem position in lhw lhl3 roots, whereas the lhw root formed one protoxylem and one or two metaxylem vessels. Conversely, overexpression of LHL3 enhanced xylem development in the roots. Moreover, N-1-naphthylphthalamic acid caused ectopic LHL3 expression in accordance with induced auxin maximum. These results suggest that LHL3 plays a positive role in xylem differentiation downstream of auxin.

  16. mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish

    PubMed Central

    Koltowska, Katarzyna; Paterson, Scott; Bower, Neil I.; Baillie, Gregory J.; Lagendijk, Anne K.; Astin, Jonathan W.; Chen, Huijun; Francois, Mathias; Crosier, Philip S.; Taft, Ryan J.; Simons, Cas; Smith, Kelly A.; Hogan, Benjamin M.

    2015-01-01

    The lymphatic vasculature plays roles in tissue fluid balance, immune cell trafficking, fatty acid absorption, cancer metastasis, and cardiovascular disease. Lymphatic vessels form by lymphangiogenesis, the sprouting of new lymphatics from pre-existing vessels, in both development and disease contexts. The apical signaling pathway in lymphangiogenesis is the VEGFC/VEGFR3 pathway, yet how signaling controls cellular transcriptional output remains unknown. We used a forward genetic screen in zebrafish to identify the transcription factor mafba as essential for lymphatic vessel development. We found that mafba is required for the migration of lymphatic precursors after their initial sprouting from the posterior cardinal vein. mafba expression is enriched in sprouts emerging from veins, and we show that mafba functions cell-autonomously during lymphatic vessel development. Mechanistically, Vegfc signaling increases mafba expression to control downstream transcription, and this regulatory relationship is dependent on the activity of SoxF transcription factors, which are essential for mafba expression in venous endothelium. Here we identify an indispensable Vegfc–SoxF–Mafba pathway in lymphatic development. PMID:26253536

  17. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5.

    PubMed

    Baker, Paul J; Boucher, Dave; Bierschenk, Damien; Tebartz, Christina; Whitney, Paul G; D'Silva, Damian B; Tanzer, Maria C; Monteleone, Mercedes; Robertson, Avril A B; Cooper, Matthew A; Alvarez-Diaz, Silvia; Herold, Marco J; Bedoui, Sammy; Schroder, Kate; Masters, Seth L

    2015-10-01

    Humans encode two inflammatory caspases that detect cytoplasmic LPS, caspase-4 and caspase-5. When activated, these trigger pyroptotic cell death and caspase-1-dependent IL-1β production; however the mechanism underlying this process is not yet confirmed. We now show that a specific NLRP3 inhibitor, MCC950, prevents caspase-4/5-dependent IL-1β production elicited by transfected LPS. Given that both caspase-4 and caspase-5 can detect cytoplasmic LPS, it is possible that these proteins exhibit some degree of redundancy. Therefore, we generated human monocytic cell lines in which caspase-4 and caspase-5 were genetically deleted either individually or together. We found that the deletion of caspase-4 suppressed cell death and IL-1β production following transfection of LPS into the cytoplasm, or in response to infection with Salmonella typhimurium. Although deletion of caspase-5 did not confer protection against transfected LPS, cell death and IL-1β production were reduced after infection with Salmonella. Furthermore, double deletion of caspase-4 and caspase-5 had a synergistic effect in the context of Salmonella infection. Our results identify the NLRP3 inflammasome as the specific platform for IL-1β maturation, downstream of cytoplasmic LPS detection by caspase-4/5. We also show that both caspase-4 and caspase-5 are functionally important for appropriate responses to intracellular Gram-negative bacteria.

  18. mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of PTEN Loss

    PubMed Central

    Ghosh, Susmita; Varela, Lidenys; Sood, Akshay; Park, Ben Ho; Lotan, Tamara L.

    2013-01-01

    Oncogenic signaling pathways are tightly regulated by negative feedback circuits and relief of these circuits represents a common mechanism of tumor drug resistance. Although the significance of these feedback pathways for signal transduction is evident, their relevance for cellular differentiation and morphogenesis in a genetically-defined context is unclear. In this study, we used isogenic benign mammary organotypic cultures to interrogate the role of mTOR-mediated negative feedback in the specific setting of PTEN inactivation. We found that mTOR signaling promoted basal-like differentiation and repressed nuclear hormone receptor expression after short-term PTEN loss in murine cell cultures analyzed ex vivo. Unexpectedly, we found that PTEN inactivation inhibited growth factor-induced epithelial invasion, and that downstream mTOR-mediated signaling feedback was both necessary and sufficient for this effect. Mechanistically, using isogenic MCF10A cells with and without somaticPTEN deletion, we showed that mTOR inhibition promoted EGF-mediated epithelial invasion by de-repressing upstream EGFR, SRC and PI3K signaling. In addition to offering new signal transduction insights, these results bring to light a number of important and potentially clinically relevant cellular consequences of mTOR inhibition in the specific context of PTEN loss, including modulation of hormone and growth factor responsiveness and promotion of epithelial invasion. Our findings prompt future investigations of the possibility that mTOR inhibitor therapy may not only be ineffective but even deleterious in tumors with PTEN loss. PMID:23774212

  19. Upland-wetland connectivity provides a significant nexus between isolated wetlands and downstream water bodies

    NASA Astrophysics Data System (ADS)

    Mclaughlin, D. L.; Kaplan, D. A.; Cohen, M. J.

    2013-12-01

    Recent rulings by the U.S. Supreme Court have limited federal protection over isolated wetlands, requiring documentation of a 'significant nexus' to a navigable water body to ensure federal jurisdiction. Despite geographic isolation, isolated wetlands influence the surficial aquifer dynamics that regulate baseflow to surface water systems. Due to differences in specific yield (Sy) between upland soils and inundated wetlands, responses of the upland water table to atmospheric fluxes (precipitation, P, and evapotranspiration, ET) are amplified relative to wetland water levels, leading to reversals in the hydraulic gradient between the two systems. As such, wetlands act as a water sink during wet cycles (via wetland exfiltration) and a source (via infiltration) during drier times, regulating both the surficial aquifer and its baseflow to downstream systems. To explore the importance of this wetland function at the landscape scale, we integrated models of soil moisture, upland water table, and wetland stage to simulate the hydrology of a low-relief, depressional landscape. We quantified the hydrologic buffering effect of wetlands by calculating the relative change in the standard deviation (SD) of water table elevation between model runs with and without wetlands. Using this model we explored the effects wetland area and spatial distribution over a range of climatic drivers (P and ET) and soil types. Increasing wetland cumulative area and/or density reduced water table variability relative to landscapes without wetlands, supporting the idea that wetlands stabilize regional hydrologic variation, but also increased mean water table depth because of sustained high ET rates in wetlands during dry periods. Maintaining high cumulative wetland area, but with fewer wetlands, markedly reduced the effect of wetland area, highlighting the importance of small, distributed wetlands on water table regulation. Simulating a range of climate scenarios suggested that the capacity of

  20. Wind-Driven Ecological Flow Regimes Downstream from Hydropower Dams

    NASA Astrophysics Data System (ADS)

    Kern, J.; Characklis, G. W.

    2012-12-01

    Conventional hydropower can be turned on and off quicker and less expensively than thermal generation (coal, nuclear, or natural gas). These advantages enable hydropower utilities to respond to rapid fluctuations in energy supply and demand. More recently, a growing renewable energy sector has underlined the need for flexible generation capacity that can complement intermittent renewable resources such as wind power. While wind power entails lower variable costs than other types of generation, incorporating it into electric power systems can be problematic. Due to variable and unpredictable wind speeds, wind power is difficult to schedule and must be used when available. As a result, integrating large amounts of wind power into the grid may result in atypical, swiftly changing demand patterns for other forms of generation, placing a premium on sources that can be rapidly ramped up and down. Moreover, uncertainty in wind power forecasts will stipulate increased levels of 'reserve' generation capacity that can respond quickly if real-time wind supply is less than expected. These changes could create new hourly price dynamics for energy and reserves, altering the short-term financial signals that hydroelectric dam operators use to schedule water releases. Traditionally, hourly stream flow patterns below hydropower dams have corresponded in a very predictable manner to electricity demand, whose primary factors are weather (hourly temperature) and economic activity (workday hours). Wind power integration has the potential to yield more variable, less predictable flows at hydro dams, flows that at times could resemble reciprocal wind patterns. An existing body of research explores the impacts of standard, demand-following hydroelectric dams on downstream ecological flows; but weighing the benefits of increased reliance on wind power against further impacts to ecological flows may be a novel challenge for the environmental community. As a preliminary step in meeting this

  1. Downstream Propagation of Thermal Pollution in Urban Streams

    NASA Astrophysics Data System (ADS)

    Somers, K. A.; Urban, D. L.; Bernhardt, E. S.; Losordo, M.

    2011-12-01

    Cities create "heat islands" with air temperatures up to 12 degrees C greater than surrounding areas and impervious surface temperatures reaching 50 degrees C greater than the air. Streams that drain urban areas tend to be hotter at baseflow due to warmer air temperatures and decreased riparian canopy cover. Further, urban stormflow routes precipitation over hot impervious surfaces and through storm drains directly into streams, creating rapid changes in stream temperatures. The resulting alterations in stream thermal regimes directly stress aquatic organisms and indirectly lead to changes in stream microbial activity and dissolved oxygen concentrations. To date, there has been little work done to understand how urban heating of streams propagates downstream from thermal pollution sources. In response to this lack, we used a fiber optic distributed temperature sensor as well as multiple individual temperature loggers to measure high spatiotemporal resolution patterns of stream temperature along 1.5 km of Mud Creek in Durham, NC. Mud Creek originates in the storm drains of a suburban neighborhood, where high-density residential complexes with large amounts of impervious surface are connected directly to the stream. The stream flows in a confined channel alongside apartment complexes for 0.5 km before entering a protected forest area. At baseflow, we found temperature was heterogeneous and explained primarily by canopy openness, rather than the amount of development upstream of the location. During summer stormflows, stream temperatures became more homogeneous and increased by up to 4 degrees C due to runoff at the top of the reach. These peak temperatures were dampened to only 2 degrees C increases after 1 km of travel through mature forest. In contrast, a fully forested tributary to Mud Creek decreased in temperature for the same storm events. This spatial propagation of stormflow heat pulses will substantially limit our ability to protect urban stream ecosystems.

  2. Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages

    PubMed Central

    Kramberger, Petra; Urbas, Lidija; Štrancar, Aleš

    2015-01-01

    Downstream processing of nanoplexes (viruses, virus-like particles, bacteriophages) is characterized by complexity of the starting material, number of purification methods to choose from, regulations that are setting the frame for the final product and analytical methods for upstream and downstream monitoring. This review gives an overview on the nanoplex downstream challenges and chromatography based analytical methods for efficient monitoring of the nanoplex production. PMID:25751122

  3. Coupling of downstream RNA polymerase-promoter interactions with formation of catalytically competent transcription initiation complex

    PubMed Central

    Mekler, Vladimir; Minakhin, Leonid; Borukhov, Sergei; Mustaev, Arkady; Severinov, Konstantin

    2014-01-01

    Bacterial RNA polymerase (RNAP) makes extensive contacts with duplex DNA downstream of the transcription bubble in initiation and elongation complexes. We investigated the role of downstream interactions in formation of catalytically competent transcription initiation complex by measuring initiation activity of stable RNAP complexes with model promoter DNA fragments whose downstream ends extend from +3 to +21 relative to the transcription start site at +1. We found that DNA downstream of position +6 does not play a significant role in transcription initiation when RNAP-promoter interactions upstream of the transcription start site are strong and promoter melting region is AT-rich. Further shortening of downstream DNA dramatically reduces efficiency of transcription initiation. The boundary of minimal downstream DNA duplex needed for efficient transcription initiation shifted further away from the catalytic center upon increasing the GC content of promoter melting region or in the presence of bacterial stringent response regulators DksA and ppGpp. These results indicate that the strength of RNAP-downstream DNA interactions has to reach a certain threshold to retain the catalytically competent conformation of the initiation complex and that establishment of contacts between RNAP and downstream DNA can be coupled with promoter melting. The data further suggest that RNAP interactions with DNA immediately downstream of the transcription bubble are particularly important for initiation of transcription. We hypothesize that these active center-proximal contacts stabilize the DNA template strand in the active center cleft and/or position the RNAP clamp domain to allow RNA synthesis. PMID:25311862

  4. Transcriptional regulation of kinases downstream of the T cell receptor: another immunomodulatory mechanism of glucocorticoids

    PubMed Central

    2014-01-01

    Background Glucocorticoids affect peripheral immune responses, including modulation of T-cell activation, differentiation, and apoptosis. The quantity and quality of T-cell receptor (TCR)-triggered intracellular signals modulate T-cell function. Thus, glucocorticoids may affect T cells by interfering with the TCR signaling cascade. The purpose of the study was to search for glucocorticoid-modulated kinases downstream of the TCR. Methods Gene modulation in lymphoid cells either treated with glucocorticoids or from glucocorticoid-treated mice was studied using a RNase protection assay, real-time PCR, and western blotting. The sensitivity of genetically modified thymocytes to glucocorticoid-induced apoptosis was studied by performing hypotonic propidium iodide staining and flow cytometry. The Student’s t-test was employed for statistical evaluation. Results We found that transcription of Itk, a non-receptor tyrosine kinase of the Tec family, was up-regulated in a mouse T-cell hybridoma by the synthetic glucocorticoid dexamethasone. In contrast, dexamethasone down-regulated the expression of Txk, a Tec kinase that functions redundantly with Itk, and Lck, the Src kinase immediately downstream of the TCR. We investigated the expression of Itk, Txk, and Lck in thymocytes and mature lymphocytes following in vitro and in vivo dexamethasone treatment at different time points and doses. Kinase expression was differentially modulated and followed distinct kinetics. Itk was up-regulated in all cell types and conditions tested. Txk was strongly up-regulated in mature lymphocytes but only weakly up-regulated or non-modulated in thymocytes in vitro or in vivo, respectively. Conversely, Lck was down-regulated in thymocytes, but not modulated or up-regulated in mature lymphocytes in the different experimental conditions. This complex behaviour correlates with the presence of both positive and negative glucocorticoid responsive elements (GRE and nGRE, respectively) in the Itk, Txk

  5. The Metastasis Suppressor, N-MYC Downstream-regulated Gene-1 (NDRG1), Down-regulates the ErbB Family of Receptors to Inhibit Downstream Oncogenic Signaling Pathways.

    PubMed

    Kovacevic, Zaklina; Menezes, Sharleen V; Sahni, Sumit; Kalinowski, Danuta S; Bae, Dong-Hun; Lane, Darius J R; Richardson, Des R

    2016-01-15

    N-MYC downstream-regulated gene-1 (NDRG1) is a potent growth and metastasis suppressor that acts through its inhibitory effects on a wide variety of cellular signaling pathways, including the TGF-β pathway, protein kinase B (AKT)/PI3K pathway, RAS, etc. To investigate the hypothesis that its multiple effects could be regulated by a common upstream effector, the role of NDRG1 on the epidermal growth factor receptor (EGFR) and other members of the ErbB family, namely human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3), was examined. We demonstrate that NDRG1 markedly decreased the expression and activation of EGFR, HER2, and HER3 in response to the epidermal growth factor (EGF) ligand, while also inhibiting formation of the EGFR/HER2 and HER2/HER3 heterodimers. In addition, NDRG1 also decreased activation of the downstream MAPKK in response to EGF. Moreover, novel anti-tumor agents of the di-2-pyridylketone class of thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, which markedly up-regulate NDRG1, were found to inhibit EGFR, HER2, and HER3 expression and phosphorylation in cancer cells. However, the mechanism involved appeared dependent on NDRG1 for di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, but was independent of this metastasis suppressor for di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone. This observation demonstrates that small structural changes in thiosemicarbazones result in marked alterations in molecular targeting. Collectively, these results reveal a mechanism for the extensive downstream effects on cellular signaling attributed to NDRG1. Furthermore, this study identifies a novel approach for the treatment of tumors resistant to traditional EGFR inhibitors. PMID:26534963

  6. eQTL networks unveil enriched mRNA master integrators downstream of complex disease-associated SNPs.

    PubMed

    Li, Haiquan; Pouladi, Nima; Achour, Ikbel; Gardeux, Vincent; Li, Jianrong; Li, Qike; Zhang, Hao Helen; Martinez, Fernando D; 'Skip' Garcia, Joe G N; Lussier, Yves A

    2015-12-01

    The causal and interplay mechanisms of Single Nucleotide Polymorphisms (SNPs) associated with complex diseases (complex disease SNPs) investigated in genome-wide association studies (GWAS) at the transcriptional level (mRNA) are poorly understood despite recent advancements such as discoveries reported in the Encyclopedia of DNA Elements (ENCODE) and Genotype-Tissue Expression (GTex). Protein interaction network analyses have successfully improved our understanding of both single gene diseases (Mendelian diseases) and complex diseases. Whether the mRNAs downstream of complex disease genes are central or peripheral in the genetic information flow relating DNA to mRNA remains unclear and may be disease-specific. Using expression Quantitative Trait Loci (eQTL) that provide DNA to mRNA associations and network centrality metrics, we hypothesize that we can unveil the systems properties of information flow between SNPs and the transcriptomes of complex diseases. We compare different conditions such as naïve SNP assignments and stringent linkage disequilibrium (LD) free assignments for transcripts to remove confounders from LD. Additionally, we compare the results from eQTL networks between lymphoblastoid cell lines and liver tissue. Empirical permutation resampling (p<0.001) and theoretic Mann-Whitney U test (p<10(-30)) statistics indicate that mRNAs corresponding to complex disease SNPs via eQTL associations are likely to be regulated by a larger number of SNPs than expected. We name this novel property mRNA hubness in eQTL networks, and further term mRNAs with high hubness as master integrators. mRNA master integrators receive and coordinate the perturbation signals from large numbers of polymorphisms and respond to the personal genetic architecture integratively. This genetic signal integration contrasts with the mechanism underlying some Mendelian diseases, where a genetic polymorphism affecting a single protein hub produces a divergent signal that affects a large

  7. eQTL networks unveil enriched mRNA master integrators downstream of complex disease-associated SNPs.

    PubMed

    Li, Haiquan; Pouladi, Nima; Achour, Ikbel; Gardeux, Vincent; Li, Jianrong; Li, Qike; Zhang, Hao Helen; Martinez, Fernando D; Garcia, Joe G N 'Skip'; Lussier, Yves A

    2015-12-01

    The causal and interplay mechanisms of Single Nucleotide Polymorphisms (SNPs) associated with complex diseases (complex disease SNPs) investigated in genome-wide association studies (GWAS) at the transcriptional level (mRNA) are poorly understood despite recent advancements such as discoveries reported in the Encyclopedia of DNA Elements (ENCODE) and Genotype-Tissue Expression (GTex). Protein interaction network analyses have successfully improved our understanding of both single gene diseases (Mendelian diseases) and complex diseases. Whether the mRNAs downstream of complex disease genes are central or peripheral in the genetic information flow relating DNA to mRNA remains unclear and may be disease-specific. Using expression Quantitative Trait Loci (eQTL) that provide DNA to mRNA associations and network centrality metrics, we hypothesize that we can unveil the systems properties of information flow between SNPs and the transcriptomes of complex diseases. We compare different conditions such as naïve SNP assignments and stringent linkage disequilibrium (LD) free assignments for transcripts to remove confounders from LD. Additionally, we compare the results from eQTL networks between lymphoblastoid cell lines and liver tissue. Empirical permutation resampling (p<0.001) and theoretic Mann-Whitney U test (p<10(-30)) statistics indicate that mRNAs corresponding to complex disease SNPs via eQTL associations are likely to be regulated by a larger number of SNPs than expected. We name this novel property mRNA hubness in eQTL networks, and further term mRNAs with high hubness as master integrators. mRNA master integrators receive and coordinate the perturbation signals from large numbers of polymorphisms and respond to the personal genetic architecture integratively. This genetic signal integration contrasts with the mechanism underlying some Mendelian diseases, where a genetic polymorphism affecting a single protein hub produces a divergent signal that affects a large

  8. Observations of Particle Acceleration Associated with Small-Scale Magnetic Islands Downstream of Interplanetary Shocks

    NASA Astrophysics Data System (ADS)

    Khabarova, Olga V.; Zank, Gary P.; Li, Gang; Malandraki, Olga E.; le Roux, Jakobus A.; Webb, Gary M.

    2016-04-01

    We have recently shown both theoretically (Zank et al. 2014, 2015; le Roux et al. 2015) and observationally (Khabarova et al. 2015) that dynamical small-scale magnetic islands play a significant role in local particle acceleration in the supersonic solar wind. We discuss here observational evidence for particle acceleration at shock waves that is enhanced by the recently proposed mechanism of particle energization by both island contraction and the reconnection electric field generated in merging or contracting magnetic islands downstream of the shocks (Zank et al. 2014, 2015; le Roux et al. 2015). Both observations and simulations suppose formation of magnetic islands in the turbulent wake of heliospheric or interplanetary shocks (ISs) (Turner et al. 2013; Karimabadi et al. 2014; Chasapis et al. 2015). A combination of the DSA mechanism with acceleration by magnetic island dynamics explain why the spectra of energetic particles that are supposed to be accelerated at heliospheric shocks are sometimes harder than predicted by DSA theory (Zank et al. 2015). Moreover, such an approach allows us to explain and describe other unusual behaviour of accelerated particles, such as when energetic particle flux intensity peaks are observed downstream of heliospheric shocks instead of peaking directly at the shock according to DSA theory. Zank et al. (2015) predicted the peak location to be behind the heliospheric termination shock (HTS) and showed that the distance from the shock to the peak depends on particle energy, which is in agreement with Voyager 2 observations. Similar particle behaviour is observed near strong ISs in the outer heliosphere as observed by Voyager 2. Observations show that heliospheric shocks are accompanied by current sheets, and that IS crossings always coincide with sharp changes in the IMF azimuthal angle and the IMF strength, which is typical for strong current sheets. The presence of current sheets in the vicinity of ISs acts to magnetically

  9. Divergent Expression Regulation of Gonad Development Genes in Medaka Shows Incomplete Conservation of the Downstream Regulatory Network of Vertebrate Sex Determination

    PubMed Central

    Herpin, Amaury; Adolfi, Mateus C.; Nicol, Barbara; Hinzmann, Maria; Schmidt, Cornelia; Klughammer, Johanna; Engel, Mareen; Tanaka, Minoru; Guiguen, Yann; Schartl, Manfred

    2013-01-01

    Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of “master sex-determining genes” at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought. PMID:23883523

  10. Characterizing the evolution of genetic variance using genetic covariance tensors.

    PubMed

    Hine, Emma; Chenoweth, Stephen F; Rundle, Howard D; Blows, Mark W

    2009-06-12

    Determining how genetic variance changes under selection in natural populations has proved to be a very resilient problem in evolutionary genetics. In the same way that understanding the availability of genetic variance within populations requires the simultaneous consideration of genetic variance in sets of functionally related traits, determining how genetic variance changes under selection in natural populations will require ascertaining how genetic variance-covariance (G) matrices evolve. Here, we develop a geometric framework using higher-order tensors, which enables the empirical characterization of how G matrices have diverged among populations. We then show how divergence among populations in genetic covariance structure can then be associated with divergence in selection acting on those traits using key equations from evolutionary theory. Using estimates of G matrices of eight male sexually selected traits from nine geographical populations of Drosophila serrata, we show that much of the divergence in genetic variance occurred in a single trait combination, a conclusion that could not have been reached by examining variation among the individual elements of the nine G matrices. Divergence in G was primarily in the direction of the major axes of genetic variance within populations, suggesting that genetic drift may be a major cause of divergence in genetic variance among these populations.

  11. Identification of two-component system elements downstream of AHK5 in the stomatal closure response of Arabidopsis thaliana.

    PubMed

    Mira-Rodado, Virtudes; Veerabagu, Manikandan; Witthöft, Janika; Teply, Julia; Harter, Klaus; Desikan, Radhika

    2012-11-01

    To optimize water use efficiency, plants regulate stomatal closure through a complex signaling process. Hydrogen peroxide (H₂O₂) is produced in response to several environmental stimuli, and has been identified as a key second messenger involved in the regulation of stomatal aperture. The Arabidopsis histidine kinase 5 (AHK5) has been shown to regulate stomatal closure in response to H₂O₂ and other stimuli that depend on H₂O₂. AHK5 is a member of the two-component system (TCS) in Arabidopsis. The plant TCS comprises three different protein types: the hybrid histidine kinases (HKs), the phosphotransfer proteins (HPs) and the response regulators (RRs). Here we determined TCS elements involved in H₂O₂- and ethylene-dependent stomatal closure downstream of AHK5. By yeast and in planta interaction assays and functional studies, AHP1, 2 and 5 as well as the response regulators ARR4 and ARR7 were identified acting downstream of AHK5 in the ethylene and H₂O₂ response pathways of guard cells. Furthermore, we demonstrate that aspartate phosphorylation of ARR4 is only required for the H₂O₂- but not for the ethylene-induced stomatal closure response. Our data suggest the presence of a complex TCS signaling network comprising of at least AHK5, several AHPs and response regulators, which modulate stomatal closure in response to H₂O₂ and ethylene.

  12. Collisionless relaxation of downstream ion distributions in low-Mach number shocks

    SciTech Connect

    Gedalin, M.; Friedman, Y.; Balikhin, M.

    2015-07-15

    Collisionlessly formed downstream distributions of ions in low-Mach number shocks are studied. General expressions for the asymptotic value of the ion density and pressure are derived for the directly transmitted ions. An analytical approximation for the overshoot strength is suggested for the low-β case. Spatial damping scale of the downstream magnetic oscillations is estimated.

  13. Downstream approaches to phosphorus management in agricultural landscapes: Regional applicability and use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review provides a synthesis of conservation practices that are aimed at improving water quality by retaining phosphorus (P) downstream of runoff genesis. The review is structured around specific downstream practices that are prevalent in various parts of the United States, but also focuses on t...

  14. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... gasoline downstream from refineries and importers? 80.210 Section 80.210 Protection of Environment... Gasoline Sulfur Gasoline Sulfur Standards § 80.210 What sulfur standards apply to gasoline downstream from refineries and importers? The sulfur standard for gasoline at any point in the gasoline distribution...

  15. A critical role of downstream RNA polymerase-promoter interactions in the formation of initiation complex.

    PubMed

    Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

    2011-06-24

    Nucleation of promoter melting in bacteria is coupled with RNA polymerase (RNAP) binding to a conserved -10 promoter element located at the upstream edge of the transcription bubble. The mechanism of downstream propagation of the transcription bubble to include the transcription start site is unclear. Here we introduce new model downstream fork junction promoter fragments that specifically bind RNAP and mimic the downstream segment of promoter complexes. We demonstrate that RNAP binding to downstream fork junctions is coupled with DNA melting around the transcription start point. Consequently, certain downstream fork junction probes can serve as transcription templates. Using a protein beacon fluorescent method, we identify structural determinants of affinity and transcription activity of RNAP-downstream fork junction complexes. Measurements of RNAP interaction with double-stranded promoter fragments reveal that the strength of RNAP interactions with downstream DNA plays a critical role in promoter opening and that the length of the downstream duplex must exceed a critical length for efficient formation of transcription competent open promoter complex.

  16. Molecular and Genetic Analysis of Hormone-Regulated Differential Cell Elongation in Arabidopsis

    SciTech Connect

    Ecker, Joseph R.

    2005-09-15

    We have utilized the response of Arabidopsis seedlings to the plant hormone ethylene to identify new genes involved in the regulation of ethylene biosynthesis, perception, signal transduction and differential cell growth. In building a genetic framework for the action of these genes, we have developed a molecular model that has facilitated our understanding of the molecular requirements of ethylene for cell elongation processes. The ethylene response pathway in Arabidopsis appears to be primarily linear and is defined by the genes: ETR1, ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, EIN3, EIN5, EIN6, and EIN. Downstream branches identified by the HLS1, EIR1, and AUX1 genes involve interactions with other hormonal (auxin) signals in the process of differential cell elongation in the hypocotyl hook. Cloning and characterization of HLS1 (and three HLL genes) and ETO1 (and ETOL genes) in my laboratory has been supported under this award. HLS1 is required for differential elongation of cells in the hypocotyl and may act in the establishment of hormone gradients. Also during the previous period, we have identified and characterized a gene that genetically acts upstream of the ethylene receptors. ETO1 encodes negative regulators of ethylene biosynthesis.

  17. Molecular and Genetic Analysis of Hormone-Regulated Differential Cell Elongation in Arabidopsis

    SciTech Connect

    Ecker, Joseph R.

    2002-12-03

    The authors have utilized the response of Arabidopsis seedlings to the plant hormone ethylene to identify new genes involved in the regulation of ethylene biosynthesis, perception, signal transduction and differential cell growth. In building a genetic framework for the action of these genes, they developed a molecular model that has facilitated the understanding of the molecular requirements of ethylene for cell elongation processes. The ethylene response pathway in Arabidopsis appears to be primarily linear and is defined by the genes: ETR1, ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, EIN3, EIN5 EIN6, and EIN. Downstream branches identified by the HLS1, EIR1, and AUX1 genes involve interactions with other hormonal (auxin) signals in the process of differential cell elongation in the hypocotyl hook. Cloning and characterization of HLS1 and three HLS1-LIKE genes in the laboratory has been supported under this award. HLS1 is required for differential elongation of cells in the hypocotyl and may act in the establishment of hormone gradients. Also during the award period, they have identified and begun preliminary characterization of two genes that genetically act upstream of the ethylene receptors. ETO1 and RAN1 encode negative regulators of ethylene biosynthesis and signaling respectively. Progress on the analysis of these genes along with HOOKLESS1 is described.

  18. Downstream boundary effects on the frequency of self-excited oscillations in transonic diffuser flows

    NASA Technical Reports Server (NTRS)

    Hsieh, T.; Coakley, T. J.

    1987-01-01

    An investigation of downstream boundary effects on the frequency of self-excited oscillations in two-dimensional, separated transonic diffuser flows has been conducted numerically by solving the compressible, Reynolds-averaged, thin-layer Navier-Stokes equation with a two-equation turbulence model. It was found that the unsteady diffuser flowfields are very sensitive to the location of the downstream boundary. Extension of the diffuser downstream boundary significantly reduces the frequency and amplitude of oscillations for pressure, velocity and shock. Computational results suggest that the mechanism causing the self-excited oscillation changes from viscous convective wave dominated oscillations to inviscid acoustic wave dominated oscillations when the location of downstream boundary varies from 8.66 to 134.7 throat height. The existence of a suction slot in the experimental setup obscures the physical downstream boundary and, therefore, presents a difficulty for quantitative comparisons between computation and experiment.

  19. Experimental and analytical investigation of fan flow interaction with downstream struts

    NASA Technical Reports Server (NTRS)

    Olsen, T. L.; Ng, W. F.; Obrien, W. F., Jr.

    1985-01-01

    An investigation which was designed to provide insight into the fundamental aspects of fan rotor-downstream strut interaction was undertaken. High response, miniature pressure transducers were embedded in the rotor blades of an experimental fan rig. Five downstream struts were placed at several downstream locations in the discharge flow annulus of the single-stage machine. Significant interaction of the rotor blade surface pressures with the flow disturbance produced by the downstream struts was measured. Several numerical procedures for calculating the quasi-steady rotor response due to downstream flow obstructions were developed. A preliminary comparison of experimental and calculated fluctuating blade pressures on the rotor blades shows general agreement between the experimental and calculated values.

  20. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components.

    PubMed Central

    Leberer, E; Dignard, D; Harcus, D; Thomas, D Y; Whiteway, M

    1992-01-01

    In the yeast Saccharomyces cerevisiae the G-protein beta gamma subunits have been shown to trigger downstream events of the pheromone response pathway. We have identified a new gene, designated STE20, which encodes a protein kinase homologue with sequence similarity to protein kinase C, which is required to transmit the pheromone signal from G beta gamma to downstream components of the signalling pathway. Overproduction of the kinase suppresses the mating defect of dominant-negative G beta mutations providing genetic evidence for an interaction with G beta, and epistasis experiments show that this kinase functions after or at the same point as G beta gamma, but before any of the other currently identified components of the signalling pathway. This points to a potentially new mechanism of G-protein mediated signal transduction, the activation of a protein kinase through G beta gamma. Images PMID:1464311

  1. Genetic Mapping

    MedlinePlus

    ... Genetic Education Resources for Teachers Genomic Careers National DNA Day Online Education Kit Online Genetics Education Resources ... prevalent. Using various laboratory techniques, the scientists isolate DNA from these samples and examine it for unique ...

  2. Genetic Disorders

    MedlinePlus

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  3. Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options

    PubMed Central

    Uttara, Bayani; Singh, Ajay V.; Zamboni, Paolo; Mahajan, R.T

    2009-01-01

    Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer’s disease, Parkinson’s disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario. PMID:19721819

  4. FINE-SCALE GENETIC DIFFERENTIATION BETWEEN CONTAMINANT-TOLERANT AND CONTAMINANT SENSITIVE FISH POPULATIONS

    EPA Science Inventory

    Studies have suggested that environmental contaminants can act as selective forces on exposed populations of wildlife species. Chronically exposed populations have shown reduced genetic diversity and/or demonstrated other genetic changes. We evaluated the genetic structure of pop...

  5. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  6. Genetic principles.

    PubMed

    Abuelo, D

    1987-01-01

    The author discusses the basic principles of genetics, including the classification of genetic disorders and a consideration of the rules and mechanisms of inheritance. The most common pitfalls in clinical genetic diagnosis are described, with emphasis on the problem of the negative or misleading family history.

  7. Imaging Genetics

    ERIC Educational Resources Information Center

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  8. Genetic Testing

    MedlinePlus

    ... genetic tests for several reasons. These include Finding genetic diseases in unborn babies Finding out if people carry a gene for a disease and might pass it on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ...

  9. What factors control the percentage of nitrogen that gets exported downstream from man-made reservoirs?

    NASA Astrophysics Data System (ADS)

    Buonpane, J. M.; Wollheim, W. M.; Whitney, C. T.

    2015-12-01

    Man-made dams influence more than just the flow of water in a river. The build up of sediments and organic matter, increased residence times, and elevated nutrient inputs from upstream can result in increased algal growth and blooms, altered DO patterns, and can also influence the flux of nutrients from watersheds. Many of the effects of dams vary in intensity based on the geomorphology of their resulting reservoirs. In this study, we examined eight reservoirs located in four different coastal watersheds in New England, USA, to analyze the role that characteristics such as depth, width, volume, and residence time play in regards to metabolism (GPP and Respiration) and nutrient retention. At the inflows and outflow of each reservoir, we measured conductivity, dissolved oxygen, total suspended solids, nitrate, phosphate, chlorophyll, and dissolved organic carbon. Using conductivity, which is conservative, and watershed area, we created a mass balance for each watershed. In most cases the conductivity mass balance indicated that water inputs and outputs were at equilibrium during sampling, allowing us to assess the alteration of non-conservative material fluxes. Dissolved oxygen and TSS were not balanced, indicating that the reservoirs acted as both a source and a sink for DO and sediments depending upon the time of day and amount of algal activity. Similar analyses will be conducted for nutrients. The net change of each variable across the reservoirs will be related to geomorphological characteristics of the reservoirs. With nutrient loading from anthropogenic sources, and increased push for small dam removal, this study provides useful information regarding the consequences of dam removal to downstream aquatic ecosystems.

  10. GLABROUS INFLORESCENCE STEMS regulates trichome branching by genetically interacting with SIM in Arabidopsis.

    PubMed

    Sun, Li-Li; Zhou, Zhong-Jing; An, Li-Jun; An, Yan; Zhao, Yong-Qin; Meng, Xiao-Fang; Steele-King, Clare; Gan, Yin-Bo

    2013-07-01

    Arabidopsis trichomes are large branched single cells that protrude from the epidermis. The first morphological indication of trichome development is an increase in nuclear content resulting from an initial cycle of endoreduplication. Our previous study has shown that the C2H2 zinc finger protein GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome initiation in the inflorescence organ and for trichome branching in response to gibberellic acid signaling, although GIS gene does not play a direct role in regulating trichome cell division. Here, we describe a novel role of GIS, controlling trichome cell division indirectly by interacting genetically with a key endoreduplication regulator SIAMESE (SIM). Our molecular and genetic studies have shown that GIS might indireclty control cell division and trichome branching by acting downstream of SIM. A loss of function mutation of SIM signficantly reduced the expression of GIS. Futhermore, the overexpression of GIS rescued the trichome cluster cell phenotypes of sim mutant. The gain or loss of function of GIS had no significant effect on the expression of SIM. These results suggest that GIS may play an indirect role in regulating trichome cell division by genetically interacting with SIM. PMID:23825141

  11. GLABROUS INFLORESCENCE STEMS regulates trichome branching by genetically interacting with SIM in Arabidopsis.

    PubMed

    Sun, Li-Li; Zhou, Zhong-Jing; An, Li-Jun; An, Yan; Zhao, Yong-Qin; Meng, Xiao-Fang; Steele-King, Clare; Gan, Yin-Bo

    2013-07-01

    Arabidopsis trichomes are large branched single cells that protrude from the epidermis. The first morphological indication of trichome development is an increase in nuclear content resulting from an initial cycle of endoreduplication. Our previous study has shown that the C2H2 zinc finger protein GLABROUS INFLORESCENCE STEMS (GIS) is required for trichome initiation in the inflorescence organ and for trichome branching in response to gibberellic acid signaling, although GIS gene does not play a direct role in regulating trichome cell division. Here, we describe a novel role of GIS, controlling trichome cell division indirectly by interacting genetically with a key endoreduplication regulator SIAMESE (SIM). Our molecular and genetic studies have shown that GIS might indireclty control cell division and trichome branching by acting downstream of SIM. A loss of function mutation of SIM signficantly reduced the expression of GIS. Futhermore, the overexpression of GIS rescued the trichome cluster cell phenotypes of sim mutant. The gain or loss of function of GIS had no significant effect on the expression of SIM. These results suggest that GIS may play an indirect role in regulating trichome cell division by genetically interacting with SIM.

  12. Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila.

    PubMed

    Varma, Disha; Bülow, Margret H; Pesch, Yanina-Yasmin; Loch, Gerrit; Hoch, Michael

    2014-10-01

    Antimicrobial peptides (AMPs) are conserved cationic peptides which act both as defense molecules of the host immune system and as regulators of the commensal microbiome. Expression of AMPs is induced in response to infection by the Toll and Imd pathway. Under non-infected conditions, the transcription factor dFOXO directly regulates a set of AMP expression at low levels when nutrients are limited. Here we have analyzed whether target of rapamycin (TOR), another major regulator of growth and metabolism, also modulates AMP responses in Drosophila. We found that downregulation of TOR by feeding the drug rapamycin or by overexpressing the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk). In contrast, overexpression of Rheb, which positively regulates TOR led to a repression of the two AMPs. Genetic and pharmacological experiments indicate that Dpt and Mtk activation is controlled by the transcription factor Forkhead (FKH), the founding member of the FoxO family. Shuttling of FKH from the cytoplasm to the nucleus is induced in the fat body and in the posterior midgut in response to TOR downregulation. The FKH-dependent induction of Dpt and Mtk can be triggered in dFOXO null mutants and in immune-compromised Toll and IMD pathway mutants indicating that FKH acts in parallel to these regulators. Together, we have discovered that FKH is the second conserved member of the FoxO family cross-regulating metabolism and innate immunity. dFOXO and FKH, which are activated upon downregulation of insulin or TOR activities, respectively, act in parallel to induce different sets of AMPs, thereby modulating the immune status of metabolic tissues such as the fat body or the gut in response to the oscillating energy status of the organism.

  13. Recovery Act Milestones

    ScienceCinema

    Rogers, Matt

    2016-07-12

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  14. Recovery Act Milestones

    SciTech Connect

    Rogers, Matt

    2009-01-01

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  15. ACTS data center

    NASA Technical Reports Server (NTRS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-01-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

  16. The emerging world of synthetic genetics.

    PubMed

    Chaput, John C; Yu, Hanyang; Zhang, Su

    2012-11-21

    For over 20 years, laboratories around the world have been applying the principles of Darwinian evolution to isolate DNA and RNA molecules with specific ligand-binding or catalytic activities. This area of synthetic biology, commonly referred to as in vitro genetics, is made possible by the availability of natural polymerases that can replicate genetic information in the laboratory. Moving beyond natural nucleic acids requires organic chemistry to synthesize unnatural analogues and polymerase engineering to create enzymes that recognize artificial substrates. Progress in both of these areas has led to the emerging field of synthetic genetics, which explores the structural and functional properties of synthetic genetic polymers by in vitro evolution. This review examines recent advances in the Darwinian evolution of artificial genetic polymers and their potential downstream applications in exobiology, molecular medicine, and synthetic biology.

  17. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    PubMed

    Lavender, Christopher A; Cannady, Kimberly R; Hoffman, Jackson A; Trotter, Kevin W; Gilchrist, Daniel A; Bennett, Brian D; Burkholder, Adam B; Burd, Craig J; Fargo, David C; Archer, Trevor K

    2016-08-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment. PMID:27487356

  18. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters

    PubMed Central

    Lavender, Christopher A.; Hoffman, Jackson A.; Trotter, Kevin W.; Gilchrist, Daniel A.; Bennett, Brian D.; Burkholder, Adam B.; Fargo, David C.; Archer, Trevor K.

    2016-01-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment. PMID:27487356

  19. Downstream channel adjustment in a low-relief, glacially conditioned watershed

    NASA Astrophysics Data System (ADS)

    Thayer, James B.; Phillips, Roger T. J.; Desloges, Joseph R.

    2016-06-01

    River management practices are often informed by theoretical expectations of downstream channel adjustment, which may not be valid in low relief, glacially conditioned watersheds such as those in the lower North American Great Lakes region. Downstream trends in channel morphology and bed material size within a low-relief, glacially conditioned watershed are explored here and compared to a theoretical watershed model where slope and grain size are expected to decline exponentially. The observed channel morphology is then tested against a theoretical concept of reach-scale channel grade. The downstream hydraulic geometry relations wbf ∝ Qbf0.51S- 0.02 and dbf ∝ Qbf0.32S- 0.21 were found to best describe downstream changes in channel morphology and are consistent with some prior studies. Bed material size varies irregularly down the channel. Slope-controlled downstream fining trends are evident where inputs from glacial materials and tributaries are negligible but are masked by cobble/boulder lag deposits where the channel is cut into these glacial deposits. The asynchronous variability in slope and grain size produces downstream variations in graded and nongraded, understeepened conditions separated at τ*ex = 0. Graded reaches exist where τ*ex > 0, but an upper boundary with nongraded, oversteepened reaches is less clear. The results emphasize the geomorphic legacy of inherited slopes and sediment sources in dictating the modern downstream patterns of fluvial characteristics and morphologies in glacially conditioned, and similarly complex, watersheds.

  20. Data collection and documentation of flooding downstream of a dam failure in Mississippi

    USGS Publications Warehouse

    Van Wilson, Jr.; ,

    2005-01-01

    On March 12, 2004, the Big Bay Lake dam failed, releasing water and affecting lives and property downstream in southern Mississippi. The dam is located near Purvis, Mississippi, on Bay Creek, which flows into Lower Little Creek about 1.9 miles downstream from the dam. Lower Little Creek flows into Pearl River about 16.9 miles downstream from the dam. Knowledge of the hydrology and hydraulics of floods caused by dam breaks is essential to the design of dams. A better understanding of the risks associated with possible dam failures may help limit the loss of life and property that often occurs downstream of a dam failure. The USGS recovered flood marks at the one crossing of Bay Creek and eight crossings of Lower Little Creek. Additional flood marks were also flagged at three other bridges crossing tributaries where backwater occurred. Flood marks were recovered throughout the stream reach of about 3/4 to 15 miles downstream of the dam. Flood marks that were flagged will be surveyed so that a flood profile can be documented downstream of the Big Bay Lake dam failure. Peak discharges are also to be estimated where possible. News reports stated that the peak discharge at the dam was about 67,000 cubic feet per second. Preliminary data suggest the peak discharge from the dam failure attenuated to about 13,000 cubic feet per second at Lower Little Creek at State Highway 43, about 15 miles downstream of the dam.

  1. The dermatology acting internship.

    PubMed

    Stephens, John B; Raimer, Sharon S; Wagner, Richard F

    2011-07-15

    Acting internships are an important component of modern day medical school curriculum. Several specialties outside of internal medicine now offer acting internship experiences to fourth year medical students. We have found that a dermatology acting internship is a valuable experience for fourth year medical students who are interested in pursuing a residency in dermatology. Our experience with the dermatology acting internship over the 2010-2011 academic year is described.

  2. We all live downstream: Disaster, land change and reciprocity in a Haitian watershed

    NASA Astrophysics Data System (ADS)

    Versluis, Anna J.

    Human-environment relations and conditions in one place and time may directly affect those located elsewhere or at some future point in time. If these impacts are negative and especially if the interaction is nonreciprocal, the resulting impacts are registered as "upstream-downstream" problems. The existence of such problems is often rationalized by the lack of reciprocity between upstream and downstream communities. This study addresses the human-environment system of the Fonveret watershed in Haiti regarding the linkages among land change, the May 2004 fatal flash flood disaster, and dynamics of local upstream-downstream relationships. A mixed-methods approach drawing on satellite imagery, field collection of data, and in-person interviews is employed. The study documents the watershed's transition from a mixed pine forest and agriculture landscape in 1979 to one dominated by agriculture by the year 2000. It confirms that local residents consider this deforestation to be the primary contributing factor to the 2004 flash flood disaster, and that reforestation and better soil conservation are necessary to prevent further flood disaster. Few significant differences regarding the 2004 disaster are found between the upstream and downstream communities, perhaps because the majority of the downstream community are also (partial) members of the upstream community Finally, as expected under a reciprocal system in which more responsible actions are promoted by being "downstream" of one's own actions, this study finds that upstream land parcels managed by downstream-residing households tend to possess better soil conservation than parcels managed by upstream-residing households. The study provides an empirical example of how people manage land "upstream" of themselves when there is precedent for downstream disaster. It also demonstrates that problems with land management and flood disasters may occur in a watershed where the downstream and upstream communities are not

  3. Forgetting ACT UP

    ERIC Educational Resources Information Center

    Juhasz, Alexandra

    2012-01-01

    When ACT UP is remembered as the pinnacle of postmodern activism, other forms and forums of activism that were taking place during that time--practices that were linked, related, just modern, in dialogue or even opposition to ACT UP's "confrontational activism"--are forgotten. In its time, ACT UP was embedded in New York City, and a larger world,…

  4. Measurement of velocity deficit at the downstream of a 1:10 axial hydrokinetic turbine model

    SciTech Connect

    Gunawan, Budi; Neary, Vincent S; Hill, Craig; Chamorro, Leonardo

    2012-01-01

    Wake recovery constrains the downstream spacing and density of turbines that can be deployed in turbine farms and limits the amount of energy that can be produced at a hydrokinetic energy site. This study investigates the wake recovery at the downstream of a 1:10 axial flow turbine model using a pulse-to-pulse coherent Acoustic Doppler Profiler (ADP). In addition, turbine inflow and outflow velocities were measured for calculating the thrust on the turbine. The result shows that the depth-averaged longitudinal velocity recovers to 97% of the inflow velocity at 35 turbine diameter (D) downstream of the turbine.

  5. A simulation study of multiple ion wave generation downstream of low Mach number quasiperpendicular shocks

    NASA Technical Reports Server (NTRS)

    Motschmann, Uwe; Raeder, Joachim

    1992-01-01

    The behavior of minor ions just downstream of a low Mach number quasi-perpendicular shock is investigated both theoretically and by computer simulations. Because all ions see the same cross shock electric field their deceleration depends on their charge to mass ratio, yielding different downstream velocities. It is shown that these differences in velocity can lead to coherent wave structures in the downstream region of quasi-perpendicular shocks with a narrow transition layer. These waves are shown to be multi ion hybrid waves in contrast to mirror waves and ion cyclotron waves. Under favorable conditions these waves should be observable both at interplanetary shocks and at planetary bowshocks.

  6. A study of mirror waves generated downstream of a quasi-perpendicular shock

    NASA Technical Reports Server (NTRS)

    Lee, L. C.; Price, C. P.; Wu, C. S.; Mandt, M. E.

    1988-01-01

    A large ion temperature anisotropy, which may lead to the generation of mirror waves, is found to exist downstream of a quasi-perpendicular shock simulated by a one-dimensional hybrid code. In the case of the earth's bow shock, large-amplitude mirror waves are found to develop approximately 0.5-1 earth radii downstream of the shock ramp. It is found that the instability criterion for mirror waves in the downstream region is satisfied for shocks with a large Alfven Mach number.

  7. Channel-bed elevation changes downstream from large reservoirs in Kansas

    USGS Publications Warehouse

    Juracek, K.E.

    2001-01-01

    Channel-bed elevation changes were assessed downstream from 24 large Federal reservoirs in Kansas using information from U.S. Geological Survey streamflow-gaging stations. Changes in river/stream stage associated with mean annual discharge indicated that channel-bed lowering had occurred downstream from most of the reservoirs. The net decrease in channel-bed elevation ranged from less than 1 foot to slightly more than 9 feet. The magnitude of channel-bed lowering downstream from the reservoirs likely was related to the composition of the channel bed.

  8. Geomorphic analysis of the river response to sedimentation downstream of Mount Rainier, Washington

    USGS Publications Warehouse

    Czuba, Jonathan A.; Magirl, Christopher S.; Czuba, Christiana R.; Curran, Christopher A.; Johnson, Kenneth H.; Olsen, Theresa D.; Kimball, Halley K.; Gish, Casey C.

    2012-01-01

    A study of the geomorphology of rivers draining Mount Rainier, Washington, was completed to identify sources of sediment to the river network; to identify important processes in the sediment delivery system; to assess current sediment loads in rivers draining Mount Rainier; to evaluate if there were trends in streamflow or sediment load since the early 20th century; and to assess how rates of sedimentation might continue into the future using published climate-change scenarios. Rivers draining Mount Rainier carry heavy sediment loads sourced primarily from the volcano that cause acute aggradation in deposition reaches as far away as the Puget Lowland. Calculated yields ranged from 2,000 tonnes per square kilometer per year [(tonnes/km2)/yr] on the upper Nisqually River to 350 (tonnes/km2)/yr on the lower Puyallup River, notably larger than sediment yields of 50–200 (tonnes/km2)/yr typical for other Cascade Range rivers. These rivers can be assumed to be in a general state of sediment surplus. As a result, future aggradation rates will be largely influenced by the underlying hydrology carrying sediment downstream. The active-channel width of rivers directly draining Mount Rainier in 2009, used as a proxy for sediment released from Mount Rainier, changed little between 1965 and 1994 reflecting a climatic period that was relatively quiet hydrogeomorphically. From 1994 to 2009, a marked increase in geomorphic disturbance caused the active channels in many river reaches to widen. Comparing active-channel widths of glacier-draining rivers in 2009 to the distance of glacier retreat between 1913 and 1994 showed no correlation, suggesting that geomorphic disturbance in river reaches directly downstream of glaciers is not strongly governed by the degree of glacial retreat. In contrast, there was a correlation between active-channel width and the percentage of superglacier debris mantling the glacier, as measured in 1971. A conceptual model of sediment delivery processes

  9. Downstream energetic proton and alpha particles during quasi-parallel interplanetary shock events

    NASA Technical Reports Server (NTRS)

    Tan, L. C.; Mason, G. M.; Gloeckler, G.; Ipavich, F. M.

    1988-01-01

    This paper considers the energetic particle populations in the downstream region of three quasi-parallel interplanetary shock events, which was explored using the ISEE 3 Ultra Low Energy Charge Analyzer sensor, which unambiguously identifies protons and alpha particles using the electrostatic deflection versus residual energy technique. The downstream particles were found to exhibit anisotropies due largely to convection in the solar wind. The spectral indices of the proton and the alpha-particle distribution functions were found to be remarkably constant during the downstream period, being generally insensitive to changes in particle flux levels, magnetic field direction, and solar wind densities. In two of the three events, the proton and the alpha spectra were the same throughout the entire downstream period, supporting the prediction of diffusive shock acceleration theory.

  10. Use of spatially explicit physicochemical data to measure downstream impacts of headwater stream disturbance

    EPA Science Inventory

    Regulatory agencies need methods to quantify the influence of headwater streams on downstream water quality as a result of litigation surrounding jurisdictional criteria and the influence of mountaintop removal coal mining activities. We collected comprehensive, spatially-referen...

  11. Multispacecraft observations of energetic ions upstream and downstream of the bow shock

    NASA Technical Reports Server (NTRS)

    Scholer, M.; Moebius, E.; Kistler, L. M.; Klecker, B.; Ipavich, F. M.

    1989-01-01

    Simultaneous measurements of energetic protons and alpha particles were obtained inside and outside of the magnetopause and upstream and downstream of the bow shock. In the magnetosheath, no gradient or streaming is found in the upstream direction. The present results are consistent with first-order Fermi acceleration at the bow shock and subsequent downstream convection, and exclude the possibility of a magnetospheric source for these particles.

  12. Particle acceleration by combined diffusive shock acceleration and downstream multiple magnetic island acceleration

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.

    2015-09-01

    As a consequence of the evolutionary conditions [28; 29], shock waves can generate high levels of downstream vortical turbulence. Simulations [32-34] and observations [30; 31] support the idea that downstream magnetic islands (also called plasmoids or flux ropes) result from the interaction of shocks with upstream turbulence. Zank et al. [18] speculated that a combination of diffusive shock acceleration (DSA) and downstream reconnection-related effects associated with the dynamical evolution of a “sea of magnetic islands” would result in the energization of charged particles. Here, we utilize the transport theory [18; 19] for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets to investigate a combined DSA and downstream multiple magnetic island charged particle acceleration mechanism. We consider separately the effects of the anti-reconnection electric field that is a consequence of magnetic island merging [17], and magnetic island contraction [14]. For the merging plasmoid reconnection- induced electric field only, we find i) that the particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory, and ii) that the solution is constant downstream of the shock. For downstream plasmoid contraction only, we find that i) the accelerated particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory; ii) for a given energy, the particle intensity peaks downstream of the shock, and the peak location occurs further downstream of the shock with increasing particle energy, and iii) the particle intensity amplification for a particular particle energy, f(x, c/c0)/f(0, c/c0), is not 1, as predicted by DSA theory, but increases with increasing particle energy. These predictions can be tested against observations of electrons and ions accelerated at interplanetary shocks and the heliospheric

  13. Downstream Migration of Masu Salmon Smolt at a Diversion Facility of Dam

    NASA Astrophysics Data System (ADS)

    Hayashida, K.; Nii, H.; Kasuga, K.; Watanabe, K.

    2014-12-01

    A diversion facility was installed on the upstream of Pirika Dam in Northern Japan that produced a downstream flow into the fishway, thus allowing the fish to migrate to the sea. On the other hand, if the flow rate in the river was more than 7.00 m 3/s (design flow rate of diversion facility), masu salmon smolt were concerned about accessing the dam reservoir, because the smolt can't migrate to the sea through the diversion facility unfortunately. Therefore, the downstream migration of smolt was investigated around the diversion facility. The PIT tag system and radio transmitters as the biotelemetry were used to determine 1) whether masu salmon smolt were able to migrate downstream through the diversion facility and fishway at Pirika Dam, 2) when the smolt started to migrate downstream, 3) whether the downstream migration of smolt were affected by the flow increase in the river. It was clarified that 88% of the smolt were able to enter the diversion facility, and then 81% of the smolt were able to access the fishway. It was also clarified that smolt downstream migration had two peaks in a day (5:00 and 18:00). During the study period, although the flow rate was in the 2.21 m3/s to 30.44 m3/s range (average 6.70 m3/s), it was revealed that the diversion facility has a satisfactory function for the downstream migration of smolt as presented above. The survey clarified the downstream migration behavior of masu salmon by using two types of biotelemetry equipment. PIT tag and radio transmitter were found to be very effective in tracking the behavior of small fish such as smolt. PIT tags, in particular, require very little operating cost, because once they are inserted in the fish, they do not need human labor for tracking. It is desirable to actively introduce the biotelemetry as tracking equipment when surveying the fish migration in the river.

  14. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities

    PubMed Central

    Hayes, Maria; Tiwari, Brijesh K.

    2015-01-01

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these. PMID:26393573

  15. Organic compounds downstream from a treated-wastewater discharge near Dallas, Texas, March 1987

    USGS Publications Warehouse

    Buszka, P.M.; Barber, L.B.; Schroeder, M.P.; Becker, L.D.

    1994-01-01

    Comparison of instantaneous flux values of selected organic compounds in water from downstream sites indicates: (1) the formation of chloroform in the stream following the discharge of the treated effluent, and that (2) instream biodegradation may be decreasing concentrations of linear alkylbenzene compounds in water. The relative persistence of many of the selected organic compounds in Rowlett Creek downstream from the municipal wastewater-treatment plant indicates that they could be transported into Lake Ray Hubbard, a source of municipal water supply.

  16. User experience network. Erroneous downstream occlusion alarms may disable Smiths Medical CADD-Solis infusion pumps.

    PubMed

    2010-10-01

    Due to an issue in manufacturing, downstream occlusion (DSO) sensors in some Smiths Medical CADD-Solis infusion pumps may drift out of calibration, potentially resulting in erroneous alarms that disable the units. Hospitals experiencing the problem should return affected units to Smiths Medical for recalibration (free of charge) and should consider testing all their CADD-Solis pumps during routine maintenance to ensure that they alarm appropriately for downstream occlusions.

  17. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    PubMed

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  18. Genetic barcodes

    DOEpatents

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  19. What Use Is Population Genetics?

    PubMed

    Charlesworth, Brian

    2015-07-01

    The Genetic Society of America's Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth's research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation.

  20. What Use Is Population Genetics?

    PubMed Central

    Charlesworth, Brian

    2015-01-01

    The Genetic Society of America’s Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth’s research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation. PMID:26170438

  1. FINE CULM1 (FC1) Works Downstream of Strigolactones to Inhibit the Outgrowth of Axillary Buds in Rice

    PubMed Central

    Minakuchi, Kosuke; Kameoka, Hiromu; Yasuno, Naoko; Umehara, Mikihisa; Luo, Le; Kobayashi, Kaoru; Hanada, Atsushi; Ueno, Kotomi; Asami, Tadao; Yamaguchi, Shinjiro; Kyozuka, Junko

    2010-01-01

    Recent studies of highly branched mutants of pea, Arabidopsis and rice have demonstrated that strigolactones (SLs) act as hormones that inhibit shoot branching. The identification of genes that work downstream of SLs is required for a better understanding of how SLs control the growth of axillary buds. We found that the increased tillering phenotype of fine culm1 (fc1) mutants of rice is not rescued by the application of 1 μM GR24, a synthetic SL analog. Treatment with a high concentration of GR24 (10 μM) causes suppression of tiller growth in wild-type plants, but is not effective on fc1 mutants, implying that proper FC1 functioning is required for SLs to inhibit bud growth. Overexpression of FC1 partially rescued d3-2 defects in the tiller growth and plant height. An in situ hybridization analysis showed that FC1 mRNA accumulates in axillary buds, the shoot apical meristem, young leaves, vascular tissues and the tips of crown roots. FC1 mRNA expression was not significantly affected by GR24, suggesting that transcriptional induction may not be the mechanism by which SLs affect FC1 functioning. On the other hand, the expression level of FC1 is negatively regulated by cytokinin treatment. We propose that FC1 acts as an integrator of multiple signaling pathways and is essential to the fine-tuning of shoot branching in rice. PMID:20547591

  2. Photoperiod control of downstream movements of Atlantic salmon Salmo salar smolts.

    PubMed

    Zydlewski, G B; Stich, D S; McCormick, S D

    2014-10-01

    This study provides the first direct observations that photoperiod controls the initiation of downstream movement in Atlantic salmon Salmo salar smolts. Under simulated natural day length (LDN) conditions and seasonal increases in temperature, smolts increased their downstream movements five-fold for a period of 1 month in late spring. Under the same conditions, parr did not show changes in downstream movement behaviour. When given a shortened day length (10L:14D) beginning in late winter, smolts did not increase the number of downstream movements. An early increase in day length (16L:8D) in late winter resulted in earlier initiation and termination of downstream movements compared to the LDN group. Physiological status and behaviour were related but not completely coincident: gill Na(+) /K(+) -ATPase activity increased in all treatments and thyroid hormone was elevated prior to movement in 16L:8D treatment. The most parsimonious model describing downstream movement of smolts included synergistic effects of photoperiod treatment and temperature, indicating that peak movements occurred at colder temperatures in the 16L:8D treatment than in LDN, and temperature did not influence movement of smolts in the 10L:14D treatment. The complicated interactions of photoperiod and temperature are not surprising since many organisms have evolved to rely on correlations among environmental cues and windows of opportunity to time behaviours associated with life-history transitions. These complicated interactions, however, have serious implications for phenological adjustments and persistence of S. salar populations in response to climate change. PMID:25263186

  3. Paleopopulation genetics.

    PubMed

    Wall, Jeffrey D; Slatkin, Montgomery

    2012-01-01

    Paleopopulation genetics is a new field that focuses on the population genetics of extinct groups and ancestral populations (i.e., populations ancestral to extant groups). With recent advances in DNA sequencing technologies, we now have unprecedented ability to directly assay genetic variation from fossils. This allows us to address issues, such as past population structure, changes in population size, and evolutionary relationships between taxa, at a much greater resolution than can traditional population genetics studies. In this review, we discuss recent developments in this emerging field as well as prospects for the future. PMID:22994357

  4. Dimethyl adipimidate/Thin film Sample processing (DTS); A simple, low-cost, and versatile nucleic acid extraction assay for downstream analysis

    PubMed Central

    Shin, Yong; Lim, Swee Yin; Lee, Tae Yoon; Park, Mi Kyoung

    2015-01-01

    Sample processing, especially that involving nucleic acid extraction, is a prerequisite step for the isolation of high quantities of relatively pure DNA for downstream analyses in many life science and biomedical engineering studies. However, existing methods still have major problems, including labor-intensive time-consuming methods and high costs, as well as requirements for a centrifuge and the complex fabrication of filters and membranes. Here, we first report a versatile Dimethyl adipimidate/Thin film based Sample processing (DTS) procedure without the limitations of existing methods. This procedure is useful for the extraction of DNA from a variety of sources, including 6 eukaryotic cells, 6 bacteria cells, and 2 body fluids in a single step. Specifically, the DTS procedure does not require a centrifuge and has improved time efficiency (30 min), affordability, and sensitivity in downstream analysis. We validated the DTS procedure for the extraction of DNA from human body fluids, as well as confirmed that the quality and quantity of the extracted DNA were sufficient to allow robust detection of genetic and epigenetic biomarkers in downstream analysis. PMID:26370251

  5. Genetic analysis of a hydrophobic domain of coxsackie B3 virus protein 2B: a moderate degree of hydrophobicity is required for a cis-acting function in viral RNA synthesis.

    PubMed Central

    van Kuppeveld, F J; Galama, J M; Zoll, J; Melchers, W J

    1995-01-01

    Coxsackie B virus protein 2B contains near its C terminus a hydrophobic domain with an amino acid composition that is characteristic for transmembrane regions. A molecular genetic approach was followed to define the role of this domain in virus reproduction and to study the structural and hydrophobic requirements of the domain. Nine substitution mutations were introduced in an infectious cDNA clone of coxsackie B3 virus. The effects of the mutations were studied in vivo by transfection of Buffalo green monkey cells with copy RNA transcripts. The results reported here suggest that a critical degree of hydrophobicity of the domain is essential for virus growth. The mutations S77M, C75M, I64S, and V66S, which caused either a small increase or decrease in mean hydrophobicity, yielded viable viruses. The double mutations S77M/C75M and I64S/V6-6S, which caused a more pronounced increase or decrease in hydrophobicity, were nonviable. Negatively charged residues (mutations A71E, I73E, and A71E/I73E) abolished virus growth. The mutations had no effect on the synthesis and processing of the viral polyprotein. Replication and complementation were studied by using a subgenomic coxsackievirus replicon containing the luciferase gene in place of the capsid coding region. Analysis of luciferase accumulation demonstrated that the mutations cause primary defects in viral RNA synthesis that cannot be complemented by wild-type protein 2B provided in trans. The hydrophobic domain is predicted by computer analysis to form a multimeric transmembrane helix. The proposed interaction with the membrane and the implications of the mutations on this interaction are discussed. PMID:7494289

  6. Sex reduces genetic variation: a multidisciplinary review.

    PubMed

    Gorelick, Root; Heng, Henry H Q

    2011-04-01

    For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence for sex decreasing genetic variation appears in ecology, paleontology, population genetics, and cancer biology. The common thread among many of these disciplines is that sex acts like a coarse filter, weeding out major changes, such as chromosomal rearrangements (that are almost always deleterious), but letting minor variation, such as changes at the nucleotide or gene level (that are often neutral), flow through the sexual sieve. Sex acts as a constraint on genomic and epigenetic variation, thereby limiting adaptive evolution. The diverse reasons for sex reducing genetic variation (especially at the genome level) and slowing down evolution may provide a sufficient benefit to offset the famed costs of sex.

  7. Comparative analysis of four methods to extract DNA from paraffin-embedded tissues: effect on downstream molecular applications

    PubMed Central

    2010-01-01

    Background A large portion of tissues stored worldwide for diagnostic purposes is formalin-fixed and paraffin-embedded (FFPE). These FFPE-archived tissues are an extremely valuable source for retrospective (genetic) studies. These include mutation screening in cancer-critical genes as well as pathogen detection. In this study we evaluated the impact of several widely used DNA extraction methods on the quality of molecular diagnostics on FFPE tissues. Findings We compared 4 DNA extraction methods from 4 identically processed FFPE mammary-, prostate-, colon- and lung tissues with regard to PCR inhibition, real time SNP detection and amplifiable fragment size. The extraction methods, with and without proteinase K pre-treatment, tested were: 1) heat-treatment, 2) QIAamp DNA-blood-mini-kit, 3) EasyMAG NucliSens and 4) Gentra Capture-Column-kit. Amplifiable DNA fragment size was assessed by multiplexed 200-400-600 bp PCR and appeared highly influenced by the extraction method used. Proteinase K pre-treatment was a prerequisite for proper purification of DNA from FFPE. Extractions with QIAamp, EasyMAG and heat-treatment were found suitable for amplification of fragments up to 400 bp from all tissues, 600 bp amplification was marginally successful (best was QIAamp). QIAamp and EasyMAG extracts were found suitable for downstream real time SNP detection. Gentra extraction was unsuitable. Hands-on time was lowest for heat-treatment, followed by EasyMAG. Conclusions We conclude that the extraction method plays an important role with regard to performance in downstream molecular applications. PMID:20840759

  8. Act II of the Sunshine Act.

    PubMed

    Pham-Kanter, Genevieve

    2014-11-01

    To coincide with the introduction in the United States of the Sunshine Act, Genevieve Pham-Kanter discusses what we need to look for to fight hidden bias and deliberate or unconscious corruption. Please see later in the article for the Editors' Summary.

  9. Genetic Engineering

    ERIC Educational Resources Information Center

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  10. Linking ligand perception by PEPR pattern recognition receptors to cytosolic Ca2+ elevation and downstream immune signaling in plants

    PubMed Central

    Walker, Robin K.; Zhao, Yichen; Berkowitz, Gerald A.

    2012-01-01

    Little is known about molecular steps linking perception of pathogen invasion by cell surface sentry proteins acting as pattern recognition receptors (PRRs) to downstream cytosolic Ca2+ elevation, a critical step in plant immune signaling cascades. Some PRRs recognize molecules (such as flagellin) associated with microbial pathogens (pathogen-associated molecular patterns, PAMPs), whereas others bind endogenous plant compounds (damage-associated molecular patterns, DAMPs) such as peptides released from cells upon attack. This work focuses on the Arabidopsis DAMPs plant elicitor peptides (Peps) and their receptors, PEPR1 and PEPR2. Pep application causes in vivo cGMP generation and downstream signaling that is lost when the predicted PEPR receptor guanylyl cyclase (GC) active site is mutated. Pep-induced Ca2+ elevation is attributable to cGMP activation of a Ca2+ channel. Some differences were identified between Pep/PEPR signaling and the Ca2+-dependent immune signaling initiated by the flagellin peptide flg22 and its cognate receptor Flagellin-sensing 2 (FLS2). FLS2 signaling may have a greater requirement for intracellular Ca2+ stores and inositol phosphate signaling, whereas Pep/PEPR signaling requires extracellular Ca2+. Maximal FLS2 signaling requires a functional Pep/PEPR system. This dependence was evidenced as a requirement for functional PEPR receptors for maximal flg22-dependent Ca2+ elevation, H2O2 generation, defense gene [WRKY33 and Plant Defensin 1.2 (PDF1.2)] expression, and flg22/FLS2-dependent impairment of pathogen growth. In a corresponding fashion, FLS2 loss of function impaired Pep signaling. In addition, a role for PAMP and DAMP perception in bolstering effector-triggered immunity (ETI) is reported; loss of function of either FLS2 or PEPR receptors impaired the hypersensitive response (HR) to an avirulent pathogen. PMID:23150556

  11. Linking ligand perception by PEPR pattern recognition receptors to cytosolic Ca2+ elevation and downstream immune signaling in plants.

    PubMed

    Ma, Yi; Walker, Robin K; Zhao, Yichen; Berkowitz, Gerald A

    2012-11-27

    Little is known about molecular steps linking perception of pathogen invasion by cell surface sentry proteins acting as pattern recognition receptors (PRRs) to downstream cytosolic Ca(2+) elevation, a critical step in plant immune signaling cascades. Some PRRs recognize molecules (such as flagellin) associated with microbial pathogens (pathogen-associated molecular patterns, PAMPs), whereas others bind endogenous plant compounds (damage-associated molecular patterns, DAMPs) such as peptides released from cells upon attack. This work focuses on the Arabidopsis DAMPs plant elicitor peptides (Peps) and their receptors, PEPR1 and PEPR2. Pep application causes in vivo cGMP generation and downstream signaling that is lost when the predicted PEPR receptor guanylyl cyclase (GC) active site is mutated. Pep-induced Ca(2+) elevation is attributable to cGMP activation of a Ca(2+) channel. Some differences were identified between Pep/PEPR signaling and the Ca(2+)-dependent immune signaling initiated by the flagellin peptide flg22 and its cognate receptor Flagellin-sensing 2 (FLS2). FLS2 signaling may have a greater requirement for intracellular Ca(2+) stores and inositol phosphate signaling, whereas Pep/PEPR signaling requires extracellular Ca(2+). Maximal FLS2 signaling requires a functional Pep/PEPR system. This dependence was evidenced as a requirement for functional PEPR receptors for maximal flg22-dependent Ca(2+) elevation, H(2)O(2) generation, defense gene [WRKY33 and Plant Defensin 1.2 (PDF1.2)] expression, and flg22/FLS2-dependent impairment of pathogen growth. In a corresponding fashion, FLS2 loss of function impaired Pep signaling. In addition, a role for PAMP and DAMP perception in bolstering effector-triggered immunity (ETI) is reported; loss of function of either FLS2 or PEPR receptors impaired the hypersensitive response (HR) to an avirulent pathogen.

  12. Evaluation of Head-of-Reservoir Conditions for Downstream Migration of Juvenile Chinook Salmon and Steelhead at Shasta Lake, California

    NASA Astrophysics Data System (ADS)

    Clancey, K. M.; Saito, L.; Svoboda, C.; Bender, M. D.; Hannon, J.; Hellmann, K. M.

    2015-12-01

    Since completion of Shasta Dam, migration of Chinook salmon and steelhead trout in the Sacramento River has been blocked, causing loss of spawning and rearing habitat. This has been a factor leading to population declines of these fish species over several decades. Winter-run Chinook salmon, spring-run Chinook salmon and steelhead trout are now listed under the Endangered Species Act. A habitat assessment of the tributaries upstream of Shasta Dam showed that the Sacramento and McCloud tributaries have suitable habitat for reintroduction of adult salmon and steelhead for spawning. Such reintroduction would require downstream passage of juvenile Chinook salmon and steelhead past Shasta Dam. To evaluate the possibility of collecting and transporting juvenile Chinook salmon and steelhead past Shasta Dam, a CE-QUAL-W2 model of Shasta Lake and the Sacramento River, McCloud River, Pit River and Squaw Creek tributaries was used to assess where and when conditions were favorable at head-of-reservoir locations upstream of proposed temperature curtains to collect juvenile fish. Head-of-reservoir is the zone of transition between the river and the upstream end of the reservoir. Criteria for evaluating locations suitable to collect these fish included water temperature and velocities in the Sacramento and McCloud tributaries. Model output was analyzed during months of downstream migration under dry, median and wet year conditions. Potential for proposed temperature curtains, anchored and floating, to improve conditions for fish migration was also evaluated with the CE-QUAL-W2 model. Use of temperature curtains to assist fish migration is a novel approach that to our knowledge has not previously been assessed for recovery of Chinook salmon and steelhead populations. Providing safe passage conditions is challenging, however the study findings may assist in formulation of a juvenile fish passage alternative that is suitable for Shasta Lake.

  13. Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation

    PubMed Central

    Zhou, X.; Unthank, J. L.; Miller, S. J.; Bills, R.

    2009-01-01

    The discovery that hemoglobin, albumin, and glutathione carry and release nitric oxide (NO) may have consequences for movement of NO by blood within microvessels. We hypothesize that NO in plasma or bound to proteins likely survives to downstream locations. To confirm this hypothesis, there must be a finite NO concentration ([NO]) in arteriolar blood, and upstream resistance vessels must be able to increase the vessel wall [NO] of downstream arterioles. Arteriolar blood NO was measured with NO-sensitive microelectrodes, and vessel wall [NO] was consistently 25–40% higher than blood [NO]. Localized suppression of NO production in large arterioles over 500–1,000 μm with l-nitroarginine reduced the [NO] ∼40%, indicating as much as 60% of the wall NO was from blood transfer. Flow in mesenteric arteries was elevated by occlusion of adjacent arteries to induce a flow-mediated increase in arterial NO production. Both arterial wall and downstream arteriolar [NO] increased and the arterioles dilated as the blood [NO] was increased. To study receptor-mediated NO generation, bradykinin was locally applied to upstream large arterioles and NO measured there and in downstream arterioles. At both sites, [NO] increased and both sets of vessels dilated. When isoproterenol was applied to the upstream vessels, they dilated, but neither the [NO] or diameter downstream arterioles increased. These observations indicate that NO can move in blood from upstream to downstream resistance vessels. This mechanism allows larger vessels that generate large [NO] to influence vascular tone in downstream vessels in response to both flow and receptor stimuli. PMID:19666847

  14. 25 CFR 700.33 - Act (The Act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88...

  15. 25 CFR 700.33 - Act (The Act).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88...

  16. 25 CFR 700.33 - Act (The Act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88...

  17. 25 CFR 700.33 - Act (The Act).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88...

  18. ACT and College Success

    ERIC Educational Resources Information Center

    Bleyaert, Barbara

    2010-01-01

    What is the relationship between ACT scores and success in college? For decades, admissions policies in colleges and universities across the country have required applicants to submit scores from a college entrance exam, most typically the ACT (American College Testing) or SAT (Scholastic Aptitude Test). This requirement suggests that high school…

  19. Americans with Disabilities Act.

    ERIC Educational Resources Information Center

    Updating School Board Policies, 1992

    1992-01-01

    Addressed to school board members, this article attempts to summarize requirements of the Americans with Disabilities Act (ADA) and its implications for school districts. It warns against hasty purchase of private compliance assistance; then provides an overview of each of the Act's five Titles which address employment practices, activities…

  20. The Clean Water Act

    SciTech Connect

    Piatt, J.

    1995-12-31

    The Federal Water Pollution Control Act, commonly called the Clean Water Act (CWA), was adopted on 18 October 1972. Since then it has been amended 18 times, the last amendments were adopted on 4 February 1987. As established, its objective is: to restore and maintain the chemical, physical, and biological integrity of the Nation`s waters. And has, as an interim goal: water quality which provides for the protection and propagation of fish, shellfish, and wildlife and provides for recreation in and on the water. It should be noted that Congress established as the Act`s ultimate goal: the discharge of pollutants into the navigable waters be eliminated. The Act set out to meet this lofty objective and goal through the development and implementation of controls on the point source discharges and the nonpoint source release of pollutants. The regulation of point and nonpoint sources as well as future requirements are discussed.

  1. Analytical prediction of the unsteady lift on a rotor caused by downstream struts

    NASA Technical Reports Server (NTRS)

    Taylor, A. C., III; Ng, W. F.

    1987-01-01

    A two-dimensional, inviscid, incompressible procedure is presented for predicting the unsteady lift on turbomachinery blades caused by the upstream potential disturbance of downstream flow obstructions. Using the Douglas-Neumann singularity superposition potential flow computer program to model the downstream flow obstructions, classical equations of thin airfoil theory are then employed, to compute the unsteady lift on the upstream rotor blades. The method is applied to a particular geometry which consists of a rotor, a downstream stator, and downstream struts which support the engine casing. Very good agreement between the Douglas-Neumann program and experimental measurements was obtained for the downstream stator-strut flow field. The calculations for the unsteady lift due to the struts were in good agreement with the experiments in showing that the unsteady lift due to the struts decays exponentially with increased axial separation of the rotor and the struts. An application of the method showed that for a given axial spacing between the rotor and the strut, strut-induced unsteady lift is a very weak function of the axial or circumferential position of the stator.

  2. Downstream Intensification Effects Associated with CO2 Laser Mitigation of Fused Silica

    SciTech Connect

    Matthews, M J; Bass, I L; Guss, G M; Widmayer, C C; Ravizza, F L

    2007-10-29

    Mitigation of 351nm laser-induced damage sites on fused silica exit surfaces by selective CO{sub 2} treatment has been shown to effectively arrest the exponential growth responsible for limiting the lifetime of optics in high-fluence laser systems. However, the perturbation to the optical surface profile following the mitigation process introduces phase contrast to the beam, causing some amount of downstream intensification with the potential to damage downstream optics. Control of the laser treatment process and measurement of the associated phase modulation is essential to preventing downstream 'fratricide' in damage-mitigated optical systems. In this work we present measurements of the surface morphology, intensification patterns and damage associated with various CO{sub 2} mitigation treatments on fused silica surfaces. Specifically, two components of intensification pattern, one on-axis and another off-axis can lead to damage of downstream optics and are related to rims around the ablation pit left from the mitigation process. It is shown that control of the rim structure around the edge of typical mitigation sites is crucial in preventing damage to downstream optics.

  3. Wave and ion evolution downstream of quasi-perpendicular bow shocks

    NASA Technical Reports Server (NTRS)

    Mckean, M. E.; Omidi, N.; Krauss-Varban, D.

    1995-01-01

    Distribution functions of ions heated in quasi-perpendicular bow shocks have a large perpendicular temperature anisotropy that provides free energy for the growth of Alfven ion cyclotron (AIC) waves and mirror waves. Both types of waves have been observed in the Earth's magnetosheath downstream of quasi-perpendicular shocks. We use a two-dimensional hybrid simulations to give a self-consistent description of the evolution of the wave spectra downstream of quasi-perpendicular shocks. Both mirror and AIC waves are identified in the simulated magnetosheath. They are generated at or near the shock front and convected away from it by the sheath plasma. Near the shock, the waves have a broad spectrum, but downstream of the shock, shorter-wavelength modes are heavily damped and only longer-wavelength modes persist. The characteristics of these surviving modes can be predicted with reasonable accuracy by linear kinetic theory appropriate for downstream conditions. We also follow the evolution of the ion distribution function. The shocked ions that provide the free energy for wave growth have a two-component distribution function. The halo is initially gyrophase-bunched and extremely anisotropic. Within a relatively short distance downstream of the shock (of the order of 10 ion inertial lengths), wave-particle interactions remove these features from the halo and reduce the anisotropy of the distribution to near-threshold levels for the mirror and AIC instabilities. A similar evolution has been observed for ions at the Earth's bow shock.

  4. Assessing downstream flood impacts due to a potential GLOF from Imja Lake in Nepal

    NASA Astrophysics Data System (ADS)

    Somos-Valenzuela, M. A.; McKinney, D. C.; Byers, A. C.; Rounce, D. R.; Portocarrero, C.; Lamsal, D.

    2014-11-01

    Glacial-dominated areas pose unique challenges to downstream communities in adapting to recent and continuing global climate change, including increased threats of glacial lake outburst floods (GLOFs) that can increase risk due to flooding of downstream communities and cause substantial impacts on regional social, environmental and economic systems. The Imja glacial lake in Nepal, with potential to generate a GLOF, was studied using a two-dimensional debris flow inundation model in order to evaluate the effectiveness of proposed measures to reduce possible flooding impacts to downstream communities by lowering the lake level. The results indicate that only minor flood impact reduction is achieved in the downstream community of Dingboche with modest (~3 m) lake lowering. Lowering the lake by 10 m shows a significant reduction in inundated area. However, lowering the lake by 20 m almost eliminates all flood impact at Dingboche. Further downstream at Phakding, the impact of the GLOF is significant and similar reductions in inundation are likely as a result of lake lowering.

  5. Assessing downstream flood impacts due to a potential GLOF from Imja Tsho in Nepal

    NASA Astrophysics Data System (ADS)

    Somos-Valenzuela, M. A.; McKinney, D. C.; Byers, A. C.; Rounce, D. R.; Portocarrero, C.; Lamsal, D.

    2015-03-01

    Glacial-dominated areas pose unique challenges to downstream communities in adapting to recent and continuing global climate change, including increased threats of glacial lake outburst floods (GLOFs) that can increase risk due to flooding of downstream communities and cause substantial impacts on regional social, environmental and economic systems. The Imja glacial lake (or Imja Tsho) in Nepal, which has the potential to generate a GLOF, was studied using a two-dimensional debris-flow inundation model in order to evaluate the effectiveness of proposed measures to reduce possible flooding impacts to downstream communities by lowering the lake level. The results indicate that only minor flood impact reduction is achieved in the downstream community of Dingboche with modest (~3 m) lake lowering. Lowering the lake by 10 m shows a significant reduction in inundated area. However, lowering the lake by 20 m almost eliminates all flood impact at Dingboche. Further downstream at Phakding, the impact of the GLOF is significant and similar reductions in inundation are likely as a result of lake lowering.

  6. Flow Structure and Turbulence Characteristics downstream of a Spanwise Suspended Linear Canopy through Laboratory Experiments

    NASA Astrophysics Data System (ADS)

    Qiao, Jundong; Delavan, Sarah

    2014-11-01

    Laboratory experiments were conducted to explore the mean flow structure and turbulence properties downstream of a spanwise suspended linear canopy in a 2-D open channel flow using the Particle Tracking Velocimetry technique. This canopy simulated the effect of one long-line structure of a mussel farm. Four experimental scenarios with the approach velocities 50, 80, 110, and 140 mm s-1 were under investigation. Three sub-layers formed downstream of the canopy. An internal canopy layer, where the time-averaged velocity decreases linearly with increasing distance downstream, a canopy mixing layer increasing in vertical extent with increasing distance downstream of the canopy, and an external canopy layer with higher velocity under the canopy, which may bring nutrients from the local ambient environment into this layer. The canopy turbulence results in upward momentum transport downstream of the canopy within a distance of 0.60 of the canopy depth and downward momentum transport beyond 1.20 of it. In the scenarios with relatively lower approach velocities 50 and 80 mm s1 , the wake turbulence results in upward momentum transport. The broader goal of this study is to offer guidelines for the design and site selection of more productive mussel farms. The results suggest that distance interval between the parallel long-lines in a mussel farm should be less than 0.6 times the height of a long-line dropper. Also, potential farm locations that are characterized with current velocity from 50 to 80 mm s1 are suggested.

  7. Chemical genetics and regeneration.

    PubMed

    Sengupta, Sumitra; Zhang, Liyun; Mumm, Jeff S

    2015-01-01

    Regeneration involves interactions between multiple signaling pathways acting in a spatially and temporally complex manner. As signaling pathways are highly conserved, understanding how regeneration is controlled in animal models exhibiting robust regenerative capacities should aid efforts to stimulate repair in humans. One way to discover molecular regulators of regeneration is to alter gene/protein function and quantify effect(s) on the regenerative process: dedifferentiation/reprograming, stem/progenitor proliferation, migration/remodeling, progenitor cell differentiation and resolution. A powerful approach for applying this strategy to regenerative biology is chemical genetics, the use of small-molecule modulators of specific targets or signaling pathways. Here, we review advances that have been made using chemical genetics for hypothesis-focused and discovery-driven studies aimed at furthering understanding of how regeneration is controlled.

  8. Genetics of impulsive behaviour

    PubMed Central

    Bevilacqua, Laura; Goldman, David

    2013-01-01

    Impulsivity, defined as the tendency to act without foresight, comprises a multitude of constructs and is associated with a variety of psychiatric disorders. Dissecting different aspects of impulsive behaviour and relating these to specific neurobiological circuits would improve our understanding of the etiology of complex behaviours for which impulsivity is key, and advance genetic studies in this behavioural domain. In this review, we will discuss the heritability of some impulsivity constructs and their possible use as endophenotypes (heritable, disease-associated intermediate phenotypes). Several functional genetic variants associated with impulsive behaviour have been identified by the candidate gene approach and re-sequencing, and whole genome strategies can be implemented for discovery of novel rare and common alleles influencing impulsivity. Via deep sequencing an uncommon HTR2B stop codon, common in one population, was discovered, with implications for understanding impulsive behaviour in both humans and rodents and for future gene discovery. PMID:23440466

  9. Genetically engineered probiotics.

    PubMed

    Steidler, Lothar

    2003-10-01

    Probiotic micro-organisms have been used for many years. Originating as food supplements, they are now most often administered orally and offer an attractive alternative for treating of intestinal disorders. A better understanding of the mechanisms by which these micro-organisms act has now opened up possibilities for designing new probiotic strains. Through genetic engineering, it is possible not only to strengthen the effects of existing strains, but also to create completely new probiotics. These need not necessarily be composed only of bacterial products but can also include elements of regulatory systems or enzymes derived from a foreign-human-source. If designed carefully and with absolute attention to biological safety in its broadest sense, the development of genetically modified probiotics has the potential to revolutionize alimentary health.

  10. Fast acting check valve

    NASA Technical Reports Server (NTRS)

    Perkins, Gerald S. (Inventor)

    1979-01-01

    A check valve which closes more rapidly to prevent wearing of the valve seat and of the valve member that seals thereagainst, including a solenoid or other actuator that aids the normal spring to quickly close the valve at approximately the time when downpath fluid flow would stop, the actuator then being deenergized. The control circuit that operates the actuator can include a pair of pressure sensors sensing pressure both upstream and downstream from the valve seat. Where the valve is utilized to control flow to or from a piston pump, energization of the actuator can be controlled by sensing when the pump piston reaches its extreme of travel.

  11. Genetic algorithms for genetic neural nets. Research report

    SciTech Connect

    Sharp, D.H.; Reinitz, J.; Mjolsness, E.

    1991-01-01

    In contrast to most synthetic neural nets, biological neural networks have a strong component of genetic determination which acts before and during experiential learning. Three broad levels of phenomena are present: long-term evolution, involving crossover as well as point mutation; a developmental process mapping genetic information to a set of cells and their internal states of gene expression (genotype to phenotype); and the subsequent synaptogenesis. We describe a very simple mathematical idealization of these three levels which combines the crossover search method of genetic algorithms with the developmental models used in our previous work on 'genetic' or 'recursively generated' artificial neural nets and elaborated into a connectionist model of biological development. Despite incorporating all three levels (evolution on genes; development of cells; synapse formation) the model may actually be far cheaper to compute with than a comparable search directly in synaptic weight space.

  12. Antibiotic Resistance in Aeromonas Upstream and Downstream of a Water Resource Recovery Facility

    PubMed Central

    Henderson, Samantha K.; Askew, Maegan L.; Risenhoover, Hollie G.; McAndrews, Chrystle R.; Kennedy, S. Dawn; Paine, C. Sue

    2014-01-01

    Aeromonas strains isolated from sediments upstream and downstream of a water resource recovery facility (WRRF) over a two-year time period were tested for susceptibility to thirteen antibiotics. Incidence of resistance to antibiotics, antibiotic resistance phenotypes, and diversity (based on resistance phenotypes) were compared in the two populations. At the beginning of the study, the upstream and downstream Aeromonas populations were different for incidence of antibiotic resistance (p < 0.01), resistance phenotypes (p < 0.005), and diversity. However, these differences declined over time and were not significant at the end of the study. These results (1) indicate that antibiotic resistance in Aeromonas in stream sediments fluctuates considerably over time and (2) suggest that WRRF effluent does not, when examined over the long term, affect antibiotic resistance in Aeromonas in downstream sediment. PMID:25327024

  13. An experimental study of turbine vane heat transfer with leading edge and downstream film cooling

    NASA Astrophysics Data System (ADS)

    Nirmalan, V.; Hylton, L. D.

    1989-06-01

    This paper presents the effects of downstream film cooling, with and without leading edge showerhead film cooling, on turbine-vane external heat transfer. Steady-state experimental measurements were made in a three-vane linear two-dimensional cascade. The principal independent parameters were maintained over ranges consistent with actual engine conditions. The test matrix was structured to provide an assessment of the independent influence of parameters of interest, namely, exit Mach number, exit Reynolds number, coolant-to-gas temperature ratio, and coolant-to-gas pressure ratio. The data obtained indicate that considerable cooling benefits can be achieved by utilizing downstream film cooling. The downstream film cooling process was shown to be a complex interaction of two competing mechanisms. The thermal dilution effect, associated with the injection of relatively cold fluid, results in a decrease in the heat transfer to the airfoil. Conversely, the turbulence augmentation, produced by the injection process, results in increased heat transfer to the airfoil.

  14. Antibiotic resistance in Aeromonas upstream and downstream of a water resource recovery facility.

    PubMed

    Cisar, Cindy R; Henderson, Samantha K; Askew, Maegan L; Risenhoover, Hollie G; McAndrews, Chrystle R; Kennedy, S Dawn; Paine, C Sue

    2014-09-01

    Aeromonas strains isolated from sediments upstream and downstream of a water resource recovery facility (WRRF) over a two-year time period were tested for susceptibility to 13 antibiotics. Incidence of resistance to antibiotics, antibiotic resistance phenotypes, and diversity (based on resistance phenotypes) were compared in the two populations. At the beginning of the study, the upstream and downstream Aeromonas populations were different for incidence of antibiotic resistance (p < 0.01), resistance phenotypes (p < 0.005), and diversity. However, these differences declined over time and were not significant at the end of the study. These results (1) indicate that antibiotic resistance in Aeromonas in stream sediments fluctuates considerably over time and (2) suggest that WRRF effluent does not, when examined over the long- term, affect antibiotic resistance in Aeromonas in downstream sediment.

  15. An experimental study of turbine vane heat transfer with leading edge and downstream film cooling

    NASA Technical Reports Server (NTRS)

    Nirmalan, V.; Hylton, L. D.

    1989-01-01

    This paper presents the effects of downstream film cooling, with and without leading edge showerhead film cooling, on turbine-vane external heat transfer. Steady-state experimental measurements were made in a three-vane linear two-dimensional cascade. The principal independent parameters were maintained over ranges consistent with actual engine conditions. The test matrix was structured to provide an assessment of the independent influence of parameters of interest, namely, exit Mach number, exit Reynolds number, coolant-to-gas temperature ratio, and coolant-to-gas pressure ratio. The data obtained indicate that considerable cooling benefits can be achieved by utilizing downstream film cooling. The downstream film cooling process was shown to be a complex interaction of two competing mechanisms. The thermal dilution effect, associated with the injection of relatively cold fluid, results in a decrease in the heat transfer to the airfoil. Conversely, the turbulence augmentation, produced by the injection process, results in increased heat transfer to the airfoil.

  16. Arthropod Genetics.

    ERIC Educational Resources Information Center

    Zumwalde, Sharon

    2000-01-01

    Introduces an activity on arthropod genetics that involves phenotype and genotype identification of the creature and the construction process. Includes a list of required materials and directions to build a model arthropod. (YDS)

  17. Genetic Discrimination

    MedlinePlus

    ... Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care ... genetic discrimination. April 25, 2007, Statement of Administration Policy, Office of Management and Budget Official Statement from the Office of ...

  18. Kinesin-1 Acts with Netrin and DCC to Maintain Sensory Neuron Position in Caenorhabditis elegans

    PubMed Central

    Barsi-Rhyne, Benjamin J.; Miller, Kristine M.; Vargas, Christopher T.; Thomas, Anthony B.; Park, Joori; Bremer, Martina; Jarecki, Jessica L.; VanHoven, Miri K.

    2013-01-01

    The organization of neurons and the maintenance of that arrangement are critical to brain function. Failure of these processes in humans can lead to severe birth defects, mental retardation, and epilepsy. Several kinesins have been shown to play important roles in cell migration in vertebrate systems, but few upstream and downstream pathway members have been identified. Here, we utilize the genetic model organism Caenorhabditis elegans to elucidate the pathway by which the C. elegans Kinesin-1 Heavy Chain (KHC)/KIF5 ortholog UNC-116 functions to maintain neuronal cell body position in the PHB sensory neurons. We find that UNC-116/KHC acts in part with the cell and axon migration molecules UNC-6/Netrin and UNC-40/DCC in this process, but in parallel to SAX-3/Robo. We have also identified several potential adaptor, cargo, and regulatory proteins that may provide insight into the mechanism of UNC-116/KHC’s function in this process. These include the cargo receptor UNC-33/CRMP2, the cargo adaptor protein UNC-76/FEZ and its regulator UNC-51/ULK, the cargo molecule UNC-69/SCOCO, and the actin regulators UNC-44/Ankyrin and UNC-34/Enabled. These genes also act in cell migration and axon outgrowth; however, many proteins that function in these processes do not affect PHB position. Our findings suggest an active posterior cell migration mediated by UNC-116/KHC occurs throughout development to maintain proper PHB cell body position and define a new pathway that mediates maintenance of neuronal cell body position. PMID:23475988

  19. Ciona Genetics

    PubMed Central

    Veeman, Michael T.; Chiba, Shota; Smith, William C.

    2010-01-01

    Ascidians, such as Ciona, are invertebrate chordates with simple embryonic body plans and small, relatively non-redundant genomes. Ciona genetics is in its infancy compared to many other model systems, but it provides a powerful method for studying this important vertebrate outgroup. Here we give basic methods for genetic analysis of Ciona, including protocols for controlled crosses both by natural spawning and by the surgical isolation of gametes; the identification and propagation of mutant lines; and strategies for positional cloning. PMID:21805273

  20. Downstream development of baroclinic waves in the midlatitude jet induced by extratropical transition: A case study

    NASA Astrophysics Data System (ADS)

    Chen, Hua

    2015-04-01

    This study uses eddy kinetic energy analysis and a targeting method to investigate how an extratropical transition (ET) event induced downstream development (the modification of the midlatitude flow downstream of the ET system) in the midlatitude jet environment. The downstream development showed distinct characteristics of "coupling development" and being "boundary-trapped". Eddies (potential disturbances) first developed at the upper levels, and these triggered lower-level eddy development, with all eddies decaying away from the tropopause and the surface. Thereafter, a lower-level eddy caught up with the upper-level eddy ahead of it, and they coupled to form a cyclone extending through the whole troposphere. Vertical ageostrophic geopotential flux may be a crucial dynamic factor throughout the eddy's lower-level growth, boundary-trapping, and coupling development. Together with barotropic conversion, the ageostrophic geopotential fluxes that were transported from Hurricane Fabian (2003) to the midlatitudes by the outflow led to downstream ridge development in the upper-level jet. The strong downstream advection of eddy kinetic energy in the exit region of the jet streak triggered downstream trough development. The well-known ridge-trough couplet thus formed. The vertical ageostrophic fluxes that were transported downward from the developed upper-level systems converged near the surface and resulted in lower-level eddy growth. Baroclinic conversion was negligible near the boundaries, while it was the main source of eddy kinetic energy at mid-levels. In the upper-level jet, potential energy was converted to the mean kinetic energy of the jet, which in turn was converted to eddy kinetic energy through barotropic conversion.

  1. Photoperiod control of downstream movements of Atlantic salmon Salmo salar smolts

    USGS Publications Warehouse

    Zydlewski, Gayle B.; Stich, Daniel S.; McCormick, Stephen D.

    2014-01-01

    This study provides the first direct observations that photoperiod controls the initiation of downstream movement in Atlantic salmon Salmo salar smolts. Under simulated natural day length (LDN) conditions and seasonal increases in temperature, smolts increased their downstream movements five-fold for a period of 1 month in late spring. Under the same conditions, parr did not show changes in downstream movement behaviour. When given a shortened day length (10L:14D) beginning in late winter, smolts did not increase the number of downstream movements. An early increase in day length (16L:8D) in late winter resulted in earlier initiation and termination of downstream movements compared to the LDN group. Physiological status and behaviour were related but not completely coincident: gill Na+/K+-ATPase activity increased in all treatments and thyroid hormone was elevated prior to movement in 16L:8D treatment. The most parsimonious model describing downstream movement of smolts included synergistic effects of photoperiod treatment and temperature, indicating that peak movements occurred at colder temperatures in the 16L:8D treatment than in LDN, and temperature did not influence movement of smolts in the 10L:14D treatment. The complicated interactions of photoperiod and temperature are not surprising since many organisms have evolved to rely on correlations among environmental cues and windows of opportunity to time behaviours associated with life-history transitions. These complicated interactions, however, have serious implications for phenological adjustments and persistence ofS. salar populations in response to climate change.

  2. Systems Genetics Implicates Cytoskeletal Genes in Oocyte Control of Cloned Embryo Quality

    PubMed Central

    Cheng, Yong; Gaughan, John; Midic, Uros; Han, Zhiming; Liang, Cheng-Guang; Patel, Bela G.; Latham, Keith E.

    2013-01-01

    Cloning by somatic cell nuclear transfer is an important technology, but remains limited due to poor rates of success. Identifying genes supporting clone development would enhance our understanding of basic embryology, improve applications of the technology, support greater understanding of establishing pluripotent stem cells, and provide new insight into clinically important determinants of oocyte quality. For the first time, a systems genetics approach was taken to discover genes contributing to the ability of an oocyte to support early cloned embryo development. This identified a primary locus on mouse chromosome 17 and potential loci on chromosomes 1 and 4. A combination of oocyte transcriptome profiling data, expression correlation analysis, and functional and network analyses yielded a short list of likely candidate genes in two categories. The major category—including two genes with the strongest genetic associations with the traits (Epb4.1l3 and Dlgap1)—encodes proteins associated with the subcortical cytoskeleton and other cytoskeletal elements such as the spindle. The second category encodes chromatin and transcription regulators (Runx1t1, Smchd1, and Chd7). Smchd1 promotes X chromosome inactivation, whereas Chd7 regulates expression of pluripotency genes. Runx1t1 has not been associated with these processes, but acts as a transcriptional repressor. The finding that cytoskeleton-associated proteins may be key determinants of early clone development highlights potential roles for cytoplasmic components of the oocyte in supporting nuclear reprogramming. The transcriptional regulators identified may contribute to the overall process as downstream effectors. PMID:23307892

  3. Endurance testing of downstream cathodes on a low-power MPD thruster

    NASA Technical Reports Server (NTRS)

    Burkhart, J. A.; Rose, J. R.

    1974-01-01

    A low-power MPD thruster with downstream cathode was tested for endurance with a series of hollow cathode designs. Failure modes and failure mechanisms were identified. A new hollow cathode (with rod inserts) has emerged which shows promise for long life. The downstream positioning of the cathode was also changed from an on-axis location to an off-axis location. Data are presented for a 1332-hour life test of this new hollow cathode located at the new off-axis location. Xenon propellant was used.

  4. Status of downstream fish passage at hydroelectric projects in the northeast, USA

    USGS Publications Warehouse

    Odeh, Mufeed; Orvis, Curtis

    1997-01-01

    In the northeastern United States several guidance, protection, and conveyance methods have been employed to assist downstream migrating fish. Overlay racks, standard bar racks with close spacing, louvers, curtain walls, guide walls, netting, and other means have been used to guide and protect fish from entrainment. The design process of these facilities comprises consideration of various factors, including flow approach, attraction flow, guidance and protection devices, bypass location, conveyance mechanism, and plunge pool conditions. This paper presents the status of the design criteria for downstream fish passage facilities at hydroelectric sites in the northeast part of the United States. Examples of existing facilities are given.

  5. Recent hydrocarbon developments in Latin America: Key issues in the downstream oil sector

    SciTech Connect

    Wu, K.; Pezeshki, S.

    1995-03-01

    This report discusses the following: (1) An overview of major issues in the downstream oil sector, including oil demand and product export availability, the changing product consumption pattern, and refineries being due for major investment; (2) Recent upstream developments in the oil and gas sector in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Trinidad and Tobago, and Venezuela; (3) Recent downstream developments in the oil and gas sector in Argentina, Chile, Colombia, Ecuador, Mexico, Peru, Cuba, and Venezuela; (4) Pipelines in Argentina, Bolivia, Brazil, Chile, and Mexico; and (5) Regional energy balance. 4 figs., 5 tabs.

  6. Analysis of the longitudinal dependence of the downstream fluence of large solar energetic proton events

    NASA Astrophysics Data System (ADS)

    Pacheco, Daniel; Sanahuja, Blai; Aran, Angels; Agueda, Neus; Jiggens, Piers

    2016-07-01

    Simulations of the solar energetic particle (SEP) intensity-time profiles are needed to estimate the radiation environment for interplanetary missions. At present, the physics-based models applied for such a purpose, and including a moving source of particles, are not able to model the portion of the SEP intensity enhancement occurring after the coronal/interplanetary shock crossing by the observer (a.k.a. the downstream region). This is the case, for example, of the shock-and-particle model used to build the SOLPENCO2 code. SOLPENCO2 provides the statistical modelling tool developed in the ESA/SEPEM project for interplanetary missions with synthetic SEP event simulations for virtual spacecraft located at heliocentric distances between 0.2 AU and 1.6 AU (http://dev.sepem.oma.be/). In this work we present an analysis of 168 individual SEP events observed at 1 AU from 1988 to 2013. We identify the solar eruptive phenomena associated with these SEP events, as well as the in-situ passage of interplanetary shocks. For each event, we quantify the amount of fluence accounted in the downstream region, i.e. after the passage of the shock, at the 11 SEPEM reference energy channels (i.e., from 5 to 300 MeV protons). First, from the subset of SEP events simultaneously detected by near Earth spacecraft (using SEPEM reference data) and by one of the STEREO spacecraft, we select those events for which the downstream region can be clearly determined. From the 8 selected multi-spacecraft events, we find that the western observations of each event have a minor downstream contribution than their eastern counterpart, and that the downstream-to-total fluence ratio of these events decreases as a function of the energy. Hence, there is a variation of the downstream fluence with the heliolongitude in SEP events. Based on this result, we study the variation of the downstream-to-total fluence ratios of the total set of individual events. We confirm the eastern-to-western decrease of the

  7. Dam impacts on downstream sediment grain size in a dryland river

    NASA Astrophysics Data System (ADS)

    Dekker, F. J.; Wilcox, A. C.

    2011-12-01

    We examined sediment characteristics on a dammed, sand dominated, dryland river to determine the pattern of grain size adjustment and the extent of sediment deficit resulting from dam-induced changes in water and sediment fluxes. We expected that conditions of sediment deficit would be manifested by coarsening immediately downstream of the dam, but that downstream fining would occur as a function of both tributary inputs and landform heterogeneity, such as canyon and wide floodplain reaches. Grain size data were collected longitudinally downstream on the Bill Williams River (BWR), a major tributary of the Colorado River in Arizona that was dammed in 1968 by Alamo Dam. We took photographs at 30m intervals for digital grain size analysis and collected bulk samples or pebble counts every 300m, for over 20% of the 58km long BWR. We used GIS to delineate the contributing area of approximately 60 ephemeral tributaries entering the BWR mainstem below the dam and to identify canyon and wide floodplain reaches. Whereas upstream of Alamo Dam, bed materials are predominantly sand-sized, in the 4km canyon reach downstream of the dam, the bed material coarsens, with an average size of 72 mm along bars, and >1 m of incision is evident. Bars fine to 33 mm and 23 mm at 8km and 28km downstream of the dam, respectively. Decreasing bar grain size downstream is explained to some extent by an exponential model with a fining coefficient of 0.033km^-1 (r^2=0.50). The grain size variation within gravel samples also decreases downstream. The gravel-dominated reach downstream of the dam lacks tributary inputs of sediments; 75% of the tributary area of the dammed BWR enters the mainstem in the river's lower half. The lower BWR is more sand dominated, which is possibly controlled by a wide, 8km long floodplain reach where surface flow is often discontinuous. Further analysis of sediment dynamics in the BWR using reservoir sedimentation and cosmogenic nuclide data are being used to determine

  8. ACTS mobile SATCOM experiments

    NASA Technical Reports Server (NTRS)

    Abbe, Brian S.; Frye, Robert E.; Jedrey, Thomas C.

    1993-01-01

    Over the last decade, the demand for reliable mobile satellite communications (satcom) for voice, data, and video applications has increased dramatically. As consumer demand grows, the current spectrum allocation at L-band could become saturated. For this reason, NASA and the Jet Propulsion Laboratory are developing the Advanced Communications Technology Satellites (ACTS) mobile terminal (AMT) and are evaluating the feasibility of K/Ka-band (20/30 GHz) mobile satcom to meet these growing needs. U.S. industry and government, acting as co-partners, will evaluate K/Ka-band mobile satcom and develop new technologies by conducting a series of applications-oriented experiments. The ACTS and the AMT testbed will be used to conduct these mobile satcom experiments. The goals of the ACTS Mobile Experiments Program and the individual experiment configurations and objectives are further presented.

  9. Assertive Community Treatment (ACT)

    MedlinePlus

    ... community treatment? Assertive community treatment (ACT) is a model of psychiatric care that can be very effective ... it the most. Similar to the “treatment team” model of an inpatient psychiatric unit, which includes nurses, ...

  10. The ACTS propagation program

    NASA Technical Reports Server (NTRS)

    Chakraborty, Dayamoy; Davarian, Faramaz

    1991-01-01

    The purpose of the Advanced Communications Technology Satellite (ACTS) is to demonstrate the feasibility of the Ka-band (20 and 30 GHz) spectrum for satellite communications, as well as to help maintain U.S. leadership in satellite communications. ACTS incorporates such innovative schemes as time division multiple access (TDMA), microwave and baseband switching, onboard regeneration, and adaptive application of coding during rain-fade conditions. The success or failure of the ACTS experiment will depend on how accurately the rain-fade statistics and fade dynamics can be predicted in order to derive an appropriate algorithm that will combat weather vagaries, specifically for links with small terminals, such as very small aperture terminals (VSAT's) where the power margin is a premium. This article describes the planning process and hardware development program that will comply with the recommendations of the ACTS propagation study groups.

  11. Identification of Candidate Downstream Targets of TGFβ Signaling During Palate Development by Genome-Wide Transcript Profiling

    PubMed Central

    Suzuki, Akiko; Chai, Yang; Hacia, Joseph G.

    2013-01-01

    Nonsyndromic orofacial clefts are common birth defects whose etiology is influenced by complex genetic and environmental factors and gene–environment interactions. Although these risk factors are not yet fully elucidated, it is known that alterations in transforming growth factor-beta (TGFβ) signaling can cause craniofacial abnormalities, including cleft palate, in mammals. To elucidate the downstream targets of TGFβ signaling in palatogenesis, we analyzed the gene expression profiles of Tgfbr2fl/fl;Wnt1-Cre mouse embryos with cleft palate and other craniofacial deformities resulting from the targeted inactivation of the Tgfbr2 gene in their cranial neural crest (CNC) cells. Relative to controls, palatal tissues obtained from Tgfbr2fl/fl;Wnt1-Cre mouse embryos at embryonic day 14.5 (E14.5) of gestation have a robust gene expression signature reflective of known defects in CNC-derived mesenchymal cell proliferation. Groups of differentially expressed genes (DEGs) were involved in diverse cellular processes and components associated with orofacial clefting, including the extracellular matrix, cholesterol metabolism, ciliogenesis, and multiple signaling pathways. A subset of the DEGs are known or suspected to be associated with an increased risk of orofacial clefting in humans and/or genetically engineered mice. Based on bioinformatics analyses, we highlight the functional relationships among differentially expressed transcriptional regulators of palatogenesis as well as transcriptional factors not previously associated with this process. We suggest that gene expression profiling studies of mice with TGFβ signaling defects provide a valuable approach for identifying candidate mechanisms by which this pathway controls cell fate during palatogenesis and its role in the etiology of human craniofacial abnormalities. PMID:23060211

  12. Reservoir stratification affects methylmercury levels in river water, plankton, and fish downstream from Balbina hydroelectric dam, Amazonas, Brazil.

    PubMed

    Kasper, Daniele; Forsberg, Bruce R; Amaral, João H F; Leitão, Rafael P; Py-Daniel, Sarah S; Bastos, Wanderley R; Malm, Olaf

    2014-01-21

    The river downstream from a dam can be more contaminated by mercury than the reservoir itself. However, it is not clear how far the contamination occurs downstream. We investigated the seasonal variation of methylmercury levels in the Balbina reservoir and how they correlated with the levels encountered downstream from the dam. Water, plankton, and fishes were collected upstream and at sites between 0.5 and 250 km downstream from the dam during four expeditions in 2011 and 2012. Variations in thermal stratification of the reservoir influenced the methylmercury levels in the reservoir and in the river downstream. Uniform depth distributions of methylmercury and oxygen encountered in the poorly stratified reservoir during the rainy season collections coincided with uniformly low methylmercury levels along the river downstream from the dam. During dry season collections, the reservoir was strongly stratified, and anoxic hypolimnion water with high methylmercury levels was exported downstream. Methylmercury levels declined gradually to 200 km downstream. In general, the methylmercury levels in plankton and fishes downstream from the dam were higher than those upstream. Higher methylmercury levels observed 200-250 km downstream from the dam during flooding season campaigns may reflect the greater inflow from tributaries and flooding of natural wetlands that occurred at this time.

  13. Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells.

    PubMed

    Wada, Takeyoshi; Asahi, Toru; Sawamura, Naoya

    2016-08-26

    The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as a thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. PMID:27329811

  14. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia.

    PubMed

    Bonetto, Andrea; Aydogdu, Tufan; Jin, Xiaoling; Zhang, Zongxiu; Zhan, Rui; Puzis, Leopold; Koniaris, Leonidas G; Zimmers, Teresa A

    2012-08-01

    Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C(2)C(12) myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia.

  15. Specific Genetic Disorders

    MedlinePlus

    ... of Genetic Terms Definitions for genetic terms Specific Genetic Disorders Many human diseases have a genetic component. ... Condition in an Adult The Undiagnosed Diseases Program Genetic Disorders Achondroplasia Alpha-1 Antitrypsin Deficiency Antiphospholipid Syndrome ...

  16. A role for genetic accommodation in evolution?

    PubMed

    Braendle, Christian; Flatt, Thomas

    2006-09-01

    Whether evolutionary change can occur by genetic assimilation, or more generally by genetic accommodation, remains controversial. Here we examine some of the experimental evidence for both phenomena. Several experiments in Drosophila suggest that assimilation is possible, and a new paper shows that a color polyphenism in the tobacco hornworm, Manduca sexta, can evolve by genetic accommodation. We argue that genetic accommodation, including assimilation, is a plausible mechanism in evolution; however, more work is required to test how this mechanism acts and how often it is involved in evolutionary change.

  17. Fate of high loads of ammonia in a pond and wetland downstream from a hazardous waste disposal site.

    PubMed

    Cutrofello, Michele; Durant, John L

    2007-07-01

    Halls Brook (eastern Massachusetts, USA) is a significant source of total dissolved ammonia (sum of NH(3) and NH(4)(+); (NH(3))(T)) to the Aberjona River, a water body listed for NH(3) impairment on the Clean Water Act section 303(d) list. We hypothesized (1) that (NH(3))(T) in Halls Brook derived from a hazardous waste site via groundwater discharging to a two-basin pond that feeds the brook; and (2) that transport of (NH(3))(T) to the Aberjona River was controlled by lacustrine and wetland processes. To test these hypotheses we measured (NH(3))(T) levels in the brook, the pond, and a wetlands directly downstream of the pond during both dry and wet weather over a ten month period. In addition, we analyzed sediment cores and nitrogen isotopes, and performed mass balance calculations. Groundwater discharge from beneath the hazardous waste site was the major source of (NH(3))(T) (20-67 kg d(-1)) and salinity to the north basin of the pond. The salty bottom waters of the north basin were anoxic on all sampling dates, and exhibited relatively stable (NH(3))(T) concentrations between 200 and 600 mg Nl(-1). These levels were >100-times higher than typical background levels, and 8-24-times above the acute effects level for (NH(3))(T) toxicity. Bottom waters from the north basin continuously spill over into the south basin contributing approximately 50% of the (NH(3))(T) load entering this basin. The remainder comes from Halls Brook, which receives (NH(3))(T) loadings from as yet unknown sources upstream. During storm events up to 50% of the mass of (NH(3))(T) was flushed from the south basin and into the wetlands. The wetlands acted as a (NH(3))(T) sink in dry weather in the growing season and a discharge-dependent (NH(3))(T) source to the Aberjona River during rainstorms. PMID:17346773

  18. AP2γ regulates neural and epidermal development downstream of the BMP pathway at early stages of ectodermal patterning

    PubMed Central

    Qiao, Yunbo; Zhu, Yue; Sheng, Nengyin; Chen, Jun; Tao, Ran; Zhu, Qingqing; Zhang, Ting; Qian, Cheng; Jing, Naihe

    2012-01-01

    Bone morphogenetic protein (BMP) inhibits neural specification and induces epidermal differentiation during ectodermal patterning. However, the mechanism of this process is not well understood. Here we show that AP2γ, a transcription factor activator protein (AP)-2 family member, is upregulated by BMP4 during neural differentiation of pluripotent stem cells. Knockdown of AP2γ facilitates mouse embryonic stem cell (ESC) neural fate determination and impairs epidermal differentiation, whereas AP2γ overexpression inhibits neural conversion and promotes epidermal commitment. In the early chick embryo, AP2γ is expressed in the entire epiblast before HH stage 3 and gradually shifts to the putative epidermal ectoderm during HH stage 4. In the future neural plate AP2γ inhibits excessive neural expansion and it also promotes epidermal development in the surface ectoderm. Moreover, AP2γ knockdown in ESCs and chick embryos partially rescued the neural inhibition and epidermal induction effects of BMP4. Mechanistic studies showed that BMP4 directly regulates AP2γ expression through Smad1 binding to the AP2γ promoter. Taken together, we propose that during the early stages of ectodermal patterning in the chick embryo, AP2γ acts downstream of the BMP pathway to restrict precocious neural expansion in the prospective neural plate and initiates epidermal differentiation in the future epidermal ectoderm. PMID:22945355

  19. Microarray identification of novel genes downstream of Six1, a critical factor in cranial placode, somite and kidney development

    PubMed Central

    Yan, Bo; Neilson, Karen M.; Ranganathan, Ramya; Maynard, Thomas; Streit, Andrea; Moody, Sally A.

    2014-01-01

    Background Six1 plays an important role in the development of several vertebrate organs, including cranial sensory placodes, somites and kidney. Although Six1 mutations cause one form of Branchio-Otic Syndrome (BOS), the responsible gene in many patients has not been identified; genes that act downstream of Six1 are potential BOS candidates. Results We sought to identify novel genes expressed during placode, somite and kidney development by comparing gene expression between control and Six1-expressing ectodermal explants. The expression patterns of 19 of the significantly up-regulated and 11 of the significantly down-regulated genes were assayed from cleavage to larval stages. 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in BOS, and 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related Branchio-Otic-Renal (BOR) syndrome. We also identified the chick homologues of 5 genes and show that they have conserved expression patterns. Conclusions Of the 30 genes selected for expression analyses, all are expressed at many of the developmental times and appropriate tissues to be regulated by Six1. Many have the potential to play a role in the disruption of hearing and kidney function seen in BOS/BOR patients. PMID:25403746

  20. Design and Experimental Investigation of a Single-stage Turbine with a Downstream Stator

    NASA Technical Reports Server (NTRS)

    Plohr, Henry W; Holeski, Donald E; Forrette, Robert E

    1957-01-01

    The high-work-output turbine had an experimental efficiency of 0.830 at the design point and a maximum efficiency of 0.857. The downstream stator was effective in providing axial flow out of the turbine for almost the whole range of turbine operation.

  1. Propagation characteristics of waves upstream and downstream of quasi-parallel shocks

    NASA Technical Reports Server (NTRS)

    Krauss-Varban, D.; Omidi, N.

    1993-01-01

    The propagation characteristics of waves upstream and downstream of quasi-parallel shocks are investigated by using 2D hybrid simulations. At low Alfven Mach numbers, M(A) below about 2, the shock is initially associated with upstream phase-standing whistlers. At later times, backstreaming ions excite longer-wavelength whistlers via the right-hand resonant ion/ion instability. These waves propagate along the magnetic field at a group velocity no smaller than the upstream flow speed, so that the waves remain in the upstream region. At higher MA (above about 3), these waves are convected back into the shock, causing its reformation and downstream perturbations. Shock transmitted waves mode-convert into Alfven/ion-cyclotron waves which have a wave vector along the shock normal (pointing upstream) and convect downstream. The 2D simulation results confirm our earlier suggestion that the upstream waves should be field aligned, and that their convection into the downstream is associated with linear mode conversion into the Alfven/ion-cyclotron branch.

  2. Interference in transcription of overexpressed genes by promoter-proximal downstream sequences

    PubMed Central

    Turchinovich, A.; Surowy, H. M.; Tonevitsky, A. G.; Burwinkel, B.

    2016-01-01

    Despite a high sequence homology among four human RNAi-effectors Argonaute proteins and their coding sequences, the efficiency of ectopic overexpression of AGO3 and AGO4 coding sequences in human cells is greatly reduced as compared to AGO1 and AGO2. While investigating this phenomenon, we documented the existence of previously uncharacterized mechanism of gene expression regulation, which is manifested in greatly varying basal transcription levels from the RNApolII promoters depending on the promoter-proximal downstream sequences. Specifically, we show that distinct overexpression of Argonaute coding sequences cannot be explained by mRNA degradation in the cytoplasm or nucleus, and exhibits on transcriptional level. Furthermore, the first 1000–2000 nt located immediately downstream the promoter had the most critical influence on ectopic gene overexpression. The transcription inhibiting effect, associated with those downstream sequences, subsided with increasing distance to the promoter and positively correlated with promoter strength. We hypothesize that the same mechanism, which we named promoter proximal inhibition (PPI), could generally contribute to basal transcription levels of genes, and could be mainly responsible for the essence of difficult-to-express recombinant proteins. Finally, our data reveal that expression of recombinant proteins in human cells can be greatly enhanced by using more permissive promoter adjacent downstream sequences. PMID:27485701

  3. Concentration of radionuclides in fresh water fish downstream of Rancho Seco Nuclear Generating Plant

    SciTech Connect

    Noshkin, V.E.; Eagle, R.J.; Dawson, J.M.; Brunk, J.L.; Wong, X.M.

    1984-12-27

    Fish were collected for radionuclide analysis over a 5-month period in 1984 from creeks downstream of the Rancho Seco Nuclear Generating Plant, which has been discharging quantities of some fission and activation products to the waterway since 1981. Among the fish, the bluegill was selected for intensive study because it is very territorial and the radionuclide concentrations detected should be representative of the levels in the local environment at the downstream locations sampled. Among the gamma-emitting radionuclides routinely released, only /sup 134/Cs and /sup 137/Cs were detected in the edible flesh of fish. Concentrations in the flesh of fish decreased with distance from the plant. The relationship between concentration and distance was determined to be exponential. Exponential equations were generated to estimate concentrations in fish at downstream locations where no site-specific information was available. Mean concentrations of /sup 137/Cs in bluegill collected during April, May, July and August from specific downstream stations were not significantly different in spite of the release of 131 mCi to the creeks between April and August. The concentrations in fish are not responding to changes in water concentrations brought about by plant discharges. Diet appears to be a more significant factor than size or weight or water concentration in regulating body burdens of /sup 137/Cs in these fish.

  4. Polarization Setup and Polarimetry for 2 IRs, and Status of Downstream Polarimeter Designs

    SciTech Connect

    Moffeit, Kenneth; Woods, Mike; Nosochkov, Yuri; Schuler, Peter; Moenig, Klaus; Oliver, W.; /Tufts U.

    2005-06-29

    A spin rotation scheme for the International Linear Collider (ILC) is presented that allows the polarization spin vector to be tuned independently for different Interaction Regions (IR). A scheme to allow rapid helicity switching for polarized positrons is discussed. Comments on the downstream polarimeter designs are given.

  5. Changes in biodiversity and ecosystem function downstream from mountaintop removal and valley fill coal mining

    EPA Science Inventory

    Mountaintop removal and valley fill coal mining has altered the physicochemical landscape of the Central Appalachian region in the U.S. Increased specific conductance and levels of component ions downstream from valley fill sites are toxic to aquatic life and can negatively impa...

  6. USE OF GEOSPATIAL DATA TO PREDICT DOWNSTREAM IMPACTS OF COAL MINING IN AN APPALACHIAN WATERSHED

    EPA Science Inventory

    Mountaintop removal and valley filling is a method of mining coal that results in burial of Appalachian headwater streams. Leaching of fill material often results in elevated ion concentrations below fills. A primary objective of this study was to quantify downstream extent of mi...

  7. Biochemistry in an Industrial Context: Methods of Protein Purification and Downstream Processing.

    ERIC Educational Resources Information Center

    Weathers, Pamela J.

    1988-01-01

    Explores a graduate level bioprocess engineering course in protein purification and downstream processing. Designed to provide students with hands-on training in the design and implementation of product processing for the biotechnology industry. Includes syllabus and plan of study. (MVL)

  8. From Process Development to Manufacturing: Lab-Intensive Courses in Downstream Bioprocessing

    ERIC Educational Resources Information Center

    Gilleskie, Gary L.; Reeves, Baley A.

    2014-01-01

    Most chemical engineering graduates work in industry, a fact that underscores the need for courses to provide experiences that prepare them for industry. The Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has addressed this need by developing and delivering a comprehensive downstream bioprocessing program…

  9. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT: STORMWATER SOURCE AREA TREATMENT DEVICE: HYDRO INTERNATIONAL DOWNSTREAM DEFENDER®

    EPA Science Inventory

    Verification testing of the Hydro International Downstream Defender® was conducted at the Madison Water Utility in Madison, Wisconsin. The system was designed for a drainage basin estimated at 1.9 acres in size, but during intense storm events, the system received water from an a...

  10. Hemodynamics analysis of patient-specific carotid bifurcation: a CFD model of downstream peripheral vascular impedance.

    PubMed

    Dong, Jingliang; Wong, Kelvin K L; Tu, Jiyuan

    2013-04-01

    The study of cardiovascular models was presented in this paper based on medical image reconstruction and computational fluid dynamics. Our aim is to provide a reality platform for the purpose of flow analysis and virtual intervention outcome predication for vascular diseases. By connecting two porous mediums with transient permeability at the downstream of the carotid bifurcation branches, a downstream peripheral impedance model was developed, and the effect of the downstream vascular bed impedance can be taken into consideration. After verifying its accuracy with a healthy carotid bifurcation, this model was implemented in a diseased carotid bifurcation analysis. On the basis of time-averaged wall shear stress, oscillatory shear index, and the relative residence time, fractions of abnormal luminal surface were highlighted, and the atherosclerosis was assessed from a hemodynamic point of view. The effect of the atherosclerosis on the transient flow division between the two branches because of the existence of plaque was also analysed. This work demonstrated that the proposed downstream peripheral vascular impedance model can be used for computational modelling when the outlets boundary conditions are not available, and successfully presented the potential of using medical imaging and numerical simulation to provide existing clinical prerequisites for diagnosis and therapeutic treatment.

  11. Effect of Pulsed Plasma Jets on the Recovering Boundary Layer Downstream of a Reflected Shock Interaction

    NASA Astrophysics Data System (ADS)

    Greene, Benton; Clemens, Noel; Magari, Patrick; Micka, Daniel; Ueckermann, Mattheus

    2015-11-01

    Shock-induced turbulent boundary layer separation can have many detrimental effects in supersonic inlets including flow distortion and instability, structural fatigue, poor pressure recovery, and unstart. The current study investigates the effect of pulsed plasma jets on the recovering boundary layer downstream of a reflected shock wave-boundary layer interaction. The effects of pitch and skew angle of the jet as well as the heating parameter and discharge time scale are tested using several pulsing frequencies. In addition, the effect of the plasma jets on the undisturbed boundary layer at 6 mm and 11 mm downstream of the jets is measured. A pitot-static pressure probe is used to measure the velocity profile of the boundary layer 35 mm downstream of the plasma jets, and the degree of boundary layer distortion is compared between the different models and run conditions. Additionally, the effect of each actuator configuration on the shape of the mean separated region is investigated using surface oil flow visualization. Previous studies with lower energy showed a weak effect on the downstream boundary layer. The current investigation will attempt to increase this effect using a higher-energy discharge. Funded by AFRL through and SBIR in collaboration with Creare, LLC.

  12. VIEW OF FOSSIL CREEK DIVERSION DAM FROM DOWNSTREAM (INCLUDES 1950s ...

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

    VIEW OF FOSSIL CREEK DIVERSION DAM FROM DOWNSTREAM (INCLUDES 1950s AUTOMATIC/REMOTE CONTROL SLUICE GATE IN UPPER CENTER OF DAM, NORTH SIDE). LOOKING NORTH-NORTHWEST - Childs-Irving Hydroelectric Project, Fossil Creek Diversion Dam, Forest Service Road 708/502, Camp Verde, Yavapai County, AZ

  13. Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

    PubMed

    Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

    2013-05-01

    Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

  14. DETAILED ENDOCRINE ASSESSMENTS IN WILD FISH DOWNSTREAM OF PULP AND PAPER MILLS IN NORTHERN ALBERTA, CANADA

    EPA Science Inventory

    2001. Detailed Endocrine Assessments in Wild Fish Downstream of Pulp and Paper Mills in Northern Alberta, Canada (Abstract). In: Environmental Sciences in the 21st Century: Paradigms, Opportunities, and Challenges: Abstract Book: SETAC 21st Annual Meeting, 12-16 November 2000, N...

  15. Downstream variation in bankfull width of wadeable streams across the conterminous United States

    EPA Science Inventory

    Bankfull channel width is a fundamental measure of stream size and a key parameter of interest for many applications in hydrology, fluvial geomorphology, and stream ecology. We developed downstream hydraulic geometry relationships for bankfull channel width w as a function of dra...

  16. Headwater effects on downstream waters: Legal perspectives, science needs, and assessment approaches

    EPA Science Inventory

    Headwater streams make up at least 53% of total stream length in the US. Although these systems are of interest for their own sake, there has recently been significant focus on how headwater streams contribute to downstream waters. This has resulted in part from recent legal op...

  17. Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

    PubMed Central

    Deffains, Marc; Iskhakova, Liliya; Katabi, Shiran; Haber, Suzanne N; Israel, Zvi; Bergman, Hagai

    2016-01-01

    The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson's disease and other BG-related disorders. DOI: http://dx.doi.org/10.7554/eLife.16443.001 PMID:27552049

  18. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false What sulfur standards apply to... Gasoline Sulfur Gasoline Sulfur Standards § 80.210 What sulfur standards apply to gasoline downstream from refineries and importers? The sulfur standard for gasoline at any point in the gasoline distribution...

  19. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false What sulfur standards apply to... Gasoline Sulfur Gasoline Sulfur Standards § 80.210 What sulfur standards apply to gasoline downstream from refineries and importers? The sulfur standard for gasoline at any point in the gasoline distribution...

  20. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false What sulfur standards apply to... Gasoline Sulfur Gasoline Sulfur Standards § 80.210 What sulfur standards apply to gasoline downstream from refineries and importers? The sulfur standard for gasoline at any point in the gasoline distribution...

  1. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false What sulfur standards apply to... Gasoline Sulfur Gasoline Sulfur Standards § 80.210 What sulfur standards apply to gasoline downstream from refineries and importers? The sulfur standard for gasoline at any point in the gasoline distribution...

  2. 19 CFR 351.223 - Procedures for initiation of downstream product monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Procedures for initiation of downstream product monitoring. 351.223 Section 351.223 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE... description of any relationship between such producers; (6) Whether the component part is already subject...

  3. 17 CFR 270.57b-1 - Exemption for downstream affiliates of business development companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... affiliates of business development companies. 270.57b-1 Section 270.57b-1 Commodity and Securities Exchanges....57b-1 Exemption for downstream affiliates of business development companies. Notwithstanding... to any person (a) solely because that person is directly or indirectly controlled by a...

  4. 17 CFR 270.57b-1 - Exemption for downstream affiliates of business development companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... affiliates of business development companies. 270.57b-1 Section 270.57b-1 Commodity and Securities Exchanges....57b-1 Exemption for downstream affiliates of business development companies. Notwithstanding... to any person (a) solely because that person is directly or indirectly controlled by a...

  5. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1)...

  6. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1)...

  7. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1)...

  8. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1)...

  9. 40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.219 Designation and downstream requirements for GPA gasoline. The requirements...

  10. 40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.219 Designation and downstream requirements for GPA gasoline. The requirements...

  11. 40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.219 Designation and downstream requirements for GPA gasoline. The requirements...

  12. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Geographic Phase-in Program § 80.220 What are the downstream standards for GPA gasoline? (a) GPA gasoline. (1)...

  13. Subsequent to Suppression: Downstream Comprehension Consequences of Noun/Verb Ambiguity in Natural Reading

    ERIC Educational Resources Information Center

    Stites, Mallory C.; Federmeier, Kara D.

    2015-01-01

    We used eye tracking to investigate the downstream processing consequences of encountering noun/verb (NV) homographs (i.e., park) in semantically neutral but syntactically constraining contexts. Target words were followed by a prepositional phrase containing a noun that was plausible for only 1 meaning of the homograph. Replicating previous work,…

  14. The CEO's second act.

    PubMed

    Nadler, David A

    2007-01-01

    When a CEO leaves because of performance problems, the company typically recruits someone thought to be better equipped to fix what the departing executive couldn't--or wouldn't. The board places its confidence in the new person because of the present dilemma's similarity to some previous challenge that he or she dealt with successfully. But familiar problems are inevitably succeeded by less familiar ones, for which the specially selected CEO is not quite so qualified. More often than not, the experiences, skills, and temperament that yielded triumph in Act I turn out to be unequal to Act II's difficulties. In fact, the approaches that worked so brilliantly in Act I may be the very opposite of what is needed in Act II. The CEO has four choices: refuse to change, in which case he or she will be replaced; realize that the next act requires new skills and learn them; downsize or circumscribe his or her role to compensate for deficiencies; or line up a successor who is qualified to fill a role to which the incumbent's skills and interests are no longer suited. Hewlett-Packard's Carly Fiorina exemplifies the first alternative; Merrill Lynch's Stanley O'Neal the second; Google's Sergey Brin and Larry Page the third; and Quest Diagnostics' Ken Freeman the fourth. All but the first option are reasonable responses to the challenges presented in the second acts of most CEOs' tenures. And all but the first require a power of observation, a propensity for introspection, and a strain of humility that are rare in the ranks of the very people who need those qualities most. There are four essential steps executives can take to discern that they have entered new territory and to respond accordingly: recognition that their leadership style and approach are no longer working; acceptance of others' advice on why performance is faltering; analysis and understanding of the nature of the Act II shift; and, finally, decision and action.

  15. The CEO's second act.

    PubMed

    Nadler, David A

    2007-01-01

    When a CEO leaves because of performance problems, the company typically recruits someone thought to be better equipped to fix what the departing executive couldn't--or wouldn't. The board places its confidence in the new person because of the present dilemma's similarity to some previous challenge that he or she dealt with successfully. But familiar problems are inevitably succeeded by less familiar ones, for which the specially selected CEO is not quite so qualified. More often than not, the experiences, skills, and temperament that yielded triumph in Act I turn out to be unequal to Act II's difficulties. In fact, the approaches that worked so brilliantly in Act I may be the very opposite of what is needed in Act II. The CEO has four choices: refuse to change, in which case he or she will be replaced; realize that the next act requires new skills and learn them; downsize or circumscribe his or her role to compensate for deficiencies; or line up a successor who is qualified to fill a role to which the incumbent's skills and interests are no longer suited. Hewlett-Packard's Carly Fiorina exemplifies the first alternative; Merrill Lynch's Stanley O'Neal the second; Google's Sergey Brin and Larry Page the third; and Quest Diagnostics' Ken Freeman the fourth. All but the first option are reasonable responses to the challenges presented in the second acts of most CEOs' tenures. And all but the first require a power of observation, a propensity for introspection, and a strain of humility that are rare in the ranks of the very people who need those qualities most. There are four essential steps executives can take to discern that they have entered new territory and to respond accordingly: recognition that their leadership style and approach are no longer working; acceptance of others' advice on why performance is faltering; analysis and understanding of the nature of the Act II shift; and, finally, decision and action. PMID:17286076

  16. Streamflow gain-loss characteristics of Elkhead Creek downstream from Elkhead Reservoir near Craig, Colorado, 2009

    USGS Publications Warehouse

    Ruddy, Barbara C.

    2010-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Colorado Water Conservation Board, the Upper Colorado River Endangered Fish Recovery Program (UCREFRP), Colorado Division of Water Resources, and City of Craig studied the gain-loss characteristics of Elkhead Creek downstream from Elkhead Reservoir to the confluence with the Yampa River during August through October 2009. Earlier qualitative interpretation of streamflow data downstream from the reservoir indicated that there could be a transit loss of nearly 10 percent. This potential loss could be a significant portion of the releases from Elkhead Reservoir requested by UCREFRP during late summer and early fall for improving critical habitat for endangered fish downstream in the Yampa River. Information on the gain-loss characteristics was needed for the effective management of the reservoir releases. In order to determine streamflow gain-loss characteristics for Elkhead Creek, eight measurement sets were made at four strategic instream sites and at one diversion from August to early October 2009. An additional measurement set was made after the study period during low-flow conditions in November 2009. Streamflow measurements were made using an Acoustic Doppler Velocimeter to provide high accuracy and consistency, especially at low flows. During this study, streamflow ranged from about 5 cubic feet per second up to more than 90 cubic feet per second with step increments in between. Measurements were made at least 24 hours after a change in reservoir release (streamflow) during steady-state conditions. The instantaneous streamflow measurements and the streamflow volume comparisons show the reach of Elkhead Creek immediately downstream from Elkhead Reservoir to the streamflow-gaging station 09246500, Elkhead Creek near Craig, CO, is neither a gaining nor losing reach. The instantaneous measurements immediately downstream from the dam and the combined measurements of Norvell ditch plus streamflow

  17. Assessing the impacts of Three Gorges Dam on lake inundation areas across the downstream Yangtze floodplain

    NASA Astrophysics Data System (ADS)

    Wang, J.; Sheng, Y.; Wada, Y.

    2013-12-01

    China's Three Gorges Dam (TGD) has received worldwide attention due to its profound impacts on the downstream hydraulic, morphological, and ecological systems. The TGD operation results in direct alternation of the discharge to the middle and lower Yangtze reach, manifested as regulated flow and reduced sediment load. TGD's flow regulation, typically described as water storage in fall while release in winter and spring, interferes with the natural seasonality of downstream Yangtze River levels which are essentially important to the inundation dynamics of surrounding lakes/wetlands in the Yangtze floodplain. Concurrent decrease of sediment load has caused chronic downstream channel erosion which lowers Yangtze level in relation to flow and further affects the sustainability of riparian lakes and the related ecosystems. By integrating satellite observations, in situ measurement, and hydrologic simulations, this study presents a systematic assessment of the TGD impacts on the inundation areas of six major freshwater lakes across the entire Yangtze basin downstream of the TGD, during the time period from TGD's initial impoundment in June 2003 to early 2012. Despite the small number, the six targeted lakes cover a total area of ~5,000 km2 accounting for ~25% of the freshwater lake area in China, and were identified as the only natural lakes that remain in open connection to the Yangtze River across the downstream floodplain. Using daily MODIS imagery from 2000 to 2012, we revealed a significant year-round decline in the aggregated inundation area of the studied lakes by an average of ~580 km2 or 17.7% from the pre-dam to post-dam period (i.e., before and after June, 2003). To diagnose TGD's contribution to such lake area decline, we followed a two-step procedure by first quantifying the TGD impacts on the seasonal level regime along the complete longitudinal range of the Yangtze River downstream from TGD to the estuary [Wang et al., 2013], and then estimating the

  18. The role of grazers and shredders in the retention and downstream transport of a PCB in lotic environments

    SciTech Connect

    Sallenave, R.M. . Dept. of Environmental Biology); Day, K.E. ); Kreutzweiser, D.P. . Forest Pest Management Inst.)

    1994-11-01

    Field studies using flow-through artificial stream channels were conducted between May and October 1992 to study the role of the feeding activity of grazing and shredding invertebrates in promoting downstream transport of 2,2[prime],4,4[prime],5,5[prime]-hexachlorobiphenyl (HCBP). Plant material was labeled with [[sup 14]C]HCBP and fed to selected invertebrate species, and accrual of radioactivity by downstream collector species (Hydropsyche spp.) was measured. Downstream transport of HCBP was significantly increased by the presence of the grazer Elimia livescens in the upstream sections of the channels as demonstrated by significantly higher levels of radioactivity in hydropsychid larvae located downstream. Similarly, movement of HCBP downstream was significantly greater in channels containing the shredder Hydatophylax argus than in channels without shredders. These results suggest that the feeding processes of benthic invertebrates may play an important role in the downstream transport of particle-bound hydrophobic organic compounds.

  19. Geomorphic analysis of the river response to sedimentation downstream of Mount Rainier, Washington

    USGS Publications Warehouse

    Czuba, Jonathan A.; Magirl, Christopher S.; Czuba, Christiana R.; Curran, Christopher A.; Johnson, Kenneth H.; Olsen, Theresa D.; Kimball, Halley K.; Gish, Casey C.

    2012-01-01

    A study of the geomorphology of rivers draining Mount Rainier, Washington, was completed to identify sources of sediment to the river network; to identify important processes in the sediment delivery system; to assess current sediment loads in rivers draining Mount Rainier; to evaluate if there were trends in streamflow or sediment load since the early 20th century; and to assess how rates of sedimentation might continue into the future using published climate-change scenarios. Rivers draining Mount Rainier carry heavy sediment loads sourced primarily from the volcano that cause acute aggradation in deposition reaches as far away as the Puget Lowland. Calculated yields ranged from 2,000 tonnes per square kilometer per year [(tonnes/km2)/yr] on the upper Nisqually River to 350 (tonnes/km2)/yr on the lower Puyallup River, notably larger than sediment yields of 50–200 (tonnes/km2)/yr typical for other Cascade Range rivers. These rivers can be assumed to be in a general state of sediment surplus. As a result, future aggradation rates will be largely influenced by the underlying hydrology carrying sediment downstream. The active-channel width of rivers directly draining Mount Rainier in 2009, used as a proxy for sediment released from Mount Rainier, changed little between 1965 and 1994 reflecting a climatic period that was relatively quiet hydrogeomorphically. From 1994 to 2009, a marked increase in geomorphic disturbance caused the active channels in many river reaches to widen. Comparing active-channel widths of glacier-draining rivers in 2009 to the distance of glacier retreat between 1913 and 1994 showed no correlation, suggesting that geomorphic disturbance in river reaches directly downstream of glaciers is not strongly governed by the degree of glacial retreat. In contrast, there was a correlation between active-channel width and the percentage of superglacier debris mantling the glacier, as measured in 1971. A conceptual model of sediment delivery processes

  20. Energy-saving scheme based on downstream packet scheduling in ethernet passive optical networks

    NASA Astrophysics Data System (ADS)

    Zhang, Lincong; Liu, Yejun; Guo, Lei; Gong, Xiaoxue

    2013-03-01

    With increasing network sizes, the energy consumption of Passive Optical Networks (PONs) has grown significantly. Therefore, it is important to design effective energy-saving schemes in PONs. Generally, energy-saving schemes have focused on sleeping the low-loaded Optical Network Units (ONUs), which tends to bring large packet delays. Further, the traditional ONU sleep modes are not capable of sleeping the transmitter and receiver independently, though they are not required to transmit or receive packets. Clearly, this approach contributes to wasted energy. Thus, in this paper, we propose an Energy-Saving scheme that is based on downstream Packet Scheduling (ESPS) in Ethernet PON (EPON). First, we design both an algorithm and a rule for downstream packet scheduling at the inter- and intra-ONU levels, respectively, to reduce the downstream packet delay. After that, we propose a hybrid sleep mode that contains not only ONU deep sleep mode but also independent sleep modes for the transmitter and the receiver. This ensures that the energy consumed by the ONUs is minimal. To realize the hybrid sleep mode, a modified GATE control message is designed that involves 10 time points for sleep processes. In ESPS, the 10 time points are calculated according to the allocated bandwidths in both the upstream and the downstream. The simulation results show that ESPS outperforms traditional Upstream Centric Scheduling (UCS) scheme in terms of energy consumption and the average delay for both real-time and non-real-time packets downstream. The simulation results also show that the average energy consumption of each ONU in larger-sized networks is less than that in smaller-sized networks; hence, our ESPS is better suited for larger-sized networks.