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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. Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase

    PubMed Central

    Ohya, Ken-ichi; Kajigaya, Sachiko; Kitanaka, Akira; Yoshida, Koji; Miyazato, Akira; Yamashita, Yoshihiro; Yamanaka, Takeo; Ikeda, Uichi; Shimada, Kazuyuki; Ozawa, Keiya; Mano, Hiroyuki

    1999-01-01

    Tec, Btk, Itk, Bmx, and Txk constitute the Tec family of protein tyrosine kinases (PTKs), a family with the distinct feature of containing a pleckstrin homology (PH) domain. Tec acts in signaling pathways triggered by the B cell antigen receptor (BCR), cytokine receptors, integrins, and receptor-type PTKs. Although upstream regulators of Tec family kinases are relatively well characterized, little is known of the downstream effectors of these enzymes. The yeast two-hybrid system has identified several proteins that interact with the kinase domain of Tec, one of which is now revealed to be a previously unknown docking protein termed BRDG1 (BCR downstream signaling 1). BRDG1 contains a proline-rich motif, a PH domain, and multiple tyrosine residues that are potential target sites for Src homology 2 domains. In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling. PMID:10518561

  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. PMID:22700464

  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. PMID:27192741

  8. The ciliary protein Nek8/Nphp9 acts downstream of Inv/Nphp2 during pronephros morphogenesis and left-right establishment in zebrafish.

    PubMed

    Fukui, Hajime; Shiba, Dai; Asakawa, Kazuhide; Kawakami, Koichi; Yokoyama, Takahiko

    2012-07-30

    Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease. Among 12 reported Nphp gene products, Inv/Nphp2, Nphp3 and Nek8/Nphp9 are localized to the proximal segment in the primary cilium. However, the functional relationships are unknown. This study focused on phenotype analysis of nek8 knockdown embryos and the genetic relationship between nek8 and inv in zebrafish. Knockdown of nek8 produced both pronephric cysts and abnormal cardiac looping. Simultaneous knockdown of nek8 and inv synergistically increased the incidence of these defects. Interestingly, nek8 mRNA rescued inv morphant phenotypes, although inv mRNA could not rescue nek8 morphant phenotypes. These results suggest that Nek8 acts downstream of Inv function. PMID:22687244

  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. WOX4 and WOX14 act downstream of the PXY receptor kinase to regulate plant vascular proliferation independently of any role in vascular organisation

    PubMed Central

    Etchells, J. Peter; Provost, Claire M.; Mishra, Laxmi; Turner, Simon R.

    2013-01-01

    In plants, the cambium and procambium are meristems from which vascular tissue is derived. In contrast to most plant cells, stem cells within these tissues are thin and extremely long. They are particularly unusual as they divide down their long axis in a highly ordered manner, parallel to the tangential axis of the stem. CLAVATA3-LIKE/ESR-RELATED 41 (CLE41) and PHLOEM INTERCALATED WITH XYLEM (PXY) are a multifunctional ligand-receptor pair that regulate vascular cell division, vascular organisation and xylem differentiation in vascular tissue. A transcription factor gene, WUSCHEL HOMEOBOX RELATED 4 (WOX4) has been shown to act downstream of PXY. Here we show that WOX4 acts redundantly with WOX14 in the regulation of vascular cell division, but that these genes have no function in regulating vascular organisation. Furthermore, we identify an interaction between PXY and the receptor kinase ERECTA (ER) that affects the organisation of the vascular tissue but not the rate of cell division, suggesting that cell division and vascular organisation are genetically separable. Our observations also support a model whereby tissue organisation and cell division are integrated via PXY and ER signalling, which together coordinate development of different cell types that are essential for normal stem formation. PMID:23578929

  11. 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…

  12. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor.

    PubMed

    Schlisio, Susanne; Kenchappa, Rajappa S; Vredeveld, Liesbeth C W; George, Rani E; Stewart, Rodney; Greulich, Heidi; Shahriari, Kristina; Nguyen, Nguyen V; Pigny, Pascal; Dahia, Patricia L; Pomeroy, Scott L; Maris, John M; Look, A Thomas; Meyerson, Matthew; Peeper, Daniel S; Carter, Bruce D; Kaelin, William G

    2008-04-01

    VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural crest-derived tumors. Using an unbiased shRNA screen we found that the kinesin KIF1Bbeta acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. KIF1Bbeta maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function KIF1Bbeta missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that KIF1Bbeta is a pathogenic target of these deletions. PMID:18334619

  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. Late-acting dominant lethal genetic systems and mosquito control

    PubMed Central

    Phuc, Hoang Kim; Andreasen, Morten H; Burton, Rosemary S; Vass, Céline; Epton, Matthew J; Pape, Gavin; Fu, Guoliang; Condon, Kirsty C; Scaife, Sarah; Donnelly, Christl A; Coleman, Paul G; White-Cooper, Helen; Alphey, Luke

    2007-01-01

    Background Reduction or elimination of vector populations will tend to reduce or eliminate transmission of vector-borne diseases. One potential method for environmentally-friendly, species-specific population control is the Sterile Insect Technique (SIT). SIT has not been widely used against insect disease vectors such as mosquitoes, in part because of various practical difficulties in rearing, sterilization and distribution. Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality. Results We investigated by mathematical modeling the effect of manipulating the stage of development at which death occurs (lethal phase) in an SIT program against a density-dependence-limited insect population. We found late-acting lethality to be considerably more effective than early-acting lethality. No such strains of a vector insect have been described, so as a proof-of-principle we constructed a strain of the principal vector of the dengue and yellow fever viruses, Aedes (Stegomyia) aegypti, with the necessary properties of dominant, repressible, highly penetrant, late-acting lethality. Conclusion Conventional SIT induces early-acting (embryonic) lethality, but genetic methods potentially allow the lethal phase to be tailored to the program. For insects with strong density-dependence, we show that lethality after the density-dependent phase would be a considerable improvement over conventional methods. For density-dependent parameters estimated from field data for Aedes aegypti, the critical release ratio for population elimination is modeled to be 27% to 540% greater for early-acting rather than late-acting lethality. Our success in developing a mosquito strain with the key features that the modeling indicated were desirable demonstrates the feasibility of this approach for improved SIT for disease

  15. COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis

    PubMed Central

    Okamura, Masashi; Kudo, Hiromi; Wakabayashi, Ken-ichi; Tanaka, Toshiya; Nonaka, Aya; Uchida, Aoi; Tsutsumi, Shuichi; Sakakibara, Iori; Naito, Makoto; Osborne, Timothy F.; Hamakubo, Takao; Ito, Sadayoshi; Aburatani, Hiroyuki; Yanagisawa, Masashi; Kodama, Tatsuhiko; Sakai, Juro

    2009-01-01

    Wnt signaling through β-catenin and TCF maintains preadipocytes in an un-differentiated proliferative state; however, the molecular pathway has not been completely defined. By integrating gene expression microarray, chromatin immunoprecipitation-chip, and cell-based experimental approaches, we show that Wnt/β-catenin signaling activates the expression of COUP-TFII which recruits the SMRT corepressor complex to the first introns located downstream from the first exons of both PPARγ1 and γ2 mRNAs. This maintains the local chromatin in a hypoacetylated state and represses PPARγ gene expression to inhibit adipogenesis. Our experiments define the COUP-TFII/SMRT complex as a previously unappreciated component of the linear pathway that directly links Wnt/β-catenin signaling to repression of PPARγ gene expression and the inhibition of adipogenesis. PMID:19307559

  16. 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

  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. 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

  19. 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

  20. Genes That Act Downstream of Sensory Neurons to Influence Longevity, Dauer Formation, and Pathogen Responses in Caenorhabditis elegans

    PubMed Central

    Lee, Dongyeop; Kenyon, Cynthia; Lee, Seung-Jae

    2012-01-01

    The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems. PMID:23284299

  1. Catabolite repression of the Bacillus subtilis hut operon requires a cis-acting site located downstream of the transcription initiation site.

    PubMed Central

    Wray, L V; Pettengill, F K; Fisher, S H

    1994-01-01

    Expression of the Bacillus subtilis hut operon is subject to regulation by catabolite repression. A set of hut-lacZ transcriptional fusions was constructed and used to identify two cis-acting sites involved in catabolite repression. The hutOCR1 operator site lies immediately downstream of the hut promoter and weakly regulates hut expression in response to catabolite repression. The downstream hutOCR2 operator site lies within the hutP gene, between positions +203 and +216, and is required for wild-type levels of catabolite repression. Both the hutOCR1 and hutOCR2 operators have sequence similarity to the sites which mediate catabolite repression of several other B. subtilis genes. Two mutations which relieve catabolite repression of hut expression were found to alter the nucleotide sequence of the hutOCR2 operator. Catabolite repression of hut expression was partially relieved in strains containing the ccpA mutation but not in strains containing either the pai or hpr mutation. Images PMID:8144455

  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. PMID:26786211

  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. 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

  5. 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. 

  6. 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

  7. 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

  8. The ZEB1 Transcription Factor Acts in a Negative Feedback Loop with miR200 Downstream of Ras and Rb1 to Regulate Bmi1 Expression*

    PubMed Central

    Liu, Yongqing; Sánchez-Tilló, Ester; Lu, Xiaoqin; Huang, Li; Clem, Brian; Telang, Sucheta; Jenson, Alfred B.; Cuatrecasas, Miriam; Chesney, Jason; Postigo, Antonio; Dean, Douglas C.

    2014-01-01

    Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin-dependent kinase inhibitors (cdki). It is unclear how Ras causes repression of Bmi1 in primary cells to suppress tumor formation while inducing the gene in cancer cells to drive tumor progression. Ras also induces the EMT transcription factor ZEB1 to trigger tumor invasion and metastasis. Beyond its well-documented role in EMT, ZEB1 is important for maintaining repression of cdki. Indeed, heterozygous mutation of ZEB1 is sufficient for elevated cdki expression, leading to premature senescence of primary cells. A similar phenotype is evident with Bmi1 mutation. We show that activation of Rb1 in response to mutant Ras causes dominant repression of ZEB1 in primary cells, but loss of the Rb1 pathway is a hallmark of cancer cells and in the absence of such Rb1 repression Ras induces ZEB1 in cancer cells. ZEB1 represses miR-200 in the context of a mutual repression loop. Because miR-200 represses Bmi1, induction of ZEB1 leads to induction of Bmi1. Rb1 pathway status then dictates the opposing effects of mutant Ras on the ZEB1-miR-200 loop in primary versus cancer cells. This loop not only triggers EMT, surprisingly we show it acts downstream of Ras to regulate Bmi1 expression and thus the critical decision between oncogene-induced senescence and tumor initiation. PMID:24371144

  9. 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.

  10. 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

  11. 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

  12. Plasma membrane receptor-like kinase leaf panicle 2 acts downstream of the DROUGHT AND SALT TOLERANCE transcription factor to regulate drought sensitivity in rice

    PubMed Central

    Wu, Fuqing; Sheng, Peike; Tan, Junjie; Chen, Xiuling; Lu, Guangwen; Ma, Weiwei; Heng, Yueqin; Lin, Qibing; Zhu, Shanshan; Wang, Jiulin; Wang, Jie; Guo, Xiuping; Zhang, Xin; Lei, Cailin; Wan, Jianmin

    2015-01-01

    Drought is a recurring climatic hazard that reduces the crop yields. To avoid the negative effects of drought on crop production, extensive efforts have been devoted to investigating the complex mechanisms of gene expression and signal transduction during drought stress. Receptor-like kinases (RLKs) play important roles in perceiving extracellular stimuli and activating downstream signalling responses. The rice genome contains >1100 RLK genes, of which only two are reported to function in drought stress. A leucine-rich repeat (LRR)-RLK gene named Leaf Panicle 2 (LP2) was previously found to be strongly expressed in leaves and other photosynthetic tissues, but its function remains unclear. In the present study, it was shown that the expression of LP2 was down-regulated by drought and abscisic acid (ABA). Transgenic plants overexpressing LP2 accumulated less H2O2, had more open stomata in leaves, and showed hypersensitivity to drought stress. Further investigation revealed that transcription of LP2 was directly regulated by the zinc finger transcription factor DROUGHT AND SALT TOLERANCE (DST). In addition, LP2 was identified as a functional kinase localized to the plasma membrane and interacted with the drought-responsive aquaporin proteins OsPIP1; 1, OsPIP1; 3, and OsPIP2; 3. Thus, the findings provided evidence that the LRR-RLK LP2, transcriptionally regulated by the drought-related transcription factor DST, served as a negative regulator in drought response. PMID:25385766

  13. Systemic injection of CK2.3, a novel peptide acting downstream of Bone Morphogenetic Protein receptor BMPRIa, leads to increased trabecular bone mass

    PubMed Central

    Akkiraju, Hemanth; Bonor, Jeremy; Olli, Kristine; Bowen, Chris; Bragdon, Beth; Coombs, Harold; Donahue, Leah Rae; Duncan, Randall; Nohe, Anja

    2014-01-01

    Bone Morphogenetic Protein 2 (BMP2) regulates bone integrity by driving both osteogenesis and osteoclastogenesis. However, BMP2 as a therapeutic has significant drawbacks. We have designed a novel peptide CK2.3 that blocks the interaction of Casein Kinase 2 (CK2) with Bone Morphogenetic Protein Receptor type Ia (BMPRIa), thereby activating BMP signaling pathways in the absence of ligand. Here, we show that CK2.3 induced mineralization in primary osteoblast cultures isolated from calvaria and bone marrow stromal cells (BMSCs) of 8 week old mice. Further, systemic tail vein injections of CK2.3 in 8 week old mice resulted in increased bone mineral density (BMD) and mineral apposition rate (MAR). In situ immunohistochemistry of the femur found that CK2.3 injection induced phosphorylation of extracellular signal-related kinase (ERK), but not Smad in osteocytes and osteoblasts, suggesting that CK2.3 signaling occurred through Smad independent pathway. Finally mice injected with CK2.3 exhibited decreased osteoclast differentiation and osteoclast activity. These data indicate that the novel mimetic peptide CK2.3 activated BMPRIa downstream signaling to enhance bone formation without the increase in osteoclast activity that accompanies BMP 2 stimulation. PMID:25331517

  14. Plasma membrane receptor-like kinase leaf panicle 2 acts downstream of the DROUGHT AND SALT TOLERANCE transcription factor to regulate drought sensitivity in rice.

    PubMed

    Wu, Fuqing; Sheng, Peike; Tan, Junjie; Chen, Xiuling; Lu, Guangwen; Ma, Weiwei; Heng, Yueqin; Lin, Qibing; Zhu, Shanshan; Wang, Jiulin; Wang, Jie; Guo, Xiuping; Zhang, Xin; Lei, Cailin; Wan, Jianmin

    2015-01-01

    Drought is a recurring climatic hazard that reduces the crop yields. To avoid the negative effects of drought on crop production, extensive efforts have been devoted to investigating the complex mechanisms of gene expression and signal transduction during drought stress. Receptor-like kinases (RLKs) play important roles in perceiving extracellular stimuli and activating downstream signalling responses. The rice genome contains >1100 RLK genes, of which only two are reported to function in drought stress. A leucine-rich repeat (LRR)-RLK gene named Leaf Panicle 2 (LP2) was previously found to be strongly expressed in leaves and other photosynthetic tissues, but its function remains unclear. In the present study, it was shown that the expression of LP2 was down-regulated by drought and abscisic acid (ABA). Transgenic plants overexpressing LP2 accumulated less H₂O₂, had more open stomata in leaves, and showed hypersensitivity to drought stress. Further investigation revealed that transcription of LP2 was directly regulated by the zinc finger transcription factor DROUGHT AND SALT TOLERANCE (DST). In addition, LP2 was identified as a functional kinase localized to the plasma membrane and interacted with the drought-responsive aquaporin proteins OsPIP1; 1, OsPIP1; 3, and OsPIP2; 3. Thus, the findings provided evidence that the LRR-RLK LP2, transcriptionally regulated by the drought-related transcription factor DST, served as a negative regulator in drought response. PMID:25385766

  15. 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. PMID:25727780

  16. 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

  17. Rho/ROCK acts downstream of lysophosphatidic acid receptor 1 in modulating P2X3 receptor-mediated bone cancer pain in rats

    PubMed Central

    Wu, Jing-xiang; Yuan, Xiao-min; Wang, Qiong; Wei, Wang

    2016-01-01

    Background Lysophosphatidic acid receptor 1 and Rho/ROCK signaling is implicated in bone cancer pain development. However, it remains unknown whether the two signaling pathways function together in P2X3 receptor-mediated bone cancer pain. Results In this study, using a rat model of bone cancer, we examined the expression of P2X3 and lysophosphatidic acid receptor 1 in rat dorsal root ganglion neurons and further dissected whether lysophosphatidic acid receptor 1 and Rho/ROCK-mediated pathways interacted in modulating rat pain behavior. Bone cancer was established by inoculating Walker 256 cells into the left tibia of female Wistar rats. We observed a gradual and yet significant decline in mean paw withdrawal threshold in rats with bone cancer, but not in control rats. Our immunohistochemical staining revealed that the number of P2X3- and lysophosphatidic acid receptor 1-positive dorsal root ganglion neurons was significantly greater in rats with bone cancer than control rats. Lysophosphatidic acid receptor 1 blockade with VPC32183 significantly attenuated decline in mean paw withdrawal threshold. Flinching behavior test further showed that lysophosphatidic acid receptor 1 inhibition with VPC32183 transiently but significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Rho inhibition by intrathecal BoTXC3 caused a rapid reversal in decline in mean paw withdrawal threshold of rats with bone cancer. Flinching behavior test showed that BoTXC3 transiently and significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Similar findings were observed with ROCK inhibition by intrathecal Y27632. Furthermore, VPC32183 and BoTXC3 effectively aborted the appearance of lysophosphatidic acid-induced calcium influx peak. Conclusions Lysophosphatidic acid and its receptor LPAR1, acting through the Rho-ROCK pathway, regulate P2X3 receptor in the development of both mechanical and spontaneous pain in bone cancer. PMID:27094551

  18. 4-Aminoethylamino-emodin – a novel potent inhibitor of GSK-3β– acts as an insulin-sensitizer avoiding downstream effects of activated β-catenin

    PubMed Central

    Gebhardt, Rolf; Lerche, Katja S; Götschel, Frank; Günther, Robert; Kolander, Jens; Teich, Lars; Zellmer, Sebastian; Hofmann, Hans-Jörg; Eger, Kurt; Hecht, Andreas; Gaunitz, Frank

    2010-01-01

    Abstract Glycogen synthase kinase-3β (GSK-3β) is a key target and effector of downstream insulin signalling. Using comparative protein kinase assays and molecular docking studies we characterize the emodin-derivative 4-[N-2-(aminoethyl)-amino]-emodin (L4) as a sensitive and potent inhibitor of GSK-3β with peculiar features. Compound L4 shows a low cytotoxic potential compared to other GSK-3β inhibitors determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and cellular ATP levels. Physiologically, L4 acts as an insulin-sensitizing agent that is able to enhance hepatocellular glycogen and fatty acid biosynthesis. These functions are particularly stimulated in the presence of elevated concentrations of glucose and in synergy with the hormone action at moderate but not high insulin levels. In contrast to other low molecular weight GSK-3β inhibitors (SB216763 and LiCl) or Wnt-3α-conditioned medium, however, L4 does not induce reporter and target genes of activated β-catenin such as TOPflash, Axin2 and glutamine synthetase. Moreover, when present together with SB216763 or LiCl, L4 counteracts expression of TOPflash or induction of glutamine synthetase by these inhibitors. Because L4 slightly activates β-catenin on its own, these results suggest that a downstream molecular step essential for activation of gene transcription by β-catenin is also inhibited by L4. It is concluded that L4 represents a potent insulin-sensitizing agent favouring physiological effects of insulin mediated by GSK-3β inhibition but avoiding hazardous effects such as activation of β-catenin-dependent gene expression which may lead to aberrant induction of cell proliferation and cancer. PMID:19228266

  19. 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

  20. The R2R3-MYB–Like Regulatory Factor EOBI, Acting Downstream of EOBII, Regulates Scent Production by Activating ODO1 and Structural Scent-Related Genes in Petunia[C][W

    PubMed Central

    Spitzer-Rimon, Ben; Farhi, Moran; Albo, Boaz; Cna’ani, Alon; Ben Zvi, Michal Moyal; Masci, Tania; Edelbaum, Orit; Yu, Yixun; Shklarman, Elena; Ovadis, Marianna; Vainstein, Alexander

    2012-01-01

    Flower scent is a highly dynamic trait, under developmental, spatial, and diurnal regulation. The mechanism governing scent production is only beginning to be unraveled. In petunia (Petunia hybrida), EMISSION OF BENZENOIDS II (EOBII) controls transcription of both the shikimate pathway-regulating MYB factor ODORANT1 (ODO1) and phenylpropanoid scent-related structural genes. A promoter-activation screen identified an R2R3-MYB–like regulatory factor of phenylpropanoid volatile biosynthesis acting downstream of EOBII, designated EOBI. EOBI silencing led to downregulation of ODO1 and numerous structural scent-related genes from both the shikimate and phenylpropanoid pathways. The ability of EOBI to directly activate ODO1, as revealed by electrophoretic mobility shift assay and yeast one-hybrid analysis, place EOBI upstream of ODO1 in regulating substrate availability for volatile biosynthesis. Interestingly, ODO1-silenced transgenic petunia flowers accumulated higher EOBI transcript levels than controls, suggesting a complex feedback loop between these regulatory factors. The accumulation pattern of EOBI transcript relative to EOBII and ODO1, and the effect of up/downregulation of EOBII on transcript levels of EOBI and ODO1, further support these factors' hierarchical relationships. The dependence of scent production on EOBI expression and its direct interaction with both regulatory and structural genes provide evidence for EOBI’s wide-ranging involvement in the production of floral volatiles. PMID:23275577

  1. 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

  2. MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

    PubMed Central

    Tian, Xiao-Lin; Dong, Gaofeng; Liu, Tianlei; Gomez, Zubelda A.; Wahl, Astrid; Hols, Pascal

    2013-01-01

    Streptococcus mutans develops competence for genetic transformation through a complex network that receives inputs from at least two signaling peptides, competence-stimulating peptide (CSP) and sigX-inducing peptide (XIP). The key step of competence induction is the transcriptional activation of comX, which encodes an alternative sigma factor, SigX (σX), controlling the expression of late competence genes essential for DNA uptake and recombination. In this study, we provide evidence that MecA acts as a negative regulator in the posttranslational regulation of SigX in S. mutans. Using luxAB transcriptional reporter strains, we demonstrate that MecA represses the expression of late competence genes in S. mutans grown in a complex medium that is subpermissive for competence induction by CSP. The negative regulation of competence by MecA requires the presence of a functional SigX. Accordingly, inactivation of MecA results in a prolonged competence state of S. mutans under this condition. We have also found that the AAA+ protease ClpC displays a similar repressing effect on late competence genes, suggesting that both MecA and ClpC function coordinately to regulate competence in the same regulatory circuit in S. mutans. This suggestion is strongly supported by the results of bacterial two-hybrid assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that inactivation of MecA or ClpC results in the intracellular accumulation of the SigX in S. mutans. Together, our data support the notion that MecA mediates the formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby negatively regulates genetic competence in S. mutans. PMID:24039267

  3. 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

  4. 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

  5. Neutrino Factory Downstream Systems

    SciTech Connect

    Zisman, Michael S.

    2009-12-23

    We describe the Neutrino Factory accelerator systems downstream from the target and capture area. These include the bunching and phase rotation, cooling, acceleration, and decay ring systems. We also briefly discuss the R&D program under way to develop these systems, and indicate areas where help from CERN would be invaluable.

  6. 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

  7. View downstream of timber guide wall downstream from SE corner ...

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

    View downstream of timber guide wall downstream from SE corner of lock, view towards east - St. Lucie Canal, St. Lucie Lock No. 1, St. Lucie, Cross State Canal, Okeechobee Intracoastal Waterway, Stuart, Martin County, FL

  8. The Affordable Care Act and genetic testing for inheritable cancer syndromes: impact on high-risk underserved minorities.

    PubMed

    Walcott, Farzana L; Dunn, Barbara K; DeShields, Mary; Baquet, Claudia

    2014-02-01

    Genetic testing for inheritable cancer syndromes is becoming a critical part of preventive health services. The Patient Protection and Affordable Care Act (PPACA) Essential Health Benefits package addresses breast cancer susceptibility-gene testing for women who are unaffected by cancer. The absence of provisions for 1) men, 2) cancer patients, 3) other inheritable cancer syndromes, and 4) risk-reducing interventions are limitations of PPACA. We discuss provisions and limitations of PPACA pertaining to genetic testing and effects on high-risk populations, in particular minorities. The PPACA is the beginning of an ongoing process of incorporating genetic testing in the armamentarium of cancer prevention. Future efforts should focus on ensuring equitable access to genetic testing as a preventive service under PPACA to high-risk populations other than women. Consideration should also be given to provisions for risk-reducing interventions, especially in underserved minority populations, who are known to underutilize genetic testing and may have limited financial resources for medical intervention. PMID:24583487

  9. 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

  10. 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. PMID:23476971

  11. Common genetic variants, acting additively, are a major source of risk for autism

    PubMed Central

    2012-01-01

    Background Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions Our results, when viewed in the context of results from genome

  12. 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

  13. The NAD(P)H-utilizing glutamate dehydrogenase of Bacteroides thetaiotaomicron belongs to enzyme family I, and its activity is affected by trans-acting gene(s) positioned downstream of gdhA.

    PubMed Central

    Baggio, L; Morrison, M

    1996-01-01

    Previous studies have suggested that regulation of the enzymes of ammonia assimilation in human colonic Bacteroides species is coordinated differently than in other eubacteria. The gene encoding an NAD(P)H-dependent glutamate dehydrogenase (gdhA) in Bacteroides thetaiotaomicron was cloned and expressed in Escherichia coli by mutant complementation from the recombinant plasmid pANS100. Examination of the predicted GdhA amino acid sequence revealed that this enzyme possesses motifs typical of the family I-type hexameric GDH proteins. Northern blot analysis with a gdhA-specific probe indicated that a single transcript with an electrophoretic mobility of approximately 1.6 kb was produced in both B. thetaiotaomicron and E. coli gdhA+ transformants. Although gdhA transcription was unaffected, no GdhA enzyme activity could be detected in E. coli transformants when smaller DNA fragments from pANS100, which contained the entire gdhA gene, were analyzed. Enzyme activity was restored if these E. coli strains were cotransformed with a second plasmid, which contained a 3-kb segment of DNA located downstream of the gdhA coding region. Frameshift mutagenesis within the DNA downstream of gdhA in pANS100 also resulted in the loss of GdhA enzyme activity. Collectively, these results are interpreted as evidence for the role of an additional gene product(s) in modulating the activity of GDH enzyme activity. Insertional mutagenesis experiments which led to disruption of the gdhA gene on the B. thetaiotaomicron chromosome indicated that gdhA mutants were not glutamate auxotrophs, but attempts to isolate similar mutants with insertion mutations in the region downstream of the gdhA gene were unsuccessful. PMID:8955404

  14. Region-Specific Cis- and Trans-Acting Factors Contribute to Genetic Variability in Meiotic Recombination in Maize

    PubMed Central

    Timmermans, MCP.; Das, O. P.; Bradeen, J. M.; Messing, J.

    1997-01-01

    Understanding the genetic basis for variability in recombination rates is important for general genetic studies and plant-breeding efforts. Earlier studies had suggested increased recombination frequencies in particular F(2) populations derived from the maize inbred A188. A detailed phenotypic and molecular analysis was undertaken to extend these observations and dissect the responsible factors. A heritable increase in recombination in the sh1-bz1 interval was observed in these populations. A factor causing an approximate twofold increase mapped to the A188 Sh1-Bz1 region, behaved as a dominant, cis-acting factor, affected recombination equally in male and female sporogenesis and did not reduce the wellstudied complete interference in the adjacent bz1-wx interval. This factor also did not increase recombination frequencies in the c1-sh1 and bz1-wx intervals, demonstrating independent control of recombination in adjacent intervals. Additional phenotypic analysis of recombination in the c1-sh1 and bz1-wx intervals and RFLP analysis of recombination along chromosomes 7 and 5 suggested that heritable factors controlling recombination in these intervals act largely independently and in trans. Our results show that recombination in these populations, and possibly maize in general, is controlled by both cis- and transacting factors that affect specific chromosomal regions. PMID:9215911

  15. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk.

    PubMed

    Ratner, Elena; Lu, Lingeng; Boeke, Marta; Barnett, Rachel; Nallur, Sunitha; Chin, Lena J; Pelletier, Cory; Blitzblau, Rachel; Tassi, Renata; Paranjape, Trupti; Hui, Pei; Godwin, Andrew K; Yu, Herbert; Risch, Harvey; Rutherford, Thomas; Schwartz, Peter; Santin, Alessandro; Matloff, Ellen; Zelterman, Daniel; Slack, Frank J; Weidhaas, Joanne B

    2010-08-15

    Ovarian cancer (OC) is the single most deadly form of women's cancer, typically presenting as an advanced disease at diagnosis in part due to a lack of known risk factors or genetic markers of risk. The KRAS oncogene and altered levels of the microRNA (miRNA) let-7 are associated with an increased risk of developing solid tumors. In this study, we investigated a hypothesized association between an increased risk of OC and a variant allele of KRAS at rs61764370, referred to as the KRAS-variant, which disrupts a let-7 miRNA binding site in this oncogene. Specimens obtained were tested for the presence of the KRAS-variant from nonselected OC patients in three independent cohorts, two independent ovarian case-control studies, and OC patients with hereditary breast and ovarian cancer syndrome (HBOC) as well as their family members. Our results indicate that the KRAS-variant is associated with more than 25% of nonselected OC cases. Further, we found that it is a marker for a significant increased risk of developing OC, as confirmed by two independent case-control analyses. Lastly, we determined that the KRAS-variant was present in 61% of HBOC patients without BRCA1 or BRCA2 mutations, previously considered uninformative, as well as in their family members with cancer. Our findings strongly support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC, and they suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities. PMID:20647319

  16. 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

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

    PubMed Central

    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. PMID:26751950

  18. 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

  19. Genetics

    MedlinePlus

    Homozygous; 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 ...

  20. 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 ...

  1. Limits of downstream hydraulic geometry

    NASA Astrophysics Data System (ADS)

    Wohl, Ellen

    2004-10-01

    Adjustments to flow width, depth, and velocity in response to changes in discharge are commonly characterized by using downstream hydraulic geometry relationships. The spatial limits of these relationships within a drainage basin have not been systematically quantified. Where the erosional resistance of the channel substrate is sufficiently large, hydraulic driving forces presumably will be unable to adjust channel form. Data sets from 10 mountain rivers in the United States, Panama, Nepal, and New Zealand are used in this study to explore the limits of downstream hydraulic geometry relationships. Where the ratio of stream power to sediment size (Ω/D84) exceeds 10,000 kg/s3, downstream hydraulic geometry is well developed; where the ratio falls below 10,000 kg/s3, downstream hydraulic geometry relationships are poorly developed. These limitations on downstream hydraulic geometry have important implications for channel engineering and simulations of landscape change.

  2. Mixed infections and the competitive fitness of faster-acting genetically modified viruses

    PubMed Central

    Zwart, Mark P; Van Der Werf, Wopke; Van Oers, Monique M; Hemerik, Lia; Van Lent, Jan M V; De Visser, J Arjan G M; Vlak, Just M; Cory, Jenny S

    2009-01-01

    Faster-acting recombinant baculoviruses have shown potential for improved suppression of insect pests, but their ecological impact on target and nontarget hosts and naturally occurring pathogens needs to be assessed. Previous studies have focused on the fitness of recombinants at the between-hosts level. However, the population structure of the transmission stages will also be decided by within-host selection. Here we have experimentally quantified the within-host competitive fitness of a fast-acting recombinant Autographa californica multicapsid nucleopolyhedrovirus missing the endogenous egt gene (vEGTDEL), by means of direct competition in single- and serial-passage experiments with its parental virus. Quantitative real-time PCR was employed to determine the ratio of these two viruses in passaged mixtures. We found that vEGTDEL had reduced within-host fitness: per passage the ratio of wild type to vEGTDEL was on average enhanced by a factor of 1.53 (single passage) and 1.68 (serial passage). There is also frequency-dependence: the higher the frequency of vEGTDEL, the stronger the selection against it is. Additionally, the virus ratio is a predictor of time to host death and virus yield. Our results show that egt is important to within-host fitness and allow for a more complete assessment of the ecological impact of recombinant baculovirus release. PMID:25567862

  3. 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... initiation of downstream product monitoring. (a) Introduction. Section 780 of the Act establishes a mechanism for monitoring imports of “downstream products.” In general, section 780 is aimed at situations...

  4. 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:

  5. 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.}

  6. 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 ...

  7. 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...

  8. Pyrvinium attenuates Hedgehog signaling downstream of smoothened.

    PubMed

    Li, Bin; Fei, Dennis Liang; Flaveny, Colin A; Dahmane, Nadia; Baubet, Valérie; Wang, Zhiqiang; Bai, Feng; Pei, Xin-Hai; Rodriguez-Blanco, Jezabel; Hang, Brian; Orton, Darren; Han, Lu; Wang, Baolin; Capobianco, Anthony J; Lee, Ethan; Robbins, David J

    2014-09-01

    The Hedgehog (HH) signaling pathway represents an important class of emerging developmental signaling pathways that play critical roles in the genesis of a large number of human cancers. The pharmaceutical industry is currently focused on developing small molecules targeting Smoothened (Smo), a key signaling effector of the HH pathway that regulates the levels and activity of the Gli family of transcription factors. Although one of these compounds, vismodegib, is now FDA-approved for patients with advanced basal cell carcinoma, acquired mutations in Smo can result in rapid relapse. Furthermore, many cancers also exhibit a Smo-independent activation of Gli proteins, an observation that may underlie the limited efficacy of Smo inhibitors in clinical trials against other types of cancer. Thus, there remains a critical need for HH inhibitors with different mechanisms of action, particularly those that act downstream of Smo. Recently, we identified the FDA-approved anti-pinworm compound pyrvinium as a novel, potent (IC50, 10 nmol/L) casein kinase-1α (CK1α) agonist. We show here that pyrvinium is a potent inhibitor of HH signaling, which acts by reducing the stability of the Gli family of transcription factors. Consistent with CK1α agonists acting on these most distal components of the HH signaling pathway, pyrvinium is able to inhibit the activity of a clinically relevant, vismodegib -resistant Smo mutant, as well as the Gli activity resulting from loss of the negative regulator suppressor of fused. We go on to demonstrate the utility of this small molecule in vivo, against the HH-dependent cancer medulloblastoma, attenuating its growth and reducing the expression of HH biomarkers. PMID:24994715

  9. 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

  10. The InterAct Project: An Examination of the Interaction of Genetic and Lifestyle Factors on the Incidence of Type 2 Diabetes in the EPIC Study

    PubMed Central

    Langenberg, C; Sharp, S; Forouhi, NG; Franks, P; Schulze, MB; Kerrison, N; Ekelund, U; Barroso, I; Panico, S; Tormo, M; Spranger, J; Griffin, S; van der Schouw, YT; Amiano, P; Ardanaz, E; Arriola, L; Balkau, B; Barricarte, A; Beulens, JWJ; Boeing, H; Bueno-de-Mesquita, HB; Buijsse, BB; Chirlaque Lopez, MD; Clavel-Chapelon, F; Crowe, FL; de Lauzon-Guillan, B; Deloukas, P; Dorronsoro, M; Drogan, DD; Froguel, P; Gonzalez, C; Grioni, S; Groop, L; Groves, C; Hainaut, P; Halkjaer, J; Hallmans, G; Hansen, T; Kaaks, R; Key, TJ; Khaw, K; Koulman, A; Mattiello, A; Navarro, C; Nilsson, P; Norat, T; Overvad, K; Palla, L; Palli, D; Pedersen, O; Peeters, PH; Quirós, JR; Ramachandran, A; Rodriguez-Suarez, L; Rolandsson, O; Romaguera, D; Romieu, I; Sacerdote, C; Sánchez, M; Sandbaek, A; Slimani, N; Sluijs, I; Spijkerman, AMW; Teucher, B; Tjonneland, A; Tumino, R; van der A, DL; Verschuren, WMM; Tuomilehto, J; Feskens, E; McCarthy, M; Riboli, E; Wareham, NJ

    2014-01-01

    Background Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. Objective To establish a type 2 diabetes case-cohort study designed to investigate how genetic and potentially modifiable lifestyle and behavioral factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Methods Funded by the Sixth European Framework Programme, InterAct consortium partners ascertained and verified incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from 8 of the 10 EPIC countries. A pragmatic, high sensitivity approach was used for case ascertainment including multiple sources at each EPIC centre, followed by diagnostic verification. Prentice-weighted Cox regression and random effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. Results A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes that were randomly selected into the subcohort (n=778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years, 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist were 29.4 kg/m2 and 102.7 cm in men, and 30.1 kg/m2 and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall hazard ratio (95% CI) of 1.56 (1.48; 1

  11. Evidence for a trans-acting factor that regulates the transcription of class II major histocompatibility complex genes: genetic and functional analysis.

    PubMed Central

    Calman, A F; Peterlin, B M

    1988-01-01

    The study of specific trans-acting transcription factors in prokaryotes and lower eukaryotes has been greatly facilitated by genetic analysis of mutant strains deficient in such factors. We have developed such a system to study mammalian trans-acting factors that regulate the transcription of class II major histocompatibility complex genes, using the mutant cell lines RM2 and RM3. These cells, derived from the human B-cell line Raji, specifically fail to transcribe their class II major histocompatibility complex genes. Here we show that a transfected HLA-DR alpha class II major histocompatibility complex gene, like the endogenous HLA-DR alpha genes, is efficiently transcribed in Raji cells but not in RM2 or RM3 cells, demonstrating that the mutant cells are deficient in a specific trans-acting factor required for transcription of these genes. HLA-DR expression in RM2 and RM3 cells is rescued by fusion to another B-cell line but not by fusion to each other. Thus, the defects in the two cell lines are recessive and noncomplementing and define a locus whose wild-type product we designate TF-X1. We show that TF-X1 influences the activity of a 24-base-pair B-cell-specific cis-acting transcription element in the HLA-DR alpha promoter. However, in three different biochemical assays, we detect no difference between wild-type and mutant cells in the DNA-binding proteins that interact with these DNA sequences. Thus, the defective version of TF-X1 may be a DNA-binding protein that binds to the HLA-DR alpha promoter but fails to activate transcription. Alternatively, TF-X1 may not be a DNA-binding protein at all. Images PMID:3143110

  12. Diversification of a Transcription Factor Family Led to the Evolution of Antagonistically Acting Genetic Regulators of Root Hair Growth.

    PubMed

    Breuninger, Holger; Thamm, Anna; Streubel, Susanna; Sakayama, Hidetoshi; Nishiyama, Tomoaki; Dolan, Liam

    2016-06-20

    Streptophytes colonized the land some time before 470 million years ago [1-3]. The colonization coincided with an increase in morphological and cellular diversity [4-7]. This increase in diversity is correlated with a proliferation in transcription factors encoded in genomes [8-10]. This suggests that gene duplication and subsequent diversification of function was instrumental in the generation of land plant diversity. Here, we investigate the diversification of the streptophyte-specific Lotus japonicus ROOTHAIRLESS LIKE (LRL) transcription factor (TF) [11, 12] subfamily of basic loop helix (bHLH) proteins by comparing gene function in early divergent and derived land plant species. We report that the single Marchantia polymorpha LRL gene acts as a general growth regulator required for rhizoid development, a function that has been partially conserved throughout multicellular streptophytes. In contrast, the five relatively derived Arabidopsis thaliana LRL genes comprise two antagonistically acting groups of differentially expressed genes. The diversification of LRL genes accompanied the evolution of an antagonistic regulatory element controlling root hair development. PMID:27265398

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Genetically Detoxified Mutants of Heat-Labile Toxin from Escherichia coli Are Able To Act as Oral Adjuvants

    PubMed Central

    Douce, Gill; Giannelli, Valentina; Pizza, Mariagrazia; Lewis, David; Everest, Paul; Rappuoli, Rino; Dougan, Gordon

    1999-01-01

    Detoxified mutants of the Escherichia coli heat-labile toxin (LT) act as mucosal adjuvants to intranasally presented coadministered antigens. Here, we compare the adjuvant activity of a panel of detoxified derivatives of LT, using both intranasal (i.n.) and oral (p.o.) routes of administration. The mutants used as adjuvants varied in sensitivity to proteases and toxicity. With keyhole limpet hemocyanin (KLH) as the bystander antigen, the immune responses to i.n. immunizations were consistently higher than the equivalent p.o.-delivered proteins. LT-G192, a mutant which demonstrates a 10-fold reduction in toxicity in vitro, demonstrated wild-type adjuvant activity both i.n. and p.o., inducing similar titers of KLH specific antibody in the sera and immunoglobulin A in local mucosal secretions as wild-type LT. In line with previous data, the nontoxic holotoxoid LT-K63 induced intermediate immune responses in both the serum and mucosal secretions which were lower than those achieved with wild-type LT but at least 10-fold higher than those measured when the antigen was administered with LT-B. Although significant levels of local and systemic anti-KLH antibodies were induced following p.o. immunization with LT-K63, cellular proliferative responses to KLH was poor or undetectable. In contrast, LT and LT-G192 induced significant T-cell responses to KLH following p.o. immunization. These proliferating cells secreted both gamma interferon and interleukin-5, suggesting that the type of immune response induced following p.o. coimmunization with LT and purified protein is a mixed Th1/Th2 response. PMID:10456880

  18. Genetically detoxified mutants of heat-labile toxin from Escherichia coli are able to act as oral adjuvants.

    PubMed

    Douce, G; Giannelli, V; Pizza, M; Lewis, D; Everest, P; Rappuoli, R; Dougan, G

    1999-09-01

    Detoxified mutants of the Escherichia coli heat-labile toxin (LT) act as mucosal adjuvants to intranasally presented coadministered antigens. Here, we compare the adjuvant activity of a panel of detoxified derivatives of LT, using both intranasal (i.n.) and oral (p.o.) routes of administration. The mutants used as adjuvants varied in sensitivity to proteases and toxicity. With keyhole limpet hemocyanin (KLH) as the bystander antigen, the immune responses to i. n. immunizations were consistently higher than the equivalent p.o. -delivered proteins. LT-G192, a mutant which demonstrates a 10-fold reduction in toxicity in vitro, demonstrated wild-type adjuvant activity both i.n. and p.o., inducing similar titers of KLH specific antibody in the sera and immunoglobulin A in local mucosal secretions as wild-type LT. In line with previous data, the nontoxic holotoxoid LT-K63 induced intermediate immune responses in both the serum and mucosal secretions which were lower than those achieved with wild-type LT but at least 10-fold higher than those measured when the antigen was administered with LT-B. Although significant levels of local and systemic anti-KLH antibodies were induced following p.o. immunization with LT-K63, cellular proliferative responses to KLH was poor or undetectable. In contrast, LT and LT-G192 induced significant T-cell responses to KLH following p.o. immunization. These proliferating cells secreted both gamma interferon and interleukin-5, suggesting that the type of immune response induced following p.o. coimmunization with LT and purified protein is a mixed Th1/Th2 response. PMID:10456880

  19. Targeting pathways downstream of KRAS in lung adenocarcinoma.

    PubMed

    Zhu, Zehua; Golay, Hadrien G; Barbie, David A

    2014-08-01

    Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted therapy. Much of the current focus has been directed at inhibiting the activation of RAF/MAPK and PI3K/AKT signaling, but clinical trials combining multiple different agents that target these pathways have failed to show significant activity. In this article, we will discuss the evidence for RAF and PI3K as key downstream RAS effectors, as well as the RAL guanine exchange factor, which is equally essential for transformation. Furthermore, we will delineate alternative pathways, including cytokine activation and autophagy, which are co-opted by oncogenic RAS signaling and also represent attractive targets for therapy. Finally, we will present strategies for combining inhibitors of these downstream KRAS signaling pathways in a rational fashion, as multitargeted therapy will be required to achieve a cure. PMID:25303301

  20. Targeting pathways downstream of KRAS in lung adenocarcinoma

    PubMed Central

    Zhu, Zehua; Golay, Hadrien G; Barbie, David A

    2014-01-01

    Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted therapy. Much of the current focus has been directed at inhibiting the activation of RAF/MAPK and PI3K/AKT signaling, but clinical trials combining multiple different agents that target these pathways have failed to show significant activity. In this article, we will discuss the evidence for RAF and PI3K as key downstream RAS effectors, as well as the RAL guanine exchange factor, which is equally essential for transformation. Furthermore, we will delineate alternative pathways, including cytokine activation and autophagy, which are co-opted by oncogenic RAS signaling and also represent attractive targets for therapy. Finally, we will present strategies for combining inhibitors of these downstream KRAS signaling pathways in a rational fashion, as multitargeted therapy will be required to achieve a cure. PMID:25303301

  1. Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

    PubMed Central

    Zaade, Daniela; Schmitz, Jennifer; Benke, Eileen; Klare, Sabrina; Seidel, Kerstin; Kirsch, Sebastian; Goldin-Lang, Petra; Zollmann, Frank S.; Unger, Thomas; Funke-Kaiser, Heiko

    2013-01-01

    The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis. PMID:23469216

  2. 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.

  3. Downstream prediction using a nonlinear prediction method

    NASA Astrophysics Data System (ADS)

    Adenan, N. H.; Noorani, M. S. M.

    2013-11-01

    The estimation of river flow is significantly related to the impact of urban hydrology, as this could provide information to solve important problems, such as flooding downstream. The nonlinear prediction method has been employed for analysis of four years of daily river flow data for the Langat River at Kajang, Malaysia, which is located in a downstream area. The nonlinear prediction method involves two steps; namely, the reconstruction of phase space and prediction. The reconstruction of phase space involves reconstruction from a single variable to the m-dimensional phase space in which the dimension m is based on optimal values from two methods: the correlation dimension method (Model I) and false nearest neighbour(s) (Model II). The selection of an appropriate method for selecting a combination of preliminary parameters, such as m, is important to provide an accurate prediction. From our investigation, we gather that via manipulation of the appropriate parameters for the reconstruction of the phase space, Model II provides better prediction results. In particular, we have used Model II together with the local linear prediction method to achieve the prediction results for the downstream area with a high correlation coefficient. In summary, the results show that Langat River in Kajang is chaotic, and, therefore, predictable using the nonlinear prediction method. Thus, the analysis and prediction of river flow in this area can provide river flow information to the proper authorities for the construction of flood control, particularly for the downstream area.

  4. Differential Allelic Expression in the Human Genome: A Robust Approach To Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene Expression

    PubMed Central

    Serre, David; Gurd, Scott; Ge, Bing; Sladek, Robert; Sinnett, Donna; Harmsen, Eef; Bibikova, Marina; Chudin, Eugene; Barker, David L.; Dickinson, Todd; Fan, Jian-Bing; Hudson, Thomas J.

    2008-01-01

    The recent development of whole genome association studies has lead to the robust identification of several loci involved in different common human diseases. Interestingly, some of the strongest signals of association observed in these studies arise from non-coding regions located in very large introns or far away from any annotated genes, raising the possibility that these regions are involved in the etiology of the disease through some unidentified regulatory mechanisms. These findings highlight the importance of better understanding the mechanisms leading to inter-individual differences in gene expression in humans. Most of the existing approaches developed to identify common regulatory polymorphisms are based on linkage/association mapping of gene expression to genotypes. However, these methods have some limitations, notably their cost and the requirement of extensive genotyping information from all the individuals studied which limits their applications to a specific cohort or tissue. Here we describe a robust and high-throughput method to directly measure differences in allelic expression for a large number of genes using the Illumina Allele-Specific Expression BeadArray platform and quantitative sequencing of RT-PCR products. We show that this approach allows reliable identification of differences in the relative expression of the two alleles larger than 1.5-fold (i.e., deviations of the allelic ratio larger than 60∶40) and offers several advantages over the mapping of total gene expression, particularly for studying humans or outbred populations. Our analysis of more than 80 individuals for 2,968 SNPs located in 1,380 genes confirms that differential allelic expression is a widespread phenomenon affecting the expression of 20% of human genes and shows that our method successfully captures expression differences resulting from both genetic and epigenetic cis-acting mechanisms. PMID:18454203

  5. Upstream and downstream strategies to economize biodiesel production.

    PubMed

    Hasheminejad, Meisam; Tabatabaei, Meisam; Mansourpanah, Yaghoub; Khatami far, Mahdi; Javani, Azita

    2011-01-01

    In recent years biodiesel has drawn considerable amount of attention as a clean and renewable fuel. Biodiesel is produced from renewable sources such as vegetable oils and animal fat mainly through catalytic or non-catalytic transesterification method as well as supercritical method. However, as a consequence of disadvantages of these methods, the production cost increases dramatically. This article summarizes different biodiesel production methods with a focus on their advantages and disadvantages. The downstream and upstream strategies such as using waste cooking oils, application of non-edible plant oils, plant genetic engineering, using membrane separation technology for biodiesel production, separation and purification, application of crude glycerin as an energy supplement for ruminants, glycerin ultra-purification and their consequent roles in economizing the production process are fully discussed in this article. PMID:20974530

  6. DARHT-II Downstream Beam Transport Beamline

    SciTech Connect

    Westenskow, G A; Bertolini, L R; Duffy, P T; Paul, A C

    2000-08-01

    This paper describes the mechanical design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 20-MeV, 2000-Amperes, 2-{micro}sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 20-meter long region extending from the end of the accelerator to the bremsstrahlung target. Within this proposed transport line there are 15 conventional solenoid, quadrupole and dipole magnets; as well as several specialty magnets, which transport and focus the beam to the target and to the beam dumps. There are two high power beam dumps, which are designed to absorb 80-kJ per pulse during accelerator start-up and operation. Aspects of the mechanical design of these elements are presented.

  7. 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

  8. 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.

  9. miR-326 Is Downstream of Sonic Hedgehog Signaling and Regulates the Expression of Gli2 and Smoothened

    PubMed Central

    Jiang, Zhihua; Cushing, Leah; Lü, Jining

    2014-01-01

    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. PMID:24617895

  10. 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. PMID:24617895

  11. 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

  12. 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

  13. 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.

  14. DARHT-II Downstream Transport Beamline

    SciTech Connect

    Westenskow, G A; Bertolini, L R; Duffy, P T; Paul, A C

    2001-06-06

    This paper describes the mechanical design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 18.4-MeV, 2000-Amperes, 2-{micro}sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 22-meter long region extending from the end of the accelerator to the bremsstrahlung target. Within this proposed transport line there are 12 conventional solenoid, quadrupole and dipole magnets; as well as several specialty magnets, which transport and focus the beam to the target and to the beam dumps. There are two high power beam dumps, which are designed to absorb 80-kJ per pulse during accelerator start-up and operation. Aspects of the mechanical design of these elements are presented.

  15. 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

  16. NRP2 transcriptionally regulates its downstream effector WDFY1

    PubMed Central

    Dutta, Samikshan; Roy, Sohini; Polavaram, Navatha S; Baretton, Gustavo B.; Muders, Michael H.; Batra, Surinder; Datta, Kaustubh

    2016-01-01

    Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)–protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, essential for promotion of oncogenic activation and cancer cell survival. Here, we have delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our results indicated that NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells. Thus, inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce cell death in metastatic cancer. PMID:27026195

  17. NRP2 transcriptionally regulates its downstream effector WDFY1.

    PubMed

    Dutta, Samikshan; Roy, Sohini; Polavaram, Navatha S; Baretton, Gustavo B; Muders, Michael H; Batra, Surinder; Datta, Kaustubh

    2016-01-01

    Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, essential for promotion of oncogenic activation and cancer cell survival. Here, we have delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our results indicated that NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells. Thus, inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce cell death in metastatic cancer. PMID:27026195

  18. 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

  19. 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

  20. 40 CFR 80.69 - Requirements for downstream oxygenate blending.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Requirements for downstream oxygenate... downstream oxygenate blending. The requirements of this section apply to all reformulated gasoline blendstock... annual compliance period; (D) A process for notifying oxygenate blenders and other downstream parties...

  1. Onecut1 and Onecut2 transcription factors operate downstream of Pax6 to regulate horizontal cell development.

    PubMed

    Klimova, Lucie; Antosova, Barbora; Kuzelova, Andrea; Strnad, Hynek; Kozmik, Zbynek

    2015-06-01

    Genetic studies of the last decades strongly indicated that generation of particular retinal cell types is governed by gene regulatory networks of transcription factors and their target genes. The paired and homeodomain transcription factor Pax6 plays a pivotal role in retinal development as its inactivation in the retinal progenitor cell population leads to abolished differentiation of all retinal cell types. However, until now, only a few transcription factors operating downstream of Pax6 responsible for generation of individual retinal cell types have been identified. In this study, we identified two transcription factors of the Onecut family, Onecut1 and Onecut2, as Pax6 downstream-acting factors. Onecut1 and Onecut2 were previously shown to be expressed in developing horizontal cells, retinal ganglion cells and cone photoreceptors; however, their role in differentiation of these cell types is poorly understood. In this study, we show that the horizontal cell genesis is severely disturbed in Onecut-deficient retinae. In single Onecut1 and Onecut2 mutants, the number of horizontal cells is dramatically reduced while horizontal cells are completely missing in the Onecut1/Onecut2 compound mutant. Analysis of genes involved in the horizontal cell genesis such as Foxn4, Ptf1a, Prox1 and Lim1 showed that although horizontal cells are initially formed, they are not maintained in Onecut-deficient retinae. Taken together, this study suggests the model in which Pax6 regulates the maintenance of horizontal cells through the activation of Onecut1 and Onecut2 transcription factors. PMID:25794677

  2. Identification of novel Hoxa1 downstream targets regulating hindbrain, neural crest and inner ear development

    PubMed Central

    Makki, Nadja; Capecchi, Mario R.

    2011-01-01

    Hoxgenes play a crucial role during embryonic patterning and organogenesis. Of the 39 Hox genes, Hoxa1 is the first to be expressed during embryogenesis and the only anterior Hox gene linked to a human syndrome. Hoxa1 is necessary for proper development of the brainstem, inner ear and heart in humans and mice; however, almost nothing is known about the molecular downstream targets through which it exerts its function. To gain insight into the transcriptional network regulated by this protein, we performed microarray analysis on tissue microdissected from the prospective rhombomere 3–5 region of Hoxa1 null and wild type embryos. Due to the very early and transient expression of this gene, dissections were performed on early somite stage embryos during an eight-hour time window of development. Our array yielded a list of around 300 genes differentially expressed between the two samples. Many of the identified genes play a role in a specific developmental or cellular process. Some of the validated targets regulate early neural crest induction and specification. Interestingly, three of these genes, Zic1, Hnf1b and Foxd3, were down-regulated in the posterior hindbrain, where cardiac neural crest cells arise, which pattern the outflow tract of the heart. Other targets are necessary for early inner ear development, e.g. Pax8 and Fgfr3 or are expressed in specific hindbrain neurons regulating respiration, e.g. Lhx5. These findings allow us to propose a model where Hoxa1 acts in a genetic cascade upstream of genes controlling specific aspects of embryonic development, thereby providing insight into possible mechanisms underlying the human HoxA1-syndrome. PMID:21784065

  3. 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.

  4. Downstream hydraulic geometry of alluvial rivers

    NASA Astrophysics Data System (ADS)

    Julien, P. Y.

    2015-03-01

    This article presents a three-level approach to the analysis of downstream hydraulic geometry. First, empirical concepts based on field observations of "poised" conditions in irrigation canals are examined. Second, theoretical developments have been made possible by combining basic relationships for the description of flow and sediment transport in alluvial rivers. Third, a relatively new concept of equivalent channel widths is presented. The assumption of equilibrium may describe a perpetual state of change and adjustments. The new concepts define the trade-offs between some hydraulic geometry parameters such as width and slope. The adjustment of river widths and slope typically follows a decreasing exponential function and recent developments indicate how the adjustment time scale can be quantified. Some examples are also presented to illustrate the new concepts presented and the realm of complex river systems.

  5. 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.

  6. 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

  7. Eutrophication downstream from small reservoirs in mountain rivers of Central Spain.

    PubMed

    Camargo, Julio A; Alonso, Alvaro; de la Puente, Marcos

    2005-09-01

    In this research we examined the hypothesis that upper reaches of rivers and streams can experience eutrophication as a consequence of deep releases from dams. Field studies were conducted in four mountain rivers (Tormes, Riaza, Eresma and Miraflores Rivers) of Central Spain. The watersheds of these rivers are underlain by siliceous rocks. A small deep-release storage reservoir is found in the upper reaches of each river. Two sampling sites, upstream and downstream from the reservoir, were established in stony riffles of each impounded river. Significant (P < 0.01) increases in conductivity and nutrient (NO3-N, NH4-N, PO4-P) concentrations downstream from the reservoirs were measured. Significant (P < 0.01) increases in periphyton chlorophyll a and ash-free dry biomass were also quantified at downstream sites. Significant (P < 0.01) correlation coefficients indicated that phosphate would play a more important role as the limiting nutrient for periphyton. Relative abundances of macroinvertebrate scrapers and collector-gatherers increased downstream from the reservoirs. Furthermore, taxon dominance, total density and total biomass of macroinvertebrates tended to be higher at downstream sites than at upstream sites. In contrast, taxon diversity and relative abundance of macroinvertebrate shredders decreased downstream from the reservoirs. It is concluded that small deep-release storage reservoirs, located in upper reaches of siliceous rivers, can act as nutrient sources, causing eutrophication downstream. Nutrients would ultimately come from land/forest runoff. The fact that terrestrial vegetation was not completely removed before filling reservoirs could also contribute to the eutrophication process. PMID:16039693

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 29 CFR 1601.2 - Terms defined in title VII of the Civil Rights Act, the Americans with Disabilities Act, and the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Americans with Disabilities Act, and the Genetic Information Nondiscrimination Act. 1601.2 Section 1601.2... Disabilities Act, and the Genetic Information Nondiscrimination Act. The terms person, employer, employment... Disabilities Act of 1990. The term genetic information shall have the meaning set forth in section 201 of...

  16. Downstream Hydraulic Geometry of Mountain Rivers

    NASA Astrophysics Data System (ADS)

    Wohl, E.

    2003-12-01

    The concept of downstream hydraulic geometry (DHG) was developed for fully alluvial rivers that are presumed to be capable of continually adjusting their dimensions to changes in bankfull discharge. Mountain rivers, although mostly formed in alluvium, may behave differently because discharges along the channel lack the competence to move coarse clasts introduced from colluvial processes or glaciation, or because discontinuous bedrock exposures limit channel adjustment. Consequently, the DHG of mountain rivers could reflect bankfull flows; larger magnitude, less frequent flows; or non-fluvial processes such as debris flows. The research summarized here was designed to test whether traditional DHG concepts apply to mountain rivers, and to determine when correlations between velocity, flow depth, or width, and bankfull discharge, are strongly developed. Rivers with strongly developed DHG are defined here as those with r2 values > 0.5 for at least two of the correlations. I hypothesize that a quantifiable threshold separates mountain rivers with well-developed DHG from those with poorly-developed DHG. This threshold can be expressed using a ratio of hydraulic driving forces to substrate resisting forces. As the ratio increases, the ability of bankfull flows to adjust channel dimensions should also increase. The hypothesis was tested using 8 datasets from mountain rivers in Alaska, Montana, Colorado, Panama, Nepal, and New Zealand. A ratio of either total stream power/D84, or unit stream power/D84, separates rivers with and without well-developed DHG. This approach is a simplification which ignores the presence of bedrock; the duration and frequency of flows as these affect stream power; and non-fluvial processes. However, the results suggest that mountain rivers with greater hydraulic driving forces are more likely to behave like fully alluvial rivers in terms of having well-developed DHG relations.

  17. 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

  18. 1. GENERAL EXTERIOR VIEW LOOKING SOUTHEAST AT DOWNSTREAM FACE OF ...

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

    1. GENERAL EXTERIOR VIEW LOOKING SOUTHEAST AT DOWNSTREAM FACE OF DAM/SPILLWAY. VIEW TAKEN FROM WASHINGTON SHORELINE. - Bonneville Project, Bonneville Dam, Columbia River, Bonneville, Multnomah County, OR

  19. 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

  20. 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.

  1. 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

  2. 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

  3. Genetic grafting of membrane-acting peptides to the cytotoxin dianthin augments its ability to de-stabilize lipid bilayers and enhances its cytotoxic potential as the component of transferrin-toxin conjugates.

    PubMed

    Lorenzetti, I; Meneguzzi, A; Fracasso, G; Potrich, C; Costantini, L; Chiesa, E; Legname, G; Menestrina, G; Tridente, G; Colombatti, M

    2000-05-15

    Three chimeric proteins were obtained by fusing together the dianthin gene and DNA fragments encoding for the following membrane-acting peptides: the N-terminus of protein G of the vesicular stomatitis virus (KFT25), the N terminus of the HA2 hemagglutinin of influenza virus (pHA2), and a membrane-acting peptide (pJVE). Chimeric dianthins (KFT25DIA, pHA2DIA and pJVEDIA) retained full enzymatic activity in cell-free assays and showed increased ability to induce pH-dependent calcein release from large unilamellar vesicles (LUVs). pHA2DIA and pJVEDIA also showed faster kinetics of interaction with LUVs, while KFT25DIA and pHA2DIA displayed a reduced cytotoxicity as compared to wild-type dianthin. Conjugates made by chemically cross-linking KFT25DIA or pJVEDIA and human transferrin (Tfn) showed greater cell-killing efficiency than conjugates of Tfn and wild-type dianthin. As a consequence, by fusion of membrane-acting peptides to the dianthin sequence the specificity factor (i.e., the ratio between non-specific and specific toxicity) of Tfn-KFT25DIA, Tfn-pHA2DIA and Tfn-pJVEDIA was increased with respect to that of Tfn-based conjugates made with wild-type dianthin. Taken together, our results suggest that genetic fusion of membrane-acting peptides to enzymatic cytotoxins results in the acquisition of new physico-chemical properties exploitable for designing new recombinant cytotoxins and to tackle cell-intoxication mechanisms. PMID:10797275

  4. Transcription of T cell receptor beta-chain genes is controlled by a downstream regulatory element.

    PubMed Central

    Krimpenfort, P; de Jong, R; Uematsu, Y; Dembic, Z; Ryser, S; von Boehmer, H; Steinmetz, M; Berns, A

    1988-01-01

    To characterize cis-acting elements controlling the expression of T cell receptor beta-chains we generated a number of transgenic mouse lines harboring a rearranged T cell receptor beta-chain with different extensions of 5' and 3' flanking sequences. Transcriptional analysis of transgenic mice carrying these clones showed that sequences located downstream of the polyadenylation signal of the C beta 2 region are indispensable for expression in transgenic mice. The sequences conferring enhancer activity in this fragment were further defined by transient CAT assays. Strong enhancer activity was found to reside in a 550 bp fragment located 5 kb downstream from C beta 2. The nucleotide sequence of this fragment revealed a number of oligonucleotide motifs characteristic for enhancer elements. Images PMID:3396541

  5. Genetic architecture of ethanol-responsive transcriptome variation in Saccharomyces cerevisiae strains.

    PubMed

    Lewis, Jeffrey A; Broman, Aimee T; Will, Jessica; Gasch, Audrey P

    2014-09-01

    Natural variation in gene expression is pervasive within and between species, and it likely explains a significant fraction of phenotypic variation between individuals. Phenotypic variation in acute systemic responses can also be leveraged to reveal physiological differences in how individuals perceive and respond to environmental perturbations. We previously found extensive variation in the transcriptomic response to acute ethanol exposure in two wild isolates and a common laboratory strain of Saccharomyces cerevisiae. Many expression differences persisted across several modules of coregulated genes, implicating trans-acting systemic differences in ethanol sensing and/or response. Here, we conducted expression QTL mapping of the ethanol response in two strain crosses to identify the genetic basis for these differences. To understand systemic differences, we focused on "hotspot" loci that affect many transcripts in trans. Candidate causal regulators contained within hotspots implicate upstream regulators as well as downstream effectors of the ethanol response. Overlap in hotspot targets revealed additive genetic effects of trans-acting loci as well as "epi-hotspots," in which epistatic interactions between two loci affected the same suites of downstream targets. One epi-hotspot implicated interactions between Mkt1p and proteins linked to translational regulation, prompting us to show that Mkt1p localizes to P bodies upon ethanol stress in a strain-specific manner. Our results provide a glimpse into the genetic architecture underlying natural variation in a stress response and present new details on how yeast respond to ethanol stress. PMID:24970865

  6. A Common Variant of PROK1 (V67I) Acts as a Genetic Modifier in Early Human Pregnancy through Down-Regulation of Gene Expression

    PubMed Central

    Su, Mei-Tsz; Huang, Jyun-Yuan; Tsai, Hui-Ling; Chen, Yi-Chi; Kuo, Pao-Lin

    2016-01-01

    PROK1-V67I has been shown to play a role as a modifier gene in the PROK1-PROKR system of human early pregnancy. To explore the related modifier mechanism of PROK1-V67I, we carried out a comparison study at the gene expression level and the cell function alternation of V67I, and its wild-type (WT), in transiently-transfected cells. We, respectively, performed quantitative RT-PCR and ELISA assays to evaluate the protein and/or transcript level of V67I and WT in HTR-8/SV neo, JAR, Ishikawa, and HEK293 cells. Transiently V67I- or WT-transfected HTR-8/SV neo and HEK293 cells were used to investigate cell function alternations. The transcript and protein expressions were down-regulated in all cell lines, ranging from 20% to 70%, compared with WT. There were no significant differences in the ligand activities of V67I and WT with regard to cell proliferation, cell invasion, calcium influx, and tubal formation. Both PROK1 alleles promoted cell invasion and intracellular calcium mobilization, whereas they had no significant effects on cell proliferation and tubal formation. In conclusion, the biological effects of PROK1-V67I on cell functions are similar to those of WT, and the common variant of V67I may act as a modifier in the PROK1-PROKR system through down-regulation of PROK1 expression. This study may provide a general mechanism that the common variant of V67I, modifying the disease severity of PROK1-related pathophysiologies. PMID:26828479

  7. 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

  8. 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

  9. 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

  10. Operating stability of hydroelectric stations with downstream surge tanks

    SciTech Connect

    Murav`ev, O.A.; Berlin, V.V.

    1995-10-01

    The possibilities for reducing the cross-sectional area of downstream surge tanks under the condition of providing stable regimes of the hydroelectric power plant are analyzed. Two calculation methods are described.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 22. DOWNSTREAM DETAIL OF PIER NO. 3, TRUSS TOWER AND ...

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

    22. DOWNSTREAM DETAIL OF PIER NO. 3, TRUSS TOWER AND CANTILEVER ARMS. VIEW TO NORTHEAST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  17. 24. DOWNSTREAM DETAIL OF PIER NO. 2 AND THROUGH AND ...

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

    24. DOWNSTREAM DETAIL OF PIER NO. 2 AND THROUGH AND DECK TRUSS END PANELS. VIEW TO NORTHEAST. - MacArthur Bridge, Spanning Mississippi River on Highway 34 between IA & IL, Burlington, Des Moines County, IA

  18. 12. VIEW OF DOWNSTREAM ELEVATION, LOOKING SOUTHEAST. PIER OF OLD ...

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

    12. VIEW OF DOWNSTREAM ELEVATION, LOOKING SOUTHEAST. PIER OF OLD BRIDGE IS IN FOREGROUND - Chili Bar Bridge, Spanning South Fork of American River at State Highway 193, Placerville, El Dorado County, CA

  19. 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

  20. 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...

  1. 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

  2. 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

  3. 4. DOWNSTREAM ELEVATION. DETAIL OF BUTTRESS ADDITION ON NORTHEAST WING ...

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

    4. DOWNSTREAM ELEVATION. DETAIL OF BUTTRESS ADDITION ON NORTHEAST WING WALL. - Core Creek County Bridge, Spanning Core Creek, approximately 1 mile South of State Route 332 (Newtown Bypass), Newtown, Bucks County, PA

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. View of Lake Sabrina Dam downstream face from parking lot ...

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

    View of Lake Sabrina Dam downstream face from parking lot showing concrete outlet structure on tow of dam at left edge of photo, view southeast - Bishop Creek Hydroelectric System, Plant 2, Lake Sabrina Dam, Bishop Creek, Bishop, Inyo County, CA

  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. 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

  13. 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

  14. 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

  15. VIEW OF DOWNSTREAM SIDE OF TUMALO DIVERSION DAM AND SPILLWAY, ...

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

    VIEW OF DOWNSTREAM SIDE OF TUMALO DIVERSION DAM AND SPILLWAY, WITH FISH LADDER TO RIGHT OF VIEW. FROM WEST BANK OF TUMALO CREEK. LOOKING SOUTHWEST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  16. VIEW OF BLAKELY ROAD ACROSS TUMALO DAM, DOWNSTREAM SIDE TO ...

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

    VIEW OF BLAKELY ROAD ACROSS TUMALO DAM, DOWNSTREAM SIDE TO LEFT AND RESERVOIR SIDE TO RIGHT. LOOKING WEST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  17. VIEW OF HIGHLINE DROP ON THE HIGHLINE LATERAL CANAL DOWNSTREAM ...

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

    VIEW OF HIGHLINE DROP ON THE HIGHLINE LATERAL CANAL DOWNSTREAM FROM BULLCREEK DAM AND BRIDGE. LOOKING SOUTHEAST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  18. VIEW OF DOWNSTREAM SIDE OF BULL CREEK DAM AND BRIDGE, ...

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

    VIEW OF DOWNSTREAM SIDE OF BULL CREEK DAM AND BRIDGE, WITH LATER HEADGATE ADDITION THROUGH SPILLWAY. LOOKING WEST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  19. View of downstream face of Grand Coulee Dam (from just ...

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

    View of downstream face of Grand Coulee Dam (from just below No. 3 Powerhouse), looking southwest. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  20. Detail of downstream face of dam showing water being discharged ...

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

    Detail of downstream face of dam showing water being discharged through diversion tube. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  1. 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

  2. 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

  3. 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

  4. 23. INTAKE DIVERSION DAM UNDER CONSTRUCTION, FACING NORTHWEST AND DOWNSTREAM ...

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

    23. INTAKE DIVERSION DAM UNDER CONSTRUCTION, FACING NORTHWEST AND DOWNSTREAM Photographer: Walter J. Lubken, September 17, 1906 - Roosevelt Power Canal & Diversion Dam, Parallels Salt River, Roosevelt, Gila County, AZ

  5. 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

  6. 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

  7. 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

  8. 25. GENERAL EXTERIOR VIEW LOOKING WEST, SHOWING FISH LADDER DOWNSTREAM ...

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

    25. GENERAL EXTERIOR VIEW LOOKING WEST, SHOWING FISH LADDER DOWNSTREAM FROM THE DAM/SPILLWAY ON THE WASHINGTON SHORE. - Bonneville Project, Bonneville Dam, Columbia River, Bonneville, Multnomah County, OR

  9. 2. GENERAL EXTERIOR VIEW LOOKING SOUTH, SHOWING DOWNSTREAM FACE OF ...

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

    2. GENERAL EXTERIOR VIEW LOOKING SOUTH, SHOWING DOWNSTREAM FACE OF DAM/SPILLWAY; PARKING LOT/WORK AREA ON WASHINGTON SHORE IS VISIBLE IN FOREGROUND. - Bonneville Project, Bonneville Dam, Columbia River, Bonneville, Multnomah County, OR

  10. 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

  11. 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

  12. 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

  13. 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

  14. VIEW LOOKING SOUTH SOUTHWEST AT THE DOWNSTREAM ENTRANCE INTO LOCK ...

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

    VIEW LOOKING SOUTH SOUTHWEST AT THE DOWNSTREAM ENTRANCE INTO LOCK 67. NOTE THE BEDDING TIMBERS AT BASE OF STONE WORK. THEY ARE EXPOSED ONLY AT LOW WATER. - New York State Barge Canal, Lockport Locks, Richmond Avenue, Lockport, Niagara County, NY

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 76. PALMDALE WATER COMPANY, LITTLEROCK DAM, EASTWOOD MULTIPLEARCHED TYPE: DOWNSTREAM ...

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

    76. PALMDALE WATER COMPANY, LITTLEROCK DAM, EASTWOOD MULTIPLE-ARCHED TYPE: DOWNSTREAM ELEVATION, SHEET 3; OCTOBER 2, 1919. Littlerock Water District files. - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

    PubMed Central

    2009-01-01

    Background The topology of a biological pathway provides clues as to how a pathway operates, but rationally using this topology information with observed gene expression data remains a challenge. Results We introduce a new general-purpose analytic method called Mechanistic Bayesian Networks (MBNs) that allows for the integration of gene expression data and known constraints within a signal or regulatory pathway to predict new downstream pathway targets. The MBN framework is implemented in an open-source Bayesian network learning package, the Python Environment for Bayesian Learning (PEBL). We demonstrate how MBNs can be used by modeling the early steps of the sonic hedgehog pathway using gene expression data from different developmental stages and genetic backgrounds in mouse. Using the MBN approach we are able to automatically identify many of the known downstream targets of the hedgehog pathway such as Gas1 and Gli1, along with a short list of likely targets such as Mig12. Conclusions The MBN approach shown here can easily be extended to other pathways and data types to yield a more mechanistic framework for learning genetic regulatory models. PMID:20021670

  11. 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

  12. Balancing Acts

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... from the National Institute on Deafness and Other Communication Disorders (NIDCD). It involves simulated trips down the ...

  13. 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)

  14. 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 ...

  15. The influence of downstream passage on the flow within an annular S-shaped duct

    SciTech Connect

    Sonoda, T.; Arima, T.; Oana, M.

    1998-10-01

    Experimental and numerical investigations were carried out to gain a better understanding of the flow characteristics within an annular S-shaped duct, including the influence of the shape of the downstream passage located at the exit of the duct on the flow. A duct with six struts and the same geometry as that used to connect the compressor spools on the new experimental small two-spool turbofan engine was investigated. Two types of downstream passage were used. One type had a straight annular passage and the other a curved annular passage with a meridional flow path geometry similar to that of the centrifugal compressor. Results showed that the total pressure loss near the hub is large due to instability of the flow, as compared with that near the casing. Also, a vortex related to the horseshoe vortex was observed near the casing. In the case of the curved annular passage, the total pressure loss near the hub was greatly increased compared with the case of the straight annular passage, and the spatial position of this vortex depends on the passage core pressure gradient. Furthermore, results of calculation using an in-house-developed three-dimensional Navier-Stokes code with a low-Reynolds-number {kappa}-{epsilon} turbulence model were in good qualitative agreement with experimental results. According to the simulation results, a region of very high pressure loss is observed near the hub at the duct exit with the increase of inlet boundary layer thickness. Such regions of high pressure loss may act on the downstream compressor as a large inlet distortion, and strongly affect downstream compressor performance.

  16. 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. PMID:23178830

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:26522328

  5. 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.

  6. 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.

  7. Laminar flow heat transfer downstream from U-bends

    NASA Astrophysics Data System (ADS)

    Abdelmessih, Amanie Nassif

    1987-05-01

    The laminar flow heat transfer downstream from the unheated, vertical bends in horizontal U-tubes with electrically heated straight tube sections was investigated. For each test section, local axial and peripheral wall temperatures were measured and the local peripheral heat transfer coefficients at the various locations were calculated. The investigation permitted a better understanding of the interaction of the primary, secondary and tertiary flow patterns, i.e., the combination of forced and natural convection with the centrifugal effects. Also, a correlation was developed, which predicts the heat transfer coefficient downstream from an unheated U-bend, and which can be extended to straight tubes.

  8. Van Gogh and Frizzled Act Redundantly in the Drosophila Sensory Organ Precursor Cell to Orient Its Asymmetric Division

    PubMed Central

    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. PMID:19214234

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 6. VIEW SOUTHWEST OF DOWNSTREAM FACE OF DAM WITH SPILLWAY ...

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

    6. VIEW SOUTHWEST OF DOWNSTREAM FACE OF DAM WITH SPILLWAY SECTION TO LEFT AND NON-OVERFLOW SECTION TO RIGHT - Middle Creek Hydroelectric Dam, On Middle Creek, West of U.S. Route 15, 3 miles South of Selinsgrove, Selinsgrove, Snyder County, PA

  18. 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

  19. 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

  20. 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

  1. 52. THE DOWNSTREAM FACE OF ROOSEVELT DAM. THE ROOSEVELT POWER ...

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

    52. THE DOWNSTREAM FACE OF ROOSEVELT DAM. THE ROOSEVELT POWER HOUSE IS LOCATED AT THE CENTER OF THE PHOTO WITH THE TRANSFORMER HOUSE LOCATED AT THE RIGHT. THE NORTH SPILLWAY IS AT THE FAR LEFT AND SOUTH SPILLWAY AT THE FAR RIGHT Photographer: Mark Durben, 1984 - Roosevelt Power Canal & Diversion Dam, Parallels Salt River, Roosevelt, Gila County, AZ

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 44. View of log boom (downstream) protecting fish screens at ...

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

    44. View of log boom (downstream) protecting fish screens at Dingle Basin, looking northeast from south side of basin. Photo by Brian C. Morris, Puget Power, 1989. - Puget Sound Power & Light Company, White River Hydroelectric Project, 600 North River Avenue, Dieringer, Pierce County, WA

  11. 46. View of downstream face of fish screens at Dingle ...

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

    46. View of downstream face of fish screens at Dingle Basin, looking southeast from north side of basin. Photo by Brian C. Morris, Puget Power, 1989. - Puget Sound Power & Light Company, White River Hydroelectric Project, 600 North River Avenue, Dieringer, Pierce County, WA

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Distant view from downstream of lock with southeast machinery house, ...

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

    Distant view from downstream of lock with southeast machinery house, SF 109, and timber guide wall on left, exterior view of closed lower lock gates and hydro-electric power house and dam in background, view towards west - St. Lucie Canal, St. Lucie Lock No. 1, St. Lucie, Cross State Canal, Okeechobee Intracoastal Waterway, Stuart, Martin County, FL

  20. DESCHUTES. WICKIUP DAM OUTLET WORKS. LOOKING DOWNSTREAM THROUGH VALVE HOUSE ...

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

    DESCHUTES. WICKIUP DAM OUTLET WORKS. LOOKING DOWNSTREAM THROUGH VALVE HOUSE SUNSTRUCTURE. Photocopy of historic photograph (original photograph on file at National Archives, Rocky Mountain Region, Denver, CO). Unknown USBR photographer, August 5, 1940 - Wickiup Dam, Outlet Works, Deschutes River, La Pine, Deschutes County, OR

  1. DESCHUTES. WICKIUP DAM OUTLET WORKS. LOOKING DOWNSTREAM; AFTER COMPLETION OF ...

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

    DESCHUTES. WICKIUP DAM OUTLET WORKS. LOOKING DOWNSTREAM; AFTER COMPLETION OF MONTAG & SONS CONTRACT. Photocopy of historic photograph (original photograph on file at National Archives, Rocky Mountain Region, Denver, CO). Unknown USBR photographer, November 24, 1940 - Wickiup Dam, Outlet Works, Deschutes River, La Pine, Deschutes County, OR

  2. DESCHUTES PROJECT VIEW OF DOWNSTREAM FACE OF WICKIUP DAM, ...

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

    DESCHUTES PROJECT - VIEW OF DOWNSTREAM FACE OF WICKIUP DAM, VALVE HOUSE AND STILLING BASIN OF OUTLET WORKS. Photocopy of historic photograph (original photograph on file at National Archives, Rocky Mountain Region, Denver, CO). Unknown USBR photographer, August 31, 1943 - Wickiup Dam, Outlet Works, Deschutes River, La Pine, Deschutes County, OR

  3. DESCHUTES PROJECT – WICKIUP DAM – ROCKFILL ON DOWNSTREAM FACE ...

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

    DESCHUTES PROJECT – WICKIUP DAM – ROCKFILL ON DOWNSTREAM FACE OF DAM. Photocopy of historic photographs (original photograph on file at National Archives, Rocky Mountain Region, Denver, CO). Unknown USBR Photographer, Ocotber 1, 1942 - Wickiup Dam, Deschutes River, La Pine, Deschutes County, OR

  4. View of downstream face of Grand Coulee Dam (from hillside ...

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

    View of downstream face of Grand Coulee Dam (from hillside north of No. 3 Powerhouse), looking southwest. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  5. 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

  6. 7. SEDIMENTATION CHAMBER AT 520', CONSTRUCTED 19371938, VIEWED FROM DOWNSTREAM. ...

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

    7. SEDIMENTATION CHAMBER AT 520', CONSTRUCTED 1937-1938, VIEWED FROM DOWNSTREAM. DEBRIS REMOVED FROM TOP PLANKS FOR CLARITY. ONE OF TWO SPILLWAYS SEEN AT RIGHT. FLUSH VALVE SEEN AT LOWER LEFT AND WRENCH FOR VALVES IS PROPPED AGAINST CHAMBER. - Kalaupapa Water Supply System, Waikolu Valley to Kalaupapa Settlement, Island of Molokai, Kalaupapa, Kalawao County, HI

  7. Density Fluctuations Upstream and Downstream of Interplanetary Shocks

    NASA Astrophysics Data System (ADS)

    Pitňa, A.; Šafránková, J.; Němeček, Z.; Goncharov, O.; Němec, F.; Přech, L.; Chen, C. H. K.; Zastenker, G. N.

    2016-03-01

    Interplanetary (IP) shocks as typical large-scale disturbances arising from processes such as stream-stream interactions or Interplanetary Coronal Mass Ejection (ICME) launching play a significant role in the energy redistribution, dissipation, particle heating, acceleration, etc. They can change the properties of the turbulent cascade on shorter scales. We focus on changes of the level and spectral properties of ion flux fluctuations upstream and downstream of fast forward oblique shocks. Although the fluctuation level increases by an order of magnitude across the shock, the spectral slope in the magnetohydrodynamic range is conserved. The frequency spectra upstream of IP shocks are the same as those in the solar wind (if not spoiled by foreshock waves). The spectral slopes downstream are roughly proportional to the corresponding slopes upstream, suggesting that the properties of the turbulent cascade are conserved across the shock thus, the shock does not destroy the shape of the spectrum as turbulence passes through it. Frequency spectra downstream of IP shocks often exhibit “an exponential decay” in the ion kinetic range that was earlier reported at electron scales in the solar wind or at ion scales in the interstellar medium. We suggest that the exponential shape of ion flux spectra in this range is caused by stronger damping of the fluctuations in the downstream region.

  8. 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

  9. 40 CFR 80.69 - Requirements for downstream oxygenate blending.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... blending. 80.69 Section 80.69 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.69 Requirements for downstream oxygenate blending. The requirements of this section apply to all reformulated gasoline...

  10. 40 CFR 80.69 - Requirements for downstream oxygenate blending.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... blending. 80.69 Section 80.69 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.69 Requirements for downstream oxygenate blending. The requirements of this section apply to all reformulated gasoline...

  11. 40 CFR 80.69 - Requirements for downstream oxygenate blending.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... blending. 80.69 Section 80.69 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.69 Requirements for downstream oxygenate blending. The requirements of this section apply to all reformulated gasoline...

  12. 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

  13. 4. VIEW OF DOWNSTREAM FACE OF DAM, WITH SCARS FROM ...

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

    4. VIEW OF DOWNSTREAM FACE OF DAM, WITH SCARS FROM EARTH MOVING TO CONSTRUCT DAM IN FOREGROUND, LOOKING NORTHWEST - High Mountain Dams in Upalco Unit, Five Point Lake Dam, Ashley National Forest, 12 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

  14. 14. DETAIL EXTERIOR VIEW LOOKING EAST AT DOWNSTREAM SIDE OF ...

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

    14. DETAIL EXTERIOR VIEW LOOKING EAST AT DOWNSTREAM SIDE OF NORTH END OF DAM/SPILLWAY; GANTRY CRANE ABOVE MOVABLE STONEY GATE IS VISIBLE IN CENTER BACKGROUND; FISH LADDER ON WASHINGTON SHORE IS VISIBLE IN FOREGROUND. - Bonneville Project, Bonneville Dam, Columbia River, Bonneville, Multnomah County, OR

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 1. FITZ WATERWHEEL IN DOWNSTREAM LOCATION SHOWING ELEVATED HEADRACE AND ...

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

    1. FITZ WATERWHEEL IN DOWNSTREAM LOCATION SHOWING ELEVATED HEADRACE AND ENDLESS-WIRE POWER TRANSMISSION TO MILL. LOOKING SOUTH. Photocopied July 1972 from photograph owned by Silas Starry, c. 1735 - Thomas Shepherd's Grist Mill, High Street Vicinity, Shepherdstown, Jefferson County, WV

  3. 2. WINTER VIEW OF WATERWHEEL IN DOWNSTREAM LOCATION SHOWING ELEVATED ...

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

    2. WINTER VIEW OF WATERWHEEL IN DOWNSTREAM LOCATION SHOWING ELEVATED HEADRACE AND ENDLESS-WIRE POWER TRANSMISSION TO MILL Photocopied July 1972 from photograph owned by Silas Starry, c. 1735 - Thomas Shepherd's Grist Mill, High Street Vicinity, Shepherdstown, Jefferson County, WV

  4. 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

  5. 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

  6. 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

  7. Detecting floodplain inundation based on the upstream-downstream relationship

    NASA Astrophysics Data System (ADS)

    Zhao, Tongtiegang; Shao, Quanxi

    2015-11-01

    The rise in river stage (water depth) can lead to disastrous floodplain inundation. On the basis of hydraulic simulation data, this study proposes novel data-analytical methods to infer the threshold river stage and detect floodplain inundation. A quasi-Muskingum model is derived from the classical Muskingum model to characterise the relationship between upstream and downstream river stages. Based on this model, F-test and modified Akaike information criterion AICc are introduced to test if there is a change of the upstream-downstream relationship. Furthermore, a bootstrap-based calibration-validation experiment is set up to evaluate the performance of the quasi-Muskingum model. The proposed methods are applied to a case study of the 1991 and 2001 floods in the Flinders and Norman Rivers in Northern Australia. The results show that floodplain inundation does change the upstream-downstream relationship as it drastically alters the stage-discharge relationship. To combine the quasi-Muskingum model with F-test and AICc facilitates an efficient approach to detect the change and infer the threshold river stage. The analytical testing is in concert with visual examination - the time when the river stage becomes higher than the detected threshold coincides with the beginning of floodplain inundation. Despite the change, the quasi-Muskingum model effectively captures the upstream-downstream relationship and requires a small number of samples in calibration. This study highlights the effectiveness of the data-analytical methods in dealing with the change of the upstream-downstream relationship.

  8. [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

  9. 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 ...

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

    PubMed Central

    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. PMID:26162098

  11. 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

  12. Investment prioritization based on broadscale spatial budgeting to meet downstream targets for suspended sediment loads

    NASA Astrophysics Data System (ADS)

    Lu, Hua; Moran, C. J.; Prosser, Ian P.; Derose, Ronald

    2004-09-01

    On the basis of a spatially distributed sediment budget across a large basin, costs of achieving certain sediment reduction targets in rivers were estimated. A range of investment prioritization scenarios were tested to identify the most cost-effective strategy to control suspended sediment loads. The scenarios were based on successively introducing more information from the sediment budget. The relationship between spatial heterogeneity of contributing sediment sources on cost effectiveness of prioritization was investigated. Cost effectiveness was shown to increase with sequential introduction of sediment budget terms. The solution which most decreased cost was achieved by including spatial information linking sediment sources to the downstream target location. This solution produced cost curves similar to those derived using a genetic algorithm formulation. Appropriate investment prioritization can offer large cost savings because the magnitude of the costs can vary by several times depending on what type of erosion source or sediment delivery mechanism is targeted. Target settings which only consider the erosion source rates can potentially result in spending more money than random management intervention for achieving downstream targets. Coherent spatial patterns of contributing sediment emerge from the budget model and its many inputs. The heterogeneity in these patterns can be summarized in a succinct form. This summary was shown to be consistent with the cost difference between local and regional prioritization for three of four test catchments. To explain the effect for the fourth catchment, the detail of the individual sediment sources needed to be taken into account.

  13. 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.

  14. Changing Neuroestrogens Within the Auditory Forebrain Rapidly Transform Stimulus Selectivity in a Downstream Sensorimotor Nucleus

    PubMed Central

    Remage-Healey, Luke; Joshi, Narendra R.

    2012-01-01

    The activity of sensory circuits is shaped by neuromodulators, which can have downstream consequences for both sensorimotor integration and behavioral output. Recent evidence indicates that brain-derived estrogens (‘neuroestrogens’) can act as local circuit modulators in the songbird auditory forebrain. Specifically, neuroestrogens fluctuate in the auditory caudomedial nidopallium (NCM) during social interactions and in response to song stimuli. Within minutes of elevation, neuroestrogens also enhance auditory response properties of NCM neurons, and acute blockade of estrogen production in NCM disrupts behavioral song discrimination. Here, we test the hypothesis that fluctuating neuroestrogens within NCM influence stimulus selectivity in a downstream sensorimotor nucleus (HVC) that receives indirect auditory input from NCM. Dual extracellular recordings coupled with retrodialysis delivery show that song-selectivity in HVC is rapidly enhanced by increasing neuroestrogens in NCM in adult males. Conversely, inhibiting neuroestrogen production in NCM causes a rapid decline in song-selectivity in HVC, demonstrating the endogenous nature of this modulatory network. By contrast, HVC selectivity is unaffected by neuroestrogen delivery to either nearby caudomedial mesopallium (CMM) or into HVC itself, indicating that neuroestrogen actions are restricted to NCM. In juvenile males, identical E2 treatment in NCM also does not alter HVC selectivity, consistent with a developmental maturation of the auditory network. Lastly, the rapid actions of estrogens leading to enhanced HVC selectivity appear to be mediated by membrane-bound receptors in NCM. These findings indicate that steroid-dependent modulation of sensory processing is not locally restricted and can be transmitted transynaptically to influence downstream sensorimotor and premotor targets. PMID:22699904

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    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.

  16. Systems genetics reveals key genetic elements of drought induced gene regulation in diploid potato.

    PubMed

    van Muijen, Dennis; Anithakumari, A M; Maliepaard, Chris; Visser, Richard G F; van der Linden, C Gerard

    2016-09-01

    In plants, tolerance to drought stress is a result of numerous minor effect loci in which transcriptional regulation contributes significantly to the observed phenotypes. Under severe drought conditions, a major expression quantitative trait loci hotspot was identified on chromosome five in potato. A putative Nuclear factor y subunit C4 was identified as key candidate in the regulatory cascade in response to drought. Further investigation of the eQTL hotspots suggests a role for a putative Homeobox leucine zipper protein 12 in relation to drought in potato. Genes strongly co-expressed with Homeobox leucine zipper protein 12 were plant growth regulators responsive to water deficit stress in Arabidopsis thaliana, implying a possible conserved mechanism. Integrative analysis of genetic, genomic, phenotypic and transcriptomic data provided insights in the downstream functional components of the drought response. The abscisic acid- and environmental stress-inducible protein TAS14 was highly induced by severe drought in potato and acts as a reliable biomarker for the level of stress perceived by the plant. The systems genetics approach supported a role for multiple genes responsive to severe drought stress of Solanum tuberosum. The combination of gene regulatory networks, expression quantitative trait loci mapping and phenotypic analysis proved useful for candidate gene selection. PMID:27353051

  17. Design of the DARHT-II Downstream Beamline

    SciTech Connect

    Westenskow, G A; Bertolini, L R; Chen, Y -J; Fessenden, T J; Paul, A C; Watson, J A

    2002-06-07

    This paper describes the design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT-II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 18.4-MeV, 2000-Amperes, 2-{micro}sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 22-meter long region extending from the end of the accelerator to the bremsstrahlung target. The principal element of the beam transport section is the fast deflector, or kicker system, used to generate four micropulses from the primary accelerator beam. Within this proposed transport line there are also several conventional solenoid, quadrupole and dipole magnets which transport and focus the beam to the target and to the beam dumps.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Downstream influence of swept slot injection in hypersonic turbulent flow

    NASA Technical Reports Server (NTRS)

    Hefner, J. N.; Cary, A. M., Jr.; Bushnell, D. B.

    1977-01-01

    Results of an experimental and numerical investigation of tangential swept slot injection into a thick turbulent boundary layer at Mach 6 are presented. Film cooling effectiveness, skin friction, and flow structure downstream of the swept slot injection were investigated. The data were compared with that for unswept slots, and it was found that cooling effectiveness and skin friction reductions are not significantly affected by sweeping the slot.

  3. TVA`s auto-venting turbines increase downstream aeration

    SciTech Connect

    March, P.

    1996-10-01

    Two auto-venting turbines installed at Norris Hydro Plant to increase dissolved-oxygen levels are briefly described. The turbines introduce aeration through the thrust relief openings, the deflector, the trailing edge of each blade, and the periphery of the draft tube. Downstream dissolved-oxygen levels have been increased by up to 5.5 milligrams per liter. Efficiency losses range from 0 to 4 percent, depending on operating conditions and aeration method.

  4. Reactive extraction for downstream separation of 1,3-propanediol.

    PubMed

    Malinowski, J J

    2000-01-01

    The downstream separation of 1,3-propanediol from dilute aqueous solution was studied. A process combining reversible reaction of 1, 3-propanediol with acetaldehyde to 2-methyl-1,3-dioxane and a simultaneous extraction of the product by organic solvent appears to be technically feasible and attractive. The dioxane yield was 91-92%, the overall conversion of 1,3-propanediol was ca. 98%, and recovery of dioxane into the organic extractant was 75%. PMID:10662493

  5. 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.

  6. 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.

  7. Regional Characterization of the Downstream Effects of Dams

    NASA Astrophysics Data System (ADS)

    Schmidt, J. C.; Wilcock, P. R.

    2006-05-01

    Metrics with which to assess the causes of channel change downstream from dams permit regional and watershed-scale comparison of the challenge of environmental river management and rehabilitation. Metrics based on Henderson's approximation of the Lane balance, downstream hydraulic geometry, and the Shield's relation allow distinction of general categories of channel response downstream from dams: deficit with bed incision, deficit without incision, and surplus conditions. Each of these categories can occur with or without significant changes in channel width, and channel narrowing occurs in proportion to the degree to which the post-dam flood regime is reduced from that of pre-dam conditions. It is also possible to estimate the degree of perturbation of the watershed sediment delivery rate that causes sediment deficit or surplus, based on a relation between the watershed reservoir storage ratio and the degree of flood control. Estimates of channel change based on these metrics agree well with case studies for the Rio Grande, Colorado River, Missouri River, Trinity River, and Deschutes River. Regional distinction between sediment deficit and surplus conditions is useful, because the management strategies necessary to reverse undesirable conditions differ. Case studies indicate that rehabilitation of sediment deficit river segments is more costly than for sediment surplus segments.

  8. Novel developments in butanol fermentation: Microbial genetics to agricultural substrates, process technology, and downstream processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Butanol is the major product of acetone-butanol-ethanol (ABE; ratio 3:6:1) fermentation. It can be produced from various carbohydrates such as glucose, corn, molasses, and whey permeate (a by-product of the dairy industry) using microbial strains such as Clostridium beijerinckii and/or C. acetobuty...

  9. Natural variation and genetic covariance in adult hippocampal neurogenesis

    SciTech Connect

    Kempermann, Gerd; Chesler, Elissa J; Lu, Lu; Williams, Robert; Gage, Fred

    2006-01-01

    Adult hippocampal neurogenesis is highly variable and heritable among laboratory strains of mice. Adult neurogenesis is also remarkably plastic and can be modulated by environment and activity. Here, we provide a systematic quantitative analysis of adult hippocampal neurogenesis in two large genetic reference panels of recombinant inbred strains (BXD and AXB?BXA, n ? 52 strains). We combined data on variation in neurogenesis with a new transcriptome database to extract a set of 190 genes with expression patterns that are also highly variable and that covary with rates of (i) cell proliferation, (ii) cell survival, or the numbers of surviving (iii) new neurons, and (iv) astrocytes. Expression of a subset of these neurogenesis-associated transcripts was controlled in cis across the BXD set. These self-modulating genes are particularly interesting candidates to control neurogenesis. Among these were musashi (Msi1h) and prominin1?CD133 (Prom1), both of which are linked to stem-cell maintenance and division. Twelve neurogenesis-associated transcripts had significant cis-acting quantitative trait loci, and, of these, six had plausible biological association with adult neurogenesis (Prom1, Ssbp2, Kcnq2, Ndufs2, Camk4, and Kcnj9). Only one cis- cting candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream target of ras signaling. The use of genetic reference panels coupled with phenotyping and global transcriptome profiling thus allowed insight into the complexity of the genetic control of adult neurogenesis.

  10. Plant GSK3 proteins regulate xylem cell differentiation downstream of TDIF-TDR signalling

    NASA Astrophysics Data System (ADS)

    Kondo, Yuki; Ito, Tasuku; Nakagami, Hirofumi; Hirakawa, Yuki; Saito, Masato; Tamaki, Takayuki; Shirasu, Ken; Fukuda, Hiroo

    2014-03-01

    During plant radial growth typically seen in trees, procambial and cambial cells act as meristematic cells in the vascular system to self-proliferate and differentiate into xylem cells. These two processes are regulated by a signalling pathway composed of a peptide ligand and its receptor; tracheary element differentiation inhibitory factor (TDIF) and TDIF RECEPTOR (TDR). Here we show that glycogen synthase kinase 3 proteins (GSK3s) are crucial downstream components of the TDIF signalling pathway suppressing xylem differentiation from procambial cells. TDR interacts with GSK3s at the plasma membrane and activates GSK3s in a TDIF-dependent fashion. Consistently, a specific inhibitor of plant GSK3s strongly induces xylem cell differentiation through BRI1-EMS SUPPRESSOR 1 (BES1), a well-known target transcription factor of GSK3s. Our findings provide insight into the regulation of cell fate determination in meristem maintenance.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Commissioning The Darht-II Accelerator Downstream Transport And Target

    SciTech Connect

    Ekdahl, Carl; Schulze, Martin E

    2008-01-01

    The DARHT-II accelerator produces a 2-kA, 17-MeV beam in a 1600-ns pulse. After exiting the accelerator, the pulse is sliced into four short pulses by a kicker and quadrupole septum and then transported for several meters to a tantalum target for conversion to x-rays for radiography. They describe the commissioning of the kicker, septum, transport, and multi-pulse converter target. The results of beam measurements made during the commissioning of the downstream transport are described.

  16. Flow diagnostics downstream of a tribladed rotor model

    NASA Astrophysics Data System (ADS)

    Naumov, I. V.; Rahmanov, V. V.; Okulov, V. L.; Velte, C. M.; Meyer, K. E.; Mikkelsen, R. F.

    2012-06-01

    This paper presents results of a study of vortex wake structures and measurements of instantaneous 3D velocity fields downstream of a triblade turbine model. Two operation modes of flow around the rotor with different tip speed ratios were tested. Initially the wake structures were visualized and subsequently quantitative data were recorded through velocity field restoration from particle tracks using a stereo PIV system. The study supplied flow diagnostics and recovered the instantaneous 3D velocity fields in the longitudinal cross section behind a tribladed rotor at different values of tip speed ratio. This set of data provided a basis for testing and validating assumptions and hypothesis regarding classical theories of rotors.

  17. Plasma properties downstream of a low-power Hall thruster

    SciTech Connect

    Beal, Brian E.; Gallimore, Alec D.; Hargus, William A. Jr.

    2005-12-15

    Triple Langmuir probes and emissive probes were used to measure the electron number density, electron temperature, and plasma potential downstream of a low-power Hall thruster. The results show a polytropic relation between electron temperature and electron number density throughout the sampled region. Over a large fraction of the plume, the plasma potential obeys the predictions of ambipolar expansion. Near the thruster centerline, however, observations show larger gradients of plasma potential than can be accounted for by this means. Radial profiles of plasma potential in the very-near-field plume are shown to contain large gradients that correspond in location to the boundaries of a visually intense plasma region.

  18. 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.

  19. Genetics of Cerebral Vasospasm

    PubMed Central

    Ladner, Travis R.; Zuckerman, Scott L.; Mocco, J

    2013-01-01

    Cerebral vasospasm (CV) is a major source of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). It is thought that an inflammatory cascade initiated by extravasated blood products precipitates CV, disrupting vascular smooth muscle cell function of major cerebral arteries, leading to vasoconstriction. Mechanisms of CV and modes of therapy are an active area of research. Understanding the genetic basis of CV holds promise for the recognition and treatment for this devastating neurovascular event. In our review, we summarize the most recent research involving key areas within the genetics and vasospasm discussion: (1) Prognostic role of genetics—risk stratification based on gene sequencing, biomarkers, and polymorphisms; (2) Signaling pathways—pinpointing key inflammatory molecules responsible for downstream cellular signaling and altering these mediators to provide therapeutic benefit; and (3) Gene therapy and gene delivery—using viral vectors or novel protein delivery methods to overexpress protective genes in the vasospasm cascade. PMID:23691311

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Thermal mixing layer downstream of half-heated turbulence grid

    NASA Astrophysics Data System (ADS)

    Larue, J. C.; Libby, P. A.

    1981-04-01

    Experimental and theoretical results are presented concerning the temperature in the thermal mixing layer downstream of a partially heated turbulence grid. Temperatures were measured by platinum wire thermometers located upstream and downstream of a turbulence grid consisting of 18 horizontal and 18 vertical heating rods, with the uppermost nine horizontal rods heated to a temperature about 200 C above ambient. Experimental results are presented for the mean temperature distribution, the distribution of relative temperature intensity, the distributions of the skewness and kurtosis of the temperature fluctuations, probability density functions for the temperature, the skewness of the temperature derivative and the thickness of the thermal interface in the thermal mixing layer, and are compared with previous experimental results where available. As in previous investigations, the measured intensity of the temperature fluctuations in the center of the mixing layer is found to disagree with that predicted by the analysis of Libby (1975) by 40%, and it is concluded that experiments simultaneously yielding the velocity and temperature characteristics are required to explain the discrepancy.

  6. Dynamic response of ramjet inlets to downstream perturbations

    NASA Astrophysics Data System (ADS)

    Sajben, M.; Bogar, T. J.; Kroutil, J. C.

    1983-01-01

    An external-compression inlet with high-aspect-ratio, rectangular cross sections was investigated in a semi-freejet arrangement at M(infinity) = 1.84 and zero incidence, over a wide range of super- and subcritical conditions. The response of the inlet flows to periodic perturbations imposed at the downstream end was determined. The perturbations were created by mechanical modulation of the choked exhaust area at frequencies from 20 to 360 Hz. The amplitude of the pressure fluctuations induced at the downstream end of the inlet was varied up to 8% of the time-mean static pressure at the same location. The observed oscillations were categorized according to position ranges associated with the shock motion. In supercritical oscillations, the pressure fluctuation amplitudes within the inlet were found to be linearly proportional to the fluctuation intensity at the exit station, establishing the latter as the appropriate quantity for normalization. In subcritical conditions, the inlet displays a large-amplitude natural oscillation (buzz). Superimposed excitation may couple with the natural oscillations in two distinctly different ways, both strongly nonlinear. Combinations of mean flow condition, excitation amplitude, and frequency that cause the terminal shock to move upstream of the cowl or the ramp were determined.

  7. 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

  8. Natural Origin Lycopene and Its "Green" Downstream Processing.

    PubMed

    Papaioannou, Emmanouil H; Liakopoulou-Kyriakides, Maria; Karabelas, Anastasios J

    2016-01-01

    Lycopene is an abundant natural carotenoid pigment with several biological functions (well-known for its antioxidant properties) which is under intensive investigation in recent years. Lycopene chemistry, its natural distribution, bioavailability, biological significance, and toxicological effects are briefly outlined in the first part of this review. The second, major part, deals with various modern downstream processing techniques, which are assessed in order to identify promising approaches for the recovery of lycopene and of similar lipophilic compounds. Natural lycopene is synthesized in plants and by microorganisms, with main representatives of these two categories (for industrial production) tomato and its by-products and the fungus Blakeslea trispora, respectively. Currently, there is a great deal of effort to develop efficient downstream processing for large scale production of natural-origin lycopene, with trends strongly indicating the necessity for "green" and mild extraction conditions. In this review, emphasis is placed on final product safety and ecofriendly processing, which are expected to totally dominate in the field of natural-origin lycopene extraction and purification. PMID:25671774

  9. Reverse micellar extraction for downstream processing of proteins/enzymes.

    PubMed

    Krishna, S Hari; Srinivas, N D; Raghavarao, K S M S; Karanth, N G

    2002-01-01

    New developments in the area of downstream processing are, hopefully, to fulfill the promises of modern biotechnology. The traditional separation processes such as chromatography or electrophoresis can become prohibitively expensive unless the product is of high value. Hence, there is a need to develop efficient and cost-effective downstream processing methods. Reverse micellar extraction is one such potential and a promising liquid-liquid extraction technique, which has received immense attention for isolation and purification of proteins/enzymes in the recent times. This technique is easy to scale-up and offers continuous operation. This review, besides briefly considering important physico-chemical and biological aspects, highlights the engineering aspects including mass transfer, mathematical modeling, and technology development. It also discusses recent developments in reverse micellar extraction such as affinity based separations, enzymatic reactions in reverse micelles coupled with membrane processes, reverse micellar extraction in hollow fibers, etc. Special emphasis has been given to some recent applications of this technique. PMID:11787493

  10. 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

  11. Benzene and total hydrocarbons exposures in the downstream petroleum industries.

    PubMed

    Verma, D K; Johnson, D M; Shaw, M L; des Tombe, K

    2001-01-01

    A review of studies, including both articles published in peer-reviewed journals and reports that were not peer reviewed, regarding occupational exposure to benzene and total hydrocarbons in the downstream petroleum industry operations was performed. The objective was to provide a broad estimate of exposures by compiling exposure data according to the following categories: refinery, pipeline, marine, rail, bulk terminals and trucks, service stations, underground storage tanks, tank cleaning, and site remediations. The data in each category was divided into personal occupational long-term and short-term samples. The summarized data offers valuable assistance to hygienists by providing them with an estimate and range of exposures. The traditional 8-hour time-weighted average (TWA) exposure and the 40-hour workweek do not generally coincide with exposure periods applicable to workers in marine, pipeline, railcar, and trucking operations. They are more comparable with short-term exposure or task-based exposure assessments. The marine sector has a large number of high exposures. Although relatively few workers are exposed, their exposures to benzene and total hydrocarbons are sometimes an order of magnitude higher than the respective exposure limits. It is recommended that in the future, it would be preferable to do more task-based exposure assessments and fewer traditional TWA long-term exposure assessments within the various sectors of the downstream petroleum industry. PMID:11331990

  12. Turbulence downstream of subcoronary stentless and stented aortic valves.

    PubMed

    Funder, Jonas Amstrup; Frost, Markus Winther; Wierup, Per; Klaaborg, Kaj-Erik; Hjortdal, Vibeke; Nygaard, Hans; Hasenkam, J Michael

    2011-08-11

    Regions of turbulence downstream of bioprosthetic heart valves may cause damage to blood components, vessel wall as well as to aortic valve leaflets. Stentless aortic heart valves are known to posses several hemodynamic benefits such as larger effective orifice areas, lower aortic transvalvular pressure difference and faster left ventricular mass regression compared with their stented counterpart. Whether this is reflected by diminished turbulence formation, remains to be shown. We implanted either stented pericardial valve prostheses (Mitroflow), stentless valve prostheses (Solo or Toronto SPV) in pigs or they preserved their native valves. Following surgery, blood velocity was measured in the cross sectional area downstream of the valves using 10MHz ultrasonic probes connected to a dedicated pulsed Doppler equipment. As a measure of turbulence, Reynolds normal stress (RNS) was calculated at two different blood pressures (baseline and 50% increase). We found no difference in maximum RNS measurements between any of the investigated valve groups. The native valve had significantly lower mean RNS values than the Mitroflow (p=0.004), Toronto SPV (p=0.008) and Solo valve (p=0.02). There were no statistically significant differences between the artificial valve groups (p=0.3). The mean RNS was significantly larger when increasing blood pressure (p=0.0006). We, thus, found no advantages for the stentless aortic valves compared with stented prosthesis in terms of lower maximum or mean RNS values. Native valves have a significantly lower mean RNS value than all investigated bioprostheses. PMID:21696741

  13. Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors.

    PubMed

    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

  14. Laminar-flow heat transfer downstream from U-bends

    SciTech Connect

    Abdelmessih, A.N

    1987-01-01

    The laminar-flow heat transfer downstream from the unheated, vertical bends in horizontal U-tubes with electrically heated straight tube sections was investigated. Four U-tubes with curvature ratios of 4.84, 7.66, 12.35, and 25.36 were studied. Distilled water and almost-pure ethylene glycol solutions (water content 1 to 5%) were the test fluids. For each test section, local axial and peripheral wall temperatures were measured, and the local peripheral heat-transfer coefficients at the various locations were calculated. The experiments covered the local bulk Reynolds number range of 120 to 2500. The local bulk Prandtl number varied between 4 and 110, while the Grashof number ranged from 2500 to 1,130,000. The uniform wall heat flux ranged from 900 to 4230 Btu/hr.sq.ft (3.12 to 13.33 KW/sq.m.). This investigation permitted a better understanding of the interaction of the primary, secondary, and tertiary flow patterns. Also, a correlation was developed that predicts the heat-transfer coefficient downstream from an unheated U-bend and that can be extended to straight tubes.

  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. PMID:25647024

  16. 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, ...

  17. 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 ...

  18. 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

  19. 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

  20. 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

  1. Large Wood Storage Does Not Decrease Downstream Through a Watershed

    NASA Astrophysics Data System (ADS)

    Vaughan, M.; Pasternack, G. B.; Senter, A. E.; Dahlke, H. E.

    2013-12-01

    The storage of large wood in streams at the watershed scale has long been characterized as decreasing downstream due to a transport limitation in headwater streams, and a supply limitation in larger rivers. The objective of this study was to test this hypothesis through a field study in the Upper Yuba River watershed in Northern California, USA. While most studies surveyed within the wetted channel at selected reaches of different sizes, this study measured overbank deposits of large wood in addition to those in-channel to reflect the total storage within the active river corridor, and used a stratified random sampling scheme to see if relations held at the watershed scale. The watershed is large (2,874 km2), mountainous, mostly forested, and has been dramatically altered by human activities primarily related to gold mining. One hundred fourteen field sites of varied drainage area sizes were visited, inventoried for large wood (length > 1 m, diameter > 10 cm) storage within the active river corridor, and the volume storage per river length was calculated. Inclusion of floodplains in field surveys illuminates the fact that the distribution of large wood changes within the active river corridor, while the total storage does not decrease downstream. Among many watershed-scale control variables, such as drainage area, stream order, and upslope distance, the local amount of shrub cover and bankfull channel width were the only significant predictors of large wood storage in a multiple linear regression model, both with positive coefficients. A critical literature review was also conducted to investigate the evidence for the common conceptual model. Findings were that (1) the observed downstream trend of large wood storage is largely a function of the methods employed by each study, (2) the use of storage per channel area has confounded the commonly held conceptual model, due to its correlation with channel width, and (3) there is little evidence to support the hypothesis

  2. Methylmercury in biota downstream of Arivaca lake, Arizona, USA.

    PubMed

    Marr, Carrie L H; Robertson, Kathy; Reynolds, Kevin D

    2014-04-01

    Concentrations of total mercury (Hg) and methylmercury (MeHg) were determined in water, sediment, periphyton, spiders, and amphibians from the streams and desert marsh downstream from Arivaca Lake, Arizona, to better understand their distribution and bioaccumulation. Mean concentrations of MeHg in water ranged from 0.09 to 0.93 ng/L, and mean concentrations of total Hg in sediment ranged from 10.4 to 126 μg/kg. Hg and MeHg in water and sediments downstream from Arivaca Lake were low enough that they did not exceed human health or ecological thresholds. Hg and MeHg between sites ranged from 0.11 to 1.90 μg/g Hg and 0.01 to 0.3 μg/g MeHg in periphyton, from 0.09 to 0.25 μg/g Hg and 0.04 to 0.10 μg/g MeHg in spiders, and from 0.15 to 0.38 μg/g Hg and 0.14 to 0.35 μg/g MeHg in adult bullfrogs. No Hg toxicity data exist for periphyton or spiders, but MeHg concentrations in tadpoles (0.04 ± 0.005 μg/g) were lower than those known to cause sublethal effects and subchronic mortality. The mean total Hg concentration in adult bullfrogs in the present study was 0.24 μg/g, which is slightly lower than the mean (0.37 μg/g) from an Hg-contaminated wetland in California. MeHg bioaccumulated at each successive trophic level, and MeHg bioconcentration factors from the Arivaca watershed were similar to those for periphyton but greater than amphibians in other studies. Local resource managers can use these data to determine if water should be released from Arivaca Lake to recharge the aquifer downstream or to decrease Hg methylation in the reservoir. PMID:24468966

  3. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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... downstream from refineries and import facilities, including gasoline at facilities of distributors,...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Downstream ecological effects of dams: A geomorphic perspective

    SciTech Connect

    Ligon, F.K.; Dietrich, W.E.; Trush, W.J.

    1995-03-01

    The damming of a river changes the flow of water, sediment, nutrients, energy, and biota, interrupting and altering most of a river`s ecological processes. This article discusses the importance of geomorphological analysis in river conservation and management. To illustrate how subtle geomorphological adjustments may profoundly influence the ecological relationships downstream from dames, three case studies are presented. Then a geomorphically based approach for assessing and possibly mitigating some of the environmental effects of dams by tailoring dam designed and operation is outlined. The cases are as follows: channel simplification and salmon decline on the McKenzie River in Oregon; Channel incision and reduced floodplain inundation on the Oconee river in Georgia; Increased stability of a braided river in New Zealand`s south island. 41 refs., 10 figs., 1 tab.

  12. 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

  13. Transcriptional regulatory elements downstream of the JunB gene.

    PubMed Central

    Perez-Albuerne, E D; Schatteman, G; Sanders, L K; Nathans, D

    1993-01-01

    JunB is an immediate early transcription factor that is induced by a variety of extracellular signaling agents, including growth factors, phorbol esters, and agents that elevate cyclic AMP. The mechanism of activation of the gene encoding JunB by these agents is not well understood. By using the JunB gene together with flanking DNA in transfection experiments, we show that a serum response element (SRE) and/or a cAMP response element (CRE) downstream of the gene mediate the response of the gene in mouse NIH 3T3 cells to serum, platelet-derived growth factor, basic fibroblast growth factor, phorbol ester, and forskolin. In addition, a segment of DNA just upstream of the TATA box is required for optimal activation of the gene. Images Fig. 1 Fig. 5 PMID:8265655

  14. 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

  15. 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

  16. Downstream evolution of unconfined vortices: mechanical and thermal aspects

    NASA Astrophysics Data System (ADS)

    Pérez-Saborid, M.; Herrada, M. A.; Gómez-Barea, A.; Barrero, A.

    2002-11-01

    We present a numerical study of the downstream evolution (mechanical and thermal) of vortex-jet cores whose velocity and temperature fields far from the axis match a family of inviscid and non-conducting vortices. The far-velocity field is rotational, except for a particular case which corresponds to the well-known Long's vortex. The evolution of the vortex core depends on both the conditions at a certain upstream station, characterized by the dimensionless value of the velocity at the axis, and a dimensionless swirling parameter L defined as the ratio of the values of the azimuthal and axial velocities outside the vortex core. This numerical study, based on the quasi-cylindrical approximation (QC) of the Navier Stokes equations, determines the conditions under which the vortex evolution proceeds smoothly, eventually reaching an asymptotic self-similar behaviour as described in the literature (Fernández-Feria, Fernández de la Mora & Barrero 1995; Herrada, Pérez-Saborid & Barrero 1999), or breaks in a non-slender solution (vortex breakdown). In particular, the critical value L = Lb(a) beyond which vortex breakdown occurs downstream is a function of a dimensionless parameter a characterizing the axial momentum of the vortex jet at an initial upstream station. It is found numerically that for very large values of a this vortex breakdown criterion tends to an asymptote which is precisely the value L = L* predicted by the self-similar analysis, and beyond which a self-similar structure of the vortex core does not exist. In addition, the computation of the total temperature field provides useful information on the physical mechanisms responsible for the thermal separation phenomenon observed in Ranque Hilsch tubes and other swirling jet devices. In particular, the mechanical work of viscous forces which gives rise to an intense loss of kinetic energy during the initial stages of the evolution has been identified as the physical mechanism responsible for thermal

  17. 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

  18. 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

  19. An analytical solution to river profile concavity and downstream fining

    NASA Astrophysics Data System (ADS)

    Blom, A.; Chavarrias, V.

    2014-12-01

    We present an analytical solution to the steady state upward-concave bed profile, as well as downstream fining, for a river dominated by gravel and sand. The model is based on (i) the conservation equation of streamwise momentum of the flow, (ii) the conservation equation of the mass of each grain size fraction in the surface layer of the bed (the Hirano equation) yet including sediment abrasion, and (iii) the conservation equation of total sediment mass (the Exner equation). The model includes downstream fining induced by abrasion as well as by grainsize-selective transport of gravel and sand. In order to arrive at an analytical solution, the model is deliberately kept simple through assumptions such as a constant width and no tributaries. The model is then reduced to the case of steady state conditions, which means that all time derivatives in the equations are set to zero. We find a solution to the steady state streamwise profile of both the bed slope and the volume fraction of gravel in the surface layer of the bed. Like existing empirical predictors, the analytical solution is of an exponential type. The main variables that affect the solution are the total load at the upstream boundary, the gravel fraction in this upstream load, the abrasion coefficient, the grain sizes of the sediment, and the water discharge at the upstream boundary. The below image shows an example of how the gravel fraction in the upstream load affects the solution to the longitudinal profiles of, respectively, bed slope (S), the gravel fraction at the bed surface (Fg), and the mean grain size of the sediment at the bed surface (Dgs). We can see how an increase in the gravel fraction in the upstream load results in a larger overall slope and an increase in profile concavity. It also induces an increase of the gravel fraction at the bed surface.

  20. 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.

  1. 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.

  2. Genetic variation and human longevity.

    PubMed

    Soerensen, Mette

    2012-05-01

    The overall aim of the PhD project was to elucidate the association of human longevity with genetic variation in major candidate genes and pathways of longevity. Based on a thorough literature and database search we chose to apply a pathway approach; to explore variation in genes composing the DNA damage signaling, DNA repair, GH/IGF-1/insulin signaling and pro-/antioxidant pathways. In addition, 16 genes which did not belong to the core of either pathway, however recurrently regarded as candidate genes of longevity (e.g. APOE), were included. In this way a total of 168 genes were selected for investigation. We decided to explore the genetic variation in the form of single nucleotide polymorphisms (SNPs), a highly investigated type of genetic variation. SNPs having potential functional impact (e.g. affecting binding of transcription factors) were identified, so were specific SNPs in the candidate genes previously published to be associated with human longevity. To cover the majority of the common genetic variation in the 168 gene regions (encoding regions plus 5,000 bp upstream and 1,000 downstream) we applied the tagging SNP approach via the HapMap Consortium. Consequently 1,536 SNPs were selected. The majority of the previous publications on genetic variation and human longevity had employed a case-control study design, e.g. comparing centenarians to middle-aged controls. This type of study design is somehow prone to bias introduced by for instance cohort effects, i.e. differences in characteristics of cases and controls, a kind of bias which is avoided when a prospective cohort is under study. Therefore, we chose to investigate 1,200 individuals of the Danish 1905 birth cohort, which have been followed since 1998 when the members were 92-93 years old. The genetic contribution to human longevity has been estimated to be most profound during the late part of life, thus these oldest-old individuals are excellent for investigating such effect. The follow-up survival

  3. Estimation of the Size of Genetic Bottlenecks in Cell-to-Cell Movement of Soil-Borne Wheat Mosaic Virus and the Possible Role of the Bottlenecks in Speeding Up Selection of Variations in trans-Acting Genes or Elements▿ §

    PubMed Central

    Miyashita, Shuhei; Kishino, Hirohisa

    2010-01-01

    Genetic bottlenecks facilitate the fixation and extinction of variants in populations, and viral populations are no exception to this theory. To examine the existence of genetic bottlenecks in cell-to-cell movement of plant RNA viruses, we prepared constructs for Soil-borne wheat mosaic virus RNA2 vectors carrying two different fluorescent proteins, yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP). Coinoculation of host plant leaves with the two RNA2 vectors and the wild-type RNA1 showed separation of the two vector RNA2s, mostly within seven to nine cell-to-cell movements from individual initially coinfected cells. Our statistical analysis showed that the number of viral RNA genomes establishing infection in adjacent cells after the first cell-to-cell movement from an initially infected cell was 5.97 ± 0.22 on average and 5.02 ± 0.29 after the second cell-to-cell movement. These results indicate that plant RNA viruses may generally face narrow genetic bottlenecks in every cell-to-cell movement. Furthermore, our model suggests that, rather than suffering from fitness losses caused by the bottlenecks, the plant RNA viruses are utilizing the repeated genetic bottlenecks as an essential element of rapid selection of their adaptive variants in trans-acting genes or elements to respond to host shifting and changes in the growth conditions of the hosts. PMID:19955302

  4. Genetic discrimination and the law.

    PubMed Central

    Natowicz, M R; Alper, J K; Alper, J S

    1992-01-01

    The use of genetic tests can lead to genetic discrimination, discrimination based solely on the nature of an individual's genotype. Instances of the discriminatory uses of genetic tests by employers and insurance companies have already been reported. The recently enacted Americans with Disabilities Act of 1990 (ADA), together with other federal and state laws, can be used to combat some forms of this discrimination. In this article we define and characterize genetic discrimination, discuss the applicability of the various relevant federal and state laws, including the ADA, in the areas of employment and insurance discrimination, explore the limitations of these laws, and, finally, suggest some means of overcoming these limitations. PMID:1342778

  5. 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

  6. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux.

    PubMed

    He, Yuan; Zeng, Melody Y; Yang, Dahai; Motro, Benny; Núñez, Gabriel

    2016-02-18

    Inflammasomes are intracellular protein complexes that drive the activation of inflammatory caspases. So far, four inflammasomes involving NLRP1, NLRP3, NLRC4 and AIM2 have been described that recruit the common adaptor protein ASC to activate caspase-1, leading to the secretion of mature IL-1β and IL-18 proteins. The NLRP3 inflammasome has been implicated in the pathogenesis of several acquired inflammatory diseases as well as cryopyrin-associated periodic fever syndromes (CAPS) caused by inherited NLRP3 mutations. Potassium efflux is a common step that is essential for NLRP3 inflammasome activation induced by many stimuli. Despite extensive investigation, the molecular mechanism leading to NLRP3 activation in response to potassium efflux remains unknown. Here we report the identification of NEK7, a member of the family of mammalian NIMA-related kinases (NEK proteins), 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 inflammasomes. NLRP3-activating stimuli promoted the NLRP3-NEK7 interaction in a process that was dependent on potassium efflux. NLRP3 associated with the catalytic domain of NEK7, but the catalytic activity of NEK7 was shown to be 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, was abrogated in the absence of NEK7. NEK7 was required for macrophages containing the CAPS-associated NLRP3(R258W) activating mutation to activate caspase-1. Mouse chimaeras reconstituted with wild-type, Nek7(-/-) or Nlrp3(-/-) haematopoietic cells showed 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

  7. 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)

  8. 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

  9. The impact of proglacial lakes on downstream sediment delivery

    NASA Astrophysics Data System (ADS)

    Bogen, Jim; Xu, Mengzhen; Kennie, Patricia

    2013-04-01

    This paper discusses the impact of proglacial lakes on sediment transport of three different glaciers: Nigardsbre, Engabre and Tunsbergdalsbre. All of these lakes were developed in modern time. The recession of the Nigardsbre uncovered a 1.8 km long and on average 15 m deep proglacial lake during the years 1937 to 1968. From that time the glacier front was situated entirely on land, and the sediment input and output to the lake were measured. Sediment samples were collected 2- 4 times a day and the water discharge was recorded. The sediment transport into and out of the lake was on average 10504 t yr-1 and 2340 t yr-1during the years 1968 - 1981. Thus, 23% remained in suspension at the outlet. In 2011 an excessively high transport of 32356 t yr-1was recorded, due to several large flash floods that year. A 1.9 km long and up to 90 m deep proglacial lake downstream from Engabre glacier was uncovered during the years 1930 - 1945. The average suspended sediment load delivered from the glacier during the years 1970 - 1981 amounted to 12375 t yr-1and the transport out of the lake was 2021 t yr-1, giving an average of 16% remaining in suspension. In 2000 the sediment transport into the lake amounted to 15450 t yr-1. For the Tunsbergdalsbre glacier, measurements in the early 1970s indicated that the suspended sediment transport was on average 44000 t yr-1. From 1987 to 1993 the recession of the glacier uncovered a proglacial lake. Downstream from this 0.3 km long and around 9 m deep lake, the suspended sediment load was measured as 28 000 t yr-1in 2009, indicating that as much as 64% remained in suspension. The various factors affecting the sedimentation rates in the proglacial lakes are discussed. The low sedimentation rate of the lake in front of the Tunsbergdalsbre was due to its limited length and depth. Hence the meltwater from the glacier maintains a high flow velocity. The lake will however increase its size as the glacier recedes. The two other lakes have gone

  10. Role of nitrogen in the downstream etching of silicon nitride

    SciTech Connect

    Blain, M.G.; Meisenheimer, T.L.; Stevens, J.E.

    1996-07-01

    Chemical downstream etching of silicon nitride (Si{sub 3}N{sub 4}) requires the addition of nitrogen to the discharge for obtaining efficient etch rates. A 10{percent} addition of N{sub 2} to a CF{sub 4}/O{sub 2} discharge (CF{sub 4}/O{sub 2} = 1.2, 0.525 Torr) causes a factor of 6 increase in the Si{sub 3}N{sub 4} etch rate and a 8{percent} decrease in the silicon dioxide etch rate. The result is selectivities approaching 9:1. Importantly, the conversion of CF{sub 4} to F and F-containing reactive species by the discharge decreases or remains constant as nitrogen is added to the discharge mix, indicating that the etching reaction is not limited by delivery of these species to the substrate. By measuring the amount of NO and NO{sub 2} in the etch chamber, it is found that the NO concentration increases by a factor of 6 as N{sub 2} is added, while the amount of NO{sub 2} remains small and constant. The NO signal is significantly reduced during nitride etching compared to the signal observed during a discharge with an empty etch chamber, implying that the increase in Si{sub 3}N{sub 4} etch rate is related to the formation of NO in the discharge. This view is consistent with the observation that an NF{sub 3} plasma in a quartz discharge tube results in a nitride etch rate which is a factor of 2 higher than for the same discharge in a sapphire tube. The conclusion is that the oxygen liberated by erosion of the quartz tube allows the formation of NO. That NO is a key Si{sub 3}N{sub 4} etch reactant was confirmed by performing a series of experiments in which N{sub 2}, NO, NO{sub 2}, and N{sub 2}O were injected into the discharge and then downstream in the reaction chamber during a CF{sub 4}/O{sub 2} discharge. Nitride etch rates increased significantly upon injection of NO into both discharge and etch chamber as compared to injection of the other N{sub {ital x}}O{sub {ital y}} species. {copyright} {ital 1996 American Vacuum Society}

  11. 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

  12. 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. PMID:23359424

  13. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.

    PubMed

    Uttara, Bayani; Singh, Ajay V; Zamboni, Paolo; Mahajan, R T

    2009-03-01

    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

  14. 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. PMID:19414471

  15. 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. PMID:26307844

  16. 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

  17. 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

  18. 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.

  19. Deformability-based cell selection with downstream immunofluorescence analysis.

    PubMed

    Shaw Bagnall, Josephine; Byun, Sangwon; Miyamoto, David T; Kang, Joon Ho; Maheswaran, Shyamala; Stott, Shannon L; Toner, Mehmet; Manalis, Scott R

    2016-05-16

    Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspended microchannel resonator (SMR), which can measure biophysical characteristics of a single cell based on the sensor's record of its buoyant mass as well as its precise position while it traverses through a constricted microfluidic channel. The measurement provides information regarding the amount of time a cell takes to pass through a constriction (passage time), as related to the cell's deformability and surface friction, as well as the particular manner in which it passes through. In the method presented here, cells of interest are determined based on passage time, and are collected off-chip for downstream immunofluorescence imaging. The biophysical single-cell SMR measurement can then be correlated to the molecular expression of the collected cell. This proof-of-principle is demonstrated by sorting and collecting tumor cells from cell line-spiked blood samples as well as a metastatic prostate cancer patient blood sample, identifying them by their surface protein expression and relating them to distinct SMR signal trajectories. PMID:26999591

  20. Upstream versus downstream control of meltwater plumes under ice shelves

    NASA Astrophysics Data System (ADS)

    Wells, Andrew

    2013-11-01

    In many locations the Greenland and Antarctic ice sheets discharge into the ocean through ice shelves floating on top of a warm salty ocean. The turbulent buoyancy-driven flow of meltwater beneath the sloping ice-shelf base enhances heat transfer and provides a feedback on ice melting rates, with consequences for ice sheet dynamics and predictions of sea-level rise. Previous steady-state models of meltwater plumes under ice shelves have solved for the development of flow along the slope from an initial source, corresponding to solely upstream control of the plume dynamics. I re-interpret the plume dynamics embedded within the framework of a time-dependent model, and show that the flow exhibits distinct regimes depending on the source conditions. Solutions with upstream control are physically consistent for certain source conditions, but the plume is influenced by a combination of upstream and downstream conditions in other regions of parameter space. The dynamics are illustrated for flow underneath a two-dimensional ice shelf of initially constant basal slope, and stable attracting states are determined. The implications for modelling meltwater flow under ice shelves are discussed.

  1. 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

  2. Quenching downstream of an external vapor catalyst separator

    SciTech Connect

    Forgac, J.M.; Hauschildt, F.W.; Quinn, G.P.; Rundell, D.N.; Schwartz, J.G.; Camp, M.S.

    1991-08-20

    This patent describes a catalytic cracking process. It comprises catalytically cracking feed oil in a catalytic cracking unit comprising a regenerator and at least one catalytic cracking reactor selected from the group consisting of a riser reactor and a fluidized bed reactor, in the presence of a cracking catalyst to produce a catalyst-laden stream comprising upgraded oil and coked catalyst; separating substantially all of the cracking catalyst from the catalyst laden stream in an external gross-cut separator downstream of the reactor into a catalyst rich stream comprising the coked catalyst and a product stream comprising the upgraded oil, and substantially immediately thereafter; quenching the product stream of upgraded oil discharged from the external gross-cut separator to substantially decrease thermal cracking of the upgraded oil to less valuable hydrocarbon products and light hydrocarbon gases and concurrently enhance the yield of naphtha to substantially increase the production of gasoline; regenerating the coked catalyst in a regenerator; and recycling the regenerated catalyst to the catalytic cracking reactor.

  3. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

    PubMed Central

    Wang, Hongyan; Somers, Gregory W.; Bashirullah, Arash; Heberlein, Ulrike; Yu, Fengwei; Chia, William

    2006-01-01

    The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs. PMID:17182870

  4. 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 ...

  5. Genetic counseling

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

  6. Genetic counseling

    MedlinePlus

    Genetics is the study of heredity, the process of a parent passing certain genes on to their ... certain diseases are also often determined by genes. Genetic counseling is the process where parents can learn ...

  7. 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 ...

  8. Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia.

    PubMed

    Palomero, Teresa; Odom, Duncan T; O'Neil, Jennifer; Ferrando, Adolfo A; Margolin, Adam; Neuberg, Donna S; Winter, Stuart S; Larson, Richard S; Li, Wei; Liu, X Shirley; Young, Richard A; Look, A Thomas

    2006-08-01

    Aberrant expression of 1 or more transcription factor oncogenes is a critical component of the molecular pathogenesis of human T-cell acute lymphoblastic leukemia (T-ALL); however, oncogenic transcriptional programs downstream of T-ALL oncogenes are mostly unknown. TAL1/SCL is a basic helix-loop-helix (bHLH) transcription factor oncogene aberrantly expressed in 60% of human T-ALLs. We used chromatin immunoprecipitation (ChIP) on chip to identify 71 direct transcriptional targets of TAL1/SCL. Promoters occupied by TAL1 were also frequently bound by the class I bHLH proteins E2A and HEB, suggesting that TAL1/E2A as well as TAL1/HEB heterodimers play a role in transformation of T-cell precursors. Using RNA interference, we demonstrated that TAL1 is required for the maintenance of the leukemic phenotype in Jurkat cells and showed that TAL1 binding can be associated with either repression or activation of genes whose promoters occupied by TAL1, E2A, and HEB. In addition, oligonucleotide microarray analysis of RNA from 47 primary T-ALL samples showed specific expression signatures involving TAL1 targets in TAL1-expressing compared with -nonexpressing human T-ALLs. Our results indicate that TAL1 may act as a bifunctional transcriptional regulator (activator and repressor) at the top of a complex regulatory network that disrupts normal T-cell homeostasis and contributes to leukemogenesis. PMID:16621969

  9. 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

  10. 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.

  11. 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

  12. Downstream of homeotic genes: in the heart of Hox function.

    PubMed

    Monier, Bruno; Tevy, Maria Florencia; Perrin, Laurent; Capovilla, Maria; Sémériva, Michel

    2007-01-01

    A functional organ is constituted of diverse cell types. Each one occupies a distinct position and is associated to specific morphological and physiological functions. The identification of the genetic programs controlling these elaborated and highly precise features of organogenesis is crucial to understand how a mature organ works under normal conditions, and how pathologies can develop. Recently, a number of studies have reported a critical role for Hox genes in one example of organogenesis: cardiogenesis in Drosophila. Beyond the interest in understanding the molecular basis of functional cardiogenesis, this system might provide a model for proposing new paradigms of how Hox genes achieve their action throughout development. PMID:18820463

  13. 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.

  14. Extraction and downstream processing of plant-derived recombinant proteins.

    PubMed

    Buyel, J F; Twyman, R M; Fischer, R

    2015-11-01

    Plants offer the tantalizing prospect of low-cost automated manufacturing processes for biopharmaceutical proteins, but several challenges must be addressed before such goals are realized and the most significant hurdles are found during downstream processing (DSP). In contrast to the standardized microbial and mammalian cell platforms embraced by the biopharmaceutical industry, there are many different plant-based expression systems vying for attention, and those with the greatest potential to provide inexpensive biopharmaceuticals are also the ones with the most significant drawbacks in terms of DSP. This is because the most scalable plant systems are based on the expression of intracellular proteins in whole plants. The plant tissue must therefore be disrupted to extract the product, challenging the initial DSP steps with an unusually high load of both particulate and soluble contaminants. DSP platform technologies can accelerate and simplify process development, including centrifugation, filtration, flocculation, and integrated methods that combine solid-liquid separation, purification and concentration, such as aqueous two-phase separation systems. Protein tags can also facilitate these DSP steps, but they are difficult to transfer to a commercial environment and more generic, flexible and scalable strategies to separate target and host cell proteins are preferable, such as membrane technologies and heat/pH precipitation. In this context, clarified plant extracts behave similarly to the feed stream from microbes or mammalian cells and the corresponding purification methods can be applied, as long as they are adapted for plant-specific soluble contaminants such as the superabundant protein RuBisCO. Plant-derived pharmaceutical proteins cannot yet compete directly with established platforms but they are beginning to penetrate niche markets that allow the beneficial properties of plants to be exploited, such as the ability to produce 'biobetters' with tailored

  15. MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer

    PubMed Central

    Valeri, Nicola; Braconi, Chiara; Gasparini, Pierluigi; Murgia, Claudio; Lampis, Andrea; Paulus-Hock, Viola; Hart, Jonathan R.; Ueno, Lynn; Grivennikov, Sergei I.; Lovat, Francesca; Paone, Alessio; Cascione, Luciano; Sumani, Khlea M.; Veronese, Angelo; Fabbri, Muller; Carasi, Stefania; Alder, Hansjuerg; Lanza, Giovanni; Gafa’, Roberta; Moyer, Mary P.; Ridgway, Rachel A.; Cordero, Julia; Nuovo, Gerard J.; Frankel, Wendy L.; Rugge, Massimo; Fassan, Matteo; Groden, Joanna; Vogt, Peter K.; Karin, Michael; Sansom, Owen J.; Croce, Carlo M.

    2014-01-01

    Summary MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. PMID:24735923

  16. MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.

    PubMed

    Valeri, Nicola; Braconi, Chiara; Gasparini, Pierluigi; Murgia, Claudio; Lampis, Andrea; Paulus-Hock, Viola; Hart, Jonathan R; Ueno, Lynn; Grivennikov, Sergei I; Lovat, Francesca; Paone, Alessio; Cascione, Luciano; Sumani, Khlea M; Veronese, Angelo; Fabbri, Muller; Carasi, Stefania; Alder, Hansjuerg; Lanza, Giovanni; Gafa', Roberta; Moyer, Mary P; Ridgway, Rachel A; Cordero, Julia; Nuovo, Gerard J; Frankel, Wendy L; Rugge, Massimo; Fassan, Matteo; Groden, Joanna; Vogt, Peter K; Karin, Michael; Sansom, Owen J; Croce, Carlo M

    2014-04-14

    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. PMID:24735923

  17. 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

  18. 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...

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs

    PubMed Central

    Jeong, Juhee; Li, Xue; McEvilly, Robert J.; Rosenfeld, Michael G.; Lufkin, Thomas; Rubenstein, John L. R.

    2016-01-01

    Dlx transcription factors are implicated in patterning the mammalian jaw, based on their nested expression patterns in the first branchial arch (primordium for jaw) and mutant phenotypes; inactivation of Dlx1 and Dlx2 (Dlx1/2−/−) causes defects in the upper jaw, whereas Dlx5/6−/− results in homeotic transformation of the lower jaw into upper jaw. Therefore, the ‘Dlx codes’ appear to regionalize the jaw primordium such that Dlx1/2 regulate upper jaw development, while Dlx5/6 confer the lower jaw fate. Towards identifying the genetic pathways downstream of Dlx5/6, we compared the gene expression profiles of the wild-type and Dlx5/6−/− mouse mandibular arch (prospective lower jaw). We identified 20 previously unrecognized Dlx5/6-downstream genes, of which 12 were downregulated and 8 upregulated in the mutant. We found a Dlx-regulated transcriptional enhancer in close proximity to Gbx2, one of the Dlx5/6-downstream genes, strongly suggesting that Gbx2 is a direct target of Dlx5/6. We also showed that Pou3f3 is normally expressed in the maxillary (prospective upper jaw) but not mandibular arch, is upregulated in the mandibular arch of Dlx5/6−/−, and is essential for formation of some of the maxillary arch-derived skeleton. A comparative analysis of the morphological and molecular phenotypes of various Dlx single and double mutants revealed that Dlx1, 2, 5 and 6 act both partially redundantly and antagonistically to direct differential expression of downstream genes in each domain of the first branchial arch. We propose a new model for Dlx-mediated mammalian jaw patterning. PMID:18697905

  5. Genetics of lymphatic anomalies

    PubMed Central

    Brouillard, Pascal; Boon, Laurence; Vikkula, Miikka

    2014-01-01

    Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least 20 genes that encode proteins acting around VEGFR-3 signaling but also downstream of other tyrosine kinase receptors. These mutations exert their effects via the RAS/MAPK and the PI3K/AKT pathways and explain more than a quarter of the incidence of primary lymphedema, mostly of inherited forms. More common forms may also result from multigenic effects or post-zygotic mutations. Most of the corresponding murine knockouts are homozygous lethal, while heterozygotes are healthy, which suggests differences in human and murine physiology and the influence of other factors. PMID:24590274

  6. 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

  7. FAK–MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse

    PubMed Central

    Bechara, Ahmad; Nawabi, Homaira; Moret, Frédéric; Yaron, Avraham; Weaver, Eli; Bozon, Muriel; Abouzid, Karima; Guan, Jun-Lin; Tessier-Lavigne, Marc; Lemmon, Vance; Castellani, Valérie

    2008-01-01

    Axonal receptors for class 3 semaphorins (Sema3s) are heterocomplexes of neuropilins (Nrps) and Plexin-As signalling coreceptors. In the developing cerebral cortex, the Ig superfamily cell adhesion molecule L1 associates with Nrp1. Intriguingly, the genetic removal of L1 blocks axon responses of cortical neurons to Sema3A in vitro despite the expression of Plexin-As in the cortex, suggesting either that L1 substitutes for Plexin-As or that L1 and Plexin-A are both required and mediate distinct roles. We report that association of Nrp1 with L1 but not Plexin-As mediates the recruitment and activation of a Sema3A-induced focal adhesion kinase–mitogen-activated protein kinase cascade. This signalling downstream of L1 is needed for the disassembly of adherent points formed in growth cones and subsequently their collapse response to Sema3A. Plexin-As and L1 are coexpressed and present in common complexes in cortical neurons and both dominant-negative forms of Plexin-A and L1 impair their response to Sema3A. Consistently, Nrp1-expressing cortical projections are defective in mice lacking Plexin-A3, Plexin-A4 or L1. This reveals that specific signalling activities downstream of L1 and Plexin-As cooperate for mediating the axon guidance effects of Sema3A. PMID:18464795

  8. FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse.

    PubMed

    Bechara, Ahmad; Nawabi, Homaira; Moret, Frédéric; Yaron, Avraham; Weaver, Eli; Bozon, Muriel; Abouzid, Karima; Guan, Jun-Lin; Tessier-Lavigne, Marc; Lemmon, Vance; Castellani, Valérie

    2008-06-01

    Axonal receptors for class 3 semaphorins (Sema3s) are heterocomplexes of neuropilins (Nrps) and Plexin-As signalling coreceptors. In the developing cerebral cortex, the Ig superfamily cell adhesion molecule L1 associates with Nrp1. Intriguingly, the genetic removal of L1 blocks axon responses of cortical neurons to Sema3A in vitro despite the expression of Plexin-As in the cortex, suggesting either that L1 substitutes for Plexin-As or that L1 and Plexin-A are both required and mediate distinct roles. We report that association of Nrp1 with L1 but not Plexin-As mediates the recruitment and activation of a Sema3A-induced focal adhesion kinase-mitogen-activated protein kinase cascade. This signalling downstream of L1 is needed for the disassembly of adherent points formed in growth cones and subsequently their collapse response to Sema3A. Plexin-As and L1 are coexpressed and present in common complexes in cortical neurons and both dominant-negative forms of Plexin-A and L1 impair their response to Sema3A. Consistently, Nrp1-expressing cortical projections are defective in mice lacking Plexin-A3, Plexin-A4 or L1. This reveals that specific signalling activities downstream of L1 and Plexin-As cooperate for mediating the axon guidance effects of Sema3A. PMID:18464795

  9. 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

  10. Melanoma and genetics.

    PubMed

    Nelson, Andrew A; Tsao, Hensin

    2009-01-01

    As the incidence of malignant melanoma continues to increase and with the completion of the sequencing of the human genome, there have been increasing efforts to identify the "melanoma gene(s)." Although some patients and families have significantly increased risks due to genetic predisposition, most melanoma cases are sporadic and likely result from low to moderate risk genetic factors. This review focuses on the genes that cover the greatest risk of developing melanoma. It is important to remember that many--if not most--cases of melanoma are the result of undiscovered variants. The strongest genetic risk for the development of melanoma results from heritable alterations in cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related proteins, p16/INK4a and p14/ARF. These proteins help regulate cell division and apoptosis, both of which are necessary to maintain cellular homeostasis. Other important genes include CDK4/6 and retinoblastoma (RB1), which encode downstream proteins in the same pathway as p16/INK4a and p14/ARF. Finally, we discuss the relative importance of the melanocortin 1 receptor (MC1R) gene as a moderate risk factor for melanoma. Although great advances have been made in understanding the molecular basis and genetic predisposition of melanoma, many questions still remain to be answered. Someday soon, it will be possible to predict a patient's risk of melanoma by DNA analysis; however, it is important to reconcile our tremendous technologic capabilities with documented clinical utility. PMID:19095153

  11. Interplay between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of the Hedgehog signaling pathway.

    PubMed

    Cheng, Peng; Wang, Yun-Feng; Li, Gang; Yang, Sheng-sheng; Liu, Che; Hu, Hao; Jin, Gang; Hu, Xian-Gui

    2016-01-01

    Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors. However, the function of menin and its underlying mechanisms in pancreatic ductal adenocarcinoma remain unknown. Here, we found that menin inhibited pancreatic cancer cell growth in vitro and in vivo and that its expression was gradually lost during pancreatic carcinogenesis. Menin overexpression significantly activated the expression of the cyclin-dependent kinase (CDK) inhibitors p18 and p27, accompanied with a decrease in DNA methylation levels of p18 and p27 promoters. Mechanistically, we found that interaction of menin with DNA methyltransferase 1 (Dnmt1) competitively pulled down Dnmt1 from p18 and p27 promoters, leading to the downregulation of DNA methylation levels. Moreover, menin expression was suppressed by Dnmt1 downstream of the Hedgehog signaling pathway, and menin overexpression strongly antagonized the promotion effect of hedgehog signaling on pancreatic cancer cell proliferation. Taken together, the interaction between menin and Dnmt1 reversibly regulates pancreatic cancer cell growth downstream of Hedgehog pathways with complex mutual modulation networks, suggesting that the Hedgehog/Dnmt1/menin axis is a potential molecular target for pancreatic cancer therapy. PMID:26454216

  12. 17 CFR 270.57b-1 - Exemption for downstream affiliates of business development companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption for downstream 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....

  13. 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...

  14. 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.

  15. DOWNSTREAM-WATER-LEVEL CONTROL TEST RESULTS ON THE WM LATERAL CANAL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On steep canals, distant downstream water-level control can be challenging. SacMan (Software for Automated Canal Management) was developed, in part, to test various distant downstream water level controllers. It was implemented on the WM canal of the Maricopa Stanfield Irrigation and Drainage Distri...

  16. 19 CFR 351.223 - Procedures for initiation of downstream product monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Procedures for initiation of downstream product monitoring. 351.223 Section 351.223 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Antidumping and Countervailing Duty Procedures § 351.223 Procedures for initiation of downstream...

  17. Concentrated standing tailwater: a mechanism for nutrient delivery to downstream aquatic ecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contribution of first flush runoff events from intense rainfall to downstream aquatic ecosystems are often reported in terms of sediment and nutrient delivery, with hardly any consideration to the contribution that standing, concentrated tailwater in primary aquatic systems makes to downstream nutri...

  18. 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...

  19. Downstream fish assemblage response to river impoundment varies with degree of hydrologic alteration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    River impoundments alter downstream hydrology and habitat, often resulting in significant changes in stream communities. The degree of impact of a river impoundment on downstream hydrology and biological communities can be dependent on many factors, including underlying natural hydrologic regimes an...

  20. 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.

  1. 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.

  2. 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.

  3. Downstream gradients in bioindicator responses: Point source contaminant effects on fish health

    SciTech Connect

    Marshall Adams, S.; Ham, K.D.; Greeley, M.S.; Hinton, D.E.

    1995-12-31

    To investigate potential causal relationships between contaminant exposure and biological responses in fish, a suite of bioindicators ranging from the biochemical to the community-level were measured in fish populations and communities downstream from a bleached kraft mill effluent (BKME) discharge. Downstream gradients in responses were evident in elevated hepatic mixed-function oxygenase activity, several measures of condition and bioenergetic status, growth, the health assessment index, and several fish community-level parameters. A multivariate discriminant analysis procedure, which included many of the individual bioindicators, also demonstrated a gradient in integrated health status of a sentinel fish species in the contaminated river. These downstream response gradients were probably influenced to a greater degree by contaminant discharges than by natural or anthropogenic nutrient sources downstream. Establishing causal relationships between a specific contaminant source and responses in sentinel aquatic organisms becomes relatively more straightforward when downstream gradients in biological responses are observed at multiple levels of biological organization.

  4. 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

  5. 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. PMID:26170438

  6. 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

  7. AFAP1 Is a Novel Downstream Mediator of TGF-β1 for CCN2 Induction in Osteoblasts

    PubMed Central

    Cho, Youngjin; Silverstein, Rachel; Geisinger, Max T.; Martinkovich, Stephen; Corkill, Holly; Cunnick, Jess M.; Planey, Sonia L.; Arnott, John A.

    2015-01-01

    Background CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-β1 and acts as a mediator of TGF-β1 induced matrix production in osteoblasts and Src is required for CCN2 induction by TGF-β1; however, the molecular mechanisms that control CCN2 induction in osteoblasts are poorly understood. AFAP1 binds activated forms of Src and can direct the activation of Src in certain cell types, however a role for AFAP1 downstream of TGF-β1 or in osteoblats is undefined. In this study, we investigated the role of AFAP1 for CCN2 induction by TGF-β1 in primary osteoblasts. Results We demonstrated that AFAP1 expression in osteoblasts occurs in a biphasic pattern with maximal expression levels occurring during osteoblast proliferation (~day 3), reduced expression during matrix production/maturation (~day 14–21), an a further increase in expression during mineralization (~day 21). AFAP1 expression is induced by TGF-β1 treatment in osteoblasts during days 7, 14 and 21. In osteoblasts, AFAP1 binds to Src and is required for Src activation by TGF-β1 and CCN2 promoter activity and protein induction by TGF-β1 treatment was impaired using AFAP1 siRNA, indicating the requirement of AFAP1 for CCN2 induction by TGF-β1. We also demonstrated that TGF-β1 induction of extracellular matrix protein collagen XIIa occurs in an AFAP1 dependent fashion. Conclusions This study demonstrates that AFAP1 is an essential downstream signaling component of TGF-β1 for Src activation, CCN2 induction and collagen XIIa in osteoblasts. PMID:26340021

  8. Drosophila Rolling Blackout Displays Lipase Domain-Dependent and Independent Endocytic Functions Downstream of Dynamin

    PubMed Central

    Vijayakrishnan, Niranjana; Phillips, Scott E.; Broadie, Kendal

    2010-01-01

    Drosophila temperature-sensitive rolling blackout (rbots) mutants display a total block of endocytosis in non-neuronal cells and a weaker, partial defect at neuronal synapses. RBO is an integral plasma membrane protein and is predicted to be a serine esterase. To determine if lipase activity is required for RBO function, we mutated the catalytic serine 358 to alanine in the G-X-S-X-G active site, and assayed genomic rescue of rbo mutant non-neuronal and neuronal phenotypes. The rboS358A mutant is unable to rescue rbo null 100% embryonic lethality, indicating that the lipase-domain is critical for RBO essential function. Likewise, the rboS358A mutant cannot provide any rescue of endocytic blockade in rbots Garland cells, demonstrating that the lipase-domain is indispensable for non-neuronal endocytosis. In contrast, rbots conditional paralysis, synaptic transmission block and synapse endocytic defects are all fully rescued by the rboS358A mutant, showing that the RBO lipase-domain is dispensable in neuronal contexts. We identified a synthetic lethal interaction between rbots and the well-characterized dynamin GTPase conditional shibire (shits1) mutant. In both non-neuronal cells and neuronal synapses, shits1;rbots phenocopies shits1 endocytic defects, indicating that dynamin and RBO act in the same pathway, with dynamin functioning upstream of RBO. We conclude that RBO possesses both lipase-domain dependent and scaffolding functions with differential requirements in non-neuronal versus neuronal endocytosis mechanisms downstream of dynamin GTPase activity. PMID:21029287

  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. 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.

  11. ACTS data center

    NASA Astrophysics Data System (ADS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-08-01

    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.

  12. 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.

  13. Recovery Act Milestones

    ScienceCinema

    Rogers, Matt

    2013-05-29

    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. Genetic counseling.

    PubMed

    Fraser, F C

    1974-09-01

    A workshop was sponsored by the National Genetics Foundation to evaluate and make recommendations about the status of genetic counseling, its goals, nature, achievements, and needs. The process of genetic workup and counseling is divided into 5 stages: validation of the diagnosis; obtaining family history; estimation of the risk of recurrence; helping the family make a decision and take appropriate action; and extending counseling to other members of the family. Counseling can be directed at individuals or at special groups with the potential of carrying such diseases as sickle cell amenia or Tay-Sachs. No consensus exists on an optimal counseling approach. Genetic counseling is regarded as a team effort, requiring, in addition to the counselor, laboratory facilities and a variety of specialists. The source of payment for genetic counseling services is regarded as a problem of increasing concern. Generally, the fee paid rarely covers the cost of the many procedures and it is suggested that the cost, like that of other public health services, should be subsidized by the state. Considerable argument exists over whether a genetic counselor must have a M.D. degree or whether a Ph. D. in medical genetics is suitable enough. The quality of much genetic counseling, which is often done in the office of doctors unskilled in the field, would be increased if better training in genetics were offered to medical students and if physicians were informed of the existence of counseling centers. Further, there is a growing feeling that some sort of accreditation of genetic counselors is desirable. PMID:4609197

  15. 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

  16. 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

  17. 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.

  18. Data collection and documentation of flooding downstream of a dam failure in Mississippi

    USGS Publications Warehouse

    Van Wilson, Jr., K.

    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.

  19. The evolutionary genetics of canalization.

    PubMed

    Flatt, Thomas

    2005-09-01

    Evolutionary genetics has recently made enormous progress in understanding how genetic variation maps into phenotypic variation. However why some traits are phenotypically invariant despite apparent genetic and environmental changes has remained a major puzzle. In the 1940s, Conrad Hal Waddington coined the concept and term "canalization" to describe the robustness of phenotypes to perturbation; a similar concept was proposed by Waddington's contemporary Ivan Ivanovich Schmalhausen. This paper reviews what has been learned about canalization since Waddington. Canalization implies that a genotype's phenotype remains relatively invariant when individuals of a particular genotype are exposed to different environments (environmental canalization) or when individuals of the same single- or multilocus genotype differ in their genetic background (genetic canalization). Consequently, genetic canalization can be viewed as a particular kind of epistasis, and environmental canalization and phenotypic plasticity are two aspects of the same phenomenon. Canalization results in the accumulation of phenotypically cryptic genetic variation, which can be released after a "decanalizing" event. Thus, canalized genotypes maintain a cryptic potential for expressing particular phenotypes, which are only uncovered under particular decanalizing environmental or genetic conditions. Selection may then act on this newly released genetic variation. The accumulation of cryptic genetic variation by canalization may therefore increase evolvability at the population level by leading to phenotypic diversification under decanalizing conditions. On the other hand, under canalizing conditions, a major part of the segregating genetic variation may remain phenotypically cryptic; canalization may therefore, at least temporarily, constrain phenotypic evolution. Mechanistically, canalization can be understood in terms of transmission patterns, such as epistasis, pleiotropy, and genotype by environment

  20. 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,…

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 76 FR 23625 - Notice of Filing of Consent Decree Pursuant to the Clean Water Act (“CWA”)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... of Filing of Consent Decree Pursuant to the Clean Water Act (``CWA'') Notice is hereby given that on... the United States' claims alleged in the Complaint pursuant to Section 309 of the Clean Water Act (CWA... certain storm water from its waste rock from discharging to the downstream creek and wetland....

  7. CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster

    PubMed Central

    Domanitskaya, Elena; Schüpbach, Trudi

    2012-01-01

    The Notch signaling pathway plays important roles in a variety of developmental events. The context-dependent activities of positive and negative modulators dramatically increase the diversity of cellular responses to Notch signaling. In a screen for mutations affecting the Drosophila melanogaster follicular epithelium, we isolated a mutation in CoREST that disrupts the Notch-dependent mitotic-to-endocycle switch of follicle cells at stage 6 of oogenesis. We show that Drosophila CoREST positively regulates Notch signaling, acting downstream of the proteolytic cleavage of Notch but upstream of Hindsight activity; the Hindsight gene is a Notch target that coordinates responses in the follicle cells. We show that CoREST genetically interacts with components of the Notch repressor complex, Hairless, C-terminal Binding Protein and Groucho. In addition, we demonstrate that levels of H3K27me3 and H4K16 acetylation are dramatically increased in CoREST mutant follicle cells. Our data indicate that CoREST acts as a positive modulator of the Notch pathway in the follicular epithelium as well as in wing tissue, and suggests a previously unidentified role for CoREST in the regulation of Notch signaling. Given its high degree of conservation among species, CoREST probably also functions as a regulator of Notch-dependent cellular events in other organisms. PMID:22331351

  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. 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. Wavelength remodulation scheme using DPSK downstream and upstream for DWDM-PONs

    NASA Astrophysics Data System (ADS)

    Deb, Nebras; Anis, Hanan

    2011-08-01

    We propose a novel wavelength-division-multiplexed passive optical network (WDM-PON) architecture with enhanced tolerance toward chromatic dispersion where a DPSK-modulated downstream signal with constant intensity is remodulated at the ONU side with a return to zero (RZ-DPSK). Driving the downstream modulator with a 50% RZ data enabled us to employ the pulse carver at the ONU for both removing downstream data and generating the optical RZ signal for upstream. This offers an attractive alternative to earlier proposed schemes as it allows us to use full modulation depth (FMD) and balanced detection for downstream data restoration. We experimentally demonstrate the system with both balanced and single-ended detection at 2.5Gb/s. Error-free operation has been achieved along a 20Km single mode fiber without dispersion compensation.

  12. 7. Oblique view of downstream side of Bridge Number 324.99, ...

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

    7. Oblique view of downstream side of Bridge Number 324.99, contextual view to north-northwest, 135mm lens. - Southern Pacific Railroad Shasta Route, Bridge No. 324.99, Milepost 324.99, Shasta Springs, Siskiyou County, CA

  13. 9. Downstream side of Bridge Number 324.99, showing west end, ...

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

    9. Downstream side of Bridge Number 324.99, showing west end, view to west, 90mm lens. - Southern Pacific Railroad Shasta Route, Bridge No. 324.99, Milepost 324.99, Shasta Springs, Siskiyou County, CA

  14. 8. Oblique view of downstream side of Bride Number 324.99, ...

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

    8. Oblique view of downstream side of Bride Number 324.99, view to north-northwest, 135mm lens. - Southern Pacific Railroad Shasta Route, Bridge No. 324.99, Milepost 324.99, Shasta Springs, Siskiyou County, CA

  15. 7. Oblique view of downstream side of Bridge Number 301.85, ...

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

    7. Oblique view of downstream side of Bridge Number 301.85, view to west-southwest, 135mm lens. - Southern Pacific Railroad Shasta Route, Bridge No. 301.85, Milepost 301.85, Pollard Flat, Shasta County, CA

  16. 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 ...

  17. RNA genetics

    SciTech Connect

    Domingo, E. ); Holland, J.J. . Dept. of Biology); Ahlquist, P. . Dept. of Plant Pathology)

    1988-01-01

    This book contains the proceedings on RNA genetics: Retroviruses, Viroids, and RNA recombination, Volume 2. Topics covered include: Replication of retrovirus genomes, Hepatitis B virus replication, and Evolution of RNA viruses.

  18. 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)

  19. Organic compounds downstream from a treated-wastewater discharge near Dallas, Texas, March 1987

    USGS Publications Warehouse

    Buszka, P.M.; Barber, L.B., II; 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.

  20. 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.

  1. 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

  2. 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

  3. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    PubMed

    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

  4. 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.

  5. Dimethyl adipimidate/Thin film Sample processing (DTS); A simple, low-cost, and versatile nucleic acid extraction assay for downstream analysis.

    PubMed

    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

  6. 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

  7. Genetic Screening

    PubMed Central

    Burke, Wylie; Tarini, Beth; Press, Nancy A.; Evans, James P.

    2011-01-01

    Current approaches to genetic screening include newborn screening to identify infants who would benefit from early treatment, reproductive genetic screening to assist reproductive decision making, and family history assessment to identify individuals who would benefit from additional prevention measures. Although the traditional goal of screening is to identify early disease or risk in order to implement preventive therapy, genetic screening has always included an atypical element—information relevant to reproductive decisions. New technologies offer increasingly comprehensive identification of genetic conditions and susceptibilities. Tests based on these technologies are generating a different approach to screening that seeks to inform individuals about all of their genetic traits and susceptibilities for purposes that incorporate rapid diagnosis, family planning, and expediting of research, as well as the traditional screening goal of improving prevention. Use of these tests in population screening will increase the challenges already encountered in genetic screening programs, including false-positive and ambiguous test results, overdiagnosis, and incidental findings. Whether this approach is desirable requires further empiric research, but it also requires careful deliberation on the part of all concerned, including genomic researchers, clinicians, public health officials, health care payers, and especially those who will be the recipients of this novel screening approach. PMID:21709145

  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. PMID:25369363

  9. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

  10. 40 CFR 80.524 - What sulfur content standard applies to motor vehicle diesel fuel downstream of the refinery or...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... to motor vehicle diesel fuel downstream of the refinery or importer? 80.524 Section 80.524 Protection... applies to motor vehicle diesel fuel downstream of the refinery or importer? (a) Except as provided in... standard of § 80.520(a) shall apply to all motor vehicle diesel fuel at any downstream location. (b)...

  11. 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 ...

  12. Interactions between Channel Morphology and the Propagation of Coarse Sediment Augmentations Downstream from Dams

    NASA Astrophysics Data System (ADS)

    Gaeuman, D. A.; Dickenson, S.; Pyles, M.

    2009-12-01

    Gravel augmentations are being implemented in a number of streams where natural recruitment of gravel is impeded by dams. Uncertainties relevant to the management of gravel augmentations include the quantities of gravel needed to achieve habitat benefits at downstream locations and the temporal and spatial scales over which those benefits that will be realized. The solution to such questions depends to a large extent on how gravel slugs evolve as the material is transported downstream, i.e., whether the gravel translates downstream as a coherent wave or whether it tends to disperse. A number of recent studies conducted in laboratory flumes or by numerical simulation that gravels slugs tend to disperse rather than translate. However, these studies do not consider the influence of channel morphology on slug behavior. Initial monitoring results based from 2 California streams suggest that natural channel morphology suppresses slug dispersion because the gravel tends to accumulate in discrete deposition zones. Field mapping and about 200 tracer stones implanted with passive integrated transponder (PIT) tags show that gravel recruitment piles of about 80 tons each placed in Grass Valley Creek in 2007 and 2008 were deposited as 2 new bars immediately downstream. The more upstream of the 2 bars formed during the 2007 winter and spring flood season, whereas the more downstream bar did not appear until the following year. A sharp deposition front and an absence of tracers in the reaches downstream strongly suggest that none of the added gravel was transported downstream beyond the area of bar formation in either year. A relatively small proportion of the mobilized tracer particles (59%) were located following the 2007 flood season, probably due to deep burial in the newly deposited bar and to radio interference caused by the high concentration of tracers in a small area. The proportion of newly introduced or previously-located tracers that were relocated in 2009 was

  13. 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

  14. 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.

  15. The Genetics of Hemoglobin A2 Regulation in Sickle Cell Anemia

    PubMed Central

    Griffin, Paula J.; Sebastiani, Paola; Edward, Heather; Baldwin, Clinton T.; Gladwin, Mark; Gordeuk, Victor; Chui, David H.K.; Steinberg, Martin H.

    2014-01-01

    Hemoglobin A2, a tetramer of α- and δ-globin chains, comprises less than 3% of total hemoglobin in normal adults. In northern Europeans, single nucleotide polymorphisms (SNPs) in the HBS1L-MYB locus on chromosome 6q and the HBB cluster on chromosome 11p were associated with HbA2 levels. We examined the genetic basis of HbA2 variability in sickle cell anemia using genome-wide association studies (GWAS). HbA2 levels were associated with SNPs in the HBS1L-MYB interval that affect erythropoiesis and HbF expression and SNPs in BCL11A that regulate the γ-globin genes. These effects are mediated by the association of these loci with γ-globin gene expression and fetal hemoglobin (HbF) levels. The association of polymorphisms downstream of the β-globin gene (HBB) cluster on chromosome 11 with HbA2 was not mediated by HbF. In sickle cell anemia, levels of HbA2 appear to be modulated by trans-acting genes that affect HBG expression and perhaps also elements within the β-globin gene cluster. HbA2 is expressed pancellularly and can inhibit HbS polymerization. It remains to be seen if genetic regulators of HbA2 can be exploited for therapeutic purposes. PMID:25042611

  16. Reducing the genetic redundancy of Arabidopsis PHOSPHATE TRANSPORTER1 transporters to study phosphate uptake and signaling.

    PubMed

    Ayadi, Amal; David, Pascale; Arrighi, Jean-François; Chiarenza, Serge; Thibaud, Marie-Christine; Nussaume, Laurent; Marin, Elena

    2015-04-01

    Arabidopsis (Arabidopsis thaliana) absorbs inorganic phosphate (Pi) from the soil through an active transport process mediated by the nine members of the PHOSPHATE TRANSPORTER1 (PHT1) family. These proteins share a high level of similarity (greater than 61%), with overlapping expression patterns. The resulting genetic and functional redundancy prevents the analysis of their specific roles. To overcome this difficulty, our approach combined several mutations with gene silencing to inactivate multiple members of the PHT1 family, including a cluster of genes localized on chromosome 5 (PHT1;1, PHT1;2, and PHT1;3). Physiological analyses of these lines established that these three genes, along with PHT1;4, are the main contributors to Pi uptake. Furthermore, PHT1;1 plays an important role in translocation from roots to leaves in high phosphate conditions. These genetic tools also revealed that some PHT1 transporters likely exhibit a dual affinity for phosphate, suggesting that their activity is posttranslationally controlled. These lines display significant phosphate deficiency-related phenotypes (e.g. biomass and yield) due to a massive (80%-96%) reduction in phosphate uptake activities. These defects limited the amount of internal Pi pool, inducing compensatory mechanisms triggered by the systemic Pi starvation response. Such reactions have been uncoupled from PHT1 activity, suggesting that systemic Pi sensing is most probably acting downstream of PHT1. PMID:25670816

  17. Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

    PubMed Central

    LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

    1983-01-01

    The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

  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. mab-31 and the TGF-β pathway act in the ray lineage to pattern C. elegans male sensory rays

    PubMed Central

    2010-01-01

    Background C. elegans TGF-β-like Sma/Mab signaling pathway regulates both body size and sensory ray patterning. Most of the components in this pathway were initially identified by genetic screens based on the small body phenotype, and many of these mutants display sensory ray patterning defect. At the cellular level, little is known about how and where these components work although ray structural cell has been implicated as one of the targets. Based on the specific ray patterning abnormality, we aim to identify by RNAi approach additional components that function specifically in the ray lineage to elucidate the regulatory role of TGF-β signaling in ray differentiation. Result We report here the characterization of a new member of the Sma/Mab pathway, mab-31, recovered from a genome-wide RNAi screen. mab-31 mutants showed ray cell cluster patterning defect and mis-specification of the ray identity. mab-31 encodes a nuclear protein expressed in descendants of ray precursor cells impacting on the ray cell's clustering properties, orientation of cell division plane, and fusion of structural cells. Genetic experiments also establish its relationship with other Sma/Mab pathway components and transcription factors acting upstream and downstream of the signaling event. Conclusion mab-31 function is indispensable in Sma/Mab signal recipient cells during sensory rays specification. Both mab-31 and sma-6 are required in ray lineage at the late larval stages. They act upstream of C. elegans Pax-6 homolog and repress its function. These findings suggested mab-31 is a key factor that can integrate TFG-β signals in male sensory ray lineage to define organ identity. PMID:20687916

  20. 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.

  1. 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.

  2. Enhanced Magnetic Field Perturbations and Electric Currents Observed Downstream of the High Power Helicon

    NASA Astrophysics Data System (ADS)

    Race Roberson, B.; Winglee, Robert; Ziemba, Tim; Prager, James

    2010-11-01

    The high power helicon (HPH) is a compact plasma source that can generate downstream densities of 10^17-10^18 m-3 and directed ion energies greater than 20 eV that continue to increase tens of centimeters downstream of the source. In order to understand the coupling mechanism between the helicon antenna and the plasma outside the immediate source region, measurements were made in the plasma plume downstream from the thruster of the propagating wave magnetic field and the perturbation of the axial bulk field. This magnetic field perturbation (δB) peaks at more than 15 gauss in strength downstream of the plasma source and propagates tens of centimeters downstream, cancelling the base magnetic field as it propagates. Taking the curl of this measured magnetic perturbation and assuming azimuthal symmetry suggests a peak current density of 20 kA m-2. Data will be presented that relates the cancellation of the base magnetic field to the propagation of the helicon wave and the region where the plasma current system closes.

  3. 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.

  4. 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.

  5. Kinetics of Hydrogen Oxidation Downstream of Lean Propane and Hydrogen Flames

    NASA Technical Reports Server (NTRS)

    Fine, Burton

    1961-01-01

    The decay of hydrogen was measured downstream of lean, flat, premixed hydrogen and propane-air flames seated on cooled porous burners. Experimental variables included temperature, pressure, initial equivalence ratio and diluent. Sampling of burned gas was done through uncooled quartz orifice probes, and the analysis was based on gas chromatography. An approximate treatment of the data in which diffusion was neglected led to the following rate expression for the zone downstream of hydrogen flames d[H (sub 2)] divided by (d times t) equals 1.7 times 10 (sup 10) [H (sub 2)] (sup 3) divided by (sub 2) [O (sub 2)]e (sup (-8100 divided by RT)) moles per liters per second. On the basis of a rate expression of this form, the specific rate constant for the reaction downstream of hydrogen flames was about three times as great as that determined downstream of propane flames. This result was explained on the basis of the existence of a steady state between hydrogen and carbon monoxide in the burned gas downstream of propane flames.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Darwin and Genetics

    PubMed Central

    Charlesworth, Brian; Charlesworth, Deborah

    2009-01-01

    Darwin's theory of natural selection lacked an adequate account of inheritance, making it logically incomplete. We review the interaction between evolution and genetics, showing how, unlike Mendel, Darwin's lack of a model of the mechanism of inheritance left him unable to interpret his own data that showed Mendelian ratios, even though he shared with Mendel a more mathematical and probabilistic outlook than most biologists of his time. Darwin's own “pangenesis” model provided a mechanism for generating ample variability on which selection could act. It involved, however, the inheritance of characters acquired during an organism's life, which Darwin himself knew could not explain some evolutionary situations. Once the particulate basis of genetics was understood, it was seen to allow variation to be passed intact to new generations, and evolution could then be understood as a process of changes in the frequencies of stable variants. Evolutionary genetics subsequently developed as a central part of biology. Darwinian principles now play a greater role in biology than ever before, which we illustrate with some examples of studies of natural selection that use DNA sequence data and with some recent advances in answering questions first asked by Darwin. PMID:19933231

  11. Darwin and genetics.

    PubMed

    Charlesworth, Brian; Charlesworth, Deborah

    2009-11-01

    Darwin's theory of natural selection lacked an adequate account of inheritance, making it logically incomplete. We review the interaction between evolution and genetics, showing how, unlike Mendel, Darwin's lack of a model of the mechanism of inheritance left him unable to interpret his own data that showed Mendelian ratios, even though he shared with Mendel a more mathematical and probabilistic outlook than most biologists of his time. Darwin's own "pangenesis" model provided a mechanism for generating ample variability on which selection could act. It involved, however, the inheritance of characters acquired during an organism's life, which Darwin himself knew could not explain some evolutionary situations. Once the particulate basis of genetics was understood, it was seen to allow variation to be passed intact to new generations, and evolution could then be understood as a process of changes in the frequencies of stable variants. Evolutionary genetics subsequently developed as a central part of biology. Darwinian principles now play a greater role in biology than ever before, which we illustrate with some examples of studies of natural selection that use DNA sequence data and with some recent advances in answering questions first asked by Darwin. PMID:19933231

  12. Genetic Disorders

    MedlinePlus

    ... of pregnancy loss. How do I know which tests to have? Your health care provider or a genetic counselor can discuss all of the testing options with you and help you decide based on your individual risk factors. Do I have to have these tests? Whether you want to be tested is a ...

  13. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  14. 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

  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. 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.

  17. Influence of Local Flow Field on Flow Accelerated Corrosion Downstream from an Orifice

    NASA Astrophysics Data System (ADS)

    Utanohara, Yoichi; Nagaya, Yukinori; Nakamura, Akira; Murase, Michio

    Flow accelerated corrosion (FAC) rate downstream from an orifice was measured in a high-temperature water test loop to evaluate the effects of flow field on FAC. Orifice flow was also measured using laser Doppler velocimetry (LDV) and simulated by steady RANS simulation and large eddy simulation (LES). The LDV measurements indicated the flow structure did not depend on the flow velocity in the range of Re = 2.3×104 to 1.2×105. Flow fields predicted by RANS and LES agreed well with LDV data. Measured FAC rate was higher downstream than upstream from the orifice and the maximum appeared at 2D (D: pipe diameter) downstream. The shape of the profile of the root mean square (RMS) wall shear stress predicted by LES had relatively good agreement with the shape of the profile of FAC rate. This result indicates that the effects of flow field on FAC can be evaluated using the calculated wall shear stress.

  18. Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

    PubMed Central

    2013-01-01

    Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

  19. Ectodermal dysplasia: a genetic review.

    PubMed

    Deshmukh, Seema; Prashanth, S

    2012-09-01

    Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202. PMID:25206167

  20. Ectodermal Dysplasia: A Genetic Review

    PubMed Central

    Prashanth, S

    2012-01-01

    Abstract Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202. PMID:25206167

  1. High and low latitude types of the downstream influences of the North Atlantic Oscillation

    NASA Astrophysics Data System (ADS)

    Song, Jie; Li, Chongyin; Zhou, Wen

    2014-02-01

    Using reanalysis data, we find that the downstream-propagating quasi-stationary Rossby wave train associated with the North Atlantic Oscillation (NAO) generally propagates along a high (low)-latitude pathway during warm (cold) El Niño-Southern Oscillation (ENSO) boreal winters. Consistent with the different propagation directions of the NAO-related downstream wave train, during the warm (cold) ENSO winters, the NAO is associated with significant 300 hPa geopotential height anomalies over eastern Siberia (the Arabian Sea, the east coast of Asia at around 40°N, and the North Pacific), and the near-surface air temperature perturbations associated with the NAO over the high latitudes of Asia are relatively strong (weak). Based on these differences, we argue that the NAO has two distinct types of downstream influence: a high-latitude type and a low-latitude type. Furthermore, we argue that the two types of NAO's downstream influence are modulated by the intensity of the subtropical potential vorticity (PV) meridional gradient over Africa. When this gradient is weak (strong), as in the warm (cold) ENSO winters, the NAO's downstream influence tends to be of the high (low)-latitude type. These results are further supported by analysis of intraseasonal NAO events. We separate NAO events into two categories in terms of the intensity of the subtropical PV gradient over Africa. Composites of the NAO events accompanied by a weak (strong) subtropical PV gradient show that the NAO-related downstream wave train tends to propagate along a high (low)-latitude pathway.

  2. 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.

  3. 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.

  4. Cancer Genetics Services Directory

    MedlinePlus

    ... Overview–for health professionals Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic ...

  5. Mapping genetic influences on human brain structure.

    PubMed

    Thompson, Paul; Cannon, Tyrone D; Toga, Arthur W

    2002-01-01

    Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain. PMID:12553492

  6. 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.

  7. 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.

  8. Slug is a novel downstream target of MyoD. Temporal profiling in muscle regeneration.

    PubMed

    Zhao, Po; Iezzi, Simona; Carver, Ethan; Dressman, Devin; Gridley, Thomas; Sartorelli, Vittorio; Hoffman, Eric P

    2002-08-16

    Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice. PMID:12023284

  9. 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

  10. Estimating subcatchment runoff coefficients using weather radar and a downstream runoff sensor.

    PubMed

    Ahm, Malte; Thorndahl, Søren; Rasmussen, Michael R; Bassø, Lene

    2013-01-01

    This paper presents a method for estimating runoff coefficients of urban drainage subcatchments based on a combination of high resolution weather radar data and flow measurements from a downstream runoff sensor. By utilising the spatial variability of the precipitation it is possible to estimate the runoff coefficients of the separate subcatchments. The method is demonstrated through a case study of an urban drainage catchment (678 ha) located in the city of Aarhus, Denmark. The study has proven that it is possible to use corresponding measurements of the relative rainfall distribution over the catchment and downstream runoff measurements to identify the runoff coefficients at subcatchment level. PMID:24056426

  11. 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.

  12. [Bioethics in genetic diagnosis and therapy].

    PubMed

    Takebe, H

    2000-06-01

    Human genetics, or medical genetics have been rarely taught in most of the medical schools in Japan, as there are only several medical schools with genetics departments among 80 medical schools in Japan. Bioethics has just been becoming an important issue in the medical community in Japan. People hate to be told of hereditary diseases, possibly due to the traditional concept of hereditary diseases as punishment for the evil acts of the ancestors. Recent rapid progress in genetic diagnosis and therapy, however, requires the medical community in Japan to consider the bioethical aspects related to human genetics. We need proper guidelines, and the efforts have been made by the government as well as by the Society for Familial Tumor to propose practical guidelines for human genetics. They may considerably be different from those in the Western countries. PMID:10879054

  13. Chemical Genetics in Dissecting Membrane Glycerolipid Functions.

    PubMed

    Chevalier, Florian; Carrera, Laura Cuyàs; Nussaume, Laurent; Maréchal, Eric

    2016-01-01

    Chemical genetics has emerged as a powerful approach to dissect biological processes, based on the utilization of small molecules disturbing the function of specific target proteins. By analogy with classical genetics, 'reverse chemical genetics' refers to the utilization of drugs acting on a known target, enabling its functional characterization at the levels of the cells, tissues and organisms. Likewise, 'direct chemical genetics' refers to the utilization of a drug of unknown mode of action, but triggering a phenotype of interest. In that case, one has to identify the target(s) possibly blocked (or possibly activated) by the small molecule. This chapter illustrates both approaches, like the analysis of the elongation of fatty acids, the biosynthesis of galactoglycerolipids or the catabolism of phosphoglycerolipids by reverse chemical genetics or the study of the membrane glycerolipid remodeling triggered upon phosphate starvation, by direct chemical genetics. PMID:27023235

  14. 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, ...

  15. 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.

  16. 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.

  17. Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Zhang, Weiying; Nandakumar, Nivedita; Shi, Yuhao; Manzano, Mark; Smith, Alias; Graham, Garrett; Gupta, Swati; Vietsch, Eveline E.; Laughlin, Sean Z.; Wadhwa, Mandheer; Chetram, Mahandranauth; Joshi, Mrinmayi; Wang, Fen; Kallakury, Bhaskar; Toretsky, Jeffrey; Wellstein, Anton; Yi, Chunling

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, KRAS has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), a protein regulated by the Hippo pathway during tissue development and homeostasis, was increased in human PDAC tissue compared with that in normal pancreatic epithelia. In genetically engineered KrasG12D and KrasG12D: Trp53R172H mouse models, pancreas-specific deletion of Yap halted the progression of early neoplastic lesions to PDAC without affecting normal pancreatic development and endocrine function. Although Yap was dispensable for acinar to ductal metaplasia (ADM), an initial step in the progression to PDAC, Yap was critically required for the proliferation of mutant Kras or Kras:Trp53 neoplastic pancreatic ductal cells in culture and for their growth and progression to invasive PDAC in mice. Yap functioned as a critical transcriptional switch downstream of the oncogenic KRAS–mitogen-activated protein kinase (MAPK) pathway, promoting the expression of genes encoding secretory factors that cumulatively sustained neoplastic proliferation, a tumorigenic stromal response in the tumor microenvironment, and PDAC progression in Kras and Kras: Trp53 mutant pancreas tissue. Together, our findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers. PMID:24803537

  18. 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

  19. The ACTS propagation program

    NASA Technical Reports Server (NTRS)

    Chakraborty, D.; Davarian, Faramaz

    1992-01-01

    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. The planning process and hardware development program that will comply with the recommendations of the ACTS propagation study groups are described.

  20. A Novel Synthesizing Genetic Logic Circuit: Frequency Multiplier.

    PubMed

    Chuang, Chia-Hua; Lin, Chun-Liang

    2014-01-01

    This paper presents a novel synthesizing genetic logic circuit design based on an existing synthetic genetic oscillator, which provides a function of frequency multiplier to synthesize a clock signal whose frequency is a multiple of that of the genetic oscillator. In the renowned literature, the synthetic genetic oscillator, known as a repressilator, has been successfully built in Escherichia coli to generate a periodic oscillating phenomenon through three repressive genes repress each other in a chain. On the basis of this fact, our proposed genetic frequency multiplier circuit utilizes genetic Buffers in series with a waveform-shaping circuit to reshape the genetic oscillation signal into a crisp logic clock signal. By regulating different threshold levels in the Buffer, the time length of logic high/low levels in a fundamental sinusoidal wave can be engineered to pulse-width-modulated (PWM) signals with various duty cycles. Integrating some of genetic logic XOR gates and PWM signals from the output of the Buffers, a genetic frequency multiplier circuit can be created and the clock signal with the integer-fold of frequency of the genetic oscillator is generated. The synthesized signal can be used in triggering the downstream digital genetic logic circuits. Simulation results show the applicability of the proposed idea. PMID:26356341