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Sample records for essential downstream target

  1. Downstream targets of WRKY33

    DEFF Research Database (Denmark)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John

    2008-01-01

    Innate immunity signaling pathways in both animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. In a recent publication we show that MPK4 and its substrate MKS1 interact with WRKY33 in vivo, and that WRKY33 is released from complexes with MPK4 upon infection....... Transcriptome analysis of a wrky33 loss-of-function mutant identified a subset of defense-related genes as putative targets of WRKY33. These genes include PAD3 and CYP71A13, which encode cytochrome P450 monoxygenases required for synthesis of the antimicrobial phytoalexin camalexin. Chromatin...... immunoprecipitation confirmed that WRKY33 bound the promoter of PAD3 when plants were inoculated with pathogens. Here we further discuss the involvement of two other targets of WRKY33, NUDT6 and ROF2 in defense responses against invading pathogens....

  2. Targets downstream of Cdk8 in Dictyostelium development

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    Skelton Jason

    2011-01-01

    Full Text Available Abstract Background Cdk8 is a component of the mediator complex which facilitates transcription by RNA polymerase II and has been shown to play an important role in development of Dictyostelium discoideum. This eukaryote feeds as single cells but starvation triggers the formation of a multicellular organism in response to extracellular pulses of cAMP and the eventual generation of spores. Strains in which the gene encoding Cdk8 have been disrupted fail to form multicellular aggregates unless supplied with exogenous pulses of cAMP and later in development, cdk8- cells show a defect in spore production. Results Microarray analysis revealed that the cdk8- strain previously described (cdk8-HL contained genome duplications. Regeneration of the strain in a background lacking detectable gene duplication generated strains (cdk8-2 with identical defects in growth and early development, but a milder defect in spore generation, suggesting that the severity of this defect depends on the genetic background. The failure of cdk8- cells to aggregate unless rescued by exogenous pulses of cAMP is consistent with a failure to express the catalytic subunit of protein kinase A. However, overexpression of the gene encoding this protein was not sufficient to rescue the defect, suggesting that this is not the only important target for Cdk8 at this stage of development. Proteomic analysis revealed two potential targets for Cdk8 regulation, one regulated post-transcriptionally (4-hydroxyphenylpyruvate dioxygenase (HPD and one transcriptionally (short chain dehydrogenase/reductase (SDR1. Conclusions This analysis has confirmed the importance of Cdk8 at multiple stages of Dictyostelium development, although the severity of the defect in spore production depends on the genetic background. Potential targets of Cdk8-mediated gene regulation have been identified in Dictyostelium which will allow the mechanism of Cdk8 action and its role in development to be determined.

  3. Integrative analysis of RUNX1 downstream pathways and target genes

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    Liu Marjorie

    2008-07-01

    Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease

  4. Energy deposition in a thin copper target downstream and off-axis of a proton-radiography target

    International Nuclear Information System (INIS)

    Greene, G.A.; Finfrock, C.C.; Snead, C.L.; Hanson, A.L.; Murray, M.M.

    2002-01-01

    A series of proton energy-deposition experiments was conducted to measure the energy deposited in a copper target located downstream and off-axis of a high-energy proton-radiography target. The proton/target interactions involved low-intensity bunches of protons at 24 GeV/c onto a spherical target consisting of concentric shells of tungsten and copper. The energy-deposition target was placed at five locations downstream of the proton-radiography target, off-axis of the primary beam transport, and was either unshielded or shielded by 5 or 10 cm of lead. Maximum temperature rises measured in the energy-deposition target due to single bunches of 5x10 10 protons on the proton-radiography target were approximately 20 mK per bunch. The data indicated that the scattered radiation was concentrated close to the primary transport axis of the beam line. The energy deposited in the energy-deposition target was reduced by moving the target radially away from the primary transport axis. Placing lead shielding in front of the target further reduced the energy deposition. The measured temperature rises of the energy-deposition target were empirically correlated with the distance from the source, the number of protons incident on the proton-radiography target, the thickness of the lead shielding, and the angle of the energy-deposition target off-axis of the beam line from the proton-radiography target. The correlation of the experimental data that was developed provides a starting point for the evaluation of the shielding requirements for devices downstream of proton-radiography targets such as superconducting magnets

  5. MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling

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    Wang, Yelin [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Hu, Chen; Cheng, Jun [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Chen, Binquan [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Ke, Qinghong; Lv, Zhen; Wu, Jian [Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Zhou, Yanfeng, E-mail: zyfhdj@yahoo.com [Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

    2014-04-18

    Highlights: • MiR-145 expression is down-regulated in HCC tissues and inversely related with IRS1 levels. • MiR-145 directly targets IRS1 in HCC cells. • Restored expression of miR-145 suppressed HCC cell proliferation and growth. • MiR-145 induced IRS1 under-expression potentially reduced downstream AKT signaling. - Abstract: Accumulating evidences have proved that dysregulation of microRNAs (miRNAs) is involved in cancer initiation and progression. In this study, we showed that miRNA-145 level was significantly decreased in hepatocellular cancer (HCC) tissues and cell lines, and its low expression was inversely associated with the abundance of insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling. We verified IRS1 as a direct target of miR-145 using Western blotting and luciferase reporter assay. Further, the restoration of miR-145 in HCC cell lines suppressed cancer cell growth, owing to down-regulated IRS1 expression and its downstream Akt/FOXO1 signaling. Our results demonstrated that miR-145 could inhibit HCC through targeting IRS1 and its downstream signaling, implicating the loss of miR-145 regulation may be a potential molecular mechanism causing aberrant oncogenic signaling in HCC.

  6. Pharmacological therapeutics targeting the secondary defects and downstream pathology of Duchenne muscular dystrophy

    Science.gov (United States)

    Spinazzola, Janelle M.; Kunkel, Louis M.

    2016-01-01

    Introduction Since the identification of the dystrophin gene in 1986, a cure for Duchenne muscular dystrophy (DMD) has yet to be discovered. Presently, there are a number of genetic-based therapies in development aimed at restoration and/or repair of the primary defect. However, growing understanding of the pathophysiological consequences of dystrophin absence has revealed several promising downstream targets for the development of therapeutics. Areas covered In this review, we discuss various strategies for DMD therapy targeting downstream consequences of dystrophin absence including loss of muscle mass, inflammation, fibrosis, calcium overload, oxidative stress, and ischemia. The rationale of each approach and the efficacy of drugs in preclinical and clinical studies are discussed. Expert opinion For the last 30 years, effective DMD drug therapy has been limited to corticosteroids, which are associated with a number of negative side effects. Our knowledge of the consequences of dystrophin absence that contribute to DMD pathology has revealed several potential therapeutic targets. Some of these approaches may have potential to improve or slow disease progression independently or in combination with genetic-based approaches. The applicability of these pharmacological therapies to DMD patients irrespective of their genetic mutation, as well as the potential benefits even for advanced stage patients warrants their continued investigation. PMID:28670506

  7. Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.

    Science.gov (United States)

    Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi

    2017-03-21

    This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon

  8. Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise

    DEFF Research Database (Denmark)

    Kristensen, Dorte Enggaard; Albers, Peter Hjorth; Prats, Clara

    2015-01-01

    are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstream targets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of m. vastus lateralis from healthy men before and after two exercise trials; A) continuous cycling......AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggest muscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK and downstream targets during exercise has not been proven. We hypothesized that AMPK subunits...... (CON) 30 min at 69 ± 1% VO2peak or B) interval cycling (INT) 30 min with 6 × 1.5 min high-intense bouts peaking at 95 ± 2% VO2peak . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (-71%) was found. α1 , α2 , β2 and γ1 AMPK expression was similar between fibre types...

  9. Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

    2010-01-01

    Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

  10. Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast

    NARCIS (Netherlands)

    Kuijper, Arno; Groep, P. van der; Wall, E. van der; Diest, P.J. van

    2005-01-01

    INTRODUCTION Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance

  11. Transcription Factors Expressed in Lateral Organ Boundaries: Identification of Downstream Targets

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    Springer, Patricia S

    2010-07-12

    The processes of lateral organ initiation and patterning are central to the generation of mature plant form. Characterization of the molecular mechanisms underlying these processes is essential to our understanding of plant development. Communication between the shoot apical meristem and initiating organ primordia is important both for functioning of the meristem and for proper organ patterning, and very little is known about this process. In particular, the boundary between meristem and leaf is emerging as a critical region that is important for SAM maintenance and regulation of organogenesis. The goal of this project was to characterize three boundary-expressed genes that encode predicted transcription factors. Specifically, we have studied LATERAL ORGAN BOUNDARIES (LOB), LATERAL ORGAN FUSION1 (LOF1), and LATERAL ORGAN FUSION2 (LOF2). LOB encodes the founding member of the LOB-DOMAIN (LBD) plant-specific DNA binding transcription factor family and LOF1 and LOF2 encode paralogous MYB-domain transcription factors. We characterized the genetic relationship between these three genes and other boundary and meristem genes. We also used an ectopic inducible expression system to identify direct targets of LOB.

  12. The Drosophila FoxA ortholog Fork head regulates growth and gene expression downstream of Target of rapamycin.

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    Margret H Bülow

    2010-12-01

    Full Text Available Forkhead transcription factors of the FoxO subfamily regulate gene expression programs downstream of the insulin signaling network. It is less clear which proteins mediate transcriptional control exerted by Target of rapamycin (TOR signaling, but recent studies in nematodes suggest a role for FoxA transcription factors downstream of TOR. In this study we present evidence that outlines a similar connection in Drosophila, in which the FoxA protein Fork head (FKH regulates cellular and organismal size downstream of TOR. We find that ectopic expression and targeted knockdown of FKH in larval tissues elicits different size phenotypes depending on nutrient state and TOR signaling levels. FKH overexpression has a negative effect on growth under fed conditions, and this phenotype is not further exacerbated by inhibition of TOR via rapamycin feeding. Under conditions of starvation or low TOR signaling levels, knockdown of FKH attenuates the size reduction associated with these conditions. Subcellular localization of endogenous FKH protein is shifted from predominantly cytoplasmic on a high-protein diet to a pronounced nuclear accumulation in animals with reduced levels of TOR or fed with rapamycin. Two putative FKH target genes, CG6770 and cabut, are transcriptionally induced by rapamycin or FKH expression, and silenced by FKH knockdown. Induction of both target genes in heterozygous TOR mutant animals is suppressed by mutations in fkh. Furthermore, TOR signaling levels and FKH impact on transcription of the dFOXO target gene d4E-BP, implying a point of crosstalk with the insulin pathway. In summary, our observations show that an alteration of FKH levels has an effect on cellular and organismal size, and that FKH function is required for the growth inhibition and target gene induction caused by low TOR signaling levels.

  13. An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

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    Chang-Min Lee

    Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

  14. Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action.

    Science.gov (United States)

    Nagaraj, Karthik; Lapkina-Gendler, Lena; Sarfstein, Rive; Gurwitz, David; Pasmanik-Chor, Metsada; Laron, Zvi; Yakar, Shoshana; Werner, Haim

    2018-01-30

    Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered. Recent genomic analyses identified a series of metabolic genes that are overrepresented in patients with LS. Given the augmented expression of these genes in a low IGF1 milieu, we hypothesized that they may constitute targets for IGF1 action. Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor, being commonly silenced by genetic or epigenetic events in cancer cells. Consistent with its enhanced expression in LS, we provide evidence that TXNIP gene expression is negatively regulated by IGF1. These results were corroborated in animal studies. In addition, we show that oxidative and glucose stresses led to marked increases in TXNIP expression. Supplementation of IGF1 attenuated TXNIP levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of TXNIP Augmented TXNIP expression in LS may account for cancer protection in this condition. Finally, TXNIP levels could be potentially useful in the clinic as a predictive or diagnostic biomarker for IGF1R-targeted therapies.

  15. Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Wada, Takeyoshi; Asahi, Toru; Sawamura, Naoya

    2016-01-01

    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. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.

  16. Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Takeyoshi [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Asahi, Toru [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Sawamura, Naoya, E-mail: naoya.sawamura@gmail.com [Faculty of Science and Engineering, Waseda University, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan); Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480 (Japan)

    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. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.

  17. Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2.

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    David A Roeseler

    Full Text Available Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during embryogenesis. Gain-and loss-of-function studies in several vertebrate species have demonstrated a requirement for Gbx2 in development of the anterior hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the target genes through which GBX2 exerts its effects remain obscure. Using chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq analysis in a human prostate cancer cell line, we identified cis-regulatory elements bound by GBX2 to provide insight into its direct downstream targets. The analysis revealed more than 286 highly significant candidate target genes, falling into various functional groups, of which 51% are expressed in the nervous system. Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1, and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and USH2A, and are plausible candidates contributing to the developmental defects in Gbx2(-/- mice. We show through gel shift analyses that sequences within the promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/- embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates transcriptional activity through the promoter of EEF1A1, suggesting that GBX2 could also regulate gene expression indirectly via EEF1A. Taken together, our studies show that GBX2 plays a dynamic role in development and diseases.

  18. Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets

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    Learta Oruqaj

    2016-10-01

    Full Text Available Aims: Parathyroid hormone-related protein (PTHrP is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined. Materials and methods: C57 bl/6 mice were randomized to either normal diet or high fat diet at an age of 6 weeks. Seven months later, the mice were euthanized and the lung was removed and frozen in fluid nitrogen until use. Samples were analyzed by real-time RT-PCR and western blot. Leptin deficient mice were used to investigate the effect of leptin on pulmonary expression of PTHrP more directly. A subgroup of mice with and without high fat diet underwent in vivo ischemia (45 min and reperfusion (4 weeks. Finally, experiments were repeated with prolonged high-fat diet. Key findings: High fat diet increased plasma leptin levels by 30.4% and the pulmonary mRNA expression of PTHrP (1,447-fold, PTH-1 receptor (4.21-fold, and PTHrP-downstream targets ADRP (7.54-fold and PPARγ (5.27-fold. Pulmonary PTHrP expression was reduced in leptin deficient mice by 88% indicating leptin dependent regulation. High fat diet further improved changes in pulmonary adaptation caused by ischemia/reperfusion (1.48-fold increased PTH-1 receptor protein expression. These effects were lost during prolonged high fat diet. Significance: This study established that physiological regulation of leptin plasma levels by high fat diet affects the pulmonary PTHrP expression and of PTHrP downstream targets. Modification of pulmonary expression of PTH-1 receptors by high fat diet after myocardial infarction suggests that the identified interaction may

  19. Potential downstream target genes of aberrant ETS transcription factors are differentially affected in Ewing's sarcoma and prostate carcinoma.

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    Maria J Camões

    Full Text Available FLI1 and ERG, the major ETS transcription factors involved in rearrangements in the Ewing's sarcoma family of tumors (ESFT and in prostate carcinomas (PCa, respectively, belong to the same subfamily, having 98% sequence identity in the DNA binding domain. We therefore decided to investigate whether the aberrant transcription factors in both malignancies have some common downstream targets. We crossed a publicly available list of all putative EWSR1-FLI1 target genes in ESFT with our microarray expression data on 24 PCa and 6 non-malignant prostate tissues (NPT and choose four genes among the top-most differentially expressed between PCa with (PCa ERG+ and without (PCa ETS- ETS fusion genes (HIST1H4L, KCNN2, ECRG4 and LDOC1, as well as four well-validated direct targets of the EWSR1-FLI1 chimeric protein in ESFT (NR0B1, CAV1, IGFBP3 and TGFBR2. Using quantitative expression analysis in 16 ESFT and seven alveolar rhabdomyosarcomas (ARMS, we were able to validate the four genes previously described as direct targets of the EWSR1-FLI1 oncoprotein, showing overexpression of CAV1 and NR0B1 and underexpression of IGFBP3 and TGFBR2 in ESFT as compared to ARMS. Although none of these four genes showed significant expression differences between PCa ERG+ and PCa ETS-, CAV1, IGFBP3 and TGFBR2 were less expressed in PCa in an independent series of 56 PCa and 15 NPT, as also observed for ECRG4 and LDOC1, suggesting a role in prostate carcinogenesis in general. On the other hand, we demonstrate for the first time that both HIST1H4L and KCNN2 are significantly overexpressed in PCa ERG+ and that ERG binds to the promoter of these genes. Conversely, KCNN2 was found underexpressed in ESFT relative to ARMS, suggesting that the EWSR1-ETS oncoprotein may have the opposite effect of ERG rearrangements in PCa. We conclude that aberrant ETS transcription factors modulate target genes differently in ESFT and PCa.

  20. Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.

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    Tohru Fujiwara

    Full Text Available Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10 and idiopathic thrombocytopenic purpura (n = 13, and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01. Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.

  1. Pituitary adenylate cyclase activating polypeptide (PACAP signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target.

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    Tamás Juhász

    Full Text Available Pituitary adenylate cyclase activating polypeptide (PACAP is an important neurotrophic factor influencing differentiation of neuronal elements and exerting protecting role during traumatic injuries or inflammatory processes of the central nervous system. Although increasing evidence is available on its presence and protecting function in various peripheral tissues, little is known about the role of PACAP in formation of skeletal components. To this end, we aimed to map elements of PACAP signalling in developing cartilage under physiological conditions and during oxidative stress. mRNAs of PACAP and its receptors (PAC1,VPAC1, VPAC2 were detectable during differentiation of chicken limb bud-derived chondrogenic cells in micromass cell cultures. Expression of PAC1 protein showed a peak on days of final commitment of chondrogenic cells. Administration of either the PAC1 receptor agonist PACAP 1-38, or PACAP 6-38 that is generally used as a PAC1 antagonist, augmented cartilage formation, stimulated cell proliferation and enhanced PAC1 and Sox9 protein expression. Both variants of PACAP elevated the protein expression and activity of the Ca-calmodulin dependent Ser/Thr protein phosphatase calcineurin. Application of PACAPs failed to rescue cartilage formation when the activity of calcineurin was pharmacologically inhibited with cyclosporine A. Moreover, exogenous PACAPs prevented diminishing of cartilage formation and decrease of calcineurin activity during oxidative stress. As an unexpected phenomenon, PACAP 6-38 elicited similar effects to those of PACAP 1-38, although to a different extent. On the basis of the above results, we propose calcineurin as a downstream target of PACAP signalling in differentiating chondrocytes either in normal or pathophysiological conditions. Our observations imply the therapeutical perspective that PACAP can be applied as a natural agent that may have protecting effect during joint inflammation and/or may promote

  2. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-01-01

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

  3. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2014-09-12

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

  4. Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.

    Science.gov (United States)

    Xiong, Fangjie; Zhang, Rui; Meng, Zhigang; Deng, Kexuan; Que, Yumei; Zhuo, Fengping; Feng, Li; Guo, Sundui; Datla, Raju; Ren, Maozhi

    2017-01-01

    The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis. Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR-suppressed plants could be rescued by up-regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR-S6K2 signaling in Arabidopsis. By combining pharmacological with genetic and biochemical approaches, we determined that the TOR-S6K2-BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  5. Stromal progesterone receptors mediate induction of Indian Hedgehog (IHH) in uterine epithelium and its downstream targets in uterine stroma.

    Science.gov (United States)

    Simon, Liz; Spiewak, Kerry A; Ekman, Gail C; Kim, Jaeyeon; Lydon, John P; Bagchi, Milan K; Bagchi, Indrani C; DeMayo, Francesco J; Cooke, Paul S

    2009-08-01

    Uterine receptivity to embryo implantation depends on appropriate progesterone (P4) and estrogen stimulation. P4 rapidly stimulates production of the morphogen Indian hedgehog (IHH) in murine uterine epithelium as well as downstream molecules in the hedgehog pathway such as Patched homolog 1 (PTCH1) and nuclear receptor subfamily 2, group F, member 2 (NR2F2) in uterine stroma. Studies using IHH-null mice indicate that IHH is obligatory for the normal P4 response in the uterus. To determine whether IHH induction in uterine epithelium is mediated through P4 receptor (PR) in epithelium (E) and/or stroma (S), we produced tissue recombinants using uteri from neonatal PR knockout (ko) mice and wild-type (wt) mice containing PR in S and/or E or lacking PR altogether using a tissue recombinant methodology and assessed their response to P4. In tissue recombinants containing wt-S (wt-S + wt-E and wt-S + ko-E), P4 induced Ihh mRNA expression at 6 h that was 6-fold greater than in oil-treated controls (P Ihh mRNA expression was unaffected by P4 in ko-S + ko-E and ko-S + wt-E grafts despite epithelial PR expression in the latter. Nr2f2 and Ptch1 mRNA expression was similar in that it was stimulated by P4 only in recombinants containing stromal PR. These results indicate that stromal PR is both necessary and sufficient for P4 stimulation of epithelial IHH as well as downstream events such as PTCH1 and NR2F2 increases in stroma.

  6. Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes

    Directory of Open Access Journals (Sweden)

    Hall Ross S

    2010-04-01

    Full Text Available Abstract Background New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Saccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset. Results Cross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from Ancylostoma caninum and Haemonchus contortus - two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools. Conclusions The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.

  7. Experimental and numerical study on the flow pattern of the ADS windowless spallation target with a second free surface downstream using model fluid water

    International Nuclear Information System (INIS)

    Xiong, Zhenqin; Gu, Hanyang; Gong, Shenjie

    2015-01-01

    Highlights: • A windowless spallation target with a buffer tank is tested. • Shape of the main free surface is recorded. • Streamline is obtained with the planar laser induced fluorescence method. • Stability of free surface is improved by the buffer tank. • Flow structure is simulated using RNG k-e turbulence model and VOF model. - Abstract: The windowless spallation targets are a promising design solution for accelerator driven system (ADS) due to their extended life compared to the spallation targets with a window. Keeping the stability of the free surface and reducing the recirculation zone is one of the key tasks for the design of a windowless spallation target. A windowless spallation target with a second free surface downstream (which is a buffer used to stabilize the main free surface of the flow) is studied experimentally and numerically using water at atmospheric pressure. By using planar laser induced fluorescence technique (LIF), the flow pattern inside the target zone is visualized for Reynolds numbers varying between 3.5 × 10 4 and 7.0 × 10 4 and pressure differences from 100 to 804 Pa. The experimental results reveal that the stability of the free surface is improved by adding a buffer in the downstream thus making it easier to control the height of the surface. The effect of the pressure difference between the void above the second free surface (high pressure side) and beam pipe (low pressure side) on the flow pattern is analyzed, as well as the inlet flow rate. The height of the surface length decreases with an increase in the pressure difference. The formation of the spallation zone is simulated with Fluent using the LES turbulence model and VOF model. The interface predicted agrees well with the experimental results

  8. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory

    NARCIS (Netherlands)

    Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

    2017-01-01

    Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either

  9. Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

    Science.gov (United States)

    Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

    2017-05-23

    The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  10. The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals.

    Science.gov (United States)

    Su, Y C; Maurel-Zaffran, C; Treisman, J E; Skolnik, E Y

    2000-07-01

    We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct

  11. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets

    Science.gov (United States)

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore; Parrinello, Nunziatina; Fløyel, Tina; Ragusa, Marco; Rabuazzo, Agata Maria; Størling, Joachim; Purrello, Francesco; Di Pietro, Cinzia; Purrello, Michele

    2014-01-01

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic α and β cell lines (αTC1-6 and βTC1) with proinflammatory cytokines IL-1β, IFN-γ, and TNF-α at doses that specifically induce apoptosis of βTC1 significantly increased the amount of mRNA and protein encoded by Cebpa and its proapoptotic targets, Arl6ip5 and Tnfrsf10b, in βTC1 but not in αTC1-6. Cebpa knockdown in βTC1 significantly decreased cytokine-induced apoptosis, together with the amount of Arl6ip5 and Tnfrsf10b. Analysis of the network comprising CEBPA, its targets, their first interactants, and proteins encoded by genes known to regulate cytokine-induced apoptosis in pancreatic β cells (genes from the apoptotic machinery and from MAPK and NFkB pathways) revealed that CEBPA, ARL6IP5, TNFRSF10B, TRAF2, and UBC are the top five central nodes. In silico analysis further suggests TRAF2 as trait d'union node between CEBPA and the NFkB pathway. Our results strongly suggest that Cebpa is a key regulator within the apoptotic network activated in pancreatic β cells during insulitis, and Arl6ip5, Tnfrsf10b, Traf2, and Ubc are key executioners of this program. PMID:24943845

  12. Salicylic Acid Suppresses Jasmonic Acid Signaling Downstream of SCFCOI1-JAZ by Targeting GCC Promoter Motifs via Transcription Factor ORA59[C][W][OA

    Science.gov (United States)

    Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C.; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P.; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C.M.; Pieterse, Corné M.J.

    2013-01-01

    Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCFCOI1, which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCFCOI1-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59. PMID:23435661

  13. Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59.

    Science.gov (United States)

    Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C M; Pieterse, Corné M J

    2013-02-01

    Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCF(COI1), which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCF(COI1)-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59.

  14. Improved Algorithms for Blending Dam Releases to Meet Downstream Water-Temperature Targets in the CE-QUAL-W2 Water-Quality Model

    Science.gov (United States)

    Rounds, S. A.; Buccola, N. L.

    2014-12-01

    The two-dimensional (longitudinal, vertical) water-quality model CE-QUAL-W2, version 3.7, was enhanced with new features to help dam operators and managers efficiently explore and optimize potential solutions for temperature management downstream of thermally stratified reservoirs. Such temperature management often is accomplished by blending releases from multiple dam outlets that access water of different temperatures at different depths in the reservoir. The original blending algorithm in this version of the model was limited to mixing releases from two outlets at a time, and few constraints could be imposed. The new enhanced blending algorithm allows the user to (1) specify a time-series of target release temperatures, (2) designate from 2 to 10 floating or fixed-elevation outlets for blending, (3) impose maximum head constraints as well as minimum and maximum flow constraints for any blended outlet, and (4) set a priority designation for each outlet that allows the model to choose which outlets to use and how to balance releases among them. The modified model was tested against a previously calibrated model of Detroit Lake on the North Santiam River in northwestern Oregon, and the results compared well. The enhanced model code is being used to evaluate operational and structural scenarios at multiple dam/reservoir systems in the Willamette River basin in Oregon, where downstream temperature management for endangered fish is a high priority for resource managers and dam operators. These updates to the CE-QUAL-W2 blending algorithm allow scenarios involving complicated dam operations and/or hypothetical outlet structures to be evaluated more efficiently with the model, with decreased need for multiple/iterative model runs or preprocessing of model inputs to fully characterize the operational constraints.

  15. Elevated YAP and its downstream targets CCN1 and CCN2 in basal cell carcinoma: impact on keratinocyte proliferation and stromal cell activation.

    Science.gov (United States)

    Quan, Taihao; Xu, Yiru; Qin, Zhaoping; Robichaud, Patrick; Betcher, Stephanie; Calderone, Ken; He, Tianyuan; Johnson, Timothy M; Voorhees, John J; Fisher, Gary J

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional co-activator of hippo signaling pathway, which plays an important role in organ size control and tumorigenesis. Here we report that YAP and its downstream transcriptional targets CCN1 and CCN2 are markedly elevated in keratinocytes in human skin basal cell carcinoma tumor islands. In human keratinocytes, knockdown of YAP significantly reduced expression of CCN1 and CCN2, and repressed proliferation and survival. This inhibition of proliferation and survival was rescued by restoration of CCN1 expression, but not by CCN2 expression. In basal cell carcinoma stroma, CCN2-regulated genes type I collagen, fibronectin, and α-smooth muscle actin were highly expressed. Furthermore, atomic force microscopy revealed increased tissue stiffness in basal cell carcinoma stroma compared to normal dermis. These data provide evidence that up-regulation of YAP in basal cell carcinoma impacts both aberrant keratinocyte proliferation, via CCN1, and tumor stroma cell activation and stroma remodeling, via CCN2. Targeting YAP and/or CCN1 and CCN2 may provide clinical benefit in basal cell carcinoma. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data

    Directory of Open Access Journals (Sweden)

    Xin Li

    2008-06-01

    Full Text Available Abstract Background Target genes of a transcription factor (TF Pou5f1 (Oct3/4 or Oct4, which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES cells, have previously been identified based on their response to Pou5f1 manipulation and occurrence of Chromatin-immunoprecipitation (ChIP-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation. Results To reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR Pou5f1 suppression and published ChIP data, we identified 420 tentative target genes (TTGs for Pou5f1. The majority of TTGs (372 were down-regulated after Pou5f1 suppression, indicating that the Pou5f1 functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that Sox2 and Nanog also function mostly as transcription activators in cooperation with Pou5f1. Conclusion We have identified the most reliable sets of direct target genes for key pluripotency genes – Pou5f1, Sox2, and Nanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly.

  17. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory.

    Science.gov (United States)

    Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

    2017-12-21

    Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA. Copyright © 2017 by the Congress of Neurological Surgeons

  18. Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

    Science.gov (United States)

    Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

    2017-07-01

    We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

  19. The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

    Directory of Open Access Journals (Sweden)

    Baca Chan

    2017-05-01

    Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

  20. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia Essential Oil on Central Nervous System Targets

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    Víctor López

    2017-05-01

    Full Text Available Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide.

  1. Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets

    Science.gov (United States)

    López, Víctor; Nielsen, Birgitte; Solas, Maite; Ramírez, Maria J.; Jäger, Anna K.

    2017-01-01

    Lavender essential oil is traditionally used and approved by the European Medicines Agency (EMA) as herbal medicine to relieve stress and anxiety. Some animal and clinical studies reveal positive results in models of anxiety and depression although very little research has been done on molecular mechanisms. Our work consisted of evaluating the effects of lavender (Lavandula angustifolia) essential oil on central nervous system well-established targets, such as MAO-A, SERT, GABAAand NMDA receptors as well as in vitro models of neurotoxicity. The results showed that lavender essential oil and its main components exert affinity for the glutamate NMDA-receptor in a dose-dependent manner with an IC50 value of 0.04 μl/mL for lavender oil. In addition, lavender and linalool were also able to bind the serotonin transporter (SERT) whereas they did not show affinity for GABAA-benzodiazepine receptor. In three different models of neurotoxicity, lavender did not enhance the neurotoxic insult and improved viability of SH-SY5Y cells treated with hydrogen peroxide. According to our data, the anxiolytic and antidepressant-like effects attributed to lavender may be due to an antagonism on the NMDA-receptor and inhibition of SERT. This study suggests that lavender essential oil may exert pharmacological properties via modulating the NMDA receptor, the SERT as well as neurotoxicity induced by hydrogen peroxide. PMID:28579958

  2. Mining predicted essential genes of Brugia malayi for nematode drug targets.

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar

    Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.

  3. Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular Targets in the Antidepressant-Like Effect of Creatine.

    Science.gov (United States)

    Cunha, Mauricio P; Budni, Josiane; Ludka, Fabiana K; Pazini, Francis L; Rosa, Julia Macedo; Oliveira, Ágatha; Lopes, Mark W; Tasca, Carla I; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2016-07-01

    Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 μg/mouse, icv, PI3K inhibitor), ZnPP (10 μg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 μg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 μg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

  4. Eukaryotic initiation factor 2α--a downstream effector of mammalian target of rapamycin--modulates DNA repair and cancer response to treatment.

    Directory of Open Access Journals (Sweden)

    Liron Tuval-Kochen

    Full Text Available In an effort to circumvent resistance to rapamycin--an mTOR inhibitor--we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells. Addition of salubrinal--an inhibitor of eIF2α dephosphorylation--decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival. Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones. Similar to salubrinal--the phosphomimetic eIF2α variant--S51D--increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair. Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids. In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor--vorinostat. Finally, the catalytic competitive inhibitor of mTOR--Ku-0063794--increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation. These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for

  5. CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM).

    Science.gov (United States)

    Debnath, Anjan; Calvet, Claudia M; Jennings, Gareth; Zhou, Wenxu; Aksenov, Alexander; Luth, Madeline R; Abagyan, Ruben; Nes, W David; McKerrow, James H; Podust, Larissa M

    2017-12-01

    Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.

  6. CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM.

    Directory of Open Access Journals (Sweden)

    Anjan Debnath

    2017-12-01

    Full Text Available Primary Amoebic Meningoencephalitis (PAM is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51 target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.

  7. Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death

    Directory of Open Access Journals (Sweden)

    Fasel Nicolas

    2010-11-01

    Full Text Available Abstract Apoptosis is a normal component of the development and health of multicellular organisms. However, apoptosis is now considered a prerogative of unicellular organisms, including the trypanosomatids of the genera Trypanosoma spp. and Leishmania spp., causative agents of some of the most important neglected human diseases. Trypanosomatids show typical hallmarks of apoptosis, although they lack some of the key molecules contributing to this process in metazoans, like caspase genes, Bcl-2 family genes and the TNF-related family of receptors. Despite the lack of these molecules, trypanosomatids appear to have the basic machinery to commit suicide. The components of the apoptotic execution machinery of these parasites are slowly coming into light, by targeting essential processes and pathways with different apoptogenic agents and inhibitors. This review will be confined to the events known to drive trypanosomatid parasites to apoptosis.

  8. MEDICI: Mining Essentiality Data to Identify Critical Interactions for Cancer Drug Target Discovery and Development | Office of Cancer Genomics

    Science.gov (United States)

    Protein-protein interactions (PPIs) mediate the transmission and regulation of oncogenic signals that are essential to cellular proliferation and survival, and thus represent potential targets for anti-cancer therapeutic discovery. Despite their significance, there is no method to experimentally disrupt and interrogate the essentiality of individual endogenous PPIs. The ability to computationally predict or infer PPI essentiality would help prioritize PPIs for drug discovery and help advance understanding of cancer biology.

  9. Analysis of essential Arabidopsis nuclear genes encoding plastid-targeted proteins.

    Science.gov (United States)

    Savage, Linda J; Imre, Kathleen M; Hall, David A; Last, Robert L

    2013-01-01

    The Chloroplast 2010 Project (http://www.plastid.msu.edu/) identified and phenotypically characterized homozygous mutants in over three thousand genes, the majority of which encode plastid-targeted proteins. Despite extensive screening by the community, no homozygous mutant alleles were available for several hundred genes, suggesting that these might be enriched for genes of essential function. Attempts were made to generate homozygotes in ~1200 of these lines and 521 of the homozygous viable lines obtained were deposited in the Arabidopsis Biological Resource Center (http://abrc.osu.edu/). Lines that did not yield a homozygote in soil were tested as potentially homozygous lethal due to defects either in seed or seedling development. Mutants were characterized at four stages of development: developing seed, mature seed, at germination, and developing seedlings. To distinguish seed development or seed pigment-defective mutants from seedling development mutants, development of seeds was assayed in siliques from heterozygous plants. Segregating seeds from heterozygous parents were sown on supplemented media in an attempt to rescue homozygous seedlings that could not germinate or survive in soil. Growth of segregating seeds in air and air enriched to 0.3% carbon dioxide was compared to discover mutants potentially impaired in photorespiration or otherwise responsive to CO2 supplementation. Chlorophyll fluorescence measurements identified CO2-responsive mutants with altered photosynthetic parameters. Examples of genes with a viable mutant allele and one or more putative homozygous-lethal alleles were documented. RT-PCR of homozygotes for potentially weak alleles revealed that essential genes may remain undiscovered because of the lack of a true null mutant allele. This work revealed 33 genes with two or more lethal alleles and 73 genes whose essentiality was not confirmed with an independent lethal mutation, although in some cases second leaky alleles were identified.

  10. Analysis of essential Arabidopsis nuclear genes encoding plastid-targeted proteins.

    Directory of Open Access Journals (Sweden)

    Linda J Savage

    Full Text Available The Chloroplast 2010 Project (http://www.plastid.msu.edu/ identified and phenotypically characterized homozygous mutants in over three thousand genes, the majority of which encode plastid-targeted proteins. Despite extensive screening by the community, no homozygous mutant alleles were available for several hundred genes, suggesting that these might be enriched for genes of essential function. Attempts were made to generate homozygotes in ~1200 of these lines and 521 of the homozygous viable lines obtained were deposited in the Arabidopsis Biological Resource Center (http://abrc.osu.edu/. Lines that did not yield a homozygote in soil were tested as potentially homozygous lethal due to defects either in seed or seedling development. Mutants were characterized at four stages of development: developing seed, mature seed, at germination, and developing seedlings. To distinguish seed development or seed pigment-defective mutants from seedling development mutants, development of seeds was assayed in siliques from heterozygous plants. Segregating seeds from heterozygous parents were sown on supplemented media in an attempt to rescue homozygous seedlings that could not germinate or survive in soil. Growth of segregating seeds in air and air enriched to 0.3% carbon dioxide was compared to discover mutants potentially impaired in photorespiration or otherwise responsive to CO2 supplementation. Chlorophyll fluorescence measurements identified CO2-responsive mutants with altered photosynthetic parameters. Examples of genes with a viable mutant allele and one or more putative homozygous-lethal alleles were documented. RT-PCR of homozygotes for potentially weak alleles revealed that essential genes may remain undiscovered because of the lack of a true null mutant allele. This work revealed 33 genes with two or more lethal alleles and 73 genes whose essentiality was not confirmed with an independent lethal mutation, although in some cases second leaky alleles

  11. Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liao, Hsien-Ching; Chen, Mei-Yu

    2012-02-24

    The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3(ts) mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3(ts) mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600-840) of Avo1 and a C-terminal region of Ypk2. Ypk2(334-677), a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2(334-677) in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.

  12. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    Directory of Open Access Journals (Sweden)

    Eberhart Charles G

    2010-11-01

    Full Text Available Abstract Background The Sonic hedgehog (Shh signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63% and primary astrocytoma tumor samples (32%, but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes.

  13. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    International Nuclear Information System (INIS)

    Shahi, Mehdi H; Afzal, Mohammad; Sinha, Subrata; Eberhart, Charles G; Rey, Juan A; Fan, Xing; Castresana, Javier S

    2010-01-01

    The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes

  14. Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor

    Science.gov (United States)

    Keane, Maureen; Deyo, Steve; Abosch, Aviva; Bajwa, Jawad A.; Johnson, Matthew D.

    2012-08-01

    Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.

  15. Essential pathway identification: from in silico analysis to potential antifungal targets in Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Thykær, Jette; Andersen, Mikael Rørdam; Baker, S. E.

    2009-01-01

    with the reactions, we identified orthologous candidate essential genes in Aspergillus fumigatus. Our predictions are validated in part by the modes of action for some antifungal drugs and by molecular genetic studies of essential genes in A. fumigatus and other fungi. The use of metabolic models to predict...... of 1190 biochemically unique reactions that are associated with 871 open reading frames. Through a systematic in silico deletion of single metabolic reactions using this model, several essential metabolic pathways were identified for A. niger. A total of 138 reactions were identified as being essential...... biochemical reactions during growth on a minimal glucose medium. The majority of the reactions grouped into essential biochemical pathways covering cell wall biosynthesis, amino acid biosynthesis, energy metabolism and purine and pyrimidine metabolism. Based on the A. niger open reading frames associated...

  16. Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension.

    OpenAIRE

    Smithies, O; Maeda, N

    1995-01-01

    Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These di...

  17. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Ze-Jun Wang

    2018-05-01

    Full Text Available Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, oral administration, and aromatherapy. Recent studies show that essential oils are emerging as a promising source for modulation of the GABAergic system and sodium ion channels. This review summarizes the recent findings regarding the pharmacological properties of essential oils and compounds from the oils and the mechanisms underlying their effects. Specifically, the review focuses on the essential oils and their constituents targeting the GABAergic system and sodium channels, and their antinociceptive, anxiolytic, and anticonvulsant properties. Some constituents target transient receptor potential (TRP channels to exert analgesic effects. Some components could interact with multiple therapeutic target proteins, for example, inhibit the function of sodium channels and, at the same time, activate GABAA receptors. The review concentrates on perspective compounds that could be better candidates for new drug development in the control of pain and anxiety syndromes.

  18. Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature.

    Science.gov (United States)

    Slemc, Lucija; Kunej, Tanja

    2016-11-01

    Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes (HIF-1α-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1α-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS ( http://apps.webofknowledge.com/ ), HGNC ( http://www.genenames.org/ ), NCBI ( http://www.ncbi.nlm.nih.gov/ ), Ensemblv.84 ( http://www.ensembl.org/index.html ), DAVID Bioinformatics Resources ( https://david.ncifcrf.gov /), and Disease Ontology database ( http://disease-ontology.org/ ). From 51 papers, we collected 98 HIF-1α TGs found to be associated with 20 pathways, including metabolism of carbohydrates and pathways in cancer. Reanalysis of genomic coordinates of published HREs (hypoxia response elements) revealed six polymorphisms within HRE sites (HRE-SNPs): ABCG2, ACE, CA9, and CP. Due to large heterogeneity of results presentation in scientific literature, we also propose a first step towards reporting standardization of HIF-1α-target interactions consisting of ten relevant data types. Suggested minimal checklist for reporting will enable faster development of a complete catalog of HIF-1α-TGs, data sharing, bioinformatics analyses, and setting novel more targeted hypotheses. The proposed format for data standardization is not yet complete but presents a baseline for further optimization of the protocol with additional details, for example, regarding the experimental validation.

  19. India's Downstream Petroleum Sector

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This study provides a holistic examination of pricing and investment dynamics in India's downstream petroleum sector. It analyses the current pricing practices, highlights the tremendous fiscal cost of current pricing and regulatory arrangements, and examines the sectoral investment dynamics. It also looks at potential paths towards market-based reform along which the Indian government may move, while at the same time protecting energy market access for India's large poor population.

  20. Fluorescence Imaging Analysis of Upstream Regulators and Downstream Targets of STAT3 in Melanoma Precursor Lesions Obtained from Patients Before and After Systemic Low-Dose Interferon-α Treatment

    Directory of Open Access Journals (Sweden)

    Amanda Pfaff Smith

    2003-01-01

    Full Text Available Atypical nevi are the precursors and risk markers of melanoma. Apart from persistently monitoring these nevocytic lesions and resecting them at the earliest signs of clinical changes, there is as yet no systemic clinical treatment available to interfere with their progression to melanoma. To explore clinical treatments that might interfere with and possibly prevent atypical nevus progression, a previous study documented that 3 months systemic low-dose interferon-α (IFN-α treatment of patients with a clinical history of melanoma and numerous atypical nevi, led to inactivation of the STAT1 and STAT3 transcription factors in atypical nevi. Based upon this finding, we initiated a second study to determine whether systemic low-dose IFN-α treatment also impairs the expression of upstream regulators and downstream targets of STAT1 and STAT3 in atypical nevi. Using cyanine dye-conjugated antibodies, fluorescence imaging analysis revealed expression of JAK2, JNK1, AKT1, NF-κB, and IFN-αβ receptor in benign and atypical nevi, and early- and advanced-stage melanomas. To determine possible changes in the level of expression of these molecules in atypical nevi, excised before and after 3 months of systemic low-dose IFN-α treatment, newly designed optical imaging software was used to quantitate the captured fluorescent hybridization signals on a cell-by-cell basis and across an entire nevus section. The results of this analysis did not provide evidence that systemic low-dose IFN-α treatment alters the level of expression of upstream regulators or downstream targets of STAT1 and STAT3.

  1. Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes.

    Science.gov (United States)

    Chang, Hsin-Fang; Bzeih, Hawraa; Schirra, Claudia; Chitirala, Praneeth; Halimani, Mahantappa; Cordat, Emmanuelle; Krause, Elmar; Rettig, Jens; Pattu, Varsha

    2016-09-15

    CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process. Copyright © 2016 by The American Association of Immunologists, Inc.

  2. Targeting Plant Ethylene Responses by Controlling Essential Protein-Protein Interactions in the Ethylene Pathway.

    Science.gov (United States)

    Bisson, Melanie M A; Groth, Georg

    2015-08-01

    The gaseous plant hormone ethylene regulates many processes of high agronomic relevance throughout the life span of plants. A central element in ethylene signaling is the endoplasmic reticulum (ER)-localized membrane protein ethylene insensitive2 (EIN2). Recent studies indicate that in response to ethylene, the extra-membranous C-terminal end of EIN2 is proteolytically processed and translocated from the ER to the nucleus. Here, we report that the conserved nuclear localization signal (NLS) mediating nuclear import of the EIN2 C-terminus provides an important domain for complex formation with ethylene receptor ethylene response1 (ETR1). EIN2 lacking the NLS domain shows strongly reduced affinity for the receptor. Interaction of EIN2 and ETR1 is also blocked by a synthetic peptide of the NLS motif. The corresponding peptide substantially reduces ethylene responses in planta. Our results uncover a novel mechanism and type of inhibitor interfering with ethylene signal transduction and ethylene responses in plants. Disruption of essential protein-protein interactions in the ethylene signaling pathway as shown in our study for the EIN2-ETR1 complex has the potential to guide the development of innovative ethylene antagonists for modern agriculture and horticulture. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  3. The Peroxisomal Targeting Signal 1 in sterol carrier protein 2 is autonomous and essential for receptor recognition

    Directory of Open Access Journals (Sweden)

    Bond Charles S

    2011-03-01

    Full Text Available Abstract Background The majority of peroxisomal matrix proteins destined for translocation into the peroxisomal lumen are recognised via a C-terminal Peroxisomal Target Signal type 1 by the cycling receptor Pex5p. The only structure to date of Pex5p in complex with a cargo protein is that of the C-terminal cargo-binding domain of the receptor with sterol carrier protein 2, a small, model peroxisomal protein. In this study, we have tested the contribution of a second, ancillary receptor-cargo binding site, which was found in addition to the characterised Peroxisomal Target Signal type 1. Results To investigate the function of this secondary interface we have mutated two key residues from the ancillary binding site and analyzed the level of binding first by a yeast-two-hybrid assay, followed by quantitative measurement of the binding affinity and kinetics of purified protein components and finally, by in vivo measurements, to determine translocation capability. While a moderate but significant reduction of the interaction was found in binding assays, we were not able to measure any significant defects in vivo. Conclusions Our data therefore suggest that at least in the case of sterol carrier protein 2 the contribution of the second binding site is not essential for peroxisomal import. At this stage, however, we cannot rule out that other cargo proteins may require this ancillary binding site.

  4. Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

    Science.gov (United States)

    Carlson, Kaitlin S; Whitney, Meredith S; Gadziola, Marie A; Deneris, Evan S; Wesson, Daniel W

    2016-01-01

    The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 ( Tph2 ), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

  5. Downstream product marketing

    International Nuclear Information System (INIS)

    Pantelidis, J.

    1997-01-01

    Petro-Canada's views regarding energy deregulation were presented. Their experience with gasoline retailing and their response to competition was also discussed. Petro-Canada regards deregulation as a good thing in terms of its promotion of fair competition. Industrial and residential consumers of energy will benefit from more efficient and innovative service. Today's consumers are very well informed about existing energy products and while they are incredibly price sensitive, they still want to buy value. The relevance of brand names in a competitive market was examined. One reaction to the demanding customer has been to augment the base product (the fuel) with other things, such as convenience store items, car washes, specialized bay businesses and promotional offerings. Petro-Canada has been successful in improving sales volumes with these sales strategies, and profits achieved indicate good target audience acceptance. Shareholders and the board of directors also appear to be in agreement with the Corporation's performance to date

  6. An array of Escherichia coli clones over-expressing essential proteins: A new strategy of identifying cellular targets of potent antibacterial compounds

    International Nuclear Information System (INIS)

    Xu, H. Howard; Real, Lilian; Bailey, Melissa Wu

    2006-01-01

    With the advancement of high throughput screening, it has become easier and faster to discover hit compounds that inhibit proliferation of bacterial cells. However, development in technologies used to identify cellular targets of potent antibacterial inhibitors has lagged behind. Here, we describe a novel strategy of target identification for antibacterial inhibitors using an array of Escherichia coli clones each over-expressing one essential protein. In a proof-of-concept study, eight essential genes were cloned into pLex5BA vector under the control of an inducible promoter. Over-expression of target proteins was confirmed. For two clones, one over-expressing FabI and the other over-expressing MurA enzymes, the host cells became 17- and 139-fold more resistant to the specific inhibitors triclosan and phosphomycin, respectively, while the susceptibility of other clones towards these inhibitors remained unchanged after induction of gene expression. Target identification via target protein over-expression was demonstrated using both mixed clone and individual clone assay formats

  7. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting

    KAUST Repository

    Abdel-Haleem, Alyaa M.; Hefzi, Hooman; Mineta, Katsuhiko; Gao, Xin; Gojobori, Takashi; Palsson, Bernhard O.; Lewis, Nathan E.; Jamshidi, Neema

    2018-01-01

    and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species

  8. Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line

    International Nuclear Information System (INIS)

    Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O.; Coughlin, Jason J.; Garofoli, Daniella; Ewen, Catherine; Davidson, Courtney E.; Ghaffari, Mazyar; Kane, Kevin P.; Lacy, Paige; Logan, Michael R.; Befus, A. Dean; Bleackley, R. Chris; Moqbel, Redwan

    2008-01-01

    Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Our data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 μg/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo

  9. DARHT-II Downstream Transport Beamline

    International Nuclear Information System (INIS)

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

    2001-01-01

    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 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

  10. Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

    NARCIS (Netherlands)

    Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

    2014-01-01

    Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways

  11. Continuous downstream processing of biopharmaceuticals.

    Science.gov (United States)

    Jungbauer, Alois

    2013-08-01

    Continuous manufacturing has been applied in many different industries but has been pursued reluctantly in biotechnology where the batchwise process is still the standard. A shift to continuous operation can improve productivity of a process and substantially reduce the footprint. Continuous operation also allows robust purification of labile biomolecules. A full set of unit operations is available to design continuous downstream processing of biopharmaceuticals. Chromatography, the central unit operation, is most advanced in respect to continuous operation. Here, the problem of 'batch' definition has been solved. This has also paved the way for implementation of continuous downstream processing from a regulatory viewpoint. Economic pressure, flexibility, and parametric release considerations will be the driving force to implement continuous manufacturing strategies in future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom.

    Science.gov (United States)

    Berger, Philipp; Sirkowski, Erich E; Scherer, Steven S; Suter, Ueli

    2004-11-01

    Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.

  13. Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

    Science.gov (United States)

    Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

    2017-11-01

    The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting.

    Directory of Open Access Journals (Sweden)

    Alyaa M Abdel-Haleem

    2018-01-01

    Full Text Available Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale metabolic models (GeMMs of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1, choline, and pantothenate (vitamin B5 metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.

  15. Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting

    KAUST Repository

    Abdel-Haleem, Alyaa M.

    2018-01-04

    Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale models (GEMs) of metabolism for five life cycle stages and five species of Plasmodium spanning the blood, transmission, and mosquito stages. The stage-specific models of Plasmodium falciparum uncovered stage-dependent changes in central carbon metabolism and predicted potential targets that could affect several life cycle stages. The species-specific models further highlight differences between experimental animal models and the human-infecting species. Comparisons between human- and rodent-infecting species revealed differences in thiamine (vitamin B1), choline, and pantothenate (vitamin B5) metabolism. Thus, we show that genome-scale analysis of multiple stages and species of Plasmodium can prioritize potential drug targets that could be both anti-malarials and transmission blocking agents, in addition to guiding translation from non-human experimental disease models.

  16. Operational optimization in the downstream; Otimizacao operacional no downstream

    Energy Technology Data Exchange (ETDEWEB)

    Silberman, Luis; Cunha, Filipe Silveira Ramos da [Petroleo Ipiranga, Porto Alegre, RS (Brazil)

    2004-07-01

    On the present competitive down stream's market, there is a great necessity of optimization aiming to guarantee the best price and quality of our clients. Our goal is to attend these expectations while we guarantee an efficient operation. The greatest question is how far we are from the ideal model. This way, a lot of projects have been executed during the last years aiming the operational optimization of all our activities. We divide the projects in 4 areas: Logistic (new modals distribution), Transport (transport optimization - quality and more deliveries with less trucks), Client Support (Internet Ipiranga and Support Center), Distribution Terminals Productivity (automation and environment). This work intend to present our ideal, perfect and complete Downstream Operation model. We will talk about how close we are of this ideal model and we will present the projects that we had already developed and implanted on the automation of the terminals and the logistics area. (author)

  17. Dead end1 is an essential partner of NANOS2 for selective binding of target RNAs in male germ cell development.

    Science.gov (United States)

    Suzuki, Atsushi; Niimi, Yuki; Shinmyozu, Kaori; Zhou, Zhi; Kiso, Makoto; Saga, Yumiko

    2016-01-01

    RNA-binding proteins (RBPs) play important roles for generating various cell types in many developmental processes, including eggs and sperms. Nanos is widely known as an evolutionarily conserved RNA-binding protein implicated in germ cell development. Mouse NANOS2 interacts directly with the CCR4-NOT (CNOT) deadenylase complex, resulting in the suppression of specific RNAs. However, the mechanisms involved in target specificity remain elusive. We show that another RBP, Dead end1 (DND1), directly interacts with NANOS2 to load unique RNAs into the CNOT complex. This interaction is mediated by the zinc finger domain of NANOS2, which is essential for its association with target RNAs. In addition, the conditional deletion of DND1 causes the disruption of male germ cell differentiation similar to that observed in Nanos2-KO mice. Thus, DND1 is an essential partner for NANOS2 that leads to the degradation of specific RNAs. We also present the first evidence that the zinc finger domain of Nanos acts as a protein-interacting domain for another RBP, providing a novel insight into Nanos-mediated germ cell development. © 2015 The Authors.

  18. Downstream behavior of fission products

    International Nuclear Information System (INIS)

    Johnson, I.; Farahat, M.K.; Settle, J.L.; Johnson, C.E.; Ritzman, R.

    1986-01-01

    The downstream behavior of fission products has been investigated by injecting mixtures of CsOH, CsI, and Te into a flowing steam/hydrogen stream and determining the physical and chemical changes that took place as the gaseous mixture flowed down a reaction duct on which a temperature gradient (1000 0 to 200 0 C) had been imposed. Deposition on the wall of the duct occurred by vapor condensation in the higher temperature regions and by aerosol deposition in the remainder of the duct. Reactions in the gas stream between CsOH and CsI and between CsOH and Te had an effect on the vapor condensation. The aerosol was characterized by the use of impingement tabs placed in the gas stream

  19. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this

  20. E2F target genes: unraveling the biology

    DEFF Research Database (Denmark)

    Bracken, Adrian P; Ciro, Marco; Cocito, Andrea

    2004-01-01

    The E2F transcription factors are downstream effectors of the retinoblastoma protein (pRB) pathway and are required for the timely regulation of numerous genes essential for DNA replication and cell cycle progression. Several laboratories have used genome-wide approaches to discover novel target...

  1. A downstream voyage with mercury

    Science.gov (United States)

    Heinz, Gary

    2016-01-01

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

  2. GRP1 PH Domain, Like AKT1 PH Domain, Possesses a Sentry Glutamate Residue Essential for Specific Targeting to Plasma Membrane PI(3,4,5)P3

    Science.gov (United States)

    Pilling, Carissa; Landgraf, Kyle E.; Falke, Joseph J.

    2011-01-01

    During the appearance of the signaling lipid PI(3,4,5)P3, an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P3-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P2 and bind the rare PI(3,4,5)P3 target lipid with sufficiently high affinity. Our previous study of the E17K mutant of protein kinase B (AKT1) PH domain, together with evidence from Carpten et al (1), revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P2, thereby playing an essential role in specific PI(3,4,5)P3 targeting (2). The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P3-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P2 affinity and constitutive plasma membrane targeting. To test this hypothesis the present study investigates the E345 residue, a putative sentry glutamate, of General Receptor for Phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into GRP1 PH domain enhances PI(4,5)P2 affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P2 releases E345K GRP1 PH domain into the cytoplasm and the efficiency of this release increases when target Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K (1, 3). Analysis of available PH domain structures suggests that a lone glutamate residue (or, in some cases an aspartate) is a common, perhaps ubiquitous, feature of PI(3,4,5)P3-specific binding

  3. Rare earth industries: Downstream business

    International Nuclear Information System (INIS)

    2011-01-01

    The value chain of the rare earths business involves mining, extraction, processing, refining and the manufacture of an extensive range of downstream products which find wide applications in such industries including aerospace, consumer electronics, medical, military, automotive, renewable wind and solar energy and telecommunications. In fact the entire gamut of the high-tech industries depends on a sustainable supply of rare earths elements. The explosive demand in mobile phones is an excellent illustration of the massive potential that the rare earths business offers. In a matter of less than 20 years, the number of cell phones worldwide has reached a staggering 5 billion. Soon, going by the report of their growth in sales, the world demand for cell phones may even exceed the global population. Admittedly, the rare earths business does pose certain risks. Top among the risks are the health and safety risks. The mining, extraction and refining of rare earths produce residues and wastes which carry health and safety risks. The residues from the extraction and refining are radioactive, while their effluent waste streams do pose pollution risks to the receiving rivers and waterways. But, as clearly elaborated in a recent report by IAEA experts, there are technologies and systems available to efficiently mitigate such risks. The risks are Rare Earth manageable. However, it is crucial that the risk and waste management procedures are strictly followed and adhered to. This is where effective monitoring and surveillance throughout the life of all such rare earths facilities is crucial. Fortunately, Malaysia's regulatory standards on rare earths follow international standards. In some areas, Malaysia's regulatory regime is even more stringent than the international guidelines. (author)

  4. Lateral and vertical distribution of downstream migrating juvenile sea lamprey

    Science.gov (United States)

    Sotola, V. Alex; Miehls, Scott M.; Simard, Lee G.; Marsden, J. Ellen

    2018-01-01

    Sea lamprey is considered an invasive and nuisance species in the Laurentian Great Lakes, Lake Champlain, and the Finger Lakes of New York and is a major focus of control efforts. Currently, management practices focus on limiting the area of infestation using barriers to block migratory adults, and lampricides to kill ammocoetes in infested tributaries. No control efforts currently target the downstream-migrating post-metamorphic life stage which could provide another management opportunity. In order to apply control methods to this life stage, a better understanding of their downstream movement patterns is needed. To quantify spatial distribution of downstream migrants, we deployed fyke and drift nets laterally and vertically across the stream channel in two tributaries of Lake Champlain. Sea lamprey was not randomly distributed across the stream width and lateral distribution showed a significant association with discharge. Results indicated that juvenile sea lamprey is most likely to be present in the thalweg and at midwater depths of the stream channel. Further, a majority of the catch occurred during high flow events, suggesting an increase in downstream movement activity when water levels are higher than base flow. Discharge and flow are strong predictors of the distribution of out-migrating sea lamprey, thus managers will need to either target capture efforts in high discharge areas of streams or develop means to guide sea lamprey away from these areas.

  5. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids.

    Science.gov (United States)

    Dickinson, Jared M; Fry, Christopher S; Drummond, Micah J; Gundermann, David M; Walker, Dillon K; Glynn, Erin L; Timmerman, Kyle L; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

    2011-05-01

    The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

  6. Coriandrum sativum L. (Coriander essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    Directory of Open Access Journals (Sweden)

    Irlan de Almeida Freires

    Full Text Available Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis, as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  7. WA7 - View from downstream

    CERN Multimedia

    1977-01-01

    With this set-up the Annecy (LAPP)-CERN-Copenhagen(Niels Bohr Institute)-Genova-Oslo-University College London Collaboration investigated large-angle elastic scattering of charged mesons and antiprotons on protons, first at 20 and 30 GeV/c, later at 50 GeV/c. The beam H1 (from top) passes two CEDAR counters (centre) before entering the one-metre long liquid hydrogen target, partly inside a magnet of 1.56 T, with a field volume of about 1.50x0.75x1.50 m3. In the foreground one sees on the left the hadron calorimeter of the 'slow' arm; on the right, are scintillation hodoscopes and behind them, a treshold Cerenkov counter of the 'fast' arm.

  8. Chemical composition, toxicity and non-target effects of Pinus kesiya essential oil: An eco-friendly and novel larvicide against malaria, dengue and lymphatic filariasis mosquito vectors.

    Science.gov (United States)

    Govindarajan, Marimuthu; Rajeswary, Mohan; Benelli, Giovanni

    2016-07-01

    Mosquitoes (Diptera: Culicidae) are vectors of important parasites and pathogens causing death, poverty and social disability worldwide, with special reference to tropical and subtropical countries. The overuse of synthetic insecticides to control mosquito vectors lead to resistance, adverse environmental effects and high operational costs. Therefore, the development of eco-friendly control tools is an important public health challenge. In this study, the mosquito larvicidal activity of Pinus kesiya leaf essential oil (EO) was evaluated against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti and the lymphatic filariasis vector Culex quinquefasciatus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy. GC-MS revealed that the P. kesiya EO contained 18 compounds. Major constituents were α-pinene, β-pinene, myrcene and germacrene D. In acute toxicity assays, the EO showed significant toxicity against early third-stage larvae of An. stephensi, Ae. aegypti and Cx. quinquefasciatus, with LC50 values of 52, 57, and 62µg/ml, respectively. Notably, the EO was safer towards several aquatic non-target organisms Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC50 values ranging from 4135 to 8390µg/ml. Overall, this research adds basic knowledge to develop newer and safer natural larvicides from Pinaceae plants against malaria, dengue and filariasis mosquito vectors. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Richard T Timms

    Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.

  10. PknB remains an essential and a conserved target for drug development in susceptible and MDR strains of M. Tuberculosis.

    Science.gov (United States)

    Gupta, Anamika; Pal, Sudhir K; Pandey, Divya; Fakir, Najneen A; Rathod, Sunita; Sinha, Dhiraj; SivaKumar, S; Sinha, Pallavi; Periera, Mycal; Balgam, Shilpa; Sekar, Gomathi; UmaDevi, K R; Anupurba, Shampa; Nema, Vijay

    2017-08-18

    The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India. A total of 116 isolates from North, South and West India were used in the study with a variable profile of their susceptibilities towards streptomycin, isoniazid, rifampicin, ethambutol and ofloxacin. Isolates were also spoligotyped in order to find if the conservation pattern of pknB gene remain consistent or differ with different spoligotypes. The impact of variation as found in the study was analyzed using Molecular dynamics simulations. The sequencing results with 115/116 isolates revealed the conserved nature of pknB sequences irrespective of their susceptibility status and spoligotypes. The only variation found was in one strains wherein pnkB sequence had G to A mutation at 664 position translating into a change of amino acid, Valine to Isoleucine. After analyzing the impact of this sequence variation using Molecular dynamics simulations, it was observed that the variation is causing no significant change in protein structure or the inhibitor binding. Hence, the study endorses that PknB is an ideal target for drug development and there is no pre-existing or induced resistance with respect to the sequences involved in inhibitor binding. Also if the mutation that we are reporting for the first time is found again in subsequent work, it should be checked with phenotypic profile before drawing the conclusion that it would affect the activity in any way. Bioinformatics analysis in our study

  11. The Optimedin gene is a downstream target of Pax6

    Czech Academy of Sciences Publication Activity Database

    Grinchuk, O.; Kozmik, Zbyněk; Wu, X.; Tomarev, S.

    2005-01-01

    Roč. 280, č. 42 (2005), s. 35228-35237 ISSN 0021-9258 R&D Projects: GA ČR GA204/04/1358 Institutional research plan: CEZ:AV0Z50520514 Keywords : Pax6 * optimedin * promotor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.854, year: 2005

  12. The role of headwater streams in downstream water quality

    Science.gov (United States)

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

    2007-01-01

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

  13. Upstream-downstream cooperation approach in Guanting Reservoir watershed.

    Science.gov (United States)

    Yang, Zhi-Feng; Zhang, Wen-Guo

    2005-01-01

    A case study is introduced and discussed concerning water dispute of misuse and pollution between up- and down-stream parts. The relations between water usage and local industrial structures are analyzed. Results show it is important to change industrial structures of the target region along with controlling water pollution by technical and engineering methods. Three manners of upstream-downstream cooperation are presented and discussed based on the actual conditions of Guangting Reservoir watershed. Two typical scenarios are supposed and studied along with the local plan on water resources development. The best solution for this cooperation presents a good way to help the upstream developing in a new pattern of eco-economy.

  14. Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.

    Science.gov (United States)

    Goldstine, Jimena V; Nahas, Shareef; Gamo, Kristin; Gartler, Stanley M; Hansen, R Scott; Roelfsema, Jeroen H; Gatti, Richard A; Marahrens, York

    2006-04-08

    Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is

  15. Philippines' downstream sector poised for growth

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    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

  16. Essential Tremor

    Science.gov (United States)

    ... Treatment There is no definitive cure for essential tremor. Symptomatic drug therapy may include propranolol or other beta blockers and primidone, an anticonvulsant drug. Eliminating tremor "triggers" ...

  17. KNIME essentials

    CERN Document Server

    Bakos, Gábor

    2013-01-01

    KNIME Essentials is a practical guide aimed at getting the results you want, as quickly as possible.""Knime Essentials"" is written for data analysts looking to quickly get up to speed using the market leader in data processing tools, KNIME. No knowledge of KNIME is required, but we will assume that you have some background in data processing.

  18. Scleroglucan: Fermentative Production, Downstream Processing and Applications

    Directory of Open Access Journals (Sweden)

    Shrikant A. Survase

    2007-01-01

    Full Text Available Exopolysaccharides produced by a variety of microorganisms find multifarious industrial applications in foods, pharmaceutical and other industries as emulsifiers, stabilizers, binders, gelling agents, lubricants, and thickening agents. One such exopolysaccharide is scleroglucan, produced by pure culture fermentation from filamentous fungi of genus Sclerotium. The review discusses the properties, fermentative production, downstream processing and applications of scleroglucan.

  19. The downstream industry compared to market

    International Nuclear Information System (INIS)

    Chevallier, B.

    2010-01-01

    J.L. Schilansky introduces here the difficult question of the downstream industry compared to market in recalling the recent structural changes (behaviour of customers, behaviour of the USA- and China-governments), the increase of the European and French regulations, the climatic change and the conjectural impact of the crisis on the refining industry. (O.M.)

  20. Astronomy essentials

    CERN Document Server

    Brass, Charles O

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Astronomy includes the historical perspective of astronomy, sky basics and the celestial coordinate systems, a model and the origin of the solar system, the sun, the planets, Kepler'

  1. Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors.

    Directory of Open Access Journals (Sweden)

    Hannah Karlsson

    Full Text Available 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.

  2. India's Downstream Petroleum Sector

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This study provides a holistic examination of pricing and investment dynamics in India's downstream petroleum sector. It analyses the current pricing practices, highlights the tremendous fiscal cost of current pricing and regulatory arrangements, and examines the sectoral investment dynamics. It also looks at potential paths towards market-based reform along which the Indian government may move, while at the same time protecting energy market access for India's large poor population.

  3. Specific intracellular signal transduction pathways downstream of CSF-1 receptors: their relationship to breast cancer local recurrence and distant relapse in vivo. Potential targets for the development of new, specific anti-breast cancer therapies to improve local control and block metastatic spread?

    International Nuclear Information System (INIS)

    Kacinski, Barry M.; Sapi, Eva; Flick, Maryann B.; Turner, Bruce; Perrotta, Peter; Maher, M. Grey; Carter, Darryl; Haffy, Bruce

    1997-01-01

    analogues such as Matrigel. Agents which pharmacologically mimic a TYR-721 →PHE mutation by interfering with the activation of elements of intracellular signal transduction downstream of this tyrosine (PI-3 kinase. pp70-S6kinase) produced similar effects. In contrast, a TYR-809→PHE mutation was without effect on anchorage independent growth or the generation of pulmonary metastases but did completely abolish protease production and rendered the transfected cells unable to invade basement membrane analogues. In a parallel line of research, we employed antibodies which recognized CSF-1R and a novel antibody we prepared to recognize CSF-1R only when phosphorylated on TYR-721 in a study of 80 T1 and T2 breast cancer patients treated with tylectomy and primary radiation therapy. Strong staining with the generic anti-CSF-1R antibody correlated strongly with local relapse (P values <.03) in this patient cohort. Staining with the antibody specific for CSF-1R phosphorylated at TYR-721 was not associated with local relapse but did correlate with the development of distant metastases in this cohort of patients, particularly in axillary node-negative patients (P < .006). Conclusion: In summary, our observations demonstrate that CSF-1R activation and phosphorylation at specific tyrosines regulates invasiveness, anchorage, independent growth and tumorigenicity in vitro and in animal models and correlates with metastatic relapse in vivo. They also suggest that such intracellular signaling pathways--particularly those triggered by the phosphorylation of TYR-721 of CSF-1R--are logical targets for the development of a new class of anti-cancer agents which specifically block breast cancer cell metastatic potential without perturbing other normal cellular metabolic processes

  4. Insight into PreImplantation Factor (PIF* mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP through essential RIKP [corrected] binding site.

    Directory of Open Access Journals (Sweden)

    Eytan R Barnea

    Full Text Available Endogenous PIF, upon which embryo development is dependent, is secreted only by viable mammalian embryos, and absent in non-viable ones. Synthetic PIF (sPIF administration promotes singly cultured embryos development and protects against their demise caused by embryo-toxic serum. To identify and characterize critical sPIF-embryo protein interactions novel biochemical and bio-analytical methods were specifically devised.FITC-PIF uptake/binding by cultured murine and equine embryos was examined and compared with scrambled FITC-PIF (control. Murine embryo (d10 lysates were fractionated by reversed-phase HPLC, fractions printed onto microarray slides and probed with Biotin-PIF, IDE and Kv1.3 antibodies, using fluorescence detection. sPIF-based affinity column was developed to extract and identify PIF-protein interactions from lysates using peptide mass spectrometry (LC/MS/MS. In silico evaluation examined binding of PIF to critical targets, using mutation analysis.PIF directly targets viable cultured embryos as compared with control peptide, which failed to bind. Multistep Biotin-PIF targets were confirmed by single-step PIF-affinity column based isolation. PIF binds protein disulfide isomerases a prolyl-4-hydroxylase β-subunit, (PDI, PDIA4, PDIA6-like containing the antioxidant thioredoxin domain. PIF also binds protective heat shock proteins (70&90, co-chaperone, BAG-3. Remarkably, PIF targets a common RIKP [corrected] site in PDI and HSP proteins. Further, single PIF amino acid mutation significantly reduced peptide-protein target bonding. PIF binds promiscuous tubulins, neuron backbones and ACTA-1,2 visceral proteins. Significant anti-IDE, while limited anti-Kv1.3b antibody-binding to Biotin-PIF positive lysates HPLC fractions were documented.Collectively, data identifies PIF shared targets on PDI and HSP in the embryo. Such are known to play a critical role in protecting against oxidative stress and protein misfolding. PIF-affinity-column is a

  5. Essential AOP

    DEFF Research Database (Denmark)

    De Fraine, Bruno; Ernst, Erik; Südholt, Mario

    2010-01-01

    Aspect-oriented programming (AOP) has produced interesting language designs, but also ad hoc semantics that needs clarification. We contribute to this clarification with a calculus that models essential AOP, both simpler and more general than existing formalizations. In AOP, advice may intercept...

  6. Highcharts essentials

    CERN Document Server

    Shahid, Bilal

    2014-01-01

    If you are a web developer with a basic knowledge of HTML, CSS, and JavaScript and want to quickly get started with this web charting technology, this is the book for you. This book will also serve as an essential guide to those who have probably used a similar library and are now looking at migrating to Highcharts.

  7. Swift essentials

    CERN Document Server

    Blewitt, Alex

    2014-01-01

    Whether you are a seasoned Objective-C developer or new to the Xcode platform, Swift Essentials will provide you with all you need to know to get started with the language. Prior experience with iOS development is not necessary, but will be helpful to get the most out of the book.

  8. Emory University: MEDICI (Mining Essentiality Data to Identify Critical Interactions) for Cancer Drug Target Discovery and Development | Office of Cancer Genomics

    Science.gov (United States)

    The CTD2 Center at Emory University has developed a computational methodology to combine high-throughput knockdown data with known protein network topologies to infer the importance of protein-protein interactions (PPIs) for the survival of cancer cells.  Applying these data to the Achilles shRNA results, the CCLE cell line characterizations, and known and newly identified PPIs provides novel insights for potential new drug targets for cancer therapies and identifies important PPI hubs.

  9. Dart essentials

    CERN Document Server

    Sikora, Martin

    2015-01-01

    This book is targeted at expert programmers in JavaScript who want to learn Dart quickly. Some previous experience with OOP programming in other languages and a good knowledge of JavaScript are assumed.

  10. A proteomic screen reveals the mitochondrial outer membrane protein Mdm34p as an essential target of the F-box protein Mdm30p.

    Science.gov (United States)

    Ota, Kazuhisa; Kito, Keiji; Okada, Satoshi; Ito, Takashi

    2008-10-01

    Ubiquitination plays various critical roles in eukaryotic cellular regulation and is mediated by a cascade of enzymes including ubiquitin protein ligase (E3). The Skp1-Cullin-F-box protein complex comprises the largest E3 family, in each member of which a unique F-box protein binds its targets to define substrate specificity. Although genome sequencing uncovers a growing number of F-box proteins, most of them have remained as "orphans" because of the difficulties in identification of their substrates. To address this issue, we tested a quantitative proteomic approach by combining the stable isotope labeling by amino acids in cell culture (SILAC), parallel affinity purification (PAP) that we had developed for efficient enrichment of ubiquitinated proteins, and mass spectrometry (MS). We applied this SILAC-PAP-MS approach to compare ubiquitinated proteins between yeast cells with and without over-expressed Mdm30p, an F-box protein implicated in mitochondrial morphology. Consequently, we identified the mitochondrial outer membrane protein Mdm34p as a target of Mdm30p. Furthermore, we found that mitochondrial defects induced by deletion of MDM30 are not only recapitulated by a mutant Mdm34p defective in interaction with Mdm30p but alleviated by ubiquitination-mimicking forms of Mdm34p. These results indicate that Mdm34p is a physiologically important target of Mdm30p.

  11. DOWNSTREAM ECOCIDE FROM UPSTREAM WATER PIRACY

    OpenAIRE

    Miah Muhammad Adel

    2012-01-01

    Upstream India and downstream Bangladesh share more than 50 international rivers. India has set up water diversion constructions in more than 50% of these rivers, the largest one being on the Bangladeshâs northwest upon the Ganges River, puts Bangladeshâs Gangetic ecosystem at stake. In some border rivers, India has set up groins on her side of river banks. Also, Indian side pumps Bangladesh river water stealthily from border-rivers. Further, India is constructing another dam and reservoir up...

  12. Linux Essentials

    CERN Document Server

    Smith, Roderick W

    2012-01-01

    A unique, full-color introduction to Linux fundamentals Serving as a low-cost, secure alternative to expensive operating systems, Linux is a UNIX-based, open source operating system. Full-color and concise, this beginner's guide takes a learning-by-doing approach to understanding the essentials of Linux. Each chapter begins by clearly identifying what you will learn in the chapter, followed by a straightforward discussion of concepts that leads you right into hands-on tutorials. Chapters conclude with additional exercises and review questions, allowing you to reinforce and measure your underst

  13. Essential SQLAlchemy

    CERN Document Server

    Copeland, Rick

    2008-01-01

    Essential SQLAlchemy introduces a high-level open-source code library that makes it easier for Python programmers to access relational databases such as Oracle, DB2, MySQL, PostgreSQL, and SQLite. SQLAlchemy has become increasingly popular since its release, but it still lacks good offline documentation. This practical book fills the gap, and because a developer wrote it, you get an objective look at SQLAlchemy's tools rather than an advocate's description of all the "cool" features. SQLAlchemy includes both a database server-independent SQL expression language and an object-relational mappe

  14. Prezi essentials

    CERN Document Server

    Sinclair, Domi

    2014-01-01

    If you want to learn Prezi, and specifically design within Prezi, this is the book for you. Perhaps you already know a bit about Prezi but have never used it, or perhaps you have used Prezi before but want to learn how to incorporate your own custom design elements. In either case, this book will get you up and running quickly. It would be helpful to have a bit of familiarity with basic design concepts and the use of Prezi, but prior experience is not essential.

  15. An Arabidopsis chloroplast-targeted Hsp101 homologue, APG6, has an essential role in chloroplast development as well as heat-stress response.

    Science.gov (United States)

    Myouga, Fumiyoshi; Motohashi, Reiko; Kuromori, Takashi; Nagata, Noriko; Shinozaki, Kazuo

    2006-10-01

    Analysis of albino or pale-green (apg) mutants is important for identifying nuclear genes responsible for chloroplast development and pigment synthesis. We have identified 38 apg mutants by screening 11 000 Arabidopsis Ds-tagged lines. One mutant, apg6, contains a Ds insertion in a gene encoding APG6 (ClpB3), a homologue of the heat-shock protein Hsp101 (ClpB1). We isolated somatic revertants and identified two Ds-tagged and one T-DNA-tagged mutant alleles of apg6. All three alleles gave the same pale-green phenotype. These results suggest that APG6 is important for chloroplast development. The APG6 protein contains a transit peptide and is localized in chloroplasts. The plastids of apg6 pale-green cells were smaller than those of the wild type, and contained undeveloped thylakoid membranes. APG6 mRNA accumulated in response to heat shock in various organs, but not in response to other abiotic stresses. Under normal conditions, APG6 is constitutively expressed in the root tips, the organ boundary region, the reproductive tissues of mature plants where plastids exist as proplastids, and slightly in the stems and leaves. In addition, constitutive overexpression of APG6 in transgenic plants inhibited chloroplast development and resulted in a mild pale-green phenotype. The amounts of chloroplast proteins related to photosynthesis were markedly decreased in apg6 mutants. These results suggest that APG6 functions as a molecular chaperone involved in plastid differentiation mediating internal thylakoid membrane formation and conferring thermotolerance to chloroplasts during heat stress. The APG6 protein is not only involved in heat-stress response in chloroplasts, but is also essential for chloroplast development.

  16. Downstream process options for the ABE fermentation.

    Science.gov (United States)

    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. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. The jet membrane-experiment: downstream sampling

    International Nuclear Information System (INIS)

    Campargue, R.

    1976-01-01

    The invasion separation effect of the free jet structure was found in 1966 at Saclay. In the Downstream Sampling Configuration patended by Campargue (1967), the light fraction is withdrawn from the supersonic central core, by skimming the separating free jet. From experimental and theoretical results obtained for gas and isotopic mixtures, the following points linked to operation and equipment costs, are considered: system description; influence of mass ratio, expansion ratio, nature of separating gas, ratio of upflow to separating jet flow, rarefaction. Fron an uninteresting aspect of Jet Membrane (elimination of background penetration), a new principle has been discovered to produce nozzle beams which may be of great interest for other separation processes involving free jets and/or molecular beams [fr

  18. The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

    Energy Technology Data Exchange (ETDEWEB)

    Hornig, Julia; Choi, K. Yeon; McGregor, Alistair, E-mail: mcgregor@medicine.tamhsc.edu

    2017-04-15

    Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234–474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.

  19. Cerebral Targeting of Acupuncture at Combined Acupoints in Treating Essential Hypertension: An Rs-fMRI Study and Curative Effect Evidence

    Directory of Open Access Journals (Sweden)

    Yanjie Wang

    2016-01-01

    Full Text Available The study attempted to explore that the synergistic effect of acupoints combination is not a simple superposition of single acupoint’s effect by comparing and analyzing the changes of blood pressure (BP, SF-36, and brain regions after acupuncture treatment. 47 patients were randomly divided into LR3+KI3 group, LR3 group, and KI3 group. Subjects received Rs-fMRI scan, BP measurement, and SF-36 questionnaires before and after treatment and short-term acupuncture treatment. After treatment, there were no significant differences in BP and SF-36 among 3 groups, compared to the case before treatment, SBP of 3 groups decreased, and DBP significantly decreased while vitality and mental health significantly increased in LR3+KI3 group. Both number and scopes of changes of brain regions in LR3+KI3 group were the largest, which mainly included BAs 3, 4, 8, 19, 21, 24, 32, 44, and 45. In conclusion, acupuncture at LR3+KI3 may auxiliarily reduce BP and improve the vitality and mental health of patients, and the changes of brain regions were related to somatesthesia, movement, vision, audition, emotion and mood, language, memory, etc. BAs 4, 9, 10, 24, 31, 32, and 46 may be the targeting brain areas of acupuncture in assisting hypotension. It is suggested that acupoints combination of LR3+KI3 maybe generates a synergistic effect, and it is not simple sum of single acupoint effect.

  20. The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting

    Science.gov (United States)

    Hornig, Julia; Choi, K. Yeon; McGregor, Alistair

    2017-01-01

    Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234–474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection. PMID:28189970

  1. Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Vincent van den Boom

    2016-01-01

    Full Text Available Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here, we find that the non-canonical PRC1.1 complex, as identified by mass-spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces cell proliferation in vitro and delays or even abrogates leukemogenesis in vivo in humanized xenograft models. PRC1.1 components are significantly overexpressed in primary AML CD34+ cells. Besides a set of genes that is targeted by PRC1 and PRC2, ChIP-seq studies show that PRC1.1 also binds a distinct set of genes that are devoid of H3K27me3, suggesting a gene-regulatory role independent of PRC2. This set encompasses genes involved in metabolism, which have transcriptionally active chromatin profiles. These data indicate that PRC1.1 controls specific genes involved in unique cell biological processes required for leukemic cell viability.

  2. Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation.

    Directory of Open Access Journals (Sweden)

    Cong-Hui Yao

    2018-03-01

    Full Text Available It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO for energy. Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I (CPT1 with low concentrations of etomoxir, the proliferation rate of various cancer cells was unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that high concentrations of etomoxir (200 μM have an off-target effect of inhibiting complex I of the electron transport chain. Surprisingly, however, when FAO was reduced further by genetic knockdown of CPT1, the proliferation rate of these same cells decreased nearly 2-fold and could not be restored by acetate or octanoic acid supplementation. Moreover, CPT1 knockdowns had altered mitochondrial morphology and impaired mitochondrial coupling, whereas cells in which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic profiling of mitochondria isolated from CPT1 knockdowns showed depleted concentrations of complex structural and signaling lipids. Additionally, expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore mitochondrial coupling. Taken together, these results suggest that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO.

  3. Essential astrophysics

    CERN Document Server

    Lang, Kenneth R

    2013-01-01

    Essential Astrophysics is a book to learn or teach from, as well as a fundamental reference volume for anyone interested in astronomy and astrophysics. It presents astrophysics from basic principles without requiring any previous study of astronomy or astrophysics. It serves as a comprehensive introductory text, which takes the student through the field of astrophysics in lecture-sized chapters of basic physical principles applied to the cosmos. This one-semester overview will be enjoyed by undergraduate students with an interest in the physical sciences, such as astronomy, chemistry, engineering or physics, as well as by any curious student interested in learning about our celestial science. The mathematics required for understanding the text is on the level of simple algebra, for that is all that is needed to describe the fundamental principles. The text is of sufficient breadth and depth to prepare the interested student for more advanced specialized courses in the future. Astronomical examples are provide...

  4. Downstream Processing of Synechocystis for Biofuel Production

    Science.gov (United States)

    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

  5. Microbial production of scleroglucan and downstream processing

    Directory of Open Access Journals (Sweden)

    Natalia Alejandra Castillo

    2015-10-01

    Full Text Available 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 beta-1,3-beta-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 EPS 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.

  6. RFX2 is a candidate downstream amplifier of A-MYB regulation in mouse spermatogenesis

    Directory of Open Access Journals (Sweden)

    Kistler Malathi K

    2009-12-01

    Full Text Available Abstract Background Mammalian spermatogenesis involves formation of haploid cells from the male germline and then a complex morphological transformation to generate motile sperm. Focusing on meiotic prophase, some tissue-specific transcription factors are known (A-MYB or suspected (RFX2 to play important roles in modulating gene expression in pachytene spermatocytes. The current work was initiated to identify both downstream and upstream regulatory connections for Rfx2. Results Searches of pachytene up-regulated genes identified high affinity RFX binding sites (X boxes in promoter regions of several new genes: Adam5, Pdcl2, and Spag6. We confirmed a strong promoter-region X-box for Alf, a germ cell-specific variant of general transcription factor TFIIA. Using Alf as an example of a target gene, we showed that its promoter is stimulated by RFX2 in transfected cells and used ChIP analysis to show that the promoter is occupied by RFX2 in vivo. Turning to upstream regulation of the Rfx2 promoter, we identified a cluster of three binding sites (MBS for the MYB family of transcription factors. Because testis is one of the few sites of A-myb expression, and because spermatogenesis arrests in pachytene in A-myb knockout mice, the MBS cluster implicates Rfx2 as an A-myb target. Electrophoretic gel-shift, ChIP, and co-transfection assays all support a role for these MYB sites in Rfx2 expression. Further, Rfx2 expression was virtually eliminated in A-myb knockout testes. Immunohistology on testis sections showed that A-MYB expression is up-regulated only after pachytene spermatocytes have clearly moved away from the tubule wall, which correlates with onset of RFX2 expression, whereas B-MYB expression, by contrast, is prevalent only in earlier spermatocytes and spermatogonia. Conclusion With an expanding list of likely target genes, RFX2 is potentially an important transcriptional regulator in pachytene spermatocytes. Rfx2 itself is a good candidate to be

  7. The GRP1 PH domain, like the AKT1 PH domain, possesses a sentry glutamate residue essential for specific targeting to plasma membrane PI(3,4,5)P(3).

    Science.gov (United States)

    Pilling, Carissa; Landgraf, Kyle E; Falke, Joseph J

    2011-11-15

    During the appearance of the signaling lipid PI(3,4,5)P(3), an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P(3)-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P(2) and bind the rare PI(3,4,5)P(3) target lipid with sufficiently high affinity. Our previous study of the E17K mutant of the protein kinase B (AKT1) PH domain, together with evidence from Carpten et al. [Carpten, J. D., et al. (2007) Nature 448, 439-444], revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P(2), thereby playing an essential role in specific PI(3,4,5)P(3) targeting [Landgraf, K. E., et al. (2008) Biochemistry 47, 12260-12269]. The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P(3)-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P(2) affinity and constitutive plasma membrane targeting. To test this hypothesis, we investigated the E345 residue, a putative sentry glutamate, of the general receptor for phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into the GRP1 PH domain enhances PI(4,5)P(2) affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in the AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P(2) releases the E345K GRP1 PH domain into the cytoplasm, and the efficiency of this release increases when Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K [Carpten, J. D., et al. (2007) Nature 448, 439-444; Lindhurst, M. J., et al

  8. Downstream-based Scheduling for Energy Conservation in Green EPONs

    KAUST Repository

    Chen, Shen; Dhaini, Ahmad R.; Ho, Pin-Han; Shihada, Basem; Shen, Gangxiang; Lin, Chih-Hao

    2012-01-01

    the ONU sleep time, it jeopardizes the quality of service (QoS) performance of the network, especially for downstream traffic in case the overlapping is based on the upstream time slot. In this paper, we study the downstream traffic performance in green

  9. A floating trap for sampling downstream migrant fishes.

    Science.gov (United States)

    Carl E. McLemore; Fred H. Everest; William R. Humphreys; Mario F. Solazzi

    1989-01-01

    Fishery scientists and managers are interested in obtaining information about downstream movements of fish species for biological and economic reasons. Different types of nets and traps have been used for this purpose with only partial success. The floating, self-cleaning downstream migrant trap described here proved successful for sampling several salmoniform and...

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

    Science.gov (United States)

    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.

  11. Downstream-based Scheduling for Energy Conservation in Green EPONs

    KAUST Repository

    Chen, Shen

    2012-05-01

    Maximizing the optical network unit’s (ONU) sleep time is an effective approach for achieving maximum energy conservation in green Ethernet passive optical networks (EPONs). While overlapping downstream and upstream ONU transmissions can maximize the ONU sleep time, it jeopardizes the quality of service (QoS) performance of the network, especially for downstream traffic in case the overlapping is based on the upstream time slot. In this paper, we study the downstream traffic performance in green EPONs under the limited service discipline and the upstream-based overlapped time window. Specifically, we first derive the expected mean packet delay, and then present a closed-form expression of the ONU sleep time, setting identical upstream/downstream transmission cycle times based on a maximum downstream traffic delay re-quirement. With the proposed system model, we present a novel downstream bandwidth allocation scheme for energy conservation in green EPONs. Simulation results verify the proposed model and highlight the advantages of our scheme over conventional approaches.

  12. Control of Delta Avulsion by Downstream Sediment Sinks

    Science.gov (United States)

    Salter, Gerard; Paola, Chris; Voller, Vaughan R.

    2018-01-01

    Understanding how fluxes are partitioned at delta bifurcations is critical for predicting patterns of land loss and gain in deltas worldwide. Although the dynamics of river deltas are influenced from both upstream and downstream, previous studies of bifurcations have focused on upstream controls. Using a quasi-1-D bifurcation model, we show that flow switching in bifurcations is strongly influenced by downstream sediment sinks. We find that coupling between upstream and downstream feedbacks can lead to oscillations in water and sediment flux partitioning. The frequency and initial rate of growth/decay of the oscillations depend on both upstream and downstream conditions, with dimensionless bifurcate length and bypass fraction emerging as key downstream parameters. With a strong offshore sink, causing bypass in the bifurcate branches, we find that bifurcation dynamics become "frozen"; that is, the bifurcation settles on a permanent discharge ratio. In contrast, under depositional conditions, we identify three dynamical regimes: symmetric; soft avulsion, where both branches remain open but the dominant branch switches; and full avulsion. Finally, we show that differential subsidence alters these regimes, with the difference in average sediment supply to each branch exactly compensating for the difference in accommodation generation. Additionally, the model predicts that bifurcations with shorter branches are less asymmetric than bifurcations with longer branches, all else equal, providing a possible explanation for the difference between backwater length distributaries, which tend to be avulsive, and relatively stable mouth-bar-scale networks. We conclude that bifurcations are sensitive both quantitatively and qualitatively to downstream sinks.

  13. Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling

    Directory of Open Access Journals (Sweden)

    I. van der Pluijm, PhD

    2016-10-01

    Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-β signaling, immune suppression may be more beneficial.

  14. OCT4 and downstream factors are expressed in human somatic urogenital epithelia and in culture of epididymal spheres

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Brunak, Søren; Kristensen, DM

    2010-01-01

    and microdissected tissues, in situ hybridisation, immunohistochemistry, and Western blotting to show that OCT4 and SOX2 together with downstream targets, UTF1 and REX1, are expressed in the human male urogenital tract. We further supported these results by analysis of DNA methylation of a region in the OCT4...

  15. Investigation of wall mass transfer characteristics downstream of an orifice

    International Nuclear Information System (INIS)

    El-Gammal, M.; Ahmed, W.H.; Ching, C.Y.

    2012-01-01

    Highlights: ► Numerical simulations were performed for the mass transfer downstream of an orifice. ► The Low Reynolds Number K-ε turbulence model was used. ► The numerical results were in good agreement with existing experimental results. ► The maximum Sherwood number downstream of the orifice was significantly affected by the Reynolds number. ► The Sherwood number profile was well correlated with the turbulence kinetic energy profile close to the wall. - Abstract: Numerical simulations were performed to determine the effect of Reynolds number and orifice to pipe diameter ratio (d o /d) on the wall mass transfer rate downstream of an orifice. The simulations were performed for d o /d of 0.475 for Reynolds number up to 70,000. The effect of d o /d was determined by performing simulations at a Reynolds number of 70,000 for d o /d of 0.375, 0.475 and 0.575. The momentum and mass transport equations were solved using the Low Reynolds Number (LRN) K-ε turbulence model. The Sherwood number (Sh) profile downstream of the orifice was in relatively good agreement with existing experimental results. The Sh increases sharply downstream of the orifice, reaching a maximum within 1–2 diameters downstream of the orifice, before relaxing back to the fully developed pipe flow value. The Sh number well downstream of the orifice was in good agreement with results for fully developed pipe flow estimated from the correlation of . The peak Sh numbers from the simulations were higher than that predicted from and .

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

    Science.gov (United States)

    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.

  17. Downstream Yangtze River levels impacted by Three Gorges Dam

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  18. Sleeving-back of horizontal wells to control downstream oil saturation and improve oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Greaves, M.; Saghr, A. M. [Bath Univ (United Kingdom)

    1998-12-31

    Air injection has become popular as an enhanced recovery technology, applicable over a wide variety of reservoir conditions including heavy, medium and light oils. One problem observed in light oil reservoirs is the tendency to desaturate the oil layer downstream of the moving front. This is particularly common in the case of thermal recovery processes. In this experiment designed to study ways to restrict the de-saturation of the oil layer, a modified horizontal producer well, incorporating a `sleeve-back` principal was used. The objective was to replicate the `toe-to-heel` displacement process occurring during heavy oil recovery, wherein downstream oil is essentially immobile due to its high viscosity. The `sleeve-back` of the well was achieved using a co-aligned, two-well assembly, so that the upstream section of the horizontal producer well was active, and continuously adjusted during propagation of the combustion front. The use of this continuous `sleeve-back` operation to control the level of de-saturation in the downstream section of a sand pack was successful as confirmed by the very high oil recovery achieved, equivalent to 93.5 per cent of oil in place. The level of CO{sub 2} production was also very high. The `sleeve-back` of the horizontal producer well made the light oil in-situ combustion more efficient compared to what would be expected in a fully-open well. The `sleeve-back` of the well also produced thermal contours in the sand pack that closely resembled those observed with heavy, highly viscous oil. By sealing-off the otherwise open well in the downstream part of the reservoir, the de-saturation of the oil layer was prevented. 9 refs., 4 tabs., 9 figs.

  19. Critical effects of downstream boundary conditions on vortex breakdown

    Science.gov (United States)

    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.

  20. Monitoring production target thickness

    International Nuclear Information System (INIS)

    Oothoudt, M.A.

    1993-01-01

    Pion and muon production targets at the Clinton P. Anderson Meson Physics Facility consist of rotating graphite wheels. The previous target thickness monitoring Procedure scanned the target across a reduced intensity beam to determine beam center. The fractional loss in current across the centered target gave a measure of target thickness. This procedure, however, required interruption of beam delivery to experiments and frequently indicated a different fractional loss than at normal beam currents. The new monitoring Procedure compares integrated ups and downs toroid current monitor readings. The current monitors are read once per minute and the integral of readings are logged once per eight-hour shift. Changes in the upstream to downstream fractional difference provide a nonintrusive continuous measurement of target thickness under nominal operational conditions. Target scans are now done only when new targets are installed or when unexplained changes in the current monitor data are observed

  1. Ion energy characteristics downstream of a high power helicon

    International Nuclear Information System (INIS)

    Prager, James; Winglee, Robert; Ziemba, Tim; Roberson, B Race; Quetin, Gregory

    2008-01-01

    The High Power Helicon eXperiment operates at higher powers (37 kW) and lower background neutral pressure than other helicon experiments. The ion velocity distribution function (IVDF) has been measured at multiple locations downstream of the helicon source and a mach 3-6 flowing plasma was observed. The helicon antenna has a direct effect in accelerating the plasma downstream of the source. Also, the IVDF is affected by the cloud of neutrals from the initial gas puff, which keeps the plasma speed low at early times near the source.

  2. Ion energy characteristics downstream of a high power helicon

    Energy Technology Data Exchange (ETDEWEB)

    Prager, James; Winglee, Robert; Ziemba, Tim; Roberson, B Race; Quetin, Gregory [University of Washington, Johnson Hall 070, Box 351310, 4000 15th Avenue NE, Seattle, WA 98195-1310 (United States)], E-mail: jprager@u.washington.edu

    2008-05-01

    The High Power Helicon eXperiment operates at higher powers (37 kW) and lower background neutral pressure than other helicon experiments. The ion velocity distribution function (IVDF) has been measured at multiple locations downstream of the helicon source and a mach 3-6 flowing plasma was observed. The helicon antenna has a direct effect in accelerating the plasma downstream of the source. Also, the IVDF is affected by the cloud of neutrals from the initial gas puff, which keeps the plasma speed low at early times near the source.

  3. Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

    DEFF Research Database (Denmark)

    Pudasaini, Nawin; Upadhyay, Pratik Pankaj; Parker, Christian Richard

    2017-01-01

    Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tablet......Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability...

  4. Subsequent to suppression: Downstream comprehension consequences of noun/verb ambiguity in natural reading

    Science.gov (United States)

    Stites, Mallory C.; Federmeier, Kara D.

    2015-01-01

    We used eye-tracking to investigate the downstream processing consequences of encountering noun/verb (NV) homographs (i.e., park) in semantically neutral but syntactically constraining contexts. Target words were followed by a prepositional phrase containing a noun that was plausible for only one meaning of the homograph. Replicating previous work, we found increased first fixation durations on NV homographs compared to unambiguous words, which persisted into the next sentence region. At the downstream noun, we found plausibility effects following ambiguous words that were correlated with the size of a reader's first fixation effect, suggesting that this effect reflects the recruitment of processing resources necessary to suppress the homograph's context-inappropriate meaning. Using these same stimuli, Lee and Federmeier (2012) found a sustained frontal negativity to the NV homographs, and, on the downstream noun, found a plausibility effect that was also positively correlated with the size of a reader's ambiguity effect. Together, these findings suggest that when only syntactic constraints are available, meaning selection recruits inhibitory mechanisms that can be measured in both first fixation slowdown and ERP ambiguity effects. PMID:25961358

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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

    2006-01-01

    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. ...

  7. Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors

    Science.gov (United States)

    Husson, Steven J.; Costa, Wagner Steuer; Wabnig, Sebastian; Stirman, Jeffrey N.; Watson, Joseph D.; Spencer, W. Clay; Akerboom, Jasper; Looger, Loren L.; Treinin, Millet; Miller, David M.; Lu, Hang; Gottschalk, Alexander

    2012-01-01

    Summary Background Nociception generally evokes rapid withdrawal behavior in order to protect the tissue from harmful insults. Most nociceptive neurons responding to mechanical insults display highly branched dendrites, an anatomy shared by Caenorhabditis elegans FLP and PVD neurons, which mediate harsh touch responses. Although several primary molecular nociceptive sensors have been characterized, less is known about modulation and amplification of noxious signals within nociceptor neurons. First, we analyzed the FLP/PVD network by optogenetics and studied integration of signals from these cells in downstream interneurons. Second, we investigated which genes modulate PVD function, based on prior single neuron mRNA profiling of PVD. Results Selectively photoactivating PVD, FLP and downstream interneurons using Channelrhodopsin-2 (ChR2) enabled functionally dissecting this nociceptive network, without interfering signals by other mechanoreceptors. Forward or reverse escape behaviors were determined by PVD and FLP, via integration by command interneurons. To identify mediators of PVD function, acting downstream of primary nocisensor molecules, we knocked down PVD-specific transcripts by RNAi and quantified light-evoked PVD-dependent behavior. Cell-specific disruption of synaptobrevin or voltage-gated Ca2+-channels (VGCCs) showed that PVD signals chemically to command interneurons. Knocking down the DEG/ENaC channel ASIC-1 and the TRPM channel GTL-1 indicated that ASIC-1 may extend PVD’s dynamic range and that GTL-1 may amplify its signals. These channels act cell-autonomously in PVD, downstream of primary mechanosensory molecules. Conclusions Our work implicates TRPM channels in modifying excitability of, and DEG/ENaCs in potentiating signal output from a mechano-nociceptor neuron. ASIC-1 and GTL-1 homologues, if functionally conserved, may denote valid targets for novel analgesics. PMID:22483941

  8. Imaging for monitoring downstream processing of fermentation broths

    DEFF Research Database (Denmark)

    Moiseyenko, Rayisa; Baum, Andreas; Jørgensen, Thomas Martini

    In relation to downstream processing of a fermentation broth coagulation/flocculation is a typical pretreatment method for separating undesirable particles/impurities from the wanted product. In the coagulation process the negatively charged impurities are destabilized by adding of a clarifying...

  9. DENSITY FLUCTUATIONS UPSTREAM AND DOWNSTREAM OF INTERPLANETARY SHOCKS

    Energy Technology Data Exchange (ETDEWEB)

    Pitňa, A.; Šafránková, J.; Němeček, Z.; Goncharov, O.; Němec, F.; Přech, L. [Charles University, Faculty of Mathematics and Physics, V Holešovičkách 2, 180 00 Prague 8 (Czech Republic); Chen, C. H. K. [Department of Physics, Imperial College London, London SW7 2AZ (United Kingdom); Zastenker, G. N., E-mail: jana.safrankova@mff.cuni.cz [Space Research Institute of Russian Academy of Sciences, Moscow, Russia, Profsoyuznaya ul. 84/32, Moscow 117997 (Russian Federation)

    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.

  10. Extreme wave phenomena in down-stream running modulated waves

    NARCIS (Netherlands)

    Andonowati, A.; Karjanto, N.; van Groesen, Embrecht W.C.

    Modulational, Benjamin-Feir, instability is studied for the down-stream evolution of surface gravity waves. An explicit solution, the soliton on finite background, of the NLS equation in physical space is used to study various phenomena in detail. It is shown that for sufficiently long modulation

  11. Downstream processing of Isochrysis galbana: a step towards microalgal biorefinery

    NARCIS (Netherlands)

    Gilbert-López, B.; Mendiola, J.A.; Fontecha, J.; Broek, van den L.A.M.; Sijtsma, L.; Cifuentes, A.; Herrero, M.; Ibáñez, E.

    2015-01-01

    An algae-based biorefinery relies on the efficient use of algae biomass through its fractionation of several valuable/bioactive compounds that can be used in industry. If this biorefinery includes green platforms as downstream processing technologies able to fulfill the requirements of green

  12. Patents and Downstream Innovation Suppression - Facts or Fiction?

    DEFF Research Database (Denmark)

    Howells, John

    the value of Kitch's prospect theory of patents, a theory that the social value of patents is that they enable the efficient coordination of technological development.    I re-examine history and legal sources bearing on Merges and Nelson's illustrative cases and find no case to illustrate downstream...

  13. Downstream flow top width prediction in a river system | Choudhury ...

    African Journals Online (AJOL)

    ANFIS, ARIMA and Hybrid Multiple Inflows Muskingum models (HMIM) were applied to simulate and forecast downstream discharge and flow top widths in a river system. The ANFIS model works on a set of linguistic rules while the ARIMA model uses a set of past values to predict the next value in a time series. The HMIM ...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Previtali, Mattia; Cuca, Branka; Barazzetti, Luigi

    2016-08-01

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

  16. Treatment of Essential Tremor

    Science.gov (United States)

    ... for PATIENTS and their FAMILIES TREATMENT OF ESSENTIAL TREMOR This fact sheet is provided to help you understand which therapies help treat essential tremor. Neurologists from the American Academy of Neurology are ...

  17. Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

    Science.gov (United States)

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-01-01

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs. DOI: http://dx.doi.org/10.7554/eLife.04640.001 PMID:26284497

  18. Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.

    Science.gov (United States)

    Korkut, Anil; Wang, Weiqing; Demir, Emek; Aksoy, Bülent Arman; Jing, Xiaohong; Molinelli, Evan J; Babur, Özgün; Bemis, Debra L; Onur Sumer, Selcuk; Solit, David B; Pratilas, Christine A; Sander, Chris

    2015-08-18

    Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.

  19. mTOR up-regulation of PFKFB3 is essential for acute myeloid leukemia cell survival

    International Nuclear Information System (INIS)

    Feng, Yonghuai; Wu, Liusong

    2017-01-01

    Although mTOR (mammalian target of rapamycin) activation is frequently observed in acute myeloid leukemia (AML) patients, the precise function and the downstream targets of mTOR are poorly understood. Here we revealed that PFKFB3, but not PFKFB1, PFKFB2 nor PFKFB4 was a novel downstream substrate of mTOR signaling pathway as PFKFB3 level was augmented after knocking down TSC2 in THP1 and OCI-AML3 cells. Importantly, PFKFB3 silencing suppressed glycolysis and cell proliferation of TSC2 silencing OCI-AML3 cells and activated apoptosis pathway. These results suggested that mTOR up-regulation of PFKFB3 was essential for AML cells survival. Mechanistically, Rapamycin treatment or Raptor knockdown reduced the expression of PFKFB3 in TSC2 knockdown cells, while Rictor silencing did not have such effect. Furthermore, we also revealed that mTORC1 up-regulated PFKFB3 was dependent on hypoxia-inducible factor 1α (HIF1α), a positive regulator of glycolysis. Moreover, PFKFB3 inhibitor PFK15 and rapamycin synergistically blunted the AML cell proliferation. Taken together, PFKFB3 was a promising drug target in AML patients harboring mTOR hyper-activation.

  20. Dead zone area at the downstream flow of barrages

    Directory of Open Access Journals (Sweden)

    Mohamed F. Sauida

    2016-12-01

    Full Text Available Flow separation is a natural phenomenon encountered at some cases downstream of barrages. The main flow is divided into current and dead zone flows. The percentage area of dead zone flow must be taken into consideration downstream of barrages, due to its negative effect on flow characteristics. Experimental studies were conducted in the Hydraulic Research Institute (HRI, on a physical regulator model with five vents. Theoretically the separation zone is described as a part of an ellipse which is practically verified by plotting velocity vectors. The results show that the percentage area of dead zone to the area through length of separation depends mainly on the expansion ratio [channel width to width of opened vents], with maximum value of 81% for operated side gates. A statistical analysis was derived, to predict the percentage area of dead zone flow to the area through length of separation.

  1. OGJ group weathered tough times upstream and downstream in 1991

    International Nuclear Information System (INIS)

    Biggs, J.B.; Price, R.B.

    1992-01-01

    With an upstream sector hit by low oil and gas prices and downstream operations squeezed by weak petroleum demand, 1991, was a tough year for the group of 22 major integrated U.S. companies Oil and Gas Journal tracks. This paper reports that the brief respite caused by the oil price spike in second half 1990 ended abruptly early in first half 1991, and it turned into a year of buckling down for most companies. They shed non-core assets, implemented strategic restructuring moves, and reduced staff. Although low prices slowed overall drilling activity for the group, oil and gas production increased slightly, and most companies reported reserves gains. Recession in the U.S. and Europe depressed demand for the group's fined products enough to pinch downstream earnings even as buoyant Asia-Pacific demand helped jack up world product sales

  2. Downstream management practices of transnational companies in institutionally vulnerable countries

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard; Milanez, Bruno

    2017-01-01

    Analyses of social and environmental management in transnational product chains focus often upstream on suppliers in socially and institutionally vulnerable countries and these suppliers' hazardous processes. Furthermore focus is on transnational companies' responsibility when they source from...... such suppliers. On the contrary, not much focus has been on transnational companies' downstream export of hazardous products to vulnerable countries and the product use in those countries. The article uses pesticides as case of hazardous products and identifies mechanisms in the downstream social...... and environmental management of a Danish pesticide company in vulnerable countries and especially in Brazil. The identified mechanisms are: the transnational company's on-going interpretation of the regulatory and ethical obligations for development and use of its hazardous products in vulnerable countries, path...

  3. International Retailing Operations: Downstream Entry and Expansion via Franchising

    OpenAIRE

    Petersen, Bent; Welch, Lawrence S.

    1999-01-01

    In this article, the shift into international franchising from other forms of operation, rather than the typical home market franchising base is explored. The focus is international retail franchising, based on a study of the Danish clothing and footwear industry. In this study it was found that Danish companies were moving into international franchising as an outcome of a more general shift from upstream wholesaling and subcontracting activities to downstream involvement in retailing activit...

  4. THE THEORY OF ESSENTIAL FACILITIES. THE PRINCIPLE OF ACCESS TO INVENTION IN CASE OF ABUSIVE REFUSAL TO LICENSE

    Directory of Open Access Journals (Sweden)

    Irina CUCER LISNIC

    2015-07-01

    Full Text Available Essential facilities designate specific inputs which are essential for the production of other downstream goods. Inputs are situated upstream and so are eligible for intellectual property protection. In order to foster competition in the downstream, holders of these inputs should be forced to give access to potential users, by offering them operating lidcenses. In other words, one must respect the exclusive right of intellectual property holder to freely exploit his invention or must he be sacrificed in favor of downstream competition ? In the present analysis we intend to analyze some of either controverted or less known judicial aspects related to the theory of essential facilities.

  5. Analysis of Petroleum Downstream Industry Potential in Riau Province

    Directory of Open Access Journals (Sweden)

    Tomi Erfando

    2017-06-01

    Full Text Available Petroleum downstream industry in Riau Province is still not optimal. The data shows that from 98,892,755 barrels lifting oil each year only 62,050,000 barrels could be processed in refinery unit II Dumai operated by PT Pertamina. There is a potential of 35-40% of downstream industry. Indonesian Government through The Ministry of Energy and Mineral Resources declared the construction of a mini refinery to boost oil processing output in the downstream sector. A feasibility study of development plan mini refinery is needed. The study includes production capacity analysis, product analysis, development & operational refinery  analysis and economic analysis. The results obtained by the mini refinery capacity is planned to process crude oil 6000 BOPD with the products produced are gasoline, kerosene, diesel and oil. Investment cost consist of is capital cost US $ 104419784 and operating cost US $ 13766734 each year with net profit earned US $ 12330063/year and rate of return from investment 11.63%

  6. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways

    DEFF Research Database (Denmark)

    Bosse, Tanja; Ehinger, Julia; Czuchra, Aleksandra

    2007-01-01

    -WASP. Instead, actin polymerization was driven by Arp2/3 complex activation through the WAVE complex downstream of Rac. Together, our data establish an intricate signaling network comprising as key molecules Cdc42 and PI3-kinase, which converge on Rac-mediated actin reorganization essential for Listeria...

  7. Discovery and characterization of novel vascular and hematopoietic genes downstream of etsrp in zebrafish.

    Directory of Open Access Journals (Sweden)

    Gustavo A Gomez

    Full Text Available The transcription factor Etsrp is required for vasculogenesis and primitive myelopoiesis in zebrafish. When ectopically expressed, etsrp is sufficient to induce the expression of many vascular and myeloid genes in zebrafish. The mammalian homolog of etsrp, ER71/Etv2, is also essential for vascular and hematopoietic development. To identify genes downstream of etsrp, gain-of-function experiments were performed for etsrp in zebrafish embryos followed by transcription profile analysis by microarray. Subsequent in vivo expression studies resulted in the identification of fourteen genes with blood and/or vascular expression, six of these being completely novel. Regulation of these genes by etsrp was confirmed by ectopic induction in etsrp overexpressing embryos and decreased expression in etsrp deficient embryos. Additional functional analysis of two newly discovered genes, hapln1b and sh3gl3, demonstrates their importance in embryonic vascular development. The results described here identify a group of genes downstream of etsrp likely to be critical for vascular and/or myeloid development.

  8. Trehalose-6-phosphate synthesis controls yeast gluconeogenesis downstream and independent of SNF1.

    Science.gov (United States)

    Deroover, Sofie; Ghillebert, Ruben; Broeckx, Tom; Winderickx, Joris; Rolland, Filip

    2016-06-01

    Trehalose-6-P (T6P), an intermediate of trehalose biosynthesis, was identified as an important regulator of yeast sugar metabolism and signaling. tps1Δ mutants, deficient in T6P synthesis (TPS), are unable to grow on rapidly fermentable medium with uncontrolled influx in glycolysis, depletion of ATP and accumulation of sugar phosphates. However, the exact molecular mechanisms involved are not fully understood. We show that SNF1 deletion restores the tps1Δ growth defect on glucose, suggesting that lack of TPS hampers inactivation of SNF1 or SNF1-regulated processes. In addition to alternative, non-fermentable carbon metabolism, SNF1 controls two major processes: respiration and gluconeogenesis. The tps1Δ defect appears to be specifically associated with deficient inhibition of gluconeogenesis, indicating more downstream effects. Consistently, Snf1 dephosphorylation and inactivation on glucose medium are not affected, as confirmed with an in vivo Snf1 activity reporter. Detailed analysis shows that gluconeogenic Pck1 and Fbp1 expression, protein levels and activity are not repressed upon glucose addition to tps1Δ cells, suggesting a link between the metabolic defect and persistent gluconeogenesis. While SNF1 is essential for induction of gluconeogenesis, T6P/TPS is required for inactivation of gluconeogenesis in the presence of glucose, downstream and independent of SNF1 activity and the Cat8 and Sip4 transcription factors. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Channel erosion in a rapidly urbanizing region of Tijuana, Mexico: Enlargement downstream of channel hardpoints

    Science.gov (United States)

    Taniguchi, Kristine; Biggs, Trent; Langendoen, Eddy; Castillo, Carlos; Gudiño, Napoleon; Yuan, Yongping; Liden, Douglas

    2016-04-01

    Urban-induced erosion in Tijuana, Mexico, has led to excessive sediment deposition in the Tijuana Estuary in the United States. Urban areas in developing countries, in contrast to developed countries, are characterized by much lower proportions of vegetation and impervious surfaces due to limited access to urban services such as road paving and landscaping, and larger proportions of exposed soils. In developing countries, traditional watershed scale variables such as impervious surfaces may not be good predictors of channel enlargement. In this research, we surveyed the stream channel network of an erodible tributary of the Tijuana River Watershed, Los Laureles Canyon, at 125 locations, including repeat surveys from 2008. Structure from Motion (SfM) and 3D photo-reconstruction techniques were used to create digital terrain models of stream reaches upstream and downstream of channel hardpoints. Channels are unstable downstream of hardpoints, with incision up to 2 meters and widening up to 12 meters. Coordinated channelization is essential to avoid piece-meal approaches that lead to channel degradation. Watershed impervious area is not a good predictor of channel erosion due to the overriding importance of hardpoints and likely to the high sediment supply from the unpaved roads which prevents channel erosion throughout the stream network.

  10. Genome-wide identification of GLABRA3 downstream genes for anthocyanin biosynthesis and trichome formation in Arabidopsis.

    Science.gov (United States)

    Gao, Chenhao; Li, Dong; Jin, Changyu; Duan, Shaowei; Qi, Shuanghui; Liu, Kaige; Wang, Hanchen; Ma, Haoli; Hai, Jiangbo; Chen, Mingxun

    2017-04-01

    GLABRA3 (GL3), a bHLH transcription factor, has previously proved to be involved in anthocyanin biosynthesis and trichome formation in Arabidopsis, however, its downstream targeted genes are still largely unknown. Here, we found that GL3 was widely present in Arabidopsis vegetative and reproductive organs. New downstream targeted genes of GL3 for anthocyanin biosynthesis and trichome formation were identified in young shoots and expanding true leaves by RNA sequencing. GL3-mediated gene expression was tissue specific in the two biological processes. This study provides new clues to further understand the GL3-mediated regulatory network of anthocyanin biosynthesis and trichome formation in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Focal Adhesion Kinase functions as an Akt downstream target in migration of colorectal cancer cells

    Czech Academy of Sciences Publication Activity Database

    Turečková, Jolana; Vojtěchová, Martina; Krausová, Michaela; Šloncová, Eva; Kořínek, Vladimír

    2009-01-01

    Roč. 2, č. 4 (2009), s. 281-290 ISSN 1936-5233 R&D Projects: GA ČR GA204/06/1658; GA MŠk 2B06077 Institutional research plan: CEZ:AV0Z50520514 Keywords : FAK * migration * invasion Subject RIV: EB - Genetics ; Molecular Biology

  12. Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

    Science.gov (United States)

    Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

    2018-03-29

    Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

  13. TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wensing, Lislaine A. [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil); Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo (Brazil); Campos, Alexandre H., E-mail: alexandre.campos@einstein.br [Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901 (Brazil)

    2014-11-01

    Chronic kidney disease (CKD) is an increasingly common condition characterized by progressive loss of functional nephrons leading to renal failure. TGF-β1-induced mesangial cell (MC) phenotype alterations have been linked to the genesis of CKD. Here we show that TGF-β1 regulates TBX3 gene expression in MC. This gene encodes for two main isoforms, TBX3.1 and TBX3+2α. TBX3.1 has been implicated in cell immortalization, proliferation and apoptosis by inhibiting p14{sup ARF}-Mdm2-p53 pathway, while TBX3+2α role has not been defined. We demonstrated that TBX3 overexpression abrogated MC apoptosis induced by serum deprivation. Moreover, we observed an enhancement in TBX3 protein expression both in glomerular and tubular regions in the model of 5/6 nephrectomy, temporally related to increased expression of TGF-β1, type IV collagen and fibronectin. Our results indicate that TBX3 acts as an anti-apoptotic factor in MC in vitro and may be involved in the mechanism by which TGF-β1 induces glomerulosclerosis and tubular fibrosis during the progression of nephropathies. - Highlights: • TBX3 isoforms are upregulated by TGF-b1 in mesangial cells. • TBX3 isoforms have different subcellular distribution profile in mesangial cells. • TBX3 isoforms exhibit antiapoptotic action in mesangial cells. • TBX3 protein is overexpressed in a model of nephropathy (5/6 nephrectomy)

  14. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra

    2015-01-01

    B-cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry-based proteomics to monitor the dynamics of BCR signaling complexes (signalosomes......) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation...... of the receptor-proximal signaling components, many of which are co-regulated by both the modifications. We illustrate the power of multilayered proteomic analyses for discovering novel BCR signaling components by demonstrating that BCR-induced phosphorylation of RAB7A at S72 prevents its association...

  15. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

    Science.gov (United States)

    Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

    2017-04-11

    Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

  16. Electric circuits essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph

  17. Calculus III essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Calculus III includes vector analysis, real valued functions, partial differentiation, multiple integrations, vector fields, and infinite series.

  18. Statistics I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics I covers include frequency distributions, numerical methods of describing data, measures of variability, parameters of distributions, probability theory, and distributions.

  19. Pre-calculus essentials

    CERN Document Server

    Woodward, Ernest

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Pre-Calculus reviews sets, numbers, operations and properties, coordinate geometry, fundamental algebraic topics, solving equations and inequalities, functions, trigonometry, exponents

  20. Transport phenomena II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration

  1. Differential equations I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Differential Equations I covers first- and second-order equations, series solutions, higher-order linear equations, and the Laplace transform.

  2. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of

    1988-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  3. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  4. Algebra & trigonometry II essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica

  5. Modern algebra essentials

    CERN Document Server

    Lutfiyya, Lutfi A

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Modern Algebra includes set theory, operations, relations, basic properties of the integers, group theory, and ring theory.

  6. Business statistics I essentials

    CERN Document Server

    Clark, Louise

    2014-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Business Statistics I includes descriptive statistics, introduction to probability, probability distributions, sampling and sampling distributions, interval estimation, and hypothesis t

  7. Computer science I essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science I includes fundamental computer concepts, number representations, Boolean algebra, switching circuits, and computer architecture.

  8. The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

    DEFF Research Database (Denmark)

    Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

    2009-01-01

    Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

  9. Flow behavior of droplets downstream of the spacer

    International Nuclear Information System (INIS)

    Kodama, Eiichiro; Morishita, Kiyohide; Aritomi, Masanori; Yano, Takashi

    1998-01-01

    The fuel spacer, of which role is to maintain an appropriate rod-to-rod clearance, is one of the components of a Boiling Water Reactor (BWR) fuel rod bundles. The fuel spacer influences flow characteristics of the liquid film in fuel rod bundles, so that its geometry influences greatly thermal hydraulics such as critical power and pressure drop therein. The purpose of this study is to clarify the effect of the spacer geometry on the core flow split downstream of the spacer. Phase Doppler Anemometry (PDA) was used for their meausrement under the conditions of a small amount of droplets in mist flows. From the experimental results, the normalized droplet velocity profiles with a spacer were split by the spacer and were different between a wider and a narrower regions in the channel, however, they became uniform at the distance far 100mm from the spacer. In the case without a spacer, the velocity was monotonously increasing nearer the rod surface with going toward the center of the channel. In the case with a spacer, the velocity profile downstream of the spacer changed in the narrower region of the channel. This tendency became more remarkable with thickening the spacer and widening clearance between the spacer and the wall. In this paper, 'drift' velocity effect was applied for the spacer model, due to the gas flows were split by the spacer which is based on the momentum balance between the narrower and wider channels. This model was confirmed from the experimental results that the droplet flowed from a wider region to a narrower one. This drift effect appeared more strongly as the spacer became thicker and the clearance did narrower. The analytical results explained qualitatively the measured ones. It is clarified that the drift effect proposed in this work was a dominant factor on droplet deposition downstream of the spacer

  10. Climate change issue table : petroleum downstream sector industry foundation paper

    International Nuclear Information System (INIS)

    Crandall, G.R.; Kelly, S.J.; Kromm, R.B.; Prime, M.G.

    1999-01-01

    An analysis of the impact of the Kyoto Protocol on the Canadian downstream petroleum industry is presented. The downstream sector includes petroleum refining, plus all activities regarding distribution, marketing and retailing of petroleum products. In 1990, the carbon dioxide (CO 2 ) emissions resulting from the production and consumption of petroleum products were about 207 megatons which is about 45 per cent of total Canadian CO 2 emissions. This report includes the analysis of the Base Case and the Kyoto Case. The Base Case is premised on the implementation of fuel sulphur reductions to meet cleaner fuels requirements and an enhanced program of refinery efficiency initiatives. Under the Base Case assumptions the CO 2 emissions from refinery operations in 2010 would be about 3.4 below 1990 levels. The Kyoto Case was developed on the basis of reductions in Canadian petroleum product demand that would be sufficient to achieve a 6 per cent reduction in GHG emissions from the production and consumption of petroleum products relative to 1990 levels. The model demonstrates the dramatic economic impact of the Kyoto Case reductions on the Canadian downstream petroleum sector. Investment requirements for capital improvements to further distillate production and to further desulphurization are estimated at $ 1.5 billion between 2005 and 2015. The reduced volume of gasoline sales would be expected to result in rationalization of retail outlets, resulting in the closure of some 2,000 retail outlets with a combined loss of about 12,000 jobs. It is suggested that similar impact in other countries that are signatory to the Kyoto Protocol could result in the shift of refining, refining industry jobs and related economic benefits to countries which are not participants in the Kyoto Protocol. 14 tabs., 6 figs., 5 appendices

  11. Alfven waves and associated energetic ions downstream from Uranus

    International Nuclear Information System (INIS)

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

    1991-01-01

    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 -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

  12. Flow diagnostics downstream of a tribladed rotor model

    DEFF Research Database (Denmark)

    Naumov, I. V.; Rahmanov, V. V.; Okulov, Valery

    2012-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Cláudia Regina Batista de Souza

    2012-07-01

    Full Text Available 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.

  14. 'Patents and Downstream Innovation Suppression - Fact or Fiction?'

    DEFF Research Database (Denmark)

    Howells, John

    Merges and Nelson have provided an empirically grounded argument that firms use pioneer patents of 'broad' scope to block downstream technological development (Merges and Nelson 1990). If this is a regular occurrence then, as they claim, they have faulted Kitch's 'prospect theory' of patents (Kitch...... 1977), a theory that is a version of the classic justification for the award of the exclusive right - that it should protect the incentive to develop property. Merges and Nelson insist that their thesis should be supported by empirical evidence and they turn to historical accounts as an important form...

  15. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  16. The insulin receptor substrate (IRS)-1 pleckstrin homology domain functions in downstream signaling.

    Science.gov (United States)

    Vainshtein, I; Kovacina, K S; Roth, R A

    2001-03-16

    The pleckstrin homology (PH) domain of the insulin receptor substrate-1 (IRS-1) plays a role in directing this molecule to the insulin receptor, thereby regulating its tyrosine phosphorylation. In this work, the role of the PH domain in subsequent signaling was studied by constructing constitutively active forms of IRS-1 in which the inter-SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase was fused to portions of the IRS-1 molecule. Chimeric molecules containing the PH domain were found to activate the downstream response of stimulating the Ser/Thr kinase Akt. A chimera containing point mutations in the PH domain that abolished the ability of this domain to bind phosphatidylinositol 4,5-bisphosphate prevented these molecules from activating Akt. These mutations also decreased by about 70% the amount of the constructs present in a particulate fraction of the cells. These results indicate that the PH domain of IRS-1, in addition to directing this protein to the receptor for tyrosine phosphorylation, functions in the ability of this molecule to stimulate subsequent responses. Thus, compromising the function of the PH domain, e.g. in insulin-resistant states, could decrease both the ability of IRS-1 to be tyrosine phosphorylated by the insulin receptor and to link to subsequent downstream targets.

  17. Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

    Science.gov (United States)

    Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

    2011-01-01

    The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Tidal Influence on Water Quality of Kapuas Kecil River Downstream

    Science.gov (United States)

    Purnaini, Rizki; Sudarmadji; Purwono, Suryo

    2018-02-01

    The Kapuas Kecil River is strongly influenced by tidal, in the dry season the intrusion of surface water is often a problem for the WTP because it causes the change of raw water quality to be processed. The purpose of this study was to examine the effect of sea tides on water quality of the Kapuas Kecil River. The study was conducted in Kapuas River downstream along ± 30 km from the upper boundary to the estuary. Water sampling is carried out during the dry and rainy season, when the tidal conditions at 7 (seven) locations of the monitoring station. Descriptive analysis methods and regression-correlation statistics are used to determine the effect of tides on water quality in Kapuas River downstream. In general, the water quality of the Kapuas Kecil River has exceeded the criteria of first class water quality, ie water that can be used for drinking water. The status of water quality of the Kapuas Kecil River based on the pollution index calculation shows the condition of the river is "mild to medium pollutants". The result of multiple linear regression analysis got the value of coefficient of determination (adjusted R square) = 0,760, which in whole show that independent variable (tidal and distance) influence to dependent variable (value of TDS) equal to 76%.

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

    Science.gov (United States)

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  1. Kappa-Electrons Downstream of the Solar Wind Termination Shock

    Science.gov (United States)

    Fahr, H. J.

    2017-12-01

    A theoretical description of the solar wind electron distribution function downstream of the termination shock under the influence of the shock-induced injection of overshooting KeV-energetic electrons will be presented. A kinetic phasespace transport equation in the bulk frame of the heliosheath plasma flow is developed for the solar wind electrons, taking into account shock-induced electron injection, convective changes, magnetic cooling processes and whistler wave-induced energy diffusion. Assuming that the local electron distribution under the prevailing Non-LTE conditions can be represented by a local kappa function with a local kappa parameter that varies with the streamline coordinates, we determine the parameters of the resulting, initial kappa distribution for the downstream electrons. From this initial function spectral electron fluxes can be derived and can be compared with those measured by the VOYAGER-1 spacecraft in the range between 40 to 70 KeV. It can then be shown that with kappa values around kappa = 6 one can in fact fit these data very satisfactorily. In addition it is shown that for isentropic electron flows kappa-distributed electrons have to undergo simultaneous changes of both parameters, i.e. kappa and theta, of the electron kappa function. It is also shown then that under the influence of energy sinks and sources the electron flux becomes non-isentropic with electron entropies changing along the streamline.

  2. Physics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physics I includes vectors and scalars, one-dimensional motion, plane motion, dynamics of a particle, work and energy, conservation of energy, dynamics of systems of particles, rotation

  3. Electronics II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet

  4. Thermodynamics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics I includes review of properties and states of a pure substance, work and heat, energy and the first law of thermodynamics, entropy and the second law of thermodynamics

  5. C programming language essentials

    CERN Document Server

    Ackermann, Ernest C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. C Programming Language discusses fundamental notions, data types and objects, expressions, statements, declarations, function and program structure, the preprocessor, and the standar

  6. Electronics I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics I covers fundamentals of semiconductor devices, junction diodes, bipolar junction transistors, power supplies, multitransistor circuits, small signals, low-frequency anal

  7. Thermodynamics II essentials

    CERN Document Server

    REA, The Editors of

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics II includes review of thermodynamic relations, power and refrigeration cycles, mixtures and solutions, chemical reactions, chemical equilibrium, and flow through nozzl

  8. Group theory I essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Group Theory I includes sets and mapping, groupoids and semi-groups, groups, isomorphisms and homomorphisms, cyclic groups, the Sylow theorems, and finite p-groups.

  9. Boolean algebra essentials

    CERN Document Server

    Solomon, Alan D

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Boolean Algebra includes set theory, sentential calculus, fundamental ideas of Boolean algebras, lattices, rings and Boolean algebras, the structure of a Boolean algebra, and Boolean

  10. Laplace transforms essentials

    CERN Document Server

    Shafii-Mousavi, Morteza

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Laplace Transforms includes the Laplace transform, the inverse Laplace transform, special functions and properties, applications to ordinary linear differential equations, Fourier tr

  11. Physical chemistry II essentials

    CERN Document Server

    REA, The Editors of

    1992-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physical Chemistry II includes reaction mechanisms, theoretical approaches to chemical kinetics, gravitational work, electrical and magnetic work, surface work, kinetic theory, collisional and transport properties of gases, statistical mechanics, matter and waves, quantum mechanics, and rotations and vibrations of atoms and molecules.

  12. Statistics II essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics II discusses sampling theory, statistical inference, independent and dependent variables, correlation theory, experimental design, count data, chi-square test, and time se

  13. Algebra & trigonometry I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry I includes sets and set operations, number systems and fundamental algebraic laws and operations, exponents and radicals, polynomials and rational expressions, eq

  14. Geometry I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Geometry I includes methods of proof, points, lines, planes, angles, congruent angles and line segments, triangles, parallelism, quadrilaterals, geometric inequalities, and geometric

  15. Transport phenomena I essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena I includes viscosity, flow of Newtonian fluids, velocity distribution in laminar flow, velocity distributions with more than one independent variable, thermal con

  16. Data structures II essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures II includes sets, trees, advanced sorting, elementary graph theory, hashing, memory management and garbage collection, and appendices on recursion vs. iteration, alge

  17. Computer science II essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science II includes organization of a computer, memory and input/output, coding, data structures, and program development. Also included is an overview of the most commonly

  18. Data structures I essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures I includes scalar variables, arrays and records, elementary sorting, searching, linked lists, queues, and appendices of binary notation and subprogram parameter passi

  19. Set theory essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Set Theory includes elementary logic, sets, relations, functions, denumerable and non-denumerable sets, cardinal numbers, Cantor's theorem, axiom of choice, and order relations.

  20. Estimating the waiting time of multi-priority emergency patients with downstream blocking.

    Science.gov (United States)

    Lin, Di; Patrick, Jonathan; Labeau, Fabrice

    2014-03-01

    To characterize the coupling effect between patient flow to access the emergency department (ED) and that to access the inpatient unit (IU), we develop a model with two connected queues: one upstream queue for the patient flow to access the ED and one downstream queue for the patient flow to access the IU. Building on this patient flow model, we employ queueing theory to estimate the average waiting time across patients. Using priority specific wait time targets, we further estimate the necessary number of ED and IU resources. Finally, we investigate how an alternative way of accessing ED (Fast Track) impacts the average waiting time of patients as well as the necessary number of ED/IU resources. This model as well as the analysis on patient flow can help the designer or manager of a hospital make decisions on the allocation of ED/IU resources in a hospital.

  1. LHC Asynchronous Beam Dump: Study of new TCDQ model and effects on downstream magnets

    CERN Document Server

    Versaci, R; Vlachoudis, V

    2012-01-01

    An asynchronous beam dump is one of the most critical accidents the LHC could face. In the effort to have a better protection of the machine, and to increase the robustness of the protection device itself, new models for the TCDQ (Target Collimator Dump Quadrupole) have been proposed and are under evaluation. Within this frame we have performed FLUKA evaluation of the energy deposition on one of the proposed models and on the downstream quadrupoles, MQY.4R6 and MQY.5R6, in order to evaluate the protection provided by the proposed model. The results of our study are compared to a similar one for a different proposed model and are input for the evaluation of the heat load on the proposed collimator.

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

    Science.gov (United States)

    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.

  3. The Integrin-Regulated Kinase PYK-2: A Therapeutic Target for Prostate Cancer

    National Research Council Canada - National Science Library

    Edlund, Magnus

    2001-01-01

    ...) . A number of promising therapeutic targets for androgen-independent and metastatic prostate cancers are contained within the signaling cascades downstream of the ECM-binding Integrin molecules...

  4. The effect of feeding a commercial essential oil product on Clostridium perfringens numbers in the intestine of broiler chickens measured by real-time PCR targeting the α-toxin-encoding gene (plc)

    DEFF Research Database (Denmark)

    Abildgaard, Lone; Højberg, Ole; Schramm, Andreas

    2010-01-01

    Proliferation of Clostridium perfringens type A in the broiler intestinal tract is related to poor growth and litter quality, and can under certain conditions lead to the development of necrotic enteritis (NE), a severe gastrointestinal disease in broilers. The aim of the present study was to inv...... quantification of C. perfringens type A in broilers, a real-time PCR assay, targeting the α-toxin-encoding plc gene, was developed for use in ileal and caecal samples and was shown to be a fast and reliable alternative to conventional plate counting....

  5. Roitt's essential immunology

    National Research Council Canada - National Science Library

    Delves, Peter J; Roitt, Ivan M

    2011-01-01

    ... of the immune system, the hallmark easy-reading style of Roitt's Essential Immunology clearly explains the key principles needed by medical and health sciences students, from the basis of immunity to clinical applications...

  6. Benign Essential Blepharospasm

    Science.gov (United States)

    ... the same for many years; and, in rare cases, improve spontaneously. Clinical Trials Throughout the U.S. and Worldwide NINDS Clinical Trials Related ... Definition Benign essential blepharospasm (BEB) is a progressive neurological ...

  7. Marketingmanagement : De essentie

    NARCIS (Netherlands)

    Kotler, P.J.; Keller, K.; Robben, H.S.J.

    2007-01-01

    'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze

  8. Marketing management : De essentie

    NARCIS (Netherlands)

    Kotler, P.J.; Keller, K.; Robben, H.S.J.

    2010-01-01

    'Marketingmanagement, de essentie' biedt een volledige introductie in modern marketingmanagement. De nieuwste concepten en onderzoeksresultaten komen aan bod. Zo wordt veel aandacht besteed aan holistische marketing en is de impact van technologische ontwikkelingen op hedendaagse marketing in deze

  9. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  10. Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb.

    Science.gov (United States)

    Lallemand, Yvan; Bensoussan, Vardina; Cloment, Cécile Saint; Robert, Benoît

    2009-07-15

    In tetrapods, the anteroposterior (AP) patterning of the limb is under the control of the antagonistic activities of the secreted factor Sonic hedgehog (Shh) and Gli3R, the truncated repressor form of the transcription factor Gli3. In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R. Consequently, in Shh null mutants, Msx genes are overexpressed and, furthermore, partially responsible for the limb phenotype. This is exemplified by the fact that reducing Msx activity in Shh mutants partially restores a normal limb development. Finally, we show that the main action of the Msx genes, in both normal and Shh(-/-) limb development, is to control cell death in the mesenchyme. We propose that, in the limb, Msx genes act downstream of the Shh/Gli3 pathway by transducing BMP signaling and that, in the absence of Shh signaling, their deregulation contributes to the extensive apoptosis that impairs limb development.

  11. Downstream ecological effects of dams: A geomorphic perspective

    International Nuclear Information System (INIS)

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

    1995-01-01

    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. Continuous downstream processing for high value biological products: A Review.

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  13. Downstream and upstream extension of the House of Quality

    DEFF Research Database (Denmark)

    Holmen, Elsebeth; Kristensen, Preben Sander

    . The transformation processes and characteristics constituting this fan were based on the knowledge possessed by the company before entering into development interaction with suppliers. If it is these characteristics which are used to express the demands of the company in the subsequent interaction process, much......Executive summary 1. During 1993-94 the authors followed a product development process in a Danish butter cookie company. The process was structured according to the Quality Function Deployment technique House of Quality. Originally, the intention was to study the prototyping process that we...... a discussion in a diabetics end-user focus group. During a series of meetings, the production manager and the sales manager transformed attributes int characteristics and constructed Houses of Quality for a sugar-free cookie. 2. Downstream on its way to the end-user, the product passes through a chain of users...

  14. Mergers and acquisitions of downstream facilities by producing countries

    Energy Technology Data Exchange (ETDEWEB)

    Ligon, D.R.

    1988-01-01

    The author discusses a phenomenon that he calls the ''re-integration'' or ''re-coupling'' of the worldwide oil industry, as foreign, particularly OPEC, producers are becoming directly involved with downstream operations in their most important markets. This phenomenon already has produced some far-reaching consequences that will become even more important and pervasive in the near future. First, he describes the factors and logic that led to these arrangements. Next, he outlines some of their practical considerations and implications. While some of the market factors described are applicable to any non-integrated producer, he spends most of his time discussing OPEC and ''neo-OPEC'' producers such as Mexico. These are the people doing the deals and are therefore probably of greatest interest.

  15. The downstream externalities of harvesting rainwater in semi-arid watersheds: an Indian case study

    NARCIS (Netherlands)

    Bouma, J.A.; Biggs, T.W.; Bouwer, L.M.

    2011-01-01

    Water-related investment projects affect downstream water availability, and therefore should account for these externalities. Few projects do, however, owing to lack of awareness, lack of data and difficulty in linking upstream investments to downstream effects. This article assesses the downstream

  16. From gravel to sand. Downstream fining of bed sediments in the lower river Rhine

    NARCIS (Netherlands)

    Frings, R.M.

    2007-01-01

    A common characteristic of many rivers is the tendency for bed sediments to become finer in downstream direction. This phenomenon, which is generally known as downstream fining, has a strong effect on the morphologic and hydrodynamic behaviour of a river. The fundamental causes of downstream

  17. Operating multireservoir hydropower systems for downstream water quality

    International Nuclear Information System (INIS)

    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

  18. Downstream cumulative effects of land use on freshwater communities

    Science.gov (United States)

    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. Python essential reference

    CERN Document Server

    Beazley, David M

    2009-01-01

    Python Essential Reference is the definitive reference guide to the Python programming language — the one authoritative handbook that reliably untangles and explains both the core Python language and the most essential parts of the Python library. Designed for the professional programmer, the book is concise, to the point, and highly accessible. It also includes detailed information on the Python library and many advanced subjects that is not available in either the official Python documentation or any other single reference source. Thoroughly updated to reflect the significant new programming language features and library modules that have been introduced in Python 2.6 and Python 3, the fourth edition of Python Essential Reference is the definitive guide for programmers who need to modernize existing Python code or who are planning an eventual migration to Python 3. Programmers starting a new Python project will find detailed coverage of contemporary Python programming idioms.

  20. Essential travel medicine

    CERN Document Server

    Zuckerman, Jane N; Leggat, Peter

    2015-01-01

    This 1st edition of Essential Travel Medicine provides an excellent concise introduction to the specialty of Travel Medicine. This core text will enable health care practitioners particularly those new to the clinical practice of Travel Medicine, to gain a fundamental understanding of the diverse and complex issues which can potentially affect the health of the many millions of people who undertake international travel. Jane N Zuckerman is joined by Gary W Brunette from CDC and Peter A Leggat from Australia as Editors. Leading international specialists in their fields have contributed authoritative chapters reflecting current knowledge to facilitate best clinical practice in the different aspects of travel medicine. The aim of Essential Travel Medicine is to provide a comprehensive guide to Travel Medicine as well as a fundamental knowledge base to support international undergraduate and postgraduate specialty training programmes in the discipline of Travel Medicine. The 1st edition of Essential Travel ...

  1. Physics Essentials For Dummies

    CERN Document Server

    Holzner, Steven

    2010-01-01

    For students who just need to know the vital concepts of physics, whether as a refresher, for exam prep, or as a reference, Physics Essentials For Dummies is a must-have guide. Free of ramp-up and ancillary material, Physics Essentials For Dummies contains content focused on key topics only. It provides discrete explanations of critical concepts taught in an introductory physics course, from force and motion to momentum and kinetics. This guide is also a perfect reference for parents who need to review critical physics concepts as they help high school students with homework assignments, as we

  2. Essentials of Computational Electromagnetics

    CERN Document Server

    Sheng, Xin-Qing

    2012-01-01

    Essentials of Computational Electromagnetics provides an in-depth introduction of the three main full-wave numerical methods in computational electromagnetics (CEM); namely, the method of moment (MoM), the finite element method (FEM), and the finite-difference time-domain (FDTD) method. Numerous monographs can be found addressing one of the above three methods. However, few give a broad general overview of essentials embodied in these methods, or were published too early to include recent advances. Furthermore, many existing monographs only present the final numerical results without specifyin

  3. Corrosion impact of reductant on DWPF and downstream facilities

    Energy Technology Data Exchange (ETDEWEB)

    Mickalonis, J. I. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Imrich, K. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Jantzen, C. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Murphy, T. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Wilderman, J. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2014-12-01

    Glycolic acid is being evaluated as an alternate reductant in the preparation of high level waste for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS). During processing, the glycolic acid is not completely consumed and small quantities of the glycolate anion are carried forward to other high level waste (HLW) facilities. The impact of the glycolate anion on the corrosion of the materials of construction throughout the waste processing system has not been previously evaluated. A literature review had revealed that corrosion data in glycolate-bearing solution applicable to SRS systems were not available. Therefore, testing was recommended to evaluate the materials of construction of vessels, piping and components within DWPF and downstream facilities. The testing, conducted in non-radioactive simulants, consisted of both accelerated tests (electrochemical and hot-wall) with coupons in laboratory vessels and prototypical tests with coupons immersed in scale-up and mock-up test systems. Eight waste or process streams were identified in which the glycolate anion might impact the performance of the materials of construction. These streams were 70% glycolic acid (DWPF feed vessels and piping), SRAT/SME supernate (Chemical Processing Cell (CPC) vessels and piping), DWPF acidic recycle (DWPF condenser and recycle tanks and piping), basic concentrated recycle (HLW tanks, evaporators, and transfer lines), salt processing (ARP, MCU, and Saltstone tanks and piping), boric acid (MCU separators), and dilute waste (HLW evaporator condensate tanks and transfer line and ETF components). For each stream, high temperature limits and worst-case glycolate concentrations were identified for performing the recommended tests. Test solution chemistries were generally based on analytical results of actual waste samples taken from the various process facilities or of prototypical simulants produced in the laboratory. The materials of construction for most vessels

  4. ESSENTIAL DYNAMICS OF PROTEINS

    NARCIS (Netherlands)

    AMADEI, A; LINSSEN, ABM; BERENDSEN, HJC

    1993-01-01

    Analysis of extended molecular dynamics (MD) simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspaces: (1) an ''essential'' subspace containing only a few degrees of freedom in which anharmonic motion occurs that

  5. Essential Palatal Myoclonus

    Directory of Open Access Journals (Sweden)

    Bhuwan Raj Pandey

    2017-06-01

    Full Text Available Introduction: Palatal myoclonus is a rare condition presenting with clicking sound in ear or muscle tremor in pharynx. There are two varieties: essential and symptomatic. Various treatment options exists ranging from watchful observation to botulinum toxin injection. We have not found any reported case of palatal myoclonus from our country. Here we present a case of essential palatal myoclonus managed with clonazepam. Case report: A young female presented in Ear Nose and Throat clinic with complain of auditory click and spontaneous rhythmic movement of throat muscles for eight months. On examination, there was involuntary, rhythmic contraction of bilateral soft-palate, uvula, and base of tongue. Neurological, eye, and peripheral examination were normal. A diagnosis of essential palatal myoclonus was made. It was managed successfully with clonazepam; patient was still on low dose clonazepam at the time of making this report. Conclusion: Essential palatal myoclonus can be clinically diagnosed and managed even in settings where MRI is not available or affordable.

  6. The 2003 essential. AREVA

    International Nuclear Information System (INIS)

    2004-07-01

    This document presents the essential activities of the Areva Group, a world nuclear industry leader. This group proposes technological solutions to produce the nuclear energy and to transport the electric power. It develops connection systems for the telecommunication, the computers and the automotive industry. Key data on the program management, the sustainable development activities and the different divisions are provided. (A.L.B.)

  7. Essentials of Risk Theory

    NARCIS (Netherlands)

    Roeser, S.; Hillerbrand, R.; Sandin, P.; Peterson, M.B.

    2012-01-01

    Risk has become one of the main topics in fields as diverse as engineering, medicine and economics, and it is also studied by social scientists, psychologists and legal scholars. This Springer Essentials version offers an overview of the in-depth handbook and highlights some of the main points

  8. Essential trichomegaly: case report

    Directory of Open Access Journals (Sweden)

    Julia Dutra Rossetto

    2013-02-01

    Full Text Available The present study reports two cases of symptomatic essential trichomegaly. Trichomegaly may develop in various diseases, including anorexia nervosa, hypothyroidism, pregnancy, pretibial myxedema, systemic lupus erythematosus, vernal keratoconjunctivitis, and uveitis. The exact incidence trichomegaly is unknown, and the condition remains sporadically reported. Two cases of symptomatic trichomegaly without any associated systemic disorder are presented in this paper.

  9. Downstream process development in biotechnological itaconic acid manufacturing.

    Science.gov (United States)

    Magalhães, Antonio Irineudo; de Carvalho, Júlio Cesar; Medina, Jesus David Coral; Soccol, Carlos Ricardo

    2017-01-01

    Itaconic acid is a promising chemical that has a wide range of applications and can be obtained in large scale using fermentation processes. One of the most important uses of this biomonomer is the environmentally sustainable production of biopolymers. Separation of itaconic acid from the fermented broth has a considerable impact in the total production cost. Therefore, optimization and high efficiency downstream processes are technological challenges to make biorefineries sustainable and economically viable. This review describes the current state of the art in recovery and purification for itaconic acid production via bioprocesses. Previous studies on the separation of itaconic acid relying on operations such as crystallization, precipitation, extraction, electrodialysis, diafiltration, pertraction, and adsorption. Although crystallization is a typical method of itaconic acid separation from fermented broth, other methods such as membrane separation and reactive extraction are promising as a recovery steps coupled to the fermentation, potentially enhancing the overall process yield. Another approach is adsorption in fixed bed columns, which efficiently separates itaconic acid. Despite recent advances in separation and recovery methods, there is still space for improvement in IA recovery and purification.

  10. Simulation of hanging dams downstream of Ossauskoski power plant

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, J.; Huokuna, M. [Finnish Environment Inst., Helsinki (Finland); Severinkangas, K.; Talvensaari, M. [Kemijoki Oy, Rovaniemi (Finland)

    2008-07-01

    Sixteen power plants have been constructed along Finland's Kemijoki River for hydroelectric power production. The Ossauskoski facility has recently undergone major renovations and upgrade, making it the sixth largest hydroelectric power plant in Finland, with a new capacity of 124 MW and an annual energy output of 501 GWh. The increase in power output and discharge may cause changes in ice conditions downstream of the power plant. The section of the river is already subjected to frazil ice problems and hanging dam formation. Discharges and adverse effects of frazil ice phenomena are likely to increase due to climate change, resulting in harm for hydropower production and the environment, particularly in flow regulated rivers where winter discharges are higher than natural discharges. As such, a study was launched to investigate a dredge plan suggested by by the electric utility Kemijoki Oy. The project involved mapping the river bed topography to identify the location and extent of hanging dams. A sounding device and ground penetrating radar was used to find the thaw regions in the ice cover. The JJT numerical river ice model was effectively used to study the effect of hanging dams on water levels. However, the ice bridging phenomena was not modelled in a reliable way by the JJT model and will be modelled in the future using the CRISSP2D numerical model. 5 refs., 11 figs.

  11. Energy taxes and subsidies downstream: transparency and dissemination

    International Nuclear Information System (INIS)

    Aissaour, A.

    2001-01-01

    The reasons why governments levy taxes are discussed with special reference to the energy sector. The article focuses on the quantitative aspect of policies and gives a guide to the relevant statistical sources. It summarises the basis of taxes and subsidies and discusses the incidence of energy taxation together with the structure of taxes and subsidies in energy downstream. It reviews the main sources of data and issues highlighted by published statistics and the impact of taxes levied on the consumption of energy products and other taxes (e.g. VAT) which directly affect end-user prices. Production-based levies such as royalties, petroleum revenue taxes, windfall taxes and import and export taxes on fuels are not discussed. The paper is presented under the sub-headings of (i) theoretical foundations in a nutshell; (ii) the incidence of taxation; (iii) the structure and main features of energy taxation (iv) base rate and level of taxation (v) sources of data and methods and (vi) observability and comparability

  12. Gellan Gum: Fermentative Production, Downstream Processing and Applications

    Directory of Open Access Journals (Sweden)

    Ishwar B. Bajaj

    2007-01-01

    Full Text Available The microbial exopolysaccharides are water-soluble polymers secreted by microorganisms during fermentation. The biopolymer gellan gum is a relatively recent addition to the family of microbial polysaccharides that is gaining much importance in food, pharmaceutical and chemical industries due to its novel properties. It is commercially produced by C. P. Kelco in Japan and the USA. Further research and development in biopolymer technology is expected to expand its use. This article presents a critical review of the available information on the gellan gum synthesized by Sphingomonas paucimobilis with special emphasis on its fermentative production and downstream processing. Rheological behaviour of fermentation broth during fermentative production of gellan gum and problems associated with mass transfer have been addressed. Information on the biosynthetic pathway of gellan gum, enzymes and precursors involved in gellan gum production and application of metabolic engineering for enhancement of yield of gellan gum has been specified. Characteristics of gellan gum with respect to its structure, physicochemical properties, rheology of its solutions and gel formation behaviour are discussed. An attempt has also been made to review the current and potential applications of gellan gum in food, pharmaceutical and other industries.

  13. Glomerular prostaglandins modulate vascular reactivity of the downstream efferent arterioles.

    Science.gov (United States)

    Arima, S; Ren, Y; Juncos, L A; Carretero, O A; Ito, S

    1994-03-01

    The balance of vascular resistance in afferent (Af-) and efferent arterioles (Ef-Arts) is a crucial factor that determines glomerular hemodynamics. We have recently reported that when Ef-Arts were perfused from the distal end of the Af-Art through the glomerulus (orthograde perfusion; OP), both angiotensin II (Ang II) and norepinephrine (NE) induced much weaker constriction than they did when Ef-Arts were perfused from the distal end (retrograde perfusion; RP). This difference was not affected by inhibiting synthesis of nitric oxide. In the present study, we tested the hypothesis that glomerular prostaglandins (PGs) may modulate vascular reactivity of the downstream Ef-Art. In addition, we examined the possible modulatory role of PGs in the Af-Art responses to Ang II or NE. Both Ang II and NE caused dose-dependent constriction of Ef-Arts with either OP or RP; however, the constriction was stronger in RP. At 10(-8) M, Ang II decreased Ef-Art diameter by 35 +/- 3.5% in OP (N = 9) compared to 73 +/- 3.9% in RP (N = 5), while 10(-6) M NE decreased the diameter by 25 +/- 3.6% in OP (N = 9) compared to 62 +/- 7.2% in RP (N = 5). Pretreatment with 5 x 10(-5) M indomethacin (Indo) did not alter basal diameter with either method of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Flume experiments on scour downstream of wood stream restoration structures

    Science.gov (United States)

    Pagliara, Stefano; Kurdistani, Sahameddin Mahmoudi

    2017-02-01

    River restoration aims to improve physical natural form and processes of a river. Techniques to control the riverbed, stabilize channel alignment, protect stream banks, and rebuild the natural habitat are an important part of river restoration projects. Rivers can be stabilized and habitat restored through techniques such as rebuilding meanders and pool-riffle sequences and managing large wood. Structures that limit channel width to accelerate the normal flows through the constricted section are referred to as stream deflectors. Single-wing, double-wing and triangular deflectors are the most commonly used types of this measure. Log-frame deflectors consist of a triangular log frame filled with rock. Deflector constructions singly or in series in low gradient meandering streams, divert base flows toward the center of the channel and, under certain conditions, increase the depth and velocity of flow thereby creating scour pools and enhancing fish habitat. Scour characteristics and morphologies downstream of log-frame deflectors have been analyzed at the hydraulic laboratory of the University of Pisa. All experiments have been carried out in clear water conditions. The results showed that the tailwater depth plays an important role on scour characteristics. In addition, it was experimentally proven that using log-frame deflectors instead of log-deflectors result in a better river bank protection. In this case, for all the tested hydraulic conditions, the scour hole never occurred close to the channel bank. Useful empirical relationships have been proposed in order to evaluate the main features of the scour geometry.

  15. Incidental potable water reuse in a Catalonian basin: living downstream

    Directory of Open Access Journals (Sweden)

    R. Mujeriego

    2017-09-01

    Full Text Available A preliminary assessment of incidental potable water reuse (IPR in the Llobregat River basin has been conducted by estimating the dilution factor of treated effluent discharges upstream of six river flow measurement sections. IPR in the Llobregat River basin is an everyday occurrence, because of the systematic discharge of treated effluents upstream of river sections used as drinking water sources. Average river flows at the Sant Joan Despí measurement section increased from 400,000 m3/d (2007 to 864,000 m3/d (2008 and to 931,000 m3/d (2013, while treated effluent discharges upstream of that section ranged from 109,000 m3/d to 114,000 m3/d in those years. The highest degree of IPR occurs downstream of the Abrera and Sant Joan Despí flow measurement sections, from where about half of the drinking water supplied to the Barcelona Metropolitan Area is abstracted. Based on average annual flows, the likelihood that drinking water produced from that river stretch contained treated effluent varied from 25% (2007 to 13% (2008 and to 12% (2013. Water agencies and drinking water production utilities have strived for decades to ensure that drinking water production satisfies applicable quality requirements and provides the required public health protection.

  16. Downstream Processing, Formulation Development and Antithrombotic Evaluation of Microbial Nattokinase.

    Science.gov (United States)

    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.

  17. Transcription factor FoxO1 is essential for enamel biomineralization.

    Directory of Open Access Journals (Sweden)

    Ross A Poché

    Full Text Available The Transforming growth factor β (Tgf-β pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta.

  18. Occurrence and removal of antibiotics and the corresponding resistance genes in wastewater treatment plants: effluents' influence to downstream water environment.

    Science.gov (United States)

    Li, Jianan; Cheng, Weixiao; Xu, Like; Jiao, Yanan; Baig, Shams Ali; Chen, Hong

    2016-04-01

    In this study, the occurrence of 8 antibiotics [3 tetracyclines (TCs), 4 sulfonamides, and 1 trimethoprim (TMP)], 12 antibiotic resistance genes (ARGs) (10 tet, 2 sul), 4 types of bacteria [no antibiotics, anti-TC, anti-sulfamethoxazole (SMX), and anti-double], and intI1 in two wastewater treatment plants (WWTPs) were assessed and their influences in downstream lake were investigated. Both WWTPs' effluent demonstrated some similarities, but the abundance and removal rate varied significantly. Results revealed that biological treatment mainly removed antibiotics and ARGs, whereas physical techniques were found to eliminate antibiotic resistance bacteria (ARBs) abundance (about 1 log for each one). UV disinfection did not significantly enhance the removal efficiency, and the release of the abundantly available target contaminants from the excess sludge may pose threats to human and the environment. Different antibiotics showed diverse influences on the downstream lake, and the concentrations of sulfamethazine (SM2) and SMX were observed to increase enormously. The total ARG abundance ascended about 0.1 log and some ARGs (e.g., tetC, intI1, tetA) increased due to the high input of the effluent. In addition, the abundance of ARB variation in the lake also changed, but the abundance of four types of bacteria remained stable in the downstream sampling sites.

  19. Simulating potential structural and operational changes for Detroit Dam on the North Santiam River, Oregon, for downstream temperature management

    Science.gov (United States)

    Buccola, Norman L.; Rounds, Stewart A.; Sullivan, Annett B.; Risley, John C.

    2012-01-01

    structural options were explored with the model scenarios. Multiple downstream temperature targets were used along with three sets of environmental forcing conditions representing cool/wet, normal, and hot/dry conditions. Five structural options at Detroit Dam were modeled, including the use of existing outlets, one hypothetical variable-elevation outlet such as a sliding gate, a hypothetical combination of a floating outlet and a fixed-elevation outlet, and a hypothetical combination of a floating outlet and a sliding gate. Finally, 14 sets of operational guidelines for Detroit Dam were explored to gain an understanding of the effects of imposing different downstream minimum streamflows, imposing minimum outflow rules to specific outlets, and managing the level of the lake with different timelines through the year. Selected subsets of these combinations of operational and structural scenarios were run through the downstream models of Big Cliff Reservoir and the North Santiam and Santiam Rivers to explore how hypothetical changes at Detroit Dam might provide improved temperatures for endangered salmonids downstream of the Detroit-Big Cliff Dam complex. Conclusions that can be drawn from these model scenarios include: *The water-temperature targets set by the U.S. Army Corps of Engineers for releases from Detroit Dam can be met through a combination of new dam outlets or a delayed drawdown of the lake in autumn. *Spring and summer dam operations greatly affect the available release temperatures and operational flexibility later in the autumn. Releasing warm water during midsummer tends to keep more cool water available for release in autumn. *The ability to meet downstream temperature targets during spring depends on the characteristics of the available outlets. Under existing conditions, although warm water sometimes is present at the lake surface in spring and early summer, such water may not be available for release if the lake level is either well below or well above the

  20. Genetics Home Reference: essential tremor

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Essential tremor Essential tremor Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Essential tremor is a movement disorder that causes involuntary, rhythmic ...

  1. Essentials of artificial intelligence

    CERN Document Server

    Ginsberg, Matt

    1993-01-01

    Since its publication, Essentials of Artificial Intelligence has beenadopted at numerous universities and colleges offering introductory AIcourses at the graduate and undergraduate levels. Based on the author'scourse at Stanford University, the book is an integrated, cohesiveintroduction to the field. The author has a fresh, entertaining writingstyle that combines clear presentations with humor and AI anecdotes. At thesame time, as an active AI researcher, he presents the materialauthoritatively and with insight that reflects a contemporary, first hand

  2. Moodle administration essentials

    CERN Document Server

    Henrick, Gavin

    2015-01-01

    If you are an experienced system administrator and know how to manage servers and set up web environments but now want to explore Moodle, this book is perfect for you. You'll get to grips with the basics and learn to manage Moodle quickly, focusing on essential tasks. Having prior knowledge of virtual learning environments would be beneficial, but is not mandatory to make the most of this book.

  3. Essentials of Endodontic Microsurgery

    Science.gov (United States)

    2010-04-01

    Holtzman DJ, et al. Quality of root-end preparations using ultrasonic and rotary instrumentation in cadavers. J Endod 2000;26:281. 39. Peters CI...00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Essentials of Endodontic Microsurgery 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT... Endodontic Program,Harvard School of Dental Medicine,Boston,MA 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND

  4. Process Improvement Essentials

    CERN Document Server

    Persse, James R

    2006-01-01

    Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration.

  5. IPv6 Essentials

    CERN Document Server

    Hagen, Silvia

    2006-01-01

    IPv6 Essentials, Second Edition provides a succinct, in-depth tour of all the new features and functions in IPv6. It guides you through everything you need to know to get started, including how to configure IPv6 on hosts and routers and which applications currently support IPv6. Aimed at system and network administrators, engineers, network designers, and IT managers, this book will help you understand, plan for, design, and integrate IPv6 into your current IPv4 infrastructure

  6. Android application security essentials

    CERN Document Server

    Rai, Pragati

    2013-01-01

    Android Application Security Essentials is packed with examples, screenshots, illustrations, and real world use cases to secure your apps the right way.If you are looking for guidance and detailed instructions on how to secure app data, then this book is for you. Developers, architects, managers, and technologists who wish to enhance their knowledge of Android security will find this book interesting. Some prior knowledge of development on the Android stack is desirable but not required.

  7. Rake task management essentials

    CERN Document Server

    Koleshko, Andrey

    2014-01-01

    A step-by-step and interactive approach explaining the Rake essentials along with code examples and advanced features. If you are a developer who is acquainted with the Ruby language and want to speed up writing the code concerned with files, then this book is for you. To start reading this book, basic Ruby knowledge is required; however, a huge amount of experience with the language is not necessary.

  8. Wind-Driven Ecological Flow Regimes Downstream from Hydropower Dams

    Science.gov (United States)

    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

  9. Improved intake design for downstream migrating fish at hydropower plants

    International Nuclear Information System (INIS)

    Mih, W.C.

    1991-01-01

    This paper reports on hydroelectric power projects on the Columbia River which provided low-cost electricity to the Pacific Northwest. However, they are detrimental to anadromous fisheries resources. Anadromous fish are migratory. They begin their life in shallow mountain streams. After several months, they migrate to the ocean, where the fish grow to maturity before their return migration. Remarkably, most anadromous fish return to spawn in their natal streams. At dams, the upstream migration of grown salmon and steelhead is accomplished through fishways. The downstream migration of juveniles remains a serious problem. Juvenile fish follow the water flow during their sea-ward migration. When passing through a turbine, fish can be severely injured due to the sudden pressure drop, high velocity shear zones, and rotating turbine blades. Stunned fish that survive the gauntlet of the turbine are easy prey for sea gulls and squawfish in the tailrace of the powerhouse. Fish mortality per turbine passage is estimated at 15 percent. With nine hydropower projected on the main steam of the Columbia River, their combined mortality is very serious. The historical Columbia River anadromous run of about 12 million fish has declined to 2.5 million in recent years. Modern high-output hydraulic turbines are designed to be placed at a lower elevation to minimize cavitation damage to turbine blades. The modern design trend of deep intake submergence has caused parallel and unsteady vortex flow patterns in the forebay, resulting in a decrease in the guiding efficiency of the screens, such as at Bonneville Second Powerhouse and at Rocky Reach Project

  10. Downstream impacts of dams: shifts in benthic invertivorous fish assemblages

    Science.gov (United States)

    Granzotti, Rafaela Vendrametto; Miranda, Leandro E.; Agostinho, Angelo A.; Gomes, Luiz Carlos

    2018-01-01

    Impoundments alter connectivity, sediment transport and water discharge in rivers and floodplains, affecting recruitment, habitat and resource availability for fish including benthic invertivorous fish, which represent an important link between primary producers and higher trophic levels in tropical aquatic ecosystems. We investigated long-term changes to water regime, water quality, and invertivorous fish assemblages pre and post impoundment in three rivers downstream of Porto Primavera Reservoir in south Brazil: Paraná, Baía and Ivinhema rivers. Impacts were distinct in the Paraná River, which is fully obstructed by the dam, less evident in the Baía River which is partially obstructed by the dam, but absent in the unimpounded Ivinhema River. Changes in water regime were reflected mainly as changes in water-level fluctuation with little effect on timing. Water transparency increased in the Paraná River post impoundment but did not change in the Baía and Ivinhema rivers. Changes in fish assemblages included a decrease in benthic invertivorous fish in the Paraná River and a shift in invertivorous fish assemblage structure in the Baía and Paraná rivers but not in the unimpounded Ivinhema River. Changes in water regime and water transparency, caused by impoundment, directly or indirectly impacted invertivorous fish assemblages. Alterations of fish assemblages following environmental changes have consequences over the entire ecosystem, including a potential decrease in the diversity of mechanisms for energy flow. We suggest that keeping existing unimpounded tributaries free of dams, engineering artificial floods, and intensive management of fish habitat within the floodplain may preserve native fish assemblages and help maintain functionality and ecosystem services in highly impounded rivers.

  11. Low cost energy in Canada: The view from downstream

    International Nuclear Information System (INIS)

    Irving, K.

    1993-01-01

    The key cost determinants of energy in Canada are analyzed and recommendations are made to ensure the competitiveness of Canadian energy costs and energy-consuming industries in the North American and world markets. Oil supplies 45% of world energy and has a key role in determining prices of all other energy forms since it serves as an incremental source of energy: its consumption changes according to economic growth, changes in weather patterns, and other factors. North America currently accounts for about a third of world oil consumption. North American oil demand is expected to remain flat over the next few decades. As Canada only produces ca 3% of world oil supply, it cannot determine oil prices. However, with an efficient downstream industry, Canada can influence the end-user price of energy. The cost structure of refined products in Canada is analyzed. The cost of raw materials is the single biggest determinant of the final product cost, followed by taxes, operating costs, and profit margin. For gasoline in Ontario, taxes account for half the retail cost, crude oil prices ca 30%, and refining costs ca 4%. Refining costs comprise about two thirds labor costs and one third energy costs. Refiner margins have not exceeded 2 cents/l since 1981, creating reluctance to invest in the refining sector. By 1994, some 200,000 bbl/d of refining capacity is expected to be shut down in Canada. Compared to refineries in the USA, Canadian refineries are smaller and have a much lower capacity to upgrade residual fuel oil to light products. Future challenges to the industry include a projected need for $5 billion in investment, largely to fund new environmental initiatives. Such an investment cannot be met through current industry profits. 12 figs., 3 tabs

  12. Enhancing an essential service

    International Nuclear Information System (INIS)

    Konow, H.

    2004-01-01

    An annual review of the activities and accomplishments of the Canadian electrical industry as a whole and those of the Association's member companies is provided. In addition to recording activities of the past year, there is also extended discussion of the strategic issues facing the industry, and the planned responses of the industry as a whole, as well as responses by individual member companies. With regard to a collective response, the Association expects significant advances in the industry's downstream business from automated distribution, which enables utilities to remotely monitor, coordinate and operate distribution components in real-time mode. Beyond that, CEA proposes to deal with the mounting pressures facing the electricity sector on the basis of a five point plan which comprises (1) establishment of an investment climate to ensure future electricity supply; (2) moving government and industry towards smart and effective regulation; (3) working to ensure a sustainable future for the next generation; (4) fostering innovation and accelerating skill development. and (5) building a strong Canadian electricity system while strengthening North American institutional arrangements. With recurring references to the blackout in August 2003, the five point plan stresses mandatory reliability standards as a means to strengthen the electricity grid in the context of North American institutional arrangements, of which the most significant example is CEA's active involvement in the North American Electric Reliability Council (NERC). The extensive discussion of the industry's collective responses to the challenges facing the industry is followed by one-page reviews of the plans and objectives of CEA's 26 member companies representing the industry from coast to coast

  13. Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages

    Science.gov (United States)

    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

  14. Aberrations and Emittance Growth in the DARHT 2nd Axis Downstream Transport

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, Martin E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-24

    The emittance of the DARHT 2nd Axis has been inferred from solenoid scans performed in the downstream transport (DST) region using a short kicked pulse. The beam spot size is measured by viewing optical transition radiation (OTR) in the near field as a function of the field (current) of a solenoid magnet (S4). The imaging station containing the OTR target is located about 100 cm downstream of the solenoid magnet. The emittance is then inferred using a beam optics code such as LAMDA or XTR by fitting the data to initial conditions upstream of the S4 solenoid magnet. The initial conditions are the beam size, beam convergence and emittance. The beam energy and current are measured. In preparation for a solenoid scan, the magnets upstream of the solenoid are adjusted to produce a round beam with no beam losses due to scraping in the beam tube. This is different from the standard tune in which the beam tune is adjusted to suppress the effects of ions and rf in the septum dump. In this standard tune, approximately 10% of the beam is lost due to scraping as the beam enters the small 3.75” ID beam tube after the septum. The normalized emittance inferred from recent solenoid scans typically ranges from 600 to 800 π(mm-mrad). This larger beam size increases the sensitivity to any non-linear fields in the Collins quadrupoles that are mounted along the small diameter beam tube. The primary magnet used to adjust the beam size in this region is the S3 solenoid magnet. Measurements made of the beam shape as the beam size was decreased showed significant structure consistent with non-linear fields. Using the measured magnetic fields in the Collins quadrupoles including higher order multipoles, the beam transport through the Collins quadrupoles is simulated and compared to the observed OTR images. The simulations are performed using the beam optics codes TRANSPORT [1] and TURTLE [2]. Estimates of the emittance growth and beam losses are made as a function of the S3

  15. Play framework essentials

    CERN Document Server

    Richard-Foy, Julien

    2014-01-01

    This book targets Java and Scala developers who already have some experience in web development and who want to master Play framework quickly and efficiently. This book assumes you have a good level of knowledge and understanding of efficient Java and Scala code.

  16. Samii's essentials in neurosurgery

    International Nuclear Information System (INIS)

    Ramina, Ricardo; Pontifical Catholic Univ. of Parana, Curitiba; Pires Aguiar, Paulo Henrique; Sao Paulo Univ.; Hospital Santa Paula, Sao Paulo; Tatagiba, Marcos

    2008-01-01

    'Samii's Essentials in Neurosurgery' contains selected papers written by internationally recognized contributors who were trained by Professor Madjid Samii in Hannover, Germany. The main topics deal with cutting-edge technology in neurosurgery, skull-base surgery, and specific peripheral nerve, spine, and vascular surgeries. The texts and a wealth of illustrations review and reinforce guidelines on the diagnosis and management of situations that readers are likely to encounter in everyday practice. This book will be of great interest to neurosurgeons, neurologists, ENT surgeons, neuroradiologists, and neurophysiotherapists. (orig.)

  17. Geometry essentials for dummies

    CERN Document Server

    Ryan, Mark

    2011-01-01

    Just the critical concepts you need to score high in geometry This practical, friendly guide focuses on critical concepts taught in a typical geometry course, from the properties of triangles, parallelograms, circles, and cylinders, to the skills and strategies you need to write geometry proofs. Geometry Essentials For Dummies is perfect for cramming or doing homework, or as a reference for parents helping kids study for exams. Get down to the basics - get a handle on the basics of geometry, from lines, segments, and angles, to vertices, altitudes, and diagonals Conque

  18. Essentials of cloud computing

    CERN Document Server

    Chandrasekaran, K

    2014-01-01

    ForewordPrefaceComputing ParadigmsLearning ObjectivesPreambleHigh-Performance ComputingParallel ComputingDistributed ComputingCluster ComputingGrid ComputingCloud ComputingBiocomputingMobile ComputingQuantum ComputingOptical ComputingNanocomputingNetwork ComputingSummaryReview PointsReview QuestionsFurther ReadingCloud Computing FundamentalsLearning ObjectivesPreambleMotivation for Cloud ComputingThe Need for Cloud ComputingDefining Cloud ComputingNIST Definition of Cloud ComputingCloud Computing Is a ServiceCloud Computing Is a Platform5-4-3 Principles of Cloud computingFive Essential Charact

  19. Autodesk Maya 2014 essentials

    CERN Document Server

    Naas, Paul

    2013-01-01

    The premiere book on getting started with Maya 2014 Whether you're just beginning, or migrating from another 3D application, this step-by-step guide is what you need to get a good working knowledge of Autodesk Maya 2014. Beautifully illustrated with full-color examples and screenshots, Autodesk Maya 2014 Essentials explains the basics of Maya as well as modeling, texturing, animating, setting a scene, and creating visual effects. You'll absorb important concepts and techniques, and learn how to confidently use Maya tools the way professionals do. Each chapter includes fun and cha

  20. Essential dynamics and relativity

    CERN Document Server

    O'Donnell, Peter J

    2014-01-01

    Essential Dynamics & Relativity provides students with an introduction to the core aspects of dynamics and special relativity. The author reiterates important ideas and terms throughout and covers concepts that are often missing from other textbooks at this level. He also places each topic within the wider constructs of the theory, without jumping from topic to topic to illustrate a point.The first section of the book focuses on dynamics, discussing the basic aspects of single particle motion and analyzing the motion of multi-particle systems. The book also explains the dynamical behavior of b

  1. 3D Animation Essentials

    CERN Document Server

    Beane, Andy

    2012-01-01

    The essential fundamentals of 3D animation for aspiring 3D artists 3D is everywhere--video games, movie and television special effects, mobile devices, etc. Many aspiring artists and animators have grown up with 3D and computers, and naturally gravitate to this field as their area of interest. Bringing a blend of studio and classroom experience to offer you thorough coverage of the 3D animation industry, this must-have book shows you what it takes to create compelling and realistic 3D imagery. Serves as the first step to understanding the language of 3D and computer graphics (CG)Covers 3D anim

  2. Twisted network programming essentials

    CERN Document Server

    Fettig, Abe

    2005-01-01

    Twisted Network Programming Essentials from O'Reilly is a task-oriented look at this new open source, Python-based technology. The book begins with recommendations for various plug-ins and add-ons to enhance the basic package as installed. It then details Twisted's collection simple network protocols, and helper utilities. The book also includes projects that let you try out the Twisted framework for yourself. For example, you'll find examples of using Twisted to build web services applications using the REST architecture, using XML-RPC, and using SOAP. Written for developers who want to s

  3. The essential David Bohm

    CERN Document Server

    Nichol, Lee

    2002-01-01

    There are few scientists of the twentieth century whose life's work has created more excitement and controversy than that of physicist David Bohm (1917-1992). For the first time in a single volume, The Essential David Bohm offers a comprehensive overview of Bohm's original works from a non-technical perspective. Including three chapters of previously unpublished material, and a forward by the Dalai Lama, each reading has been selected to highlight some aspect of the implicate order process, and to provide an introduction to one of the most provocative thinkers of our time.

  4. Microsoft Windows Security Essentials

    CERN Document Server

    Gibson, Darril

    2011-01-01

    Windows security concepts and technologies for IT beginners IT security can be a complex topic, especially for those new to the field of IT. This full-color book, with a focus on the Microsoft Technology Associate (MTA) program, offers a clear and easy-to-understand approach to Windows security risks and attacks for newcomers to the world of IT. By paring down to just the essentials, beginners gain a solid foundation of security concepts upon which more advanced topics and technologies can be built. This straightforward guide begins each chapter by laying out a list of topics to be discussed,

  5. Microsoft Windows networking essentials

    CERN Document Server

    Gibson, Darril

    2011-01-01

    The core concepts and technologies of Windows networking Networking can be a complex topic, especially for those new to the field of IT. This focused, full-color book takes a unique approach to teaching Windows networking to beginners by stripping down a network to its bare basics, thereby making each topic clear and easy to understand. Focusing on the new Microsoft Technology Associate (MTA) program, this book pares down to just the essentials, showing beginners how to gain a solid foundation for understanding networking concepts upon which more advanced topics and technologies can be built.

  6. Cisco Networking Essentials

    CERN Document Server

    McMillan, Troy

    2011-01-01

    An engaging approach for anyone beginning a career in networking As the world leader of networking products and services, Cisco products are constantly growing in demand. Yet, few books are aimed at those who are beginning a career in IT--until now. Cisco Networking Essentials provides a solid foundation on the Cisco networking products and services with thorough coverage of fundamental networking concepts. Author Troy McMillan applies his years of classroom instruction to effectively present high-level topics in easy-to-understand terms for beginners. With this indispensable full-color resour

  7. French essentials for dummies

    CERN Document Server

    Lawless, Laura K

    2011-01-01

    Just the core concepts you need to write and speak French correctly If you have some knowledge of French and want to polish your skills, French Essentials For Dummies focuses on just the core concepts you need to communicate effectively. From conjugating verbs to understanding tenses, this easy-to-follow guide lets you skip the suffering and score high at exam time. French 101 - get the lowdown on the basics, from expressing dates and times to identifying parts of speech Gender matters - see how a noun's gender determines the articles, adjectives, and pronouns y

  8. Surface chemistry essentials

    CERN Document Server

    Birdi, K S

    2013-01-01

    Surface chemistry plays an important role in everyday life, as the basis for many phenomena as well as technological applications. Common examples range from soap bubbles, foam, and raindrops to cosmetics, paint, adhesives, and pharmaceuticals. Additional areas that rely on surface chemistry include modern nanotechnology, medical diagnostics, and drug delivery. There is extensive literature on this subject, but most chemistry books only devote one or two chapters to it. Surface Chemistry Essentials fills a need for a reference that brings together the fundamental aspects of surface chemistry w

  9. Cisco networking essentials

    CERN Document Server

    McMillan, Troy

    2015-01-01

    Start a career in networking Cisco Networking Essentials, 2nd Edition provides the latest for those beginning a career in networking. This book provides the fundamentals of networking and leads you through the concepts, processes, and skills you need to master fundamental networking concepts. Thinking of taking the CCENT Cisco Certified Entry Networking Technician ICND1 Exam 100-101? This book has you covered! With coverage of important topics and objectives, each chapter outlines main points and provides clear, engaging discussion that will give you a sound understanding of core topics and c

  10. RabbitMQ essentials

    CERN Document Server

    Dossot, David

    2014-01-01

    This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

  11. miR-342-5p Regulates Neural Stem Cell Proliferation and Differentiation Downstream to Notch Signaling in Mice

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2017-04-01

    Full Text Available Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl, was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs into intermediate neural progenitors (INPs in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

  12. C/EBPβ represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19Arf

    Science.gov (United States)

    Ewing, SJ; Zhu, S; Zhu, F; House, JS; Smart, RC

    2013-01-01

    CCAAT/enhancer-binding protein-β (C/EBPβ) is a mediator of cell survival and tumorigenesis. When C/EBPβ−/− mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19Arf and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19Arf is dramatically elevated in C/EBPβ−/− epidermis and that C/EBPβ represses a p19Arf promoter reporter. To determine whether p19Arf is responsible for the proapoptotic phenotype in C/EBPβ−/− mice, C/EBPβ−/−;p19Arf−/− mice were generated. C/EBPβ−/−;p19Arf−/− mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19Arf is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPβ−/− epidermis, we generated K14-ER:Ras; C/EBPβ−/− mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPβ−/− mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPβ represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPβ may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents. PMID:18636078

  13. Focal adhesion kinase, a downstream mediator of Raf-1 signaling, suppresses cellular adhesion, migration, and neuroendocrine markers in BON carcinoid cells.

    Science.gov (United States)

    Ning, Li; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2010-05-01

    We have recently reported that activation of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2)/ERK1/2 signaling cascade in gastrointestinal carcinoid cell line (BON) alters cellular morphology and neuroendocrine phenotype. The mechanisms by which Raf-1 mediates these changes in carcinoid cells are unclear. Here, we report that activation of the Raf-1 signaling cascade in BON cells induced the expression of focal adhesion kinase (FAK) protein, suppressed the production of neuroendocrine markers, and resulted in significant decreases in cellular adhesion and migration. Importantly, inactivation of MEK1/2 by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene or abolition of FAK induction in Raf-1-activated BON cells by targeted siRNA led to reversal of the Raf-1-mediated reduction in neuroendocrine markers and cellular adhesion and migration. Phosphorylation site-specific antibodies detected the phosphorylated FAK(Tyr407), but not FAK(Tyr397), in these Raf-1-activated cells, indicating that FAK(Tyr407) may be associated with changes in the neuroendocrine phenotype. Overexpression of constitutively active FAK plasmids (wild-type FAK or FAK(Tyr397) mutant) into BON cells reduced neuroendocrine markers, whereas the FAK(Tyr407) mutant plasmid did not show any decrease in the levels of neuroendocrine markers, indicating that phosphorylation of FAK at the Tyr(407) residue may be important for these effects. Our results showed for the first time that FAK is an essential downstream effector of the Raf-1/MEK1/2/ERK1/2 signaling cascade and negatively regulated the neuroendocrine and metastatic phenotype in BON cells. (c)2010 AACR.

  14. Calcium, essential for health

    Science.gov (United States)

    Martínez de Victoria, Emilio

    2016-07-12

    Calcium (Ca) is the most abundant mineral element in our body. It accounts for about 2% of body weight. The functions of calcium are: a) functions skeletal and b) regulatory functions. Bone consists of a protein matrix that mineralizes mainly with calcium (the most abundant), phosphate and magnesium, for it is essential an adequate dietary intake of Ca, phosphorus and vitamin D. The ionic Ca (Ca2+) is essential to maintain and / or perform different specialized functions of, virtually, all body cells cellular. Because of its important functions Ca2+ must be closely regulated, keeping plasma concentrations within narrow ranges. For this reason there is an accurate response against hypocalcemia or hypercalcemia in which the parathormone, calcitriol, calcitonin and vitamin K are involved. Ca intakes in the Spanish population are low in a significant percentage of the older adult’s population, especially in women. The main source of Ca in the diet is milk and milk derivatives. Green leafy vegetables, fruits and legumes can be important sources of Ca in a Mediterranean dietary pattern. The bioavailability of dietary Ca depends on physiological and dietary factors. Physiological include age, physiological status (gestation and lactation) Ca and vitamin D status and disease. Several studies relate Ca intake in the diet and various diseases, such as osteoporosis, cancer, cardiovascular disease and obesity.

  15. Computational analysis of the flow field downstream of flow conditioners

    Energy Technology Data Exchange (ETDEWEB)

    Erdal, Asbjoern

    1997-12-31

    Technological innovations are essential for maintaining the competitiveness for the gas companies and here metering technology is one important area. This thesis shows that computational fluid dynamic techniques can be a valuable tool for examination of several parameters that may affect the performance of a flow conditioner (FC). Previous design methods, such as screen theory, could not provide fundamental understanding of how a FC works. The thesis shows, among other things, that the flow pattern through a complex geometry, like a 19-hole plate FC, can be simulated with good accuracy by a k-{epsilon} turbulence model. The calculations illuminate how variations in pressure drop, overall porosity, grading of porosity across the cross-section and the number of holes affects the performance of FCs. These questions have been studied experimentally by researchers for a long time. Now an understanding of the important mechanisms behind efficient FCs emerges from the predictions. 179 ref., 110 figs., 8 tabs.

  16. Upstream and downstream relationship in an increasingly competitive environment

    International Nuclear Information System (INIS)

    Bergmann, Burckhard

    1999-01-01

    The electricity industry in some countries in Western Europe is changing faster and more extensively than expected. The same has not been true of multi-energy sales and multi-energy mergers and the question is: Will the gas industry evolve in a similar way? A development for gas similar to that for electricity is not observed, and the author illustrates the differences. There are many uncertainties. A very important factor for developments in Western Europe will be how the major producers, Russia, Norway and the Netherlands, position themselves. But there are also unchanging actions and modes of behaviour which are justified in different market scenarios, and they are discussed. It is concluded that it is essential to ensure that policy-makers allow sufficient latitude for market forces and leave the final decision to the consumer

  17. Diphasic flow downstream of circulation-water condenser during priming

    International Nuclear Information System (INIS)

    Ibler, B.; Sabaton, M.; Canavelis, R.

    1982-01-01

    The experimental study presented here describes the experiments for visualizing diphasic flow carried out on a 1/10 model of a circulation-water condenser for a 1,300-MW nuclear power unit. The essential object of the experiments was to validate the layout for the tubing proposed by the Design Office, from the point of view of its incidence on the stability of the flows and the mechanical solidity of the structures during the relatively anarchical phase of automatic priming of the condenser. The observations made have rendered it possible firstly to analyse the pattern of flows in greater detail and secondly to conclude that a simplified and cheaper layout of pipes is acceptable without great risk [fr

  18. Target Essentiality and Centrality Characterize Drug Side Effects

    OpenAIRE

    Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan

    2013-01-01

    Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...

  19. Essentials and Targets of Water Resources Management in Kenya

    International Nuclear Information System (INIS)

    Mutuku, J. Mutinga

    2006-01-01

    Fresh water comprises of 3% of the global waters and the rest is saline and not suitable for consumption without subjecting it to expensive treatment. Water is associated with development since civilization started in areas where water was easily accessible. However, much of the 3% is locked up in the ice caps. Water scarcity in any community is associated with abject poverty. The ecosystem functions of water and it's interactions with other environmental resources are least appreciated which has contributed to over exploitation, misuse, contamination, impairment and degradation of water bodies and their catchments. Over-exploitation of ground water in some coastal areas has in turn led to of seawater into freshwater aquifers and therefore making the water from aquifers unaccessible due to salinity

  20. Targeting the Synthetic Essential Kinases of Breast Cancers

    Science.gov (United States)

    2016-05-01

    engineering via Cas9. Science 2013, 339(6121):823-826. 31. Koike-Yusa H, Li Y, Tan EP, Velasco- Herrera MD, Yusa K: Genome-wide recessive genetic screening in...Yusa H, Li Y, Tan EP, Velasco- Herrera Mdel C, Yusa K: Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA

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

    DEFF Research Database (Denmark)

    Davidsen, Claus; Liu, Suxia; Mo, Xingguo

    2015-01-01

    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......), 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...

  2. PTHrP promotes malignancy of human oral cancer cell downstream of the EGFR signaling

    International Nuclear Information System (INIS)

    Yamada, Tamaki; Tsuda, Masumi; Ohba, Yusuke; Kawaguchi, Hideaki; Totsuka, Yasunori; Shindoh, Masanobu

    2008-01-01

    Parathyroid hormone-related protein (PTHrP) is detected in many aggressive tumors and involved in malignant conversion; however, the underlying mechanism remains obscure. Here, we identified PTHrP as a mediator of epidermal growth factor receptor (EGFR) signaling to promote the malignancies of oral cancers. PTHrP mRNA was abundantly expressed in most of the quiescent oral cancer cells, and was significantly upregulated by EGF stimulation via ERK and p38 MAPK. PTHrP silencing by RNA interference, as well as EGFR inhibitor AG1478 treatment, significantly suppressed cell proliferation, migration, and invasiveness. Furthermore, combined treatment of AG1478 and PTHrP knockdown achieved synergistic inhibition of malignant phenotypes. Recombinant PTHrP substantially promoted cell motility, and rescued the inhibition by PTHrP knockdown, suggesting the paracrine/autocrine function of PTHrP. These data indicate that PTHrP contributes to the malignancy of oral cancers downstream of EGFR signaling, and may thus provide a therapeutic target for oral cancer

  3. Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

    KAUST Repository

    Barbarani, Gloria

    2017-10-20

    The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis.

  4. CypA, a gene downstream of HIF-1α, promotes the development of PDAC.

    Directory of Open Access Journals (Sweden)

    Huan Zhang

    Full Text Available Hypoxia-inducible factor-1α (HIF-1α is a highly important transcription factor involved in cell metabolism. HIF-1α promotes glycolysis and inhibits of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC. In response to tumor hypoxia, cyclophilin A (CypA is over-expressed in various cancer types, and is associated with cell apoptosis, tumor invasion, metastasis, and chemoresistance in PDAC. In this study, we showed that both HIF-1α and CypA expression were significantly associated with lymph node metastasis and tumor stage. The expression of CypA was correlated with HIF-1α. Moreover, the mRNA and protein expression of CypA markedly decreased or increased following the suppression or over-expression of HIF-1α in vitro. Chromatin immunoprecipitation analysis showed that HIF-1α could directly bind to the hypoxia response element (HRE in the CypA promoter regions and regulated CypA expression. Consistent with other studies, HIF-1α and CypA promoted PDAC cell proliferation and invasion, and suppressed apoptosis in vitro. Furthermore, we proved the combination effect of 2-methoxyestradiol and cyclosporin A both in vitro and in vivo. These results suggested that,CypA, a gene downstream of HIF-1α, could promote the development of PDAC. Thus, CypA might serve as a potential therapeutic target for PDAC.

  5. Essential numerical computer methods

    CERN Document Server

    Johnson, Michael L

    2010-01-01

    The use of computers and computational methods has become ubiquitous in biological and biomedical research. During the last 2 decades most basic algorithms have not changed, but what has is the huge increase in computer speed and ease of use, along with the corresponding orders of magnitude decrease in cost. A general perception exists that the only applications of computers and computer methods in biological and biomedical research are either basic statistical analysis or the searching of DNA sequence data bases. While these are important applications they only scratch the surface of the current and potential applications of computers and computer methods in biomedical research. The various chapters within this volume include a wide variety of applications that extend far beyond this limited perception. As part of the Reliable Lab Solutions series, Essential Numerical Computer Methods brings together chapters from volumes 210, 240, 321, 383, 384, 454, and 467 of Methods in Enzymology. These chapters provide ...

  6. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  7. Are Archetypes Essential?

    Science.gov (United States)

    Colman, Warren

    2018-06-01

    This paper distinguishes between Jung's theoretical discourse regarding the archetypes and his phenomenological account of numinous experience. For this author, the initial attraction of 'my Jung' came from both the vivid Romanticism of his descriptions of the anima and the apparent 'ground of being' offered by his theory of archetypes. However, the essentialism inherent to archetypal theory in general and the anima in particular has necessitated a re-evaluation of Jung's theory in terms of emergence theory. My own version of this emphasises the role of symbols in the constitution of affect through collective human action in the world. In this reconfiguration, the visceral energy of numinous experience is retained while the problematic theory of archetypes is no longer needed. © 2018, The Society of Analytical Psychology.

  8. Essential French grammar

    CERN Document Server

    Thacker, Mike

    2014-01-01

    Essential French Grammar is an innovative reference grammar and workbook for intermediate and advanced undergraduate students of French (CEFR levels B2 to C1). Its clear explanations of grammar are supported by contemporary examples and lively cartoon drawings.  Each chapter contains: * real-life language examples in French, with English translations * a 'key points' box and tables that summarise grammar concepts * a variety of exercises to reinforce learning * a contemporary primary source or literary extract to illustrate grammar in context. To aid your understanding, this book also contains a glossary of grammatical terms in French and English, useful verb tables and a key to the exercises. Together, these features all help you to grasp complex points of grammar and develop your French language skills.

  9. Essentials of nonlinear optics

    CERN Document Server

    Murti, Y V G S

    2014-01-01

    Current literature on Nonlinear Optics varies widely in terms of content, style, and coverage of specific topics, relative emphasis of areas and the depth of treatment. While most of these books are excellent resources for the researchers, there is a strong need for books appropriate for presenting the subject at the undergraduate or postgraduate levels in Universities. The need for such a book to serve as a textbook at the level of the bachelors and masters courses was felt by the authors while teaching courses on nonlinear optics to students of both science and engineering during the past two decades. This book has emerged from an attempt to address the requirement of presenting the subject at college level. A one-semester course covering the essentials can effectively be designed based on this.

  10. Essential real analysis

    CERN Document Server

    Field, Michael

    2017-01-01

    This book provides a rigorous introduction to the techniques and results of real analysis, metric spaces and multivariate differentiation, suitable for undergraduate courses. Starting from the very foundations of analysis, it offers a complete first course in real analysis, including topics rarely found in such detail in an undergraduate textbook such as the construction of non-analytic smooth functions, applications of the Euler-Maclaurin formula to estimates, and fractal geometry.  Drawing on the author’s extensive teaching and research experience, the exposition is guided by carefully chosen examples and counter-examples, with the emphasis placed on the key ideas underlying the theory. Much of the content is informed by its applicability: Fourier analysis is developed to the point where it can be rigorously applied to partial differential equations or computation, and the theory of metric spaces includes applications to ordinary differential equations and fractals. Essential Real Analysis will appeal t...

  11. TQM: the essential concepts.

    Science.gov (United States)

    Chambers, D W

    1998-01-01

    This is an introduction to the major concepts in total quality management, a loose collection of management approaches that focus on continuous improvement of processes, guided by routine data collection and adjustment of the processes. Customer focus and involvement of all members of an organization are also characteristics commonly found in TQM. The seventy-five-year history of the movement is sketched from its beginning in statistical work on quality assurance through the many improvements and redefinitions added by American and Japanese thinkers. Essential concepts covered include: control cycles, focus on the process rather than the defects, the GEAR model, importance of the customer, upstream quality, just-in-time, kaizen, and service quality.

  12. 40 CFR 80.210 - What sulfur standards apply to gasoline downstream from refineries and importers?

    Science.gov (United States)

    2010-07-01

    ... combined with non-S-RGAS for the sole purpose of producing midgrade gasoline. (6) Where S-RGAS is being... of the gasoline. (f) Downstream standards applicable to S-RGAS when produced or imported. (1) The downstream standard applicable to any gasoline classified as S-RGAS when produced or imported shall be...

  13. Hydrodynamic properties and distribution of bait downstream of a zooplankton trap

    DEFF Research Database (Denmark)

    Selander, Erik; Heuschele, Jan; Larsson, Ann I.

    2017-01-01

    The flow regime around a chemically baited trap is crucial for the trapping process and distribution of bait downstream of traps. We measured the flow field downstream of a trap prototype in flume experiments and mapped the distribution of bait using laser induced fluorescence. The trap produced ...

  14. 40 CFR 80.220 - What are the downstream standards for GPA gasoline?

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false What are the downstream standards for GPA gasoline? 80.220 Section 80.220 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... downstream location other than at a retail outlet or wholesale purchaser-consumer facility, and during the...

  15. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.

    2017-05-08

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  16. The brassinosteroid receptor BRI1 can generate cGMP enabling cGMP-dependent downstream signaling

    KAUST Repository

    Wheeler, Janet I.; Wong, Aloysius Tze; Marondedze, Claudius; Groen, Arnoud J.; Kwezi, Lusisizwe; Freihat, Lubna; Vyas, Jignesh; Raji, Misjudeen; Irving, Helen R.; Gehring, Christoph A

    2017-01-01

    The brassinosteroid receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is a member of the leucine rich repeat receptor like kinase family. The intracellular kinase domain of BRI1 is an active kinase and also encapsulates a guanylate cyclase catalytic centre. Using liquid chromatography tandem mass spectrometry, we confirmed that the recombinant cytoplasmic domain of BRI1 generates pmol amounts of cGMP per μg protein with a preference for magnesium over manganese as a co-factor. Importantly, a functional BRI1 kinase is essential for optimal cGMP generation. Therefore, the guanylate cyclase activity of BRI1 is modulated by the kinase while cGMP, the product of the guanylate cyclase, in turn inhibits BRI1 kinase activity. Furthermore, we show using Arabidopsis root cell cultures that cGMP rapidly potentiates phosphorylation of the downstream substrate BRASSINOSTEROID SIGNALING KINASE 1 (BSK1). Taken together, our results suggest that cGMP acts as a modulator that enhances downstream signaling while dampening signal generation from the receptor. This article is protected by copyright. All rights reserved.

  17. Ratings of Essentialism for Eight Religious Identities.

    Science.gov (United States)

    Toosi, Negin R; Ambady, Nalini

    2011-01-01

    As a social identity, religion is unique because it contains a spectrum of choice. In some religious communities, individuals are considered members by virtue of having parents of that background, and religion, culture, and ethnicity are closely intertwined. Other faith communities actively invite people of other backgrounds to join, expecting individuals to choose the religion that best fits their personal beliefs. These various methods of identification influence beliefs about the essentialist nature of religious identity. Essentialism is when social groups are considered to have deep, immutable, and inherent defining properties. In this study, college students (N=55) provided ratings of essentialism for eight religious identities: Atheist, Buddhist, Catholic, Hindu, Jewish, Muslim, Protestant, and Spiritual-but-not-religious. Significant differences in essentialism were found between the target groups. Results and implications for intergroup relations are discussed.

  18. [Resistance to target-based therapy and its circumvention].

    Science.gov (United States)

    Nishio, Kazuto

    2004-07-01

    Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

  19. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

    Science.gov (United States)

    Frost, Julianty; Galdeano, Carles; Soares, Pedro; Gadd, Morgan S.; Grzes, Katarzyna M.; Ellis, Lucy; Epemolu, Ola; Shimamura, Satoko; Bantscheff, Marcus; Grandi, Paola; Read, Kevin D.; Cantrell, Doreen A.; Rocha, Sonia; Ciulli, Alessio

    2016-11-01

    Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling.

  20. Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling

    Science.gov (United States)

    Ashton, Gabrielle H.; Morton, Jennifer P.; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.

    2012-01-01

    SUMMARY The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588

  1. Downstream events of neurogenin 3 in pancreatic endocrine differentiation

    DEFF Research Database (Denmark)

    Christ, Louise Christiane Rosenberg

    cells into insulin producing cells in vitro. The hope is that successful production of ß-cells from stem cells combined with a good protocol for the transplantation of these cells into human beings would offer an opportunity for diabetes patients to obtain a normal glucose homeostasis and be relieved......Diabetes affects more than 170 million people world wide and a prognosis suggests that the prevalence will increase over the next 30 year. In Denmark, the prevalence doubled from 1996 to 2007, where 240.000 people were affected. Diabetes is the manifestation of abnormalities regarding glucose...... target of Neurog3. The truncated Neurog3 proteins revealed that an intact bHLH domain and the region of amino acids flanking the bHLH on the N-terminal side may be involved in nuclear localisation as the proteins lacking the N-terminal domain or with a truncated bHLH domain were present to a larger...

  2. Emittance growth in the DARHT Axis-II Downstream Transport

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Jr., Carl August [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Schulze, Martin E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-04-14

    Using a particle-in-cell (PIC) code, we investigated the possibilities for emittance growth through the quadrupole magnets of the system used to transport the high-current electron beam from an induction accelerator to the bremsstrahlung converter target used for flash radiography. We found that even highly mismatched beams exhibited little emittance growth (< 6%), which we attribute to softening of their initial hard edge current distributions. We also used this PIC code to evaluate the accuracy of emittance measurements using a solenoid focal scan following the quadrupole magnets. If the beam is round after the solenoids, the simulations indicate that the measurement is highly accurate, but it is substantially inaccurate for elliptical beams

  3. Exploring the Optimal Strategy to Predict Essential Genes in Microbes

    Directory of Open Access Journals (Sweden)

    Yao Lu

    2011-12-01

    Full Text Available Accurately predicting essential genes is important in many aspects of biology, medicine and bioengineering. In previous research, we have developed a machine learning based integrative algorithm to predict essential genes in bacterial species. This algorithm lends itself to two approaches for predicting essential genes: learning the traits from known essential genes in the target organism, or transferring essential gene annotations from a closely related model organism. However, for an understudied microbe, each approach has its potential limitations. The first is constricted by the often small number of known essential genes. The second is limited by the availability of model organisms and by evolutionary distance. In this study, we aim to determine the optimal strategy for predicting essential genes by examining four microbes with well-characterized essential genes. Our results suggest that, unless the known essential genes are few, learning from the known essential genes in the target organism usually outperforms transferring essential gene annotations from a related model organism. In fact, the required number of known essential genes is surprisingly small to make accurate predictions. In prokaryotes, when the number of known essential genes is greater than 2% of total genes, this approach already comes close to its optimal performance. In eukaryotes, achieving the same best performance requires over 4% of total genes, reflecting the increased complexity of eukaryotic organisms. Combining the two approaches resulted in an increased performance when the known essential genes are few. Our investigation thus provides key information on accurately predicting essential genes and will greatly facilitate annotations of microbial genomes.

  4. Fluvial wood function downstream of beaver versus man-made dams in headwater streams in Massachusetts, USA

    Science.gov (United States)

    David, G. C.; DeVito, L. F.; Munz, K. T.; Lisius, G.

    2014-12-01

    Fluvial wood is an essential component of stream ecosystems by providing habitat, increasing accumulation of organic matter, and increasing the processing of nutrients and other materials. However, years of channel alterations in Massachusetts have resulted in low wood loads despite the afforestation that has occurred since the early 1900s. Streams have also been impacted by a large density of dams, built during industrialization, and reduction of the beaver population. Beavers were reintroduced to Massachusetts in the 1940s and they have since migrated throughout the state. Beaver dams impound water, which traps sediment and results in the development of complex channel patterns and more ecologically productive and diverse habitats than those found adjacent to man-made dams. To develop better management practices for dam removal it is essential that we understand the geomorphic and ecologic function of wood in these channels and the interconnections with floodplain dynamics and stream water chemistry. We investigate the connections among fluvial wood, channel morphology, floodplain soil moisture dynamics, and stream water chemistry in six watersheds in Massachusetts that have been impacted by either beaver or man-made dams. We hypothesize that wood load will be significantly higher below beaver dams, subsequently altering channel morphology, water chemistry, and floodplain soil moisture. Reaches are surveyed up- and downstream of each type of dam to better understand the impact dams have on the fluvial system. Surveys include a longitudinal profile, paired with dissolved oxygen and ammonium measurements, cross-section and fluvial wood surveys, hydraulic measurements, and floodplain soil moisture mapping. We found that dissolved oxygen mirrored the channel morphology, but did not vary significantly between reaches. Wood loads were significantly larger downstream of beaver dams, which resulted in significant changes to the ammonium levels. Floodplain soil moisture

  5. Rhetoric and Essentially Contested Arguments

    Science.gov (United States)

    Garver, Eugene

    1978-01-01

    Draws a connection between Gallie's essentially contested concepts and Aristotle's account of rhetorical argument by presenting a definition of Essentially Contested Argument which is used as the connecting term between rhetoric and essentially contested concepts and by demonstrating the value of making this connection. (JF)

  6. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    Directory of Open Access Journals (Sweden)

    Christopher A Lavender

    2016-08-01

    Full Text Available 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.

  7. Mercury exposure in terrestrial birds far downstream of an historical point source

    International Nuclear Information System (INIS)

    Jackson, Allyson K.; Evers, David C.; Folsom, Sarah B.; Condon, Anne M.; Diener, John; Goodrick, Lizzie F.; McGann, Andrew J.; Schmerfeld, John; Cristol, Daniel A.

    2011-01-01

    Mercury (Hg) is a persistent environmental contaminant found in many freshwater and marine ecosystems. Historical Hg contamination in rivers can impact the surrounding terrestrial ecosystem, but there is little known about how far downstream this contamination persists. In 2009, we sampled terrestrial forest songbirds at five floodplain sites up to 137 km downstream of an historical source of Hg along the South and South Fork Shenandoah Rivers (Virginia, USA). We found that blood total Hg concentrations remained elevated over the entire sampling area and there was little evidence of decline with distance. While it is well known that Hg is a pervasive and long-lasting aquatic contaminant, it has only been recently recognized that it also biomagnifies effectively in floodplain forest food webs. This study extends the area of concern for terrestrial habitats near contaminated rivers for more than 100 km downstream from a waterborne Hg point source. - Highlights: → We report blood mercury levels for terrestrial songbirds downstream of contamination. → Blood mercury levels remain elevated above reference for at least 137 km downstream. → Trends vary based on foraging guild and migration strategy. → Mercury affects terrestrial biota farther downstream than previously documented. - Blood mercury levels of forest songbirds remain elevated above reference levels for at least 137 km downstream of historical point source.

  8. Mercury exposure in terrestrial birds far downstream of an historical point source

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Allyson K., E-mail: allyson.jackson@briloon.org [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States); Evers, David C.; Folsom, Sarah B. [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); Condon, Anne M. [U.S. Fish and Wildlife Service, 6669 Short Lane, Gloucester, VA 23061 (United States); Diener, John; Goodrick, Lizzie F. [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); McGann, Andrew J. [Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States); Schmerfeld, John [U.S. Fish and Wildlife Service, 6669 Short Lane, Gloucester, VA 23061 (United States); Cristol, Daniel A. [Institute for Integrative Bird Behavior Studies, Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187 (United States)

    2011-12-15

    Mercury (Hg) is a persistent environmental contaminant found in many freshwater and marine ecosystems. Historical Hg contamination in rivers can impact the surrounding terrestrial ecosystem, but there is little known about how far downstream this contamination persists. In 2009, we sampled terrestrial forest songbirds at five floodplain sites up to 137 km downstream of an historical source of Hg along the South and South Fork Shenandoah Rivers (Virginia, USA). We found that blood total Hg concentrations remained elevated over the entire sampling area and there was little evidence of decline with distance. While it is well known that Hg is a pervasive and long-lasting aquatic contaminant, it has only been recently recognized that it also biomagnifies effectively in floodplain forest food webs. This study extends the area of concern for terrestrial habitats near contaminated rivers for more than 100 km downstream from a waterborne Hg point source. - Highlights: > We report blood mercury levels for terrestrial songbirds downstream of contamination. > Blood mercury levels remain elevated above reference for at least 137 km downstream. > Trends vary based on foraging guild and migration strategy. > Mercury affects terrestrial biota farther downstream than previously documented. - Blood mercury levels of forest songbirds remain elevated above reference levels for at least 137 km downstream of historical point source.

  9. Changes in the Mountain Cryosphere and Potential Risks to Downstream Communities: Insights from the Indian Himalayan Region

    Science.gov (United States)

    Allen, Simon; Ballesteros, Juan Antonio; Huggel, Christian; Linsbauer, Andreas; Mal, Suraj; Singh Rana, Ranbir; Singh Randhawa, Surjeet; Ruiz-Villanueva, Virginia; Salzmann, Nadine; Singh Samant, Sher; Stoffel, Markus

    2017-04-01

    Mountain environments around the world are often considered to be amongst the most sensitive to the impacts of climate change. For people living in mountain communities, there are clear challenges to be faced as their livelihoods and subsistence are directly dependent on their surrounding natural environment. But what of the wider implications for societies and large urban settlements living downstream - why should they care about the climate-driven changes occurring potentially hundreds of kilometers away in the snow and ice capped mountains? In this contribution we address this question, drawing on studies and experiences gained within joint Indo-Swiss research collaborations focused on the Indian Himalayan states of Himachal Pradesh and Uttarakhand. With the Intergovernmental Panel on Climate Change currently embarking on the scoping of their 6th Assessment Cycle, which includes a planned Special Report on Oceans and the Cryosphere, this contribution provides a timely reminder of the importance of mountain regions, and potential far-reaching consequences of changes in the mountain cryosphere. Our studies highlight several key themes which link the mountain environment to the lowland populated areas, including the role of the mountain cryosphere as a water source, far-reaching hazards and disasters that can originate from mountain regions, the role of mountains in providing essential ecosystem services, the economic importance of tourism in mountain regions, and the importance of transportation routes which pass through mountain environments. These themes are intricately linked, as for example demonstrated during the 2013 Uttarakhand flood disaster where many of the approximately 6000 fatalities were tourists visiting high mountain pilgrimage sites. As a consequence of the disaster, tourists stayed away during subsequent seasons with significant economic impacts felt across the State. In Himachal Pradesh, a key national transportation corridor is the Rohtang pass

  10. Downstream fish passage guide walls: A hydraulic scale model analysis

    Science.gov (United States)

    Mulligan, Kevin; Towler, Brett; Haro, Alexander J.; Ahlfeld, David P.

    2018-01-01

    Partial-depth guide walls are used to improve passage efficiency and reduce the delay of out-migrating anadromous fish species by guiding fish to a bypass route (i.e. weir, pipe, sluice gate) that circumvents the turbine intakes, where survival is usually lower. Evaluation and monitoring studies, however, indicate a high propensity for some fish to pass underneath, rather than along, the guide walls, compromising their effectiveness. In the present study we evaluated a range of guide wall structures to identify where/if the flow field shifts from sweeping (i.e. flow direction primarily along the wall and towards the bypass) to downward-dominant. Many migratory fish species, particularly juveniles, are known to drift with the flow and/or exhibit rheotactic behaviour during their migration. When these behaviours are present, fish follow the path of the flow field. Hence, maintaining a strong sweeping velocity in relation to the downward velocity along a guide wall is essential to successful fish guidance. Nine experiments were conducted to measure the three-dimensional velocity components upstream of a scale model guide wall set at a wide range of depths and angles to flow. Results demonstrated how each guide wall configuration affected the three-dimensional velocity components, and hence the downward and sweeping velocity, along the full length of the guide wall. In general, the velocities produced in the scale model were sweeping dominant near the water surface and either downward dominant or close to the transitional depth near the bottom of the guide wall. The primary exception to this shift from sweeping do downward flow was for the minimum guide wall angle tested in this study (15°). At 15° the flow pattern was fully sweeping dominant for every cross-section, indicating that a guide wall with a relatively small angle may be more likely to produce conditions favorable to efficient guidance. A critical next step is to evaluate the behaviour of migratory fish as

  11. SWATH2stats: An R/Bioconductor Package to Process and Convert Quantitative SWATH-MS Proteomics Data for Downstream Analysis Tools.

    Science.gov (United States)

    Blattmann, Peter; Heusel, Moritz; Aebersold, Ruedi

    2016-01-01

    SWATH-MS is an acquisition and analysis technique of targeted proteomics that enables measuring several thousand proteins with high reproducibility and accuracy across many samples. OpenSWATH is popular open-source software for peptide identification and quantification from SWATH-MS data. For downstream statistical and quantitative analysis there exist different tools such as MSstats, mapDIA and aLFQ. However, the transfer of data from OpenSWATH to the downstream statistical tools is currently technically challenging. Here we introduce the R/Bioconductor package SWATH2stats, which allows convenient processing of the data into a format directly readable by the downstream analysis tools. In addition, SWATH2stats allows annotation, analyzing the variation and the reproducibility of the measurements, FDR estimation, and advanced filtering before submitting the processed data to downstream tools. These functionalities are important to quickly analyze the quality of the SWATH-MS data. Hence, SWATH2stats is a new open-source tool that summarizes several practical functionalities for analyzing, processing, and converting SWATH-MS data and thus facilitates the efficient analysis of large-scale SWATH/DIA datasets.

  12. Measurement of velocity deficit at the downstream of a 1:10 axial hydrokinetic turbine model

    Energy Technology Data Exchange (ETDEWEB)

    Gunawan, Budi [ORNL; Neary, Vincent S [ORNL; Hill, Craig [St. Anthony Falls Laboratory, 2 Third Avenue SE, Minneapolis, MN 55414; Chamorro, Leonardo [St. Anthony Falls Laboratory, 2 Third Avenue SE, Minneapolis, MN 55414

    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.

  13. Managerial Communication. Essential Aspect of Organizational Development

    Directory of Open Access Journals (Sweden)

    Marius Florentin POPA

    2012-11-01

    Full Text Available Organizational communication is a process usually intended for exchanging messages between individuals, groups and organizational levels within the organization, in order to achieve both individual and collective targets. For any organization, communication is an essential requirement in achieving the targets, a sine qua non condition for its efficient functioning, establishing the most basic human relationships. Solely an effective communication can enable the planning and scheduling, coordination and control, motivation, consultation and active participation of an organization’s members in order to achieve the proposed goals. Therefore, there is a closely connection between the ability to communicate of each employee and the ability to lead of each manager. Based on various communication networks and various management styles, an organization shall function at the highest standards solving any problems and fulfilling any targets.

  14. Experimental investigation of fish downstream passage and turbine related fish mortality at an innovative hydro power setup

    International Nuclear Information System (INIS)

    Geiger, Franz; Cuchet, Mathilde; Rutschmann, Peter

    2016-01-01

    The fish downstream passage of small fish at the innovative TUM hydro shaft power plant concept was investigated experimentally. The behavior of 1974 inserted individuals of brown trout, grayling, barbel, minnow and bullhead of 45 mm to 220 mm body length was observed in a fully functional test setup which included a 35 kW Kaplan turbine and a horizontal screen with 20 mm bar clearance. The 24 h tests were conducted under nature like conditions whereas the laboratory environment also enabled targeted hydraulic situations and modifications of the bypass during the test series. A recapture rate of the fish of 99% and a subsequent 96 h observation period yielded detailed information about the migration behavior and instant as well as long term mortality. The results reveal the actual passage distribution of small fish between bypass and turbine and the turbine related injury and mortality rates in dependency of fish species, fish length, turbine discharge and bypass arrangement. General trends as well as species specific particularities could be deduced. The work confirms the suitability of the employed experimental approach and the ecological potential of the investigated hydro power plant concept. The behavioral barrier effect of the screen on small fish and the necessary of appropriate downstream migration corridor were proved and quantified. (authors)

  15. A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.

    Science.gov (United States)

    Ma, Hongming; Dang, Ying; Wu, Yonggan; Jia, Gengxiang; Anaya, Edgar; Zhang, Junli; Abraham, Sojan; Choi, Jang-Gi; Shi, Guojun; Qi, Ling; Manjunath, N; Wu, Haoquan

    2015-07-28

    West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the ER-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. CERN: Fixed target targets

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-03-15

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become visible for the first

  17. Physical and Chemical Connectivity of Streams and Riparian Wetlands to Downstream Waters: A Synthesis

    Science.gov (United States)

    Streams, riparian areas, floodplains, alluvial aquifers, and downstream waters (e.g., large rivers, lakes, and oceans) are interconnected by longitudinal, lateral, and vertical fluxes of water, other materials, and energy. Collectively, these interconnected waters are called fluv...

  18. The dynamics of entrepreneurship in ICT: case of mobile phones downstream services in Kenya

    NARCIS (Netherlands)

    R.N. Kanothi (Raphael)

    2009-01-01

    textabstractThe research paper explores the extent to which mobile phones downstream services, defined here as those provided using the existing connectivity, are generating opportunities for entrepreneurship development in Kenya. After identifying the services of mobile payphones, money transfer

  19. Evaluation of a Solid Phase DNA Binding Matrix for Downstream PCR Analysis

    National Research Council Canada - National Science Library

    Bader, Douglas E; Fisher, Glen R; Stratilo, Chad W

    2005-01-01

    A commercially available solid-phase DNA binding matrix (FTA cards) was evaluated for its ability to capture and release DNA for downstream gene amplification and detection assays using polymerase chain reaction (PCR...

  20. Downstream reporter gene imaging for signal transduction pathway of dopamine type 2 receptor

    International Nuclear Information System (INIS)

    Le, Uyenchi N.; Min, Jung Joon; Moon, Sung Min; Bom, Hee Seung

    2004-01-01

    The Dopamine 2 receptor (D2R) signal pathway regulates gene expression by phosphorylation of proteins including cAMP reponse element-binding protein (CREB), a transcription factor. In this study, we developed a reporter strategy using the GAL4 fusion CREB to assess the phosphorylation of CREB, one of the targets of the D2R signal transduction pathway. We used three plasmids: GAL4 fusion transactivator (pCMV-CREB), firefly luciferase reporter with GAL4 binding sites (pG5-FLUC), and D2R plasmid (pCMV-D2R). Group 1 293T cells were transiently transfected with pCMV-CREB and pG5-FLUC, and group 2 cells were transfected with all three plasmids. Transfected cells were stimulated with different concentrations of dopamine (0-200 M). For animal studies, group 1 and 2 cells (1x10 6 ) were subcutaneously injected on the left and right thigh of six nude mice, respectively. Dopamine stimiulation was performed with intraperitoneal injection of L-DOPA incombination with carbidopa, a peripheral DOPA decarboxylase inhibitor. Bioluminescence optical imaging studies were performed before and after L-DOPA injection. In cell culture studies, group 1 cells showed strong luciferase activity which implies direct activation of the signaling pathway due to growth factors contained in culture medium. Group 2 cells showed strong luciferase activity and a further increase after administration of dopamine. In animal studies, group 1 and 2 cells showed bioluminescence signal before L-DOPA injection, but signal from group 2 cells significantly increased 12 h after L-DOPA injection. The signal from group 1 cells disappeared thereafter, but group 2 cells continued to show signal until 36 h of L-DOPA injection. This study demonstrates imaging of the D2R signal transduction pathway and should be useful for noninvasive imaging of downstream effects of G-coupled protein pathways

  1. Suspended sediments from upstream tributaries as the source of downstream river sites

    Science.gov (United States)

    Haddadchi, Arman; Olley, Jon

    2014-05-01

    Understanding the efficiency with which sediment eroded from different sources is transported to the catchment outlet is a key knowledge gap that is critical to our ability to accurately target and prioritise management actions to reduce sediment delivery. Sediment fingerprinting has proven to be an efficient approach to determine the sources of sediment. This study examines the suspended sediment sources from Emu Creek catchment, south eastern Queensland, Australia. In addition to collect suspended sediments from different sites of the streams after the confluence of tributaries and outlet of the catchment, time integrated suspended samples from upper tributaries were used as the source of sediment, instead of using hillslope and channel bank samples. Totally, 35 time-integrated samplers were used to compute the contribution of suspended sediments from different upstream waterways to the downstream sediment sites. Three size fractions of materials including fine sand (63-210 μm), silt (10-63 μm) and fine silt and clay (<10 μm) were used to find the effect of particle size on the contribution of upper sediments as the sources of sediment after river confluences. And then samples were analysed by ICP-MS and -OES to find 41 sediment fingerprints. According to the results of Student's T-distribution mixing model, small creeks in the middle and lower part of the catchment were major source in different size fractions, especially in silt (10-63 μm) samples. Gowrie Creek as covers southern-upstream part of the catchment was a major contributor at the outlet of the catchment in finest size fraction (<10 μm) Large differences between the contributions of suspended sediments from upper tributaries in different size fractions necessitate the selection of appropriate size fraction on sediment tracing in the catchment and also major effect of particle size on the movement and deposition of sediments.

  2. Downstream wind flow path diversion and its effects on the performance of vertical axis wind turbine

    International Nuclear Information System (INIS)

    Maganhar, A.L.

    2015-01-01

    In the present experimental study efforts have been made to analysis path diversion effect of downstream wind flow on performance of vertical axis wind turbine (VAWT). For the blockage of downstream wind flow path at various linear displaced positions, a normal erected flat wall, semi-circular and cylindrical shapes were tested for path diverting geometries. Performance of VAWT in terms of improved rotor speed up to 45% was achieved. (author)

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

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-09-17

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  4. Scheduling with target start times

    NARCIS (Netherlands)

    Hoogeveen, J.A.; Velde, van de S.L.; Klein Haneveld, W.K.; Vrieze, O.J.; Kallenberg, L.C.M.

    1997-01-01

    We address the single-machine problem of scheduling n independent jobs subject to target start times. Target start times are essentially release times that may be violated at a certain cost. The goal is to minimize an objective function that is composed of total completion time and maximum

  5. Influence of Upstream and Downstream Compressor Stators on Rotor Exit Flow Field

    Directory of Open Access Journals (Sweden)

    Nicole L. Key

    2014-01-01

    Full Text Available Measurements acquired at the rotor exit plane illuminate the interaction of the rotor with the upstream vane row and the downstream vane row. The relative phase of the upstream and downstream vane rows is adjusted using vane clocking so that the effect of the upstream propagating potential field from the downstream stator can be distinguished from the effects associated with the wakes shed from the upstream stator. Unsteady absolute flow angle information shows that the downstream potential field causes the absolute flow angle to increase in the vicinity of the downstream stator leading edge. The presence of Stator 1 wake is also detected at this measurement plane using unsteady total pressure data. The rotor wakes are measured at different circumferential locations across the vane passage, and the influence of Stator 1 wake on the suction side of the rotor wake is evident. Also, the influence of the downstream stator is detected on the pressure side of the rotor wake for a particular clocking configuration. Understanding the role of the surrounding vane rows on rotor wake development will lead to improved comparison between experimental data and results from computational models.

  6. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  7. Essential oils and anxiolytic aromatherapy.

    Science.gov (United States)

    Setzer, William N

    2009-09-01

    A number of essential oils are currently in use as aromatherapy agents to relieve anxiety, stress, and depression. Popular anxiolytic oils include lavender (Lavandula angustifolia), rose (Rosa damascena), orange (Citrus sinensis), bergamot (Citrus aurantium), lemon (Citrus limon), sandalwood (Santalum album), clary sage (Salvia sclarea), Roman chamomile (Anthemis nobilis), and rose-scented geranium (Pelargonium spp.). This review discusses the chemical constituents and CNS effects of these aromatherapeutic essential oils, as well as recent studies on additional essential oils with anxiolytic activities.

  8. Essential Oils and Antifungal Activity

    Science.gov (United States)

    Coppola, Raffaele; De Feo, Vincenzo

    2017-01-01

    Since ancient times, folk medicine and agro-food science have benefitted from the use of plant derivatives, such as essential oils, to combat different diseases, as well as to preserve food. In Nature, essential oils play a fundamental role in protecting the plant from biotic and abiotic attacks to which it may be subjected. Many researchers have analyzed in detail the modes of action of essential oils and most of their components. The purpose of this brief review is to describe the properties of essential oils, principally as antifungal agents, and their role in blocking cell communication mechanisms, fungal biofilm formation, and mycotoxin production. PMID:29099084

  9. Cladding Heatup Prediction between Spacer Grids for the Downstream Effect Evaluation

    International Nuclear Information System (INIS)

    Park, J. Y.; Kim, M. W.

    2009-01-01

    Since a recirculation sump clogging issue by debris generated from high energy pipe line break had been invoked as GSI-191 in the US, many researches on this issue have been undertaken. Previous researches on this topic are well summarized in Bang et al. Due to comprehensive nature of the issue, it includes many area of research and one of them is the area of downstream effect evaluation. The downstream effect is involved with adverse effects of debris passing the sump screen on the downstream systems, components and piping including core and it can be further divided into an ex-vessel downstream effect and an in-vessel downstream effect. In the ex-vessel downstream effect, focus is laid on plugging of spray nozzle, wearing and abrasion of moving parts of pump and valve and etc. Otherwise, a debris effect on reactor core is focused in the in-vessel downstream effect. Since debris can be ingested in the core or the systems of downstream of sump screen during recirculation, basically the downstream effect influences long-term core cooling phase. With respect to the in-vessel downstream effect, an up-to-date evaluation methodology is well summarized in a topical report submitted to the US nuclear regulatory commission by the pressurized water reactor owners group (PWROG). The report evaluates various aspects of debris ingestion in the core such as blockage at the core inlet, collection of debris on fuel grids, plating-out of fuel, chemical precipitants, protective coatings effect and etc. Most of them are evaluated qualitative manner based on previous research results and geometrical consideration on fuel rod bundles but some of them are also backed up by quantitative calculations to corroborate the qualitative decisions. One of them is a cladding heatup calculation between spacer grids. This is done to demonstrate that the cladding temperature of a fuel rod between grids with debris deposited on the clad surface in a post- LOCA recirculation environment is below

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

    Science.gov (United States)

    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

  11. Oldman river dam mitigation program downstream vegetation project report, Volume II: The potential effects of an operating plan for the Oldman River dam on Riparian cottonwood forests

    Energy Technology Data Exchange (ETDEWEB)

    Mahoney, J.M.

    1993-01-01

    Extensive cottonwood (poplar) forests exist in the Oldman River valley downstream of the Oldman River dam. Studies of similar forests in nearby river valleys and elsewhere on the western prairies have found significant declines of some riparian forests following river damming. This investigation was initiated to determine the causes of cottonwood forest decline downstream from existing dams in southern Alberta; inventory the existing river valley forests in the Oldman Basin; establish study sites in the Oldman River forests to monitor changes in forest status following commissioning of the Oldman River dam, and evaluate the probable impact of proposed operating plans for the Oldman River dam and associated water control structures on downstream forests. This report summarizes the progress made in the analyses of the probable effects on the survival of the forests, including a discussion of the hydrological conditions essential for cottonwood forest regeneration and an explanation of the effects of altering these characteristics on riparian forests; the hydrological alterations expected along various river reaches in the Oldman Basin with the implementation of the proposed OD05 Oldman Dam operating plan; and preliminary analyses of the problem impacts of the OD05 operating plan on the cottonwood forests along these reaches.

  12. Target laboratory

    International Nuclear Information System (INIS)

    Ephraim, D.C.; Pednekar, A.R.

    1993-01-01

    A target laboratory to make stripper foils for the accelerator and various targets for use in the experiments is set up in the pelletron accelerator facility. The facilities available in the laboratory are: (1) D.C. glow discharge setup, (2) carbon arc set up, and (3) vacuum evaporation set up (resistance heating), electron beam source, rolling mill - all for target preparation. They are described. Centrifugal deposition technique is used for target preparation. (author). 3 figs

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

    Science.gov (United States)

    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

  14. Ice targets

    International Nuclear Information System (INIS)

    Pacheco, C.; Stark, C.; Tanaka, N.; Hodgkins, D.; Barnhart, J.; Kosty, J.

    1979-12-01

    This report presents a description of ice targets that were constructed for research work at the High Resolution Spectrometer (HRS) and at the Energetic Pion Channel and Spectrometer (EPICS). Reasons for using these ice targets and the instructions for their construction are given. Results of research using ice targets will be published at a later date

  15. Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor γ, controls hepatitis B virus replication

    International Nuclear Information System (INIS)

    Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin

    2011-01-01

    In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adiponectin, liver X receptor α (LXRα), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPARγ and C/EBPα. Conversely, HBV replication was upregulated by adiponectin and PPARγ agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.

  16. CEBPA exerts a specific and biologically important proapoptotic role in pancreatic β cells through its downstream network targets

    DEFF Research Database (Denmark)

    Barbagallo, Davide; Condorelli, Angelo Giuseppe; Piro, Salvatore

    2014-01-01

    Transcription factor CEBPA has been widely studied for its involvement in hematopoietic cell differentiation and causal role in hematological malignancies. We demonstrate here that it also performs a causal role in cytokine-induced apoptosis of pancreas β cells. Treatment of two mouse pancreatic ...

  17. MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets

    Directory of Open Access Journals (Sweden)

    Ferdinando Fiumara

    2015-06-01

    Full Text Available The maintenance phase of memory-related long-term facilitation (LTF of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22 that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC, another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity.

  18. MicroRNA-22 Gates Long-Term Heterosynaptic Plasticity in Aplysia through Presynaptic Regulation of CPEB and Downstream Targets.

    Science.gov (United States)

    Fiumara, Ferdinando; Rajasethupathy, Priyamvada; Antonov, Igor; Kosmidis, Stylianos; Sossin, Wayne S; Kandel, Eric R

    2015-06-30

    The maintenance phase of memory-related long-term facilitation (LTF) of synapses between sensory and motor neurons of the gill-withdrawal reflex of Aplysia depends on a serotonin (5-HT)-triggered presynaptic upregulation of CPEB, a functional prion that regulates local protein synthesis at the synapse. The mechanisms whereby serotonin regulates CPEB levels in presynaptic sensory neurons are not known. Here, we describe a sensory neuron-specific microRNA 22 (miR-22) that has multiple binding sites on the mRNA of CPEB and inhibits it in the basal state. Serotonin triggers MAPK/Erk-dependent downregulation of miR-22, thereby upregulating the expression of CPEB, which in turn regulates, through functional CPE elements, the presynaptic expression of atypical PKC (aPKC), another candidate regulator of memory maintenance. Our findings support a model in which the neurotransmitter-triggered downregulation of miR-22 coordinates the regulation of genes contributing synergistically to the long-term maintenance of memory-related synaptic plasticity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Analytical prediction of the unsteady lift on a rotor caused by downstream struts

    Science.gov (United States)

    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.

  20. Characterization equipment essential drawing plan

    International Nuclear Information System (INIS)

    WILSON, G.W.

    1999-01-01

    The purpose of this document is to list the Characterization equipment drawings that are classified as Essential Drawings. Essential Drawings: Are those drawings identified by the facility staff as necessary to directly support the safe operation of the facility or equipment (HNF 1997a). The Characterization equipment drawings identified in this report are deemed essential drawings as defined in HNF-PRO-242, Engineering Drawing Requirements (HNF 1997a). These drawings will be prepared, revised, and maintained per HNF-PRO-440, Engineering Document Change Control (HNF 1997b). All other Characterization equipment drawings not identified in this document will be considered Support drawings until the Characterization Equipment Drawing Evaluation Report is completed

  1. An experimental study on downstream of the transition of the chemically reacting liquid round free jet

    International Nuclear Information System (INIS)

    Hong, S.D.; Sugii, Y.; Okamoto, K.; Madarame, H.

    2002-01-01

    An experimental study was conducted on the chemically reacting liquid round free jet, Laser Induced Fluorescence (LIF) technique was adopted to evaluate the diffusion width of the jet into liquid streams. In the fluid engineering, it is very important to evaluate the characteristics of reacting jet for the safety of the nuclear reactor. In this study, the jet profile of downstream region far away from the transition point was evaluated, providing comparisons between reacting and non-reacting jet case. The concentration of the jet solution was varied from 0.01 mol/L to 0.5 mol/L in reacting cases. In the downstream far away from the transition point, the jet profiles between reacting cases and non-reacting cases were visualized quite different. It was concluded that the chemical reaction affects the momentum diffusion of the jet in the downstream region. (author)

  2. Photoperiod control of downstream movements of Atlantic salmon Salmo salar smolts

    Science.gov (United States)

    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 lightening and upward heavying, sorting of sediments of uniform grain size but differing in density

    Science.gov (United States)

    Viparelli, E.; Solari, L.; Hill, K. M.

    2014-12-01

    Downstream fining, i.e. the tendency for a gradual decrease in grain size in the downstream direction, has been observed and studied in alluvial rivers and in laboratory flumes. Laboratory experiments and field observations show that the vertical sorting pattern over a small Gilbert delta front is characterized by an upward fining profile, with preferential deposition of coarse particles in the lowermost part of the deposit. The present work is an attempt to answer the following questions. Are there analogous sorting patterns in mixtures of sediment particles having the same grain size but differing density? To investigate this, we performed experiments at the Hydrosystems Laboratory at the University of Illinois at Urbana-Champaign. During the experiments a Gilbert delta formed and migrated downstream allowing for the study of transport and sorting processes on the surface and within the deposit. The experimental results show 1) preferential deposition of heavy particles in the upstream part of the deposit associated with a pattern of "downstream lightening"; and 2) a vertical sorting pattern over the delta front characterized by a pattern of "upward heavying" with preferential deposition of light particles in the lowermost part of the deposit. The observed downstream lightening is analogous of the downstream fining with preferential deposition of heavy (coarse) particles in the upstream part of the deposit. The observed upward heavying was unexpected because, considering the particle mass alone, the heavy (coarse) particles should have been preferentially deposited in the lowermost part of the deposit. Further, the application of classical fractional bedload transport relations suggests that in the case of mixtures of particles of uniform size and different densities equal mobility is not approached. We hypothesize that granular physics mechanisms traditionally associated with sheared granular flows may be responsible for the observed upward heavying and for the

  4. Downstream-Conditioned Maximum Entropy Method for Exit Boundary Conditions in the Lattice Boltzmann Method

    Directory of Open Access Journals (Sweden)

    Javier A. Dottori

    2015-01-01

    Full Text Available A method for modeling outflow boundary conditions in the lattice Boltzmann method (LBM based on the maximization of the local entropy is presented. The maximization procedure is constrained by macroscopic values and downstream components. The method is applied to fully developed boundary conditions of the Navier-Stokes equations in rectangular channels. Comparisons are made with other alternative methods. In addition, the new downstream-conditioned entropy is studied and it was found that there is a correlation with the velocity gradient during the flow development.

  5. Recent hydrocarbon developments in Latin America: Key issues in the downstream oil sector

    International Nuclear Information System (INIS)

    Wu, K.; Pezeshki, S.

    1995-01-01

    This report discusses the following: (1) An overview of major issues in the downstream oil sector, including oil demand and product export availability, the changing product consumption pattern, and refineries being due for major investment; (2) Recent upstream developments in the oil and gas sector in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Trinidad and Tobago, and Venezuela; (3) Recent downstream developments in the oil and gas sector in Argentina, Chile, Colombia, Ecuador, Mexico, Peru, Cuba, and Venezuela; (4) Pipelines in Argentina, Bolivia, Brazil, Chile, and Mexico; and (5) Regional energy balance. 4 figs., 5 tabs

  6. Estimating Subcatchment Runoff Coefficients using Weather Radar and a Downstream Runoff Sensor

    DEFF Research Database (Denmark)

    Ahm, Malte; Thorndahl, Søren Liedtke; Rasmussen, Michael R.

    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....

  7. Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Poulsen, Hans S

    2010-01-01

    Overexpression and/or amplification of the epidermal growth factor receptor (EGFR) is present in 35-45% of primary glioblastoma multiforme tumors and has been correlated with a poor prognosis. In this study, we investigated the effect of cetuximab and intracellular signaling pathways downstream...... of EGFR, important for cell survival and proliferation. We show insufficient EGFR downregulation and competition with endogenous EGFR ligands upon cetuximab treatment. Dose-response experiments showed inhibition of EGFR phosphorylation without affecting two of the prominent downstream signaling pathways....... Our results indicate that amplification and/or overexpression of EGFR is an unsatisfactory predictor for response to cetuximab....

  8. Recent hydrocarbon developments in Latin America: Key issues in the downstream oil sector

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  10. Introduction to sump screen downstream effect analysis of AP1000 nuclear power plant

    International Nuclear Information System (INIS)

    Zhang Qinghua; Liu Yu; Chai Guohan

    2010-01-01

    The design of AP1000 takes into account the potential impact of debris clogging on sump screen. In this article, the technical background of sump screen issue and the design characteristics of AP1000 to address the sump screen blockage issue are introduced. The article focuses on the 'downstream effect' analysis method, acceptance criteria and analysis result of AP1000 sump screen. Although the design of AP1000 is different with traditional PWR, the author expects to bring some reference to advance the downstream effect analysis in China through the introduction. (authors)

  11. Essential idempotents and simplex codes

    Directory of Open Access Journals (Sweden)

    Gladys Chalom

    2017-01-01

    Full Text Available We define essential idempotents in group algebras and use them to prove that every mininmal abelian non-cyclic code is a repetition code. Also we use them to prove that every minimal abelian code is equivalent to a minimal cyclic code of the same length. Finally, we show that a binary cyclic code is simplex if and only if is of length of the form $n=2^k-1$ and is generated by an essential idempotent.

  12. Evaluating the Invasion of Red Cedar (Juniperus viriginiana) Downstream of Gavins Point Dam, Missouri National Recreational River

    Science.gov (United States)

    Greene, S.; Knox, J. C.

    2013-12-01

    Gavins Point Dam, the final dam on the main-stem Missouri River, alters downstream river form and function. Throughout a 59-mile downstream reach, the dam reduces overbank flooding and lowers the water surface by 1-3 meters. Under the dam-created hydro-geomorphic conditions, native cottonwood trees are unable to regenerate. The limited regeneration of native riparian cottonwoods, the lowered water surface, and the reduced overbank flooding creates a terrace environment within the riparian habitat. Consequently, red cedars, a native upland tree, are invading this new terrace-like riparian environment. To this end, we apply Bayesian statistical models to investigate patterns of red cedar riparian invasion and assess ecosystem function patterns along this flow-regulated reach. We set up plots within cottonwood stands along a 59-km reach downstream of Gavins Point Dam. Within each plot, we collected soil samples, litter samples, stem densities of trees, and collected cores of the largest cottonwood and largest red cedar in each plot. To assess influences of red cedar on soil indicators of ecosystem function and general patterns of ecosystem function within the study area, we measured organic carbon, nitrogen, pH, electrical conductivity, and hydrophobicity. To determine drivers and patterns of invasion and ecosystem function we conducted Bayesian linear regressions and means comparison tests. Red cedars existed along the floodplain prior to regulation. However, according to our tree age data and stem density data red cedars existed at a lower population than today. We found that 2 out of 565 red cedars established before the dam was completed. Also, we found no significant difference in soil properties between soils with established red cedar and soils with established cottonwood. By studying soil texture data, and interpreting fluvial geomorphic surfaces in the field and via aerial photography, we found soil texture generally reflects the type of fluvial surface

  13. The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor.

    Science.gov (United States)

    Kim, Mi Jung; Jang, In-Cheol; Chua, Nam-Hai

    2016-07-01

    The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-β-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were down-regulated in wild-type or WRI1-overexpressing plants by silencing of MED15 However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant and WRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. Reservoir stratification affects methylmercury levels in river water, plankton, and fish downstream from Balbina hydroelectric dam, Amazonas, Brazil.

    Science.gov (United States)

    Kasper, Daniele; Forsberg, Bruce R; Amaral, João H F; Leitão, Rafael P; Py-Daniel, Sarah S; Bastos, Wanderley R; Malm, Olaf

    2014-01-21

    The river downstream from a dam can be more contaminated by mercury than the reservoir itself. However, it is not clear how far the contamination occurs downstream. We investigated the seasonal variation of methylmercury levels in the Balbina reservoir and how they correlated with the levels encountered downstream from the dam. Water, plankton, and fishes were collected upstream and at sites between 0.5 and 250 km downstream from the dam during four expeditions in 2011 and 2012. Variations in thermal stratification of the reservoir influenced the methylmercury levels in the reservoir and in the river downstream. Uniform depth distributions of methylmercury and oxygen encountered in the poorly stratified reservoir during the rainy season collections coincided with uniformly low methylmercury levels along the river downstream from the dam. During dry season collections, the reservoir was strongly stratified, and anoxic hypolimnion water with high methylmercury levels was exported downstream. Methylmercury levels declined gradually to 200 km downstream. In general, the methylmercury levels in plankton and fishes downstream from the dam were higher than those upstream. Higher methylmercury levels observed 200-250 km downstream from the dam during flooding season campaigns may reflect the greater inflow from tributaries and flooding of natural wetlands that occurred at this time.

  15. Temporal progression in migratory status and sexual maturation in European silver eels during downstream migration

    NARCIS (Netherlands)

    Palstra, A.P.; Guerrero, M.A.; Klein Breteler, J.G.P.; Thillart, G.E.E.J.M.

    2011-01-01

    The onset of downstream migration of European eels is accompanied by a cessation of feeding and the start of sexual maturation which stresses the link between metabolism and sexual maturation, also suggesting an important role for exercise. Exercise has been tested with eels in swim tunnels and was

  16. Contrasting morphodynamics in alluvial fans and fan deltas: effect of the downstream boundary

    NARCIS (Netherlands)

    Dijk, M. van; Kleinhans, M.G.; Postma, G.; Kraal, E.

    2012-01-01

    Alluvial fans and fan deltas can, in principle, have exactly the same upstream conditions, but fan deltas by definition have ponding water at their downstream boundary. This ponding creates effects on the autogenic behaviour of fan deltas, such as backwater adaptation, mouth bars and backward

  17. 5 X 5 rod bundle flow field measurements downstream a PWR spacer grid

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Higor F.P.; Silva, Vitor V A.; Santos, André A.C.; Veloso, Maria A.F., E-mail: higorfabiano@gmail.com, E-mail: mdora@nuclear.ufmg.br, E-mail: vitors@cdtn.br, E-mail: aacs@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    The spacer grids are structures present in nuclear fuel assembly of Pressurized Water Reactors (PWR). They play an important structural role and also assist in heat removal through the assembly by promoting increased turbulence of the flow. Understanding the flow dynamics downstream the spacer grid is paramount for fuel element design and analysis. This paper presents water flow velocity profiles measurements downstream a spacer grid in a 5 x 5 rod bundle test rig with the objective of highlighting important fluid dynamic behavior near the grid and supplying data for CFD simulation validation. These velocity profiles were obtained at two different heights downstream the spacer grid using a LDV (Laser Doppler Velocimetry) through the top of test rig. The turbulence intensities and patterns of the swirl and cross flow were evaluated. The tests were conducted for Reynolds numbers ranging from 1.8 x 10{sup 4} to 5.4 x 10{sup 4}. This experimental research was carried out in thermo-hydraulics laboratory of Nuclear Technology Development Center – CDTN. Results show great repeatability and low uncertainties (< 1.24 %). Details of the flow field show how the mixture and turbulence induced by the spacer grid quickly decays downstream the spacer grid. It is shown that the developed methodology can supply high resolution low uncertainty results that can be used for validation of CFD simulations. (author)

  18. 5 X 5 rod bundle flow field measurements downstream a PWR spacer grid

    International Nuclear Information System (INIS)

    Castro, Higor F.P.; Silva, Vitor V A.; Santos, André A.C.; Veloso, Maria A.F.

    2017-01-01

    The spacer grids are structures present in nuclear fuel assembly of Pressurized Water Reactors (PWR). They play an important structural role and also assist in heat removal through the assembly by promoting increased turbulence of the flow. Understanding the flow dynamics downstream the spacer grid is paramount for fuel element design and analysis. This paper presents water flow velocity profiles measurements downstream a spacer grid in a 5 x 5 rod bundle test rig with the objective of highlighting important fluid dynamic behavior near the grid and supplying data for CFD simulation validation. These velocity profiles were obtained at two different heights downstream the spacer grid using a LDV (Laser Doppler Velocimetry) through the top of test rig. The turbulence intensities and patterns of the swirl and cross flow were evaluated. The tests were conducted for Reynolds numbers ranging from 1.8 x 10"4 to 5.4 x 10"4. This experimental research was carried out in thermo-hydraulics laboratory of Nuclear Technology Development Center – CDTN. Results show great repeatability and low uncertainties (< 1.24 %). Details of the flow field show how the mixture and turbulence induced by the spacer grid quickly decays downstream the spacer grid. It is shown that the developed methodology can supply high resolution low uncertainty results that can be used for validation of CFD simulations. (author)

  19. Influence of peak flow changes on the macroinvertebrate drift downstream of a Brazilian hydroelectric dam.

    Science.gov (United States)

    Castro, D M P; Hughes, R M; Callisto, M

    2013-11-01

    Successive daily peak flows from hydropower plants can disrupt aquatic ecosystems and alter the composition and structure of macroinvertebrates downstream. We evaluated the influence of peak flow changes on macroinvertebrate drift downstream of a hydroelectric plant as a basis for determining ecological flows that might reduce the disturbance of aquatic biota. The aim of this study was to assess the influence of flow fluctuations on the seasonal and daily drift patterns of macroinvertebrates. We collected macroinvertebrates during fixed flow rates (323 m3.s-1 in the wet season and 111 m3.s-1 in the dry season) and when peak flows fluctuated (378 to 481 m3.s-1 in the wet season, and 109 to 173 m3.s-1 in the dry season) in 2010. We collected 31,924 organisms belonging to 46 taxa in the four sampling periods. Taxonomic composition and densities of drifting invertebrates differed between fixed and fluctuating flows, in both wet and dry seasons, but family richness varied insignificantly. We conclude that macroinvertebrate assemblages downstream of dams are influenced by daily peak flow fluctuations. When making environmental flow decisions for dams, it would be wise to consider drifting macroinvertebrates because they reflect ecological changes in downstream biological assemblages.

  20. Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

    Science.gov (United States)

    Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

    2013-05-01

    Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

  1. Physicochemical Characteristics of River Water Downstream of a Large Tropical Hydroelectric Dam

    Directory of Open Access Journals (Sweden)

    Teck-Yee Ling

    2016-01-01

    Full Text Available Water quality in the downstream river of a hydroelectric dam may be affected by the structural design and operation. To date, little is known about the water quality downstream of the largest dam in Malaysia, the Bakun hydroelectric dam. Therefore, the objective of the study was to determine the water quality downstream of the dam when the spillway was closed and when it was opened. Results of the study indicate that the dam plays a significant role in regulating the water quality downstream of it. When the spillway was closed, pH and oxygen were lower in the river where DO was below 5 mg/L. When the spillway was opened, the water quality improved in terms of oxygen content (>8.0 mg/L, total sulphide (TS, and chemical oxygen demand (COD but deteriorated in terms of five-day biochemical oxygen demand (BOD5, total ammonia nitrogen (TAN, and total phosphorus (TP. Additionally, the intensity of the impacts, particularly BOD5, COD, and TAN, shows a declining trend as distance from the dam increases. This study shows that impacts on the water quality extend to a distance of 32 km from the dam particularly turbidity and DO and opening the spillway changes the water quality significantly.

  2. Water stress in global transboundary river basins : Significance of upstream water use on downstream stress

    NARCIS (Netherlands)

    Munia, H.; Guillaume, J. H A; Mirumachi, N.; Porkka, M.; Wada, Y.|info:eu-repo/dai/nl/341387819; Kummu, M.

    2016-01-01

    Growing population and water demand have increased pressure on water resources in various parts of the globe, including many transboundary river basins. While the impacts of upstream water use on downstream water availability have been analysed in many of these international river basins, this has

  3. Using forest carbon credits to offset emissions in the downstream business

    NARCIS (Netherlands)

    Hein, Lars

    2017-01-01

    A forthcoming report by Concawe, entitled Using Forest Carbon Credits to Offset Emissions in the Downstream Business, investigated whether, and how, forest carbon credits can be used to offset emissions from the European refining and road transport sectors. Forest carbon plays a major role in the

  4. Investigation on the intense fringe formation phenomenon downstream hot-image plane.

    Science.gov (United States)

    Hu, Yonghua; Li, Guohui; Zhang, Lifu; Huang, Wenti; Chen, Shuming

    2015-11-30

    The propagation of a high-power flat-topped Gaussian beam, which is modulated by three parallel wirelike scatterers, passing through a downstream Kerr medium slab and free spaces is investigated. A new phenomenon is found that a kind of intense fringe with intensity several times that of the incident beam can be formed in a plane downstream the Kerr medium. This kind of intense fringe is another result in the propagation process of nonlinear imaging and it locates scores of centimeters downstream the predicted hot image plane. Moreover, the intensity of this fringe can achieve the magnitude of that of hot image in corresponding single-scatterer case, and this phenomenon can arise only under certain conditions. As for the corresponding hot images, they are also formed but largely suppressed. The cause of the formation of such an intense fringe is analyzed and found related to interference in the free space downstream the Kerr medium. Moreover, the ways it is influenced by some important factors such as the wavelength of incident beam and the properties of scatterers and Kerr medium are discussed, and some important properties and relations are revealed.

  5. Linking Three Gorges Dam and downstream hydrological regimes along the Yangtze River, China

    NARCIS (Netherlands)

    Mei, X.; Dai, Z.; Van Gelder, P.H.A.J.M.; Gao, J.

    2015-01-01

    The magnitude of anthropogenic influence, especially dam regulation, on hydrological system is of scientific and practical value for large river management. As the largest dam in the world by far, Three Gorges Dam (TGD) is expected to be a strong evidence on dam impacts on downstream hydrological

  6. Regulation of notochord-specific expression of Ci-Bra downstream genes in Ciona intestinalis embryos.

    Science.gov (United States)

    Takahashi, Hiroki; Hotta, Kohji; Takagi, Chiyo; Ueno, Naoto; Satoh, Nori; Shoguchi, Eiichi

    2010-02-01

    Brachyury, a T-box transcription factor, is expressed in ascidian embryos exclusively in primordial notochord cells and plays a pivotal role in differentiation of notochord cells. Previously, we identified approximately 450 genes downstream of Ciona intestinalis Brachyury (Ci-Bra), and characterized the expression profiles of 45 of these in differentiating notochord cells. In this study, we looked for cisregulatory sequences in minimal enhancers of 20 Ci-Bra downstream genes by electroporating region within approximately 3 kb upstream of each gene fused with lacZ. Eight of the 20 reporters were expressed in notochord cells. The minimal enchancer for each of these eight genes was narrowed to a region approximately 0.5-1.0-kb long. We also explored the genome-wide and coordinate regulation of 43 Ci-Bra-downstream genes. When we determined their chromosomal localization, it became evident that they are not clustered in a given region of the genome, but rather distributed evenly over 13 of the 14 pairs of chromosomes, suggesting that gene clustering does not contribute to coordinate control of the Ci-Bra downstream gene expression. Our results might provide Insights Into the molecular mechanisms underlying notochord formation in chordates.

  7. Modelling the role of transmission companies in the downstream European gas market

    International Nuclear Information System (INIS)

    Boots, M.A.; Rijkers, F.A.M.

    2000-07-01

    This paper describes the empirical model GASTALE and shows several analyses of the European gas market using this model. These analyses are mainly focused on the role of the downstream transmission companies. Producers of natural gas are assumed to form an oligopoly throughout the paper. Considering an oligopolistic transmission structure our model results show that the level of transmitters' profits strongly depends on the possibilities of discrimination on the border prices. If price discrimination by producers is allowed, these producers collect the main part of the margins on end-use prices. Without price discrimination the transmission companies collect most of the margins. Assuming an oligopolistic downstream structure, end-use prices converge to prices corresponding to perfect competition when the number of transmitters increases. Given the oligopolistic structure of the upstream industry, it is of importance to prevent (or abolish) monopolistic structures in the downstream gas market. In the case where oligopolistic competition between downstream gas companies cannot be prevented, vertical integration should be supported (or at least not be discouraged). 14 refs

  8. 40 CFR 80.219 - Designation and downstream requirements for GPA gasoline.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Designation and downstream requirements for GPA gasoline. 80.219 Section 80.219 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... sold or dispensed for use in motor vehicles at a retail outlet or wholesale purchaser-consumer facility...

  9. Concentration of radionuclides in fresh water fish downstream of Rancho Seco Nuclear Generating Plant

    International Nuclear Information System (INIS)

    Noshkin, V.E.; Eagle, R.J.; Dawson, J.M.; Brunk, J.L.; Wong, X.M.

    1984-01-01

    Fish were collected for radionuclide analysis over a 5-month period in 1984 from creeks downstream of the Rancho Seco Nuclear Generating Plant, which has been discharging quantities of some fission and activation products to the waterway since 1981. Among the fish, the bluegill was selected for intensive study because it is very territorial and the radionuclide concentrations detected should be representative of the levels in the local environment at the downstream locations sampled. Among the gamma-emitting radionuclides routinely released, only 134 Cs and 137 Cs were detected in the edible flesh of fish. Concentrations in the flesh of fish decreased with distance from the plant. The relationship between concentration and distance was determined to be exponential. Exponential equations were generated to estimate concentrations in fish at downstream locations where no site-specific information was available. Mean concentrations of 137 Cs in bluegill collected during April, May, July and August from specific downstream stations were not significantly different in spite of the release of 131 mCi to the creeks between April and August. The concentrations in fish are not responding to changes in water concentrations brought about by plant discharges. Diet appears to be a more significant factor than size or weight or water concentration in regulating body burdens of 137 Cs in these fish

  10. NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

    Science.gov (United States)

    Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

    2012-02-01

    Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

  11. Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes.

    Science.gov (United States)

    Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K; McGraw, Timothy E

    2016-12-20

    Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin's effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes

    Directory of Open Access Journals (Sweden)

    Natasha Chaudhary

    2016-12-01

    Full Text Available Insulin activation of phosphatidylinositol 3-kinase (PI3K regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin’s effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types.

  13. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  14. Levels of essential and non-essential elements in commercially ...

    African Journals Online (AJOL)

    The focus of this study was to assess the quality of commercially packaged moringa tea brands available in the retail markets in Nigerian cities on the basis of the essential and nonessential elemental content in their tissues. Four different brands of moringa tea comprising two locally processed teas and two imported teas ...

  15. Levels of Essential and Non-Essential Elements in Commercially ...

    African Journals Online (AJOL)

    Enebi Jasper

    INTRODUCTION. Plants have been ... plant metabolism and biosynthesis and act as cofactors for ... plant body. 3 . Some metals are essential nutrients (zinc, iron, copper, and chromium), ... non-destructive analysis, increased total speed, ... oleifera play both a curative and preventive ... maintenance of cardiac rhythm. 16.

  16. Essentials of Career Interest Assessment. Essentials of Psychological Assessment Series.

    Science.gov (United States)

    Prince, Jeffrey P.; Heiser, Lisa J.

    This book is a quick reference source to guide the career professional through the essentials of using the most popular career interest tools. It summarizes important technical aspects of each inventory, and offers step-by-step guidance in the interpretation and use of the various inventories. The chapters are: (1) "Overview"; (2)…

  17. Favorable fragmentation: river reservoirs can impede downstream expansion of riparian weeds.

    Science.gov (United States)

    Rood, Stewart B; Braatne, Jeffrey H; Goater, Lori A

    2010-09-01

    River valleys represent biologically rich corridors characterized by natural disturbances that create moist and barren sites suitable for colonization by native riparian plants, and also by weeds. Dams and reservoirs interrupt the longitudinal corridors and we hypothesized that this could restrict downstream weed expansion. To consider this "reservoir impediment" hypothesis we assessed the occurrences and abundances of weeds along a 315-km river valley corridor that commenced with an unimpounded reach of the Snake River and extended through Brownlee, Oxbow, and Hells Canyon reservoirs and dams, and downstream along the Snake River. Sampling along 206 belt transects with 3610 quadrats revealed 16 noxious and four invasive weed species. Ten weeds were upland plants, with Canada thistle (Cirsium arvense) restricted to the upstream reaches, where field morning glory (Convolvulus arvensis) was also more common. In contrast, St. John's wort (Hypericum perforatum) was more abundant below the dams, and medusahead wildrye (Taeniatherum caput-medusae) occurred primarily along the reservoirs. All seven riparian species were abundant in the upstream zones but sparse or absent below the dams. This pattern was observed for the facultative riparian species, poison hemlock (Conium maculatum) and perennial pepperweed (Lepidium latifolium), the obligate riparian, yellow nut sedge (Cyperus esculentus), the invasive perennial, reed canary grass (Phalaris arundinacea), and three invasive riparian trees, Russian olive (Elaeagnus angustifolia), false indigo (Amorpha fruticosa), and tamarisk (Tamarix spp.). The hydrophyte purple loosestrife (Lythrum salicaria) was also restricted to the upstream zone. These longitudinal patterns indicate that the reservoirs have impeded the downstream expansion of riparian weeds, and this may especially result from the repetitive draw-down and refilling of Brownlee Reservoir that imposes a lethal combination of drought and flood stress. The dams and

  18. C, N, P export regimes from headwater catchments to downstream reaches

    Science.gov (United States)

    Dupas, R.; Musolff, A.; Jawitz, J. W.; Rao, P. S.; Jaeger, C. G.; Fleckenstein, J. H.; Rode, M.; Borchardt, D.

    2017-12-01

    Excessive amounts of nutrients and dissolved organic matter in freshwater bodies affect aquatic ecosystems. In this study, the spatial and temporal variability in nitrate (NO3), dissolved organic carbon (DOC) and soluble reactive phosphorus (SRP) was analyzed in the Selke river continuum from headwaters draining 1 - 3 km² catchments to downstream reaches representing spatially integrated signals from 184 - 456 km² catchments (part of TERENO - Terrestrial Environmental Observatories, in Germany). Three headwater catchments were selected as archetypes of the main landscape units (land use x lithology) present in the Selke catchment. Export regimes in headwater catchments were interpreted in terms of NO3, DOC and SRP land-to-stream transfer processes. Headwater signals were subtracted from downstream signals, with the differences interpreted in terms of in-stream processes and contribution of point-source emissions. The seasonal dynamics for NO3 were opposite those of DOC and SRP in all three headwater catchments, and spatial differences also showed NO3 contrasting with DOC and SRP. These dynamics were interpreted as the result of the interplay of hydrological and biogeochemical processes, for which riparian zones were hypothesized to play a determining role. In the two downstream reaches, NO3 was transported almost conservatively, whereas DOC was consumed and produced in the upper and lower river sections, respectively. The natural export regime of SRP in the three headwater catchments mimicked a point-source signal, which may lead to overestimation of domestic contributions in the downstream reaches. Monitoring the river continuum from headwaters to downstream reaches proved effective to investigate jointly land-to-stream and in-stream transport and transformation processes.

  19. Willingness of upstream and downstream resource managers to engage in compensation schemes for environmental services

    Directory of Open Access Journals (Sweden)

    Chapika Sangkapitux

    2009-04-01

    Full Text Available Providing compensation for agricultural conservation practices adopted by upstream farmers is still an alien concept in the Thai political context. The governance of common-pool natural resources, such as forest and water, has traditionally been under the control of powerful government line agencies, while the contribution of local communities to natural resource conservation have been hardly recognized by policy-makers. Drawing on a case study in Mae Sa watershed, Chiang Mai province, northern Thailand, this paper discusses the potential of developing compensation schemes in a socio-political context where upland farmers – mostly belonging to ethnic minority groups – tend to be considered a threat to the natural resource base rather than providers of environmental services. Based on data obtained from 371 households in the upstream communities and 151 households in the downstream communities of the watershed, upstream resource managers’ willingness to accept compensation for the conservation measures and downstream resource managers’ willingness to pay for water resource improvements were estimated through the use of choice experiments. Results from the study suggest that downstream resource managers would be willing to provide on average nearly 1% of their annual income for a substantial improvement of the quantity and quality of water resources, which could be achieved by compensating upstream farmers’ change of their agricultural systems towards more environment-friendly practices. Both willingness to pay of downstream respondents and willingness of upstream resource managers to accept compensation were positively correlated with age, education, participation in environmental conservation activities and previous experiences with droughts and/or erosion. The paper concludes that there is a clear potential for establishing compensation schemes for provision of environmental services in northern Thai watersheds. The important policy

  20. Water Stress in Global Transboundary River Basins: Significance of Upstream Water Use on Downstream Stress

    Science.gov (United States)

    Munia, H.; Guillaume, J. H. A.; Mirumachi, N.; Porkka,M.; Wada, Yoshihide; Kummu, M.

    2016-01-01

    Growing population and water demand have increased pressure on water resources in various parts of the globe, including many transboundary river basins. While the impacts of upstream water use on downstream water availability have been analyzed in many of these international river basins, this has not been systematically done at the global scale using coherent and comparable datasets. In this study, we aim to assess the change in downstream water stress due to upstream water use in the world's transboundary river basins. Water stress was first calculated considering only local water use of each sub-basin based on country-basin mesh, then compared with the situation when upstream water use was subtracted from downstream water availability. Wefound that water stress was generally already high when considering only local water use, affecting 0.95-1.44 billion people or 33%-51% of the population in transboundary river basins. After accounting for upstream water use, stress level increased by at least 1 percentage-point for 30-65 sub-basins, affecting 0.29-1.13 billion people. Altogether 288 out of 298 middle-stream and downstream sub-basin areas experienced some change in stress level. Further, we assessed whether there is a link between increased water stress due to upstream water use and the number of conflictive and cooperative events in the transboundary river basins, as captured by two prominent databases. No direct relationship was found. This supports the argument that conflicts and cooperation events originate from a combination of different drivers, among which upstream-induced water stress may play a role. Our findings contribute to better understanding of upstream-downstream dynamics in water stress to help address water allocation problems.

  1. Energy-saving scheme based on downstream packet scheduling in ethernet passive optical networks

    Science.gov (United States)

    Zhang, Lincong; Liu, Yejun; Guo, Lei; Gong, Xiaoxue

    2013-03-01

    With increasing network sizes, the energy consumption of Passive Optical Networks (PONs) has grown significantly. Therefore, it is important to design effective energy-saving schemes in PONs. Generally, energy-saving schemes have focused on sleeping the low-loaded Optical Network Units (ONUs), which tends to bring large packet delays. Further, the traditional ONU sleep modes are not capable of sleeping the transmitter and receiver independently, though they are not required to transmit or receive packets. Clearly, this approach contributes to wasted energy. Thus, in this paper, we propose an Energy-Saving scheme that is based on downstream Packet Scheduling (ESPS) in Ethernet PON (EPON). First, we design both an algorithm and a rule for downstream packet scheduling at the inter- and intra-ONU levels, respectively, to reduce the downstream packet delay. After that, we propose a hybrid sleep mode that contains not only ONU deep sleep mode but also independent sleep modes for the transmitter and the receiver. This ensures that the energy consumed by the ONUs is minimal. To realize the hybrid sleep mode, a modified GATE control message is designed that involves 10 time points for sleep processes. In ESPS, the 10 time points are calculated according to the allocated bandwidths in both the upstream and the downstream. The simulation results show that ESPS outperforms traditional Upstream Centric Scheduling (UCS) scheme in terms of energy consumption and the average delay for both real-time and non-real-time packets downstream. The simulation results also show that the average energy consumption of each ONU in larger-sized networks is less than that in smaller-sized networks; hence, our ESPS is better suited for larger-sized networks.

  2. The role of grazers and shredders in the retention and downstream transport of a PCB in lotic environments

    International Nuclear Information System (INIS)

    Sallenave, R.M.; Kreutzweiser, D.P.

    1994-01-01

    Field studies using flow-through artificial stream channels were conducted between May and October 1992 to study the role of the feeding activity of grazing and shredding invertebrates in promoting downstream transport of 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP). Plant material was labeled with [ 14 C]HCBP and fed to selected invertebrate species, and accrual of radioactivity by downstream collector species (Hydropsyche spp.) was measured. Downstream transport of HCBP was significantly increased by the presence of the grazer Elimia livescens in the upstream sections of the channels as demonstrated by significantly higher levels of radioactivity in hydropsychid larvae located downstream. Similarly, movement of HCBP downstream was significantly greater in channels containing the shredder Hydatophylax argus than in channels without shredders. These results suggest that the feeding processes of benthic invertebrates may play an important role in the downstream transport of particle-bound hydrophobic organic compounds

  3. Essential Medicines in a High Income Country: Essential to Whom?

    Science.gov (United States)

    Duong, Mai; Moles, Rebekah J; Chaar, Betty; Chen, Timothy F

    2015-01-01

    To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders

  4. Essential Medicines in a High Income Country: Essential to Whom?

    Directory of Open Access Journals (Sweden)

    Mai Duong

    Full Text Available To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML concept functions in a high income country context.In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of

  5. Tank farms essential drawing plan

    International Nuclear Information System (INIS)

    Domnoske-Rauch, L.A.

    1998-01-01

    The purpose of this document is to define criteria for selecting Essential Drawings, Support Drawings, and Controlled Print File (CPF) drawings and documents for facilities that are part of East and West Tank Farms. Also, the drawings and documents that meet the criteria are compiled separate listings. The Essential Drawing list and the Support Drawing list establish a priority for updating technical baseline drawings. The CPF drawings, denoted by an asterisk (*), defined the drawings and documents that Operations is required to maintain per the TWRS Administration Manual. The Routing Boards in Buildings 272-WA and 272-AW are not part of the CPF

  6. Analgesic Potential of Essential Oils

    Directory of Open Access Journals (Sweden)

    José Ferreira Sarmento-Neto

    2015-12-01

    Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.

  7. LANSCE target system performance

    International Nuclear Information System (INIS)

    Russell, G.J.; Gilmore, J.S.; Robinson, H.; Legate, G.L.; Bridge, A.; Sanchez, R.J.; Brewton, R.J.; Woods, R.; Hughes, H.G. III

    1989-01-01

    We measured neutron beam fluxes at LANSCE using gold foil activation techniques. We did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. We used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 10 10 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 10 10 , respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm 2 -s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of ∼25 μA of 800-MeV protons. (author)

  8. Essential Medicines in National Constitutions

    Science.gov (United States)

    Toebes, Brigit; Hogerzeil, Hans

    2016-01-01

    Abstract A constitutional guarantee of access to essential medicines has been identified as an important indicator of government commitment to the progressive realization of the right to the highest attainable standard of health. The objective of this study was to evaluate provisions on access to essential medicines in national constitutions, to identify comprehensive examples of constitutional text on medicines that can be used as a model for other countries, and to evaluate the evolution of constitutional medicines-related rights since 2008. Relevant articles were selected from an inventory of constitutional texts from WHO member states. References to states’ legal obligations under international human rights law were evaluated. Twenty-two constitutions worldwide now oblige governments to protect and/or to fulfill accessibility of, availability of, and/or quality of medicines. Since 2008, state responsibilities to fulfill access to essential medicines have expanded in five constitutions, been maintained in four constitutions, and have regressed in one constitution. Government commitments to essential medicines are an important foundation of health system equity and are included increasingly in state constitutions. PMID:27781006

  9. Intellectual Workers and Essential Freedoms.

    Science.gov (United States)

    Edley, Christopher Jr.

    2000-01-01

    Journalists and college professors deserve certain privileges, including freedom of speech and academic freedom, but they must adapt their work to increasingly diverse populations. They must confront public mistrust, convince people that these freedoms are worthwhile, and protect essential public rights through what they study and teach and to…

  10. Essential Fluid Dynamics for Scientists

    Science.gov (United States)

    Braithwaite, Jonathan

    2017-12-01

    The book is an introduction to the subject of fluid mechanics, essential for students and researchers in many branches of science. It illustrates its fundamental principles with a variety of examples drawn mainly from astrophysics and geophysics as well as from everyday experience. Prior familiarity with basic thermodynamics and vector calculus is assumed.

  11. Essential oils in broiler nutrition

    NARCIS (Netherlands)

    Lee, Kyung-woo

    2002-01-01

    Dietary antibiotics at low, subtherapeutic levels have been shown to improve growth performance in farm animals. However, there is a trend to look for alternatives to dietary antibiotics, due to occurrence of antibiotic-resistance bacteria. The present thesis explored the essential oils as the

  12. Essentials of supply chain management

    CERN Document Server

    Hugos, Michael H

    2011-01-01

    The latest thinking, strategies, developments, and technologies to stay current in supply chain management Presenting the core concepts and techniques of supply chain management in a clear, concise and easily readable style, the Third Edition of Essentials of Supply Chain Management outlines the most crucial tenets and concepts of supply chain management.

  13. Essentials for the Teacher's Toolbox

    Science.gov (United States)

    Uhler, Jennifer

    2012-01-01

    Every profession has a set of essential tools for carrying out its work. Airplane mechanics cannot repair engines without sophisticated diagnostics, wrenches, and pliers. Surgeons cannot operate without scalpels and clamps. In contrast, teaching has often been perceived as a profession requiring only students, chalk, and a blackboard in order for…

  14. Diversity - Essential quality for agronomy

    Science.gov (United States)

    Diversity is an essential quality for success in agronomy because agronomy touches everyone, everywhere in some way, and food production is crucial for every society around the world. Consider, for example, our membership, which is diverse in almost every way imaginable. This diversity brings differ...

  15. Hyper-V Replica essentials

    CERN Document Server

    Krstevski, Vangel

    2013-01-01

    a in various deployment scenarios.Hyper-V Replica Essentials is for Windows Server administrators who want to improve their system availability and speed up disaster recovery. You will need experience in Hyper-V deployment because Hyper-V Replica is built in the Hyper-V platform.

  16. Flow and mass transfer downstream of an orifice under flow accelerated corrosion conditions

    International Nuclear Information System (INIS)

    Ahmed, Wael H.; Bello, Mufatiu M.; El Nakla, Meamer; Al Sarkhi, Abdelsalam

    2012-01-01

    Highlights: ► Mass transfer downstream of orifices was numerically and experimentally investigated. ► The surface wear pattern is measured and used to validate the present numerical results. ► The maximum mass transfer coefficient found to occur at approximately 2–3 pipe diameters downstream of the orifice. ► The FAC wear rates were correlated with the turbulence kinetic energy and wall mass transfer in terms of Sherwood number. ► The current study offered very useful information for FAC engineers for better preparation of nuclear plant inspection scope. - Abstract: Local flow parameters play an important role in characterizing flow accelerated corrosion (FAC) downstream of sudden area change in power plant piping systems. Accurate prediction of the highest FAC wear rate locations enables the mitigation of sudden and catastrophic failures, and the improvement of the plant capacity factor. The objective of the present study is to evaluate the effect of the local flow and mass transfer parameters on flow accelerated corrosion downstream of an orifice. In the present study, orifice to pipe diameter ratios of 0.25, 0.5 and 0.74 were investigated numerically by solving the continuity and momentum equations at Reynolds number of Re = 20,000. Laboratory experiments, using test sections made of hydrocal (CaSO 4 ·½H 2 O) were carried out in order to determine the surface wear pattern and validate the present numerical results. The numerical results were compared to the plants data as well as to the present experiments. The maximum mass transfer coefficient found to occur at approximately 2–3 pipe diameters downstream of the orifice. This location was also found to correspond to the location of elevated turbulent kinetic energy generated within the flow separation vortices downstream of the orifice. The FAC wear rates were correlated with the turbulence kinetic energy and wall mass transfer in terms of Sherwood number. The current study found to offer very

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

    International Nuclear Information System (INIS)

    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

    2011-01-01

    Research highlights: → CD4 receptors were downregulated on the surface of HIV-1 latently infected cells. → CD4 downstream signaling molecules were suppressed in HIV-1 latently infected cells. → HIV-1 progeny can be reactivated by induction of T-cell activation signal molecules. → H3K4me3 and H3K9ac were highly enriched in CD4 downstream signaling molecules. → 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 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 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 antireservoir therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-Chang [National Institute of Health, Chungbuk (Korea, Republic of); School of Life Science and Biotechnology, Korea University, Seoul (Korea, Republic of); Kim, Hyeon Guk [National Institute of Health, Chungbuk (Korea, Republic of); Roh, Tae-Young [Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Park, Jihwan [Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Jung, Kyung-Min; Lee, Joo-Shil [National Institute of Health, Chungbuk (Korea, Republic of); Choi, Sang-Yun [School of Life Science and Biotechnology, Korea University, Seoul (Korea, Republic of); Kim, Sung Soon [National Institute of Health, Chungbuk (Korea, Republic of); Choi, Byeong-Sun, E-mail: byeongsun@korea.kr [National Institute of Health, Chungbuk (Korea, Republic of)

    2011-01-14

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

  19. RNAi-Based Identification of Gene-Specific Nuclear Cofactor Networks Regulating Interleukin-1 Target Genes

    Directory of Open Access Journals (Sweden)

    Johanna Meier-Soelch

    2018-04-01

    Full Text Available The potent proinflammatory cytokine interleukin (IL-1 triggers gene expression through the NF-κB signaling pathway. Here, we investigated the cofactor requirements of strongly regulated IL-1 target genes whose expression is impaired in p65 NF-κB-deficient murine embryonic fibroblasts. By two independent small-hairpin (shRNA screens, we examined 170 genes annotated to encode nuclear cofactors for their role in Cxcl2 mRNA expression and identified 22 factors that modulated basal or IL-1-inducible Cxcl2 levels. The functions of 16 of these factors were validated for Cxcl2 and further analyzed for their role in regulation of 10 additional IL-1 target genes by RT-qPCR. These data reveal that each inducible gene has its own (quantitative requirement of cofactors to maintain basal levels and to respond to IL-1. Twelve factors (Epc1, H2afz, Kdm2b, Kdm6a, Mbd3, Mta2, Phf21a, Ruvbl1, Sin3b, Suv420h1, Taf1, and Ube3a have not been previously implicated in inflammatory cytokine functions. Bioinformatics analysis indicates that they are components of complex nuclear protein networks that regulate chromatin functions and gene transcription. Collectively, these data suggest that downstream from the essential NF-κB signal each cytokine-inducible target gene has further subtle requirements for individual sets of nuclear cofactors that shape its transcriptional activation profile.

  20. From centriole biogenesis to cellular function: centrioles are essential for cell division at critical developmental stages.

    Science.gov (United States)

    Rodrigues-Martins, Ana; Riparbelli, Maria; Callaini, Giuliano; Glover, David M; Bettencourt-Dias, Monica

    2008-01-01

    Centrioles are essential for the formation of cilia, flagella and centrosome organization. Abnormalities in centrosome structure and number in many cancers can be associated with aberrant cell division and genomic instability.(1,2) Canonical centriole duplication occurs in coordination with the cell division cycle, such that a single new "daughter" centriole arises next to each "mother" centriole. If destroyed, or eliminated during development, centrioles can form de novo.(3-5) Here we discuss our recent data demonstrating a molecular pathway that operates in both de novo and canonical centriole biogenesis involving SAK/PLK4, SAS-6 and SAS-4.(6) We showed that centriole biogenesis is a self-assembly process locally triggered by high SAK/PLK4 activity that may or not be associated with an existing centriole. SAS-6 acts downstream of SAK/PLK4 to organize nine precentriolar units, which we call here enatosomes, fitting together laterally and longitudinally, specifying a tube-like centriole precursor.(7,8) The identification of mutants impaired in centriole biogenesis has permitted the study of the physiological consequences of their absence in the whole organism. In Drosophila, centrioles are not necessary for somatic cell divisions.(9,10) However, we show here that mitotic abnormalities arise in syncytial SAK/PLK4-derived mutant embryos resulting in lethality. Moreover male meiosis fails in both SAK/PLK4 and DSAS-4 mutant spermatids that have no centrioles. These results show diversity in the need for centrioles in cell division. This suggests that tissue specific constraints selected for different contributions of centrosome-independent and dependent mechanisms in spindle function. This heterogeneity should be taken into account both in reaching an understanding of spindle function and when designing drugs that target cell division.

  1. Phosphorylation of Nanog is Essential to Regulate Bmi1 and Promote Tumorigenesis

    Science.gov (United States)

    Xie, Xiujie; Piao, Longzhu; Cavey, Greg S.; Old, Matthew; Teknos, Theodoros N.; Mapp, Anna K; Pan, Quintin

    2014-01-01

    Emerging evidence indicates that Nanog is intimately involved in tumorigenesis in part through regulation of the cancer initiating cell population. However, the regulation and role of Nanog in tumorigenesis are still poorly understood. In this study, human Nanog was identified to be phosphorylated by human PKCε at multiple residues including T200 and T280. Our work indicated that phosphorylation at T200 and T280 modulates Nanog function through several regulatory mechanisms. Results with phosphorylation-insensitive and phosphorylation-mimetic mutant Nanog revealed that phosphorylation at T200 and T280 enhance Nanog protein stability. Moreover, phosphorylation-insensitive T200A and T280A mutant Nanog had a dominant-negative function to inhibit endogenous Nanog transcriptional activity. Inactivation of Nanog was due to impaired homodimerization, DNA binding, promoter occupancy, and p300, a transcriptional co-activator, recruitment resulting in a defect in target gene promoter activation. Ectopic expression of phosphorylation-insensitive T200A or T280A mutant Nanog reduced cell proliferation, colony formation, invasion, migration, and the cancer initiating cell population in head and neck squamous cell carcinoma (HNSCC) cells. The in vivo cancer initiating ability was severely compromised in HNSCC cells expressing phosphorylation-insensitive T200A or T280A mutant Nanog; 87.5% (14/16), 12.5% (1/8), and 0% (0/8) for control, T200A, and T280A, respectively. Nanog occupied the Bmi1 promoter to directly transactivate and regulate Bmi1. Genetic ablation and rescue experiments demonstrated that Bmi1 is a critical downstream signaling node for the pleiotropic, pro-oncogenic effects of Nanog. Taken together, our study revealed, for the first time, that post-translational phosphorylation of Nanog is essential to regulate Bmi1 and promote tumorigenesis. PMID:23708658

  2. Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories.

    Science.gov (United States)

    Kim, Hee Jin; Yang, Jin Ju; Kwon, Hunki; Kim, Changsoo; Lee, Jong Min; Chun, Phillip; Kim, Yeo Jin; Jung, Na-Yeon; Chin, Juhee; Kim, Seonwoo; Woo, Sook-Young; Choe, Yearn Seong; Lee, Kyung-Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Weiner, Michael W; Na, Duk L; Seo, Sang Won

    2016-09-01

    SEE COHEN DOI101093/AWW183 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness

  3. Gene expression programming for prediction of scour depth downstream of sills

    Science.gov (United States)

    Azamathulla, H. Md.

    2012-08-01

    SummaryLocal scour is crucial in the degradation of river bed and the stability of grade control structures, stilling basins, aprons, ski-jump bucket spillways, bed sills, weirs, check dams, etc. This short communication presents gene-expression programming (GEP), which is an extension to genetic programming (GP), as an alternative approach to predict scour depth downstream of sills. Published data were compiled from the literature for the scour depth downstream of sills. The proposed GEP approach gives satisfactory results (R2 = 0.967 and RMSE = 0.088) compared to the existing predictors (Chinnarasri and Kositgittiwong, 2008) with R2 = 0.87 and RMSE = 2.452 for relative scour depth.

  4. Re-modulated technology of WDM-PON employing different DQPSK downstream signals

    Science.gov (United States)

    Gao, Chao; Xin, Xiang-jun; Yu, Chong-xiu

    2012-11-01

    This paper proposes a kind of modulation architecture for wavelength-division-multiplexing passive optical network (WDMPON) employing optical differential quadrature phase shift keying (DQPSK) downstream signals and two different modulation formats of re-modulated upstream signals. At the optical line terminal (OLT), 10 Gbit/s signal is modulated with DQPSK. At the optical network unit (ONU), part of the downstream signal is re-modulated with on-off keying (OOK) or inverse-return-to-zero (IRZ). Simulation results show the impact on the system employing NRZ, RZ and carrier-suppressed return-to-zero (CSRZ). The analyses also reflect that the architecture can restrain chromatic dispersion and channel crosstalk, which makes it the best architecture of access network in the future.

  5. Circadian rhythms in healthy aging--effects downstream from the pacemaker

    Science.gov (United States)

    Monk, T. H.; Kupfer, D. J.

    2000-01-01

    Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

  6. Beam Halo on the LHC TCDQ Diluter System and Thermal Load on the Downstream Superconducting Magnets

    CERN Document Server

    Goddard, B; Presland, A; Redaelli, S; Robert-Démolaize, G; Sarchiapone, L; Weiler, T; Weterings, W

    2006-01-01

    The moveable single-jawed graphite TCDQ diluter must be positioned very close to the circulating LHC beam in order to prevent damage to downstream components in the event of an unsynchronised beam abort. A two-jawed graphite TCS.IR6 collimator forms part of the TCDQ system. The requirement to place the jaws close to the beam means that the system can intercept a substantial beam halo load. Initial investigations indicated a worryingly high heat load on the Q4 coils. This paper presents the updated load cases, shielding and simulation geometry, and the results of simulations of the energy deposition in the TCDQ system and in the downstream superconducting Q4 magnet. The implications for the operation of the LHC are discussed.

  7. A novel cell autolysis system for cost-competitive downstream processing.

    Science.gov (United States)

    Hajnal, Ivan; Chen, Xiangbin; Chen, Guo-Qiang

    2016-11-01

    The industrial production of low value-added biological products poses significant challenges due to cost pressures. In recent years, it has been argued that synthetic biology approaches will lead to breakthroughs that eliminate price bottlenecks for the production of a wide range of biological products including bioplastics and biofuels. One significant bottleneck lies in the necessity to break the tough cell walls of microbes in order to release intracellular products. We here report the implementation of the first synthetic biology standard part based on the lambda phage SRRz genes and a synthetic ribosome binding site (RBS) that works in Escherichia coli and Halomonas campaniensis, which enables the producer strains to induce lysis after the addition of small amounts (1-5 %) of solvents or to spontaneously lyse during the stresses of downstream processing, and thus has the potential to eliminate the mechanical cell disruption step as both an efficiency bottleneck and a significant capex barrier when implementing downstream bioprocesses.

  8. Impact of upstream and downstream constraints on a signaling module’s ultrasensitivity

    International Nuclear Information System (INIS)

    Altszyler, Edgar; Chernomoretz, Ariel; Ventura, Alejandra; Colman-Lerner, Alejandro

    2014-01-01

    Much work has been done on the study of the biochemical mechanisms that result in ultrasensitive behavior of simple biochemical modules. However, in a living cell, such modules are embedded in a bigger network that constrains the range of inputs that the module will receive as well as the range of the module’s outputs that network will be able to detect. Here, we studied how the effective ultrasensitivity of a modular system is affected by these restrictions. We use a simple setup to explore to what extent the dynamic range spanned by upstream and downstream components of an ultrasensitive module impact on the effective sensitivity of the system. Interestingly, we found for some ultrasensitive motifs that dynamic range limitations imposed by downstream components can produce effective sensitivities much larger than that of the original module when considered in isolation. (paper)

  9. Measurements of energy spectra of fast electrons from PF-1000 in the upstream and downstream directions

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowski, R.; Czaus, K.; Skladnik-Sadowska, E.; Malinowski, K.; Zebrowski, J. [The Andrzej Soltan Institute for Nuclear Studies (IPJ), 05-400 Otwock-Swierk (Poland); Sadowski, M.J. [The Andrzej Soltan Institute for Nuclear Studies (IPJ), 05-400 Otwock-Swierk (Poland); Karpinski, L.; Paduch, M.; Scholz, M. [Institute of Plasma Physics and Laser Microfusion (IPPLM), 01-497 Warsaw (Poland); Kubes, P. [Czech Technical University (CVUT), 166-27 Prague, (Czech Republic)

    2011-07-01

    The paper describes measurements of energy spectra of electrons emitted in the upstream direction along the symmetry-axis of the PF-1000 facility, operated with the deuterium filling at 21 kV, 290 kJ. The measurements were performed with a magnetic analyzer. The same analyzer was used to measure also electron beams emitted in along the symmetry-axis in the downstream direction. The recorded spectra showed that the electron-beams emitted in the upstream direction have energies in the range from about 40 keV to about 800 keV, while those in the downstream direction have energies in the range from about 60 keV to about 200 keV. These spectra confirm that in the PF (Plasma Focus) plasma column there appear strong local fields accelerating charged particles in different directions. This document is composed of a paper and a poster. (authors)

  10. Sources for increased DOC-concentrations in the groundwater downstream of the landfill Hohne (DEA)

    International Nuclear Information System (INIS)

    Bahlmann, E.; Seifert, R.; Eschenbach, A.; Kleinschmidt, V.

    2017-08-01

    Construction waste together with drilling mud and oil-contaminated soil had been deposited in the landfill Hohne from 1971. Four groundwater monitoring sites had been installed: one monitoring site upstream and three sites downstream of the landfill in three different directions. Downstream of the landfill increased concentrations of chloride, sulphate, sodium and DOC (dissolved organic carbon) had been measured over a period of years. Particularly the source of the DOC has remained unclear. Assumptions were (i) leaking of contaminants from the landfill and degradation under the landfill by microbes or plants or (ii) leaching of DOC from the soil under the landfill caused by a change in the redox potential. The determination of the DOC source was the major subject of this study.

  11. FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells.

    Science.gov (United States)

    Bourseguin, Julie; Bonet, Caroline; Renaud, Emilie; Pandiani, Charlotte; Boncompagni, Marina; Giuliano, Sandy; Pawlikowska, Patrycja; Karmous-Benailly, Houda; Ballotti, Robert; Rosselli, Filippo; Bertolotto, Corine

    2016-11-09

    Proteins involved in genetic stability maintenance and safeguarding DNA replication act not only against cancer initiation but could also play a major role in sustaining cancer progression. Here, we report that the FANC pathway is highly expressed in metastatic melanoma harboring the oncogenic microphthalmia-associated transcription factor (MiTF). We show that MiTF downregulation in melanoma cells lowers the expression of several FANC genes and proteins. Moreover, we observe that, similarly to the consequence of MiTF downregulation, FANC pathway silencing alters proliferation, migration and senescence of human melanoma cells. We demonstrate that the FANC pathway acts downstream MiTF and establish the existence of an epistatic relationship between MiTF and the FANC pathway. Our findings point to a central role of the FANC pathway in cellular and chromosomal resistance to both DNA damage and targeted therapies in melanoma cells. Thus, the FANC pathway is a promising new therapeutic target in melanoma treatment.

  12. Quantifying the Impact of geographically isolated wetlands on the downstream hydrology of a Canadian Prairie watershed

    Science.gov (United States)

    Muhammad, A.; Evenson, G. R.; Boluwade, A.; Jha, S. K.; Rasmussen, P. F.

    2016-12-01

    Hydrological processes are highly complex and strongly nonlinear and cannot be represented through simple means. Models are built to replicate these processes. However, models due to various sources of uncertainty including their structural capability often lead to inaccurate results. The aim of this study is to setup the soil water assessment tool (SWAT) for a watershed that is dominated by potholes in the Prairie region of Canada. The potholes not connected to the stream, also known as geographically isolated wetlands (GIWs), are dynamic in nature leading to a fill and spill situation due to varying surface runoff conditions. Significant land use changes have resulted in almost 70% of wetlands being lost and have posed threat of flooding to downstream areas. While some studies were devoted to identify the presence of potholes only few have explored the impacts of wetlands on the downstream hydrology. In this study, we follow Evenson et al., (2016) approach of modifying SWAT model. The modification enhances structural capability of SWAT while depicting the dynamics of wetlands at HRUs level. Redefining the formation of HRUs in such way effectively captures the spatial presence of potholes. We then routed the potholes' fill and spill hydrology to direct the flow to the potholes immediately downstream. The model was calibrated for 2005-2008 and verified over 2009-2011 at a daily time step. We tested our model with three land use change scenarios by varying the presence of potholes and evaluated its impact on the downstream hydrograph. We foresee a significant improvement in replicating stream flow using this novel approach. We believe that it will effectively improve the predictive power of SWAT for this highly complex sub basin (Upper Assiniboine catchment at Kamsack) located in Canadian Prairie.

  13. Wave propagation downstream of a high power helicon in a dipolelike magnetic field

    International Nuclear Information System (INIS)

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

    2010-01-01

    The wave propagating downstream of a high power helicon source in a diverging magnetic field was investigated experimentally. The magnetic field of the wave has been measured both axially and radially. The three-dimensional structure of the propagating wave is observed and its wavelength and phase velocity are determined. The measurements are compared to predictions from helicon theory and that of a freely propagating whistler wave. The implications of this work on the helicon as a thruster are also discussed.

  14. Preliminary Experimental Results on the Technique of Artificial River Replenishment to Mitigate Sediment Loss Downstream Dams

    Science.gov (United States)

    Franca, M. J.; Battisacco, E.; Schleiss, A. J.

    2014-12-01

    The transport of sediments by water throughout the river basins, from the steep slopes of the upstream regions to the sea level, is recognizable important to keep the natural conditions of rivers with a role on their ecology processes. Over the last decades, a reduction on the supply of sand and gravel has been observed downstream dams existing in several alpine rivers. Many studies highlight that the presence of a dam strongly modifies the river behavior in the downstream reach, in terms of morphology and hydrodynamics, with consequences on local ecology. Sediment deficit, bed armoring, river incision and bank instability are the main effects which affect negatively the aquatic habitats and the water quality. One of the proposed techniques to solve the problem of sediment deficit downstream dams, already adopted in few Japanese and German rivers although on an unsatisfactory fashion, is the artificial replenishment of these. Generally, it was verified that the erosion of the replenishments was not satisfactory and the transport rate was not enough to move the sediments to sufficient downstream distances. In order to improve and to provide an engineering answer to make this technique more applicable, a series of laboratory tests are ran as preparatory study to understand the hydrodynamics of the river flow when the replenishment technique is applied. Erodible volumes, with different lengths and submergence conditions, reproducing sediment replenishments volumes, are positioned along a channel bank. Different geometrical combinations of erodible sediment volumes are tested as well on the experimental flume. The first results of the experimental research, concerning erosion time evolution, the influence of discharge and the distance travelled by the eroded sediments, will be presented and discussed.

  15. Comparison of pitot traverses taken at varying distances downstream of obstructions.

    Science.gov (United States)

    Guffey, S E; Booth, D W

    1999-01-01

    This study determined the deviations between pitot traverses taken under "ideal" conditions--at least seven duct diameter's lengths (i.e., distance = 7D) from obstructions, elbows, junction fittings, and other disturbances to flows--with those taken downstream from commonplace disturbances. Two perpendicular 10-point, log-linear velocity pressure traverses were taken at various distances downstream of tested upstream conditions. Upstream conditions included a plain duct opening, a junction fitting, a single 90 degrees elbow, and two elbows rotated 90 degrees from each other into two orthogonal planes. Airflows determined from those values were compared with the values measured more than 40D downstream of the same obstructions under ideal conditions. The ideal measurements were taken on three traverse diameters in the same plane separated by 120 degrees in honed drawn-over-mandrel tubing. In all cases the pitot tubes were held in place by devices that effectively eliminated alignment errors and insertion depth errors. Duct velocities ranged from 1500 to 4500 ft/min. Results were surprisingly good if one employed two perpendicular traverses. When the averages of two perpendicular traverses was taken, deviations from ideal value were 6% or less even for traverses taken as close as 2D distance from the upstream disturbances. At 3D distance, deviations seldom exceeded 5%. With single diameter traverses, errors seldom exceeded 5% at 6D or more downstream from the disturbance. Interestingly, percentage deviations were about the same at high and low velocities. This study demonstrated that two perpendicular pitot traverses can be taken as close as 3D from these disturbances with acceptable (< or = 5%) deviations from measurements taken under ideal conditions.

  16. Monitoring Thermal Pollution in Rivers Downstream of Dams with Landsat ETM+ Thermal Infrared Images

    Directory of Open Access Journals (Sweden)

    Feng Ling

    2017-11-01

    Full Text Available Dams play a significant role in altering the spatial pattern of temperature in rivers and contribute to thermal pollution, which greatly affects the river aquatic ecosystems. Understanding the temporal and spatial variation of thermal pollution caused by dams is important to prevent or mitigate its harmful effect. Assessments based on in-situ measurements are often limited in practice because of the inaccessibility of water temperature records and the scarcity of gauges along rivers. By contrast, thermal infrared remote sensing provides an alternative approach to monitor thermal pollution downstream of dams in large rivers, because it can cover a large area and observe the same zone repeatedly. In this study, Landsat Enhanced Thematic Mapper Plus (ETM+ thermal infrared imagery were applied to assess the thermal pollution caused by two dams, the Geheyan Dam and the Gaobazhou Dam, located on the Qingjiang River, a tributary of the Yangtze River downstream of the Three Gorges Reservoir in Central China. The spatial and temporal characteristics of thermal pollution were analyzed with water temperatures estimated from 54 cloud-free Landsat ETM+ scenes acquired in the period from 2000 to 2014. The results show that water temperatures downstream of both dams are much cooler than those upstream of both dams in summer, and the water temperature remains stable along the river in winter, showing evident characteristic of the thermal pollution caused by dams. The area affected by the Geheyan Dam reaches beyond 20 km along the downstream river, and that affected by the Gaobazhou Dam extends beyond the point where the Qingjiang River enters the Yangtze River. Considering the long time series and global coverage of Landsat ETM+ imagery, the proposed technique in the current study provides a promising method for globally monitoring the thermal pollution caused by dams in large rivers.

  17. Estimating flow characteristics of different weir types and optimum dimensions of downstream receiving pool

    OpenAIRE

    Emiroglu, M. Emin

    2010-01-01

    This paper presents the results of a laboratory study on the flow characteristics of sharp-crested weirs, broad-crested weirs, and labyrinth weirs. The variation of the maximum bubble penetration depth for different weir types is investigated depending on overfall jet expansion, discharge, and drop height. Moreover, most efficient depth, length and width of the downstream receiving pool in an open channel system are studied by considering the penetration depth, overfall jet expansion, jet tra...

  18. SWAT Model Prediction of Phosphorus Loading in a South Carolina Karst Watershed with a Downstream Embayment

    Science.gov (United States)

    Devendra M. Amatya; Manoj K. Jha; Thomas M. Williams; Amy E. Edwards; Daniel R.. Hitchcock

    2013-01-01

    The SWAT model was used to predict total phosphorus (TP) loadings for a 1555-ha karst watershed—Chapel Branch Creek (CBC)—which drains to a lake via a reservoir-like embayment (R-E). The model was first tested for monthly streamflow predictions from tributaries draining three potential source areas as well as the downstream R-E, followed by TP loadings using data...

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

    Science.gov (United States)

    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. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  1. Target preparation

    International Nuclear Information System (INIS)

    Hinn, G.M.

    1984-01-01

    A few of the more interesting of the 210 targets prepared in the Laboratory last year are listed. In addition the author continues to use powdered silver mixed with /sup 9,10/BeO to produce sources for accelerator radio dating of Alaskan and South Polar snow. Currently, he is trying to increase production by multiple sample processing. Also the author routinely makes 3 μg/cm 2 cracked slacked carbon stripper foils and is continuing research with some degree of success in making enriched 28 Si targets starting with the oxide

  2. Essentials of radiation heat transfer

    CERN Document Server

    Balaji

    2014-01-01

    Essentials of Radiation Heat Transfer is a textbook presenting the essential, fundamental information required to gain an understanding of radiation heat transfer and equips the reader with enough knowledge to be able to tackle more challenging problems. All concepts are reinforced by carefully chosen and fully worked examples, and exercise problems are provided at the end of every chapter. In a significant departure from other books on this subject, this book completely dispenses with the network method to solve problems of radiation heat transfer in surfaces. It instead presents the powerful radiosity-irradiation method and shows how this technique can be used to solve problems of radiation in enclosures made of one to any number of surfaces. The network method is not easily scalable. Secondly, the book introduces atmospheric radiation, which is now being considered as a potentially important area, in which engineers can contribute to the technology of remote sensing and atmospheric sciences in general, b...

  3. Downstream passage of fish larvae and eggs through a small-sized reservoir, Mucuri river, Brazil

    Directory of Open Access Journals (Sweden)

    Paulo S. Pompeu

    2011-12-01

    Full Text Available In South America, one important symptom of the failure of fish passages to sustain fish migratory recruitment is the inability of eggs and larvae to reach the nurseries. This is especially so when the breeding areas are located upstream of a reservoir, and the floodplain is downstream of the dam. Therefore, the transport of fish larvae and eggs across reservoir barriers is a key factor in the development of effective conservation strategies. In this paper, we evaluate the potential for migratory fish larvae and egg transportation across a small size reservoir in eastern Brazil. We sampled fish daily between 15th October 2002 and 15th February 2003 (spawning period in the Mucuri River, immediately upstream of the reservoir and downstream of the Santa Clara Power Plant dam. Our study was the first to indicate the possibility of successful larval passage through the reservoir of a hydroelectric reservoir and dam in South America, and showed that the passage of migratory fish larvae was associated significantly with residence time of water in the reservoir. The relatively short water residence time and elevated turbidity of the Santa Clara's reservoir waters during the rainy season certainly contributed to the successful passage, and can be considered as key factors for a priori evaluations of the feasibility of a downstream larval passage.

  4. Optimizing withdrawal from drinking water reservoirs to reduce downstream temperature pollution and reservoir hypoxia.

    Science.gov (United States)

    Weber, M; Rinke, K; Hipsey, M R; Boehrer, B

    2017-07-15

    Sustainable management of drinking water reservoirs requires balancing the demands of water supply whilst minimizing environmental impact. This study numerically simulates the effect of an improved withdrawal scheme designed to alleviate the temperature pollution downstream of a reservoir. The aim was to identify an optimal withdrawal strategy such that water of a desirable discharge temperature can be supplied downstream without leading to unacceptably low oxygen concentrations within the reservoir. First, we calibrated a one-dimensional numerical model for hydrodynamics and oxygen dynamics (GLM-AED2), verifying that the model reproduced water temperatures and hypolimnetic dissolved oxygen concentrations accurately over a 5 year period. Second, the model was extended to include an adaptive withdrawal functionality, allowing for a prescribed withdrawal temperature to be found, with the potential constraint of hypolimnetic oxygen concentration. Scenario simulations on epi-/metalimnetic withdrawal demonstrate that the model is able to autonomously determine the best withdrawal height depending on the thermal structure and the hypolimnetic oxygen concentration thereby optimizing the ability to supply a desirable discharge temperature to the downstream river during summer. This new withdrawal strategy also increased the hypolimnetic raw water volume to be used for drinking water supply, but reduced the dissolved oxygen concentrations in the deep and cold water layers (hypolimnion). Implications of the results for reservoir management are discussed and the numerical model is provided for operators as a simple and efficient tool for optimizing the withdrawal strategy within different reservoir contexts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Power Plant Bromide Discharges and Downstream Drinking Water Systems in Pennsylvania.

    Science.gov (United States)

    Good, Kelly D; VanBriesen, Jeanne M

    2017-10-17

    Coal-fired power plants equipped with wet flue gas desulfurization (FGD) systems have been implicated in increasing bromide levels and subsequent increases in disinfection byproducts at downstream drinking water plants. Bromide was not included as a regulated constituent in the recent steam electric effluent limitations guidelines and standards (ELGs) since the U.S. EPA analysis suggested few drinking water facilities would be affected by bromide discharges from power plants. The present analysis uses a watershed approach to identify Pennsylvania drinking water intakes downstream of wet FGD discharges and to assess the potential for bromide discharge effects. Twenty-two (22) public drinking water systems serving 2.5 million people were identified as being downstream of at least one wet FGD discharge. During mean August conditions (generally low-flow, minimal dilution) in receiving rivers, the median predicted bromide concentrations contributed by wet FGD at Pennsylvania intake locations ranged from 5.2 to 62 μg/L for the Base scenario (including only natural bromide in coal) and from 16 to 190 μg/L for the Bromide Addition scenario (natural plus added bromide for mercury control); ranges depend on bromide loads and receiving stream dilution capacity.

  6. Multispacecraft observations of energetic ions upstream and downstream of the bow shock

    International Nuclear Information System (INIS)

    Scholer, M.; Mobius, E.; Kistler, L.M.; Klecker, B.; Ipavich, F.M.; Department of Physics and Astronomy, University of Maryland, College Park)

    1989-01-01

    We present simultaneous measurements of energetic protons and alpha particles inside and outside of the magnetopause, immediately upstream, and downstream as well as further upstream of the bow shock. A comparison between the intensity at the bow shock and further upstream results in an e-folding distance at 30 keV of similar to 6.2 R/sub E/. After transformation of the angular distribution into the solar wind frame a diffusion coefficeint of κ/sub parallel/similar to 3 R/sub E/ is obtained from the anisotropy and the intensity gradient. Immediately downstream of the bow shock the anisotropy in the shock frame is directed toward the magnetopause. After transformation into the plasma rest frame the distribution is isotropic. The intensity in the magnetosheath just outside the magnetopause is smaller than the intensity behind the bow shock. Thus, in the magnetosheath there is no gradient or streaming in the upstream direction. The spectra, intensities, and relative abundances in the magnetosheath and inside the magnetosphere are totally different. These observations are consistent with first order Fermi acceleration at the bow shock and subsequent downstream convection, and exclude a magnetospheric source for these particles. Copyright American Geophysical Union 1989

  7. Hydrological Effects of Chashm Dam on the Downstream of Talar River Watershed

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Khaleghi

    2017-02-01

    Full Text Available Introduction: In the last century, dams have constructed with the objective of water supplies for agriculture, drinking water and industry. However, the results from the performance review of dams show adverse effects on the downstream environment and the availability of water resources. The purpose of the Chashm dam construction on the TalarRiver's tributaries is the water supply for Semnan city. Materials and Methods: This study was conducted in TalarRiver watershed. TalarRiveroriginatesfrom AlborzMountains in Mazandaran province, in the southern Caspian Sea basin, in north of Iran and flows parallel with the Firouzkooh-Ghaemshahr road and it arrives to the Caspian beach area in the Malek Kala village. In order to supply the water requirements of Semnan city, the construction of Chashm dam on the TalarRiver's tributaries placed on the agenda of the Ministry of Energy. However, because of the uncontrolled exploitation of agricultural streams and invasion of privacy riverbed, the TalarRiver has acute and critical conditions from the point of hydrologic and environmental. To study the hydrological impacts of Chashm dam, Talar watershed was considered with an area of approximately 1057 square kilometers of the Pole Sefid gauging station using a rainfall-runoff model. Results and Discussion: Simulation of the study area hydrological behavior shows that the Chashm Dam average water discharge is near to 8.6 million m3. This figure will be significant changes during wet and droughtperiods. The minimum and maximum monthly discharge of the Chashm Dam watershed in August and February is equal to 0.31 and 0.55 m3/s respectively. The minimum and maximum monthly water demand in turn in October and August is equal to 0.015 and 0.4 m3/s respectively and this shows that the river discharge in June is lower than the downstream water demand. Based on confirmed studies of the Kamandab Consulting Engineers, drinking water requirement of Semnan province, water

  8. Approach to downstream planning for nearshore response and sensitive areas protection outside Prince William Sound, Alaska

    International Nuclear Information System (INIS)

    DeCola, E.G.; Robertson, T.L.; Robertson, R.; Banta, J.

    2004-01-01

    This study assessed the need for an oil spill response plan for downstream coastal communities that could be affected by oil spilled from tankers travelling in Prince William Sound, Alaska. For the purpose of oil spill contingency planning, the State of Alaska has been divided into the Kodiak and Cook Inlet sub-areas that are at risk for downstream impacts from a Prince William Sound oil spill. The 1989 Exxon Valdez oil spill provided an example of a worst-case scenario oil spill from a tanker in Prince William Sound, but the oil spill planning system that has evolved in Alaska does not adequately plan for on oil spill that originates in one sub-area of the state, but impacts other sub-areas in the downstream spill path. This study analyzed the gaps that exist in the current response planning system in the Prince William Sound, Cook Inlet and Kodiak sub-areas. A method was proposed to improve the existing response plans so that emergency response teams are better prepared to manage cross-boundary oil spills originating in Prince William Sound. The proposed method focuses on nearshore response and sensitive areas protection for coastlines and communities that are at risk for oil spills from a tanker travelling the Trans-Alaska Pipeline System (TAPS). 11 refs., 3 figs

  9. Environmental radiological studies downstream from the Rancho Seco Nuclear Power Generating Station, 1985

    International Nuclear Information System (INIS)

    Noshkin, V.E.; Wong, K.M.; Eagle, R.J.; Brunk, J.L.; Jokela, T.A.

    1986-01-01

    Information compiled in 1985 while assessing the environmental impact of radionuclides previously discharged with aqueous releases from the Rancho Seco Nuclear Power Generating Plant is presented. In October 1984, the quantities of gamma-emitting radionuclides in water discharged to Clay Creek from the plant were reduced below operationally defined detection limits for liquid effluents. However, radionuclides previously discharged persist in the downstream environment and are found in many aquatic dietary components. 134 Cs and 137 Cs are the primary gamma-emitting radionuclides detected in the edible flesh of different fish, crayfish, and frogs. Coefficients for exponential equations are generated, from a least square analysis, that relate the change in concentration of 137 Cs in fish to distance downstream and time between March and October 1985. Concentrations of 137 Cs in surface creek sediments also decreased in the downstream direction much in the same manner as concentrations decreased in fish. However, there was no significant difference in the radiocesium concentrations in surface sediements collected from comparable locations during both 1984 and 1985

  10. Transport of perfluoroalkyl substances (PFAS) from an arctic glacier to downstream locations: implications for sources.

    Science.gov (United States)

    Kwok, Karen Y; Yamazaki, Eriko; Yamashita, Nobuyoshi; Taniyasu, Sachi; Murphy, Margaret B; Horii, Yuichi; Petrick, Gert; Kallerborn, Roland; Kannan, Kurunthachalam; Murano, Kentaro; Lam, Paul K S

    2013-03-01

    Perfluoroalkyl substances (PFAS) have been globally detected in various environmental matrices, yet their fate and transport to the Arctic is still unclear, especially for the European Arctic. In this study, concentrations of 17 PFAS were quantified in two ice cores (n=26), surface snow (n=9) and surface water samples (n=14) collected along a spatial gradient in Svalbard, Norway. Concentrations of selected ions (Na(+), SO4(2-), etc.) were also determined for tracing the origins and sources of PFAS. Perfluorobutanoate (PFBA), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were the dominant compounds found in ice core samples. Taking PFOA, PFNA and perfluorooctane-sulfonate (PFOS) as examples, higher concentrations were detected in the middle layers of the ice cores representing the period of 1997-2000. Lower concentrations of C8-C12 perfluorocarboxylates (PFCAs) were detected in comparison with concentrations measured previously in an ice core from the Canadian Arctic, indicating that contamination levels in the European Arctic are lower. Average PFAS concentrations were found to be lower in surface snow and melted glacier water samples, while increased concentrations were observed in river water downstream near the coastal area. Perfluorohexanesulfonate (PFHxS) was detected in the downstream locations, but not in the glacier, suggesting existence of local sources of this compound. Long-range atmospheric transport of PFAS was the major deposition pathway for the glaciers, while local sources (e.g., skiing activities) were identified in the downstream locations. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Environmental hedging: A theory and method for reconciling reservoir operations for downstream ecology and water supply

    Science.gov (United States)

    Adams, L. E.; Lund, J. R.; Moyle, P. B.; Quiñones, R. M.; Herman, J. D.; O'Rear, T. A.

    2017-09-01

    Building reservoir release schedules to manage engineered river systems can involve costly trade-offs between storing and releasing water. As a result, the design of release schedules requires metrics that quantify the benefit and damages created by releases to the downstream ecosystem. Such metrics should support making operational decisions under uncertain hydrologic conditions, including drought and flood seasons. This study addresses this need and develops a reservoir operation rule structure and method to maximize downstream environmental benefit while meeting human water demands. The result is a general approach for hedging downstream environmental objectives. A multistage stochastic mixed-integer nonlinear program with Markov Chains, identifies optimal "environmental hedging," releases to maximize environmental benefits subject to probabilistic seasonal hydrologic conditions, current, past, and future environmental demand, human water supply needs, infrastructure limitations, population dynamics, drought storage protection, and the river's carrying capacity. Environmental hedging "hedges bets" for drought by reducing releases for fish, sometimes intentionally killing some fish early to reduce the likelihood of large fish kills and storage crises later. This approach is applied to Folsom reservoir in California to support survival of fall-run Chinook salmon in the lower American River for a range of carryover and initial storage cases. Benefit is measured in terms of fish survival; maintaining self-sustaining native fish populations is a significant indicator of ecosystem function. Environmental hedging meets human demand and outperforms other operating rules, including the current Folsom operating strategy, based on metrics of fish extirpation and water supply reliability.

  12. Elevation of transforming growth factor beta (TGFbeta) and its downstream mediators in subcutaneous foreign body capsule tissue.

    Science.gov (United States)

    Li, Allen G; Quinn, Matthew J; Siddiqui, Yasmin; Wood, Michael D; Federiuk, Isaac F; Duman, Heather M; Ward, W Kenneth

    2007-08-01

    Foreign body encapsulation represents a chronic fibrotic response and has been a major obstacle that reduces the useful life of implanted biomedical devices. The precise mechanism underlying such an encapsulation is still unknown. We hypothesized that, considering its central role in many other fibrotic conditions, transforming growth factor beta (TGFbeta) may play an important role during the formation of foreign body capsule (FBC). In the present study, we implanted mock sensors in rats subcutaneously and excised FBC samples at day 7, 21, and 48-55 postimplantation. The most abundant TGFbeta isoform in all tissues was TGFbeta1, which was expressed minimally in control tissue. The expression of both TGFbeta1 RNA and protein was significantly increased in FBC tissues at all time points, with the highest level in day 7 FBC. The number of cells stained for phosphorylated Smad2, an indication of activated TGFbeta signaling, paralleled the expression of TGFbeta. A similar dynamic change was also observed in the numbers of FBC myofibroblasts, which in response to TGFbeta, differentiate from quiescent fibroblasts and synthesize collagen. Type I collagen, the most prominent downstream target of TGFbeta in fibrosis, was found in abundance in the FBC, especially during the latter time periods. We suggest that TGFbeta plays an important role in the FBC formation. Inhibition of TGFbeta signaling could be a promising strategy in the prevention of FBC formation, thereby extending the useful life of subcutaneous implants.

  13. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Science.gov (United States)

    Shahi, Mehdi Hayat; Holt, Roseline; Rebhun, Robert B

    2014-01-01

    The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  14. Blocking signaling at the level of GLI regulates downstream gene expression and inhibits proliferation of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Mehdi Hayat Shahi

    Full Text Available The Hedgehog-GLI signaling pathway is active in a variety of human malignancies and is known to contribute to the growth and survival of human osteosarcoma cells. In this study, we examined the expression and regulation of GLI transcription factors in multiple canine osteosarcoma cell lines and analyzed the effects of inhibiting GLI with GANT61, a GLI-specific inhibitor. Compared with normal canine osteoblasts, real-time PCR showed that GLI1 and GLI2 were highly expressed in two out of three cell lines and correlated with downstream target gene expression of PTCH1and PAX6. Treatment of canine osteosarcoma cells with GANT61 resulted in decreased expression of GLI1, GLI2, PTCH1, and PAX6. Furthermore, GANT61 inhibited proliferation and colony formation in all three canine osteosarcoma cell lines. The finding that GLI signaling activity is present and active in canine osteosarcoma cells suggests that spontaneously arising osteosarcoma in dogs might serve as a good model for future preclinical testing of GLI inhibitors.

  15. Transcriptomic effects-based monitoring for endocrine active chemicals: Assessing relative contribution of treated wastewater to downstream pollution

    Science.gov (United States)

    Martinovic-Weigelt, Dalma; Mehinto, Alvine C.; Ankley, Gerald T.; Denslow, Nancy D.; Barber, Larry B.; Lee, Kathy E.; King, Ryan J.; Schoenfuss, Heiko L.; Schroeder, Anthony L.; Villeneuve, Daniel L.

    2014-01-01

    The present study investigated whether a combination of targeted analytical chemistry information with unsupervised, data-rich biological methodology (i.e., transcriptomics) could be utilized to evaluate relative contributions of wastewater treatment plant (WWTP) effluents to biological effects. The effects of WWTP effluents on fish exposed to ambient, receiving waters were studied at three locations with distinct WWTP and watershed characteristics. At each location, 4 d exposures of male fathead minnows to the WWTP effluent and upstream and downstream ambient waters were conducted. Transcriptomic analyses were performed on livers using 15 000 feature microarrays, followed by a canonical pathway and gene set enrichment analyses. Enrichment of gene sets indicative of teleost brain–pituitary–gonadal–hepatic (BPGH) axis function indicated that WWTPs serve as an important source of endocrine active chemicals (EACs) that affect the BPGH axis (e.g., cholesterol and steroid metabolism were altered). The results indicated that transcriptomics may even pinpoint pertinent adverse outcomes (i.e., liver vacuolization) and groups of chemicals that preselected chemical analytes may miss. Transcriptomic Effects-Based monitoring was capable of distinguishing sites, and it reflected chemical pollution gradients, thus holding promise for assessment of relative contributions of point sources to pollution and the efficacy of pollution remediation.

  16. Communication: essential strategies for success.

    Science.gov (United States)

    O'Connor, Mary

    2013-06-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advance organizational change, content includes evidence-based projects, tool, and resources that mobilize and sustain organizational change initiatives. In this article, the author discusses strategies for communication for change processes, whether large or small. Intentional planning and development of a communication strategy alongside, not as an afterthought, to change initiatives are essential.

  17. Essentials of nuclear medicine imaging

    CERN Document Server

    Mettler, Fred A. Jr

    2012-01-01

    Essentials of Nuclear Medicine Imaging, by Drs. Fred A Mettler and Milton J Guiberteau, provides the practical and comprehensive guidance you need to master key nuclear imaging techniques. From physics, instrumentation, quality control, and legal requirements to hot topics such as sodium fluoride, radiopharmaceuticals, and recommended pediatric administered doses and guidelines, this sixth edition covers the fundamentals and recent developments in the practice of nuclear medicine.

  18. Essential themes in Personnel economics

    OpenAIRE

    Josheski, Dushko

    2014-01-01

    In this paper are presented essential themes in the subject of personnel economics. In the first part analysis has been conducted on the impact of peer pressure on workplace behaviour. Then again models for compensation structures within firms, and their influence on the utility of work by employees. In the final section of the paper the productivity spillover effect has been analyzed, and the causes of existence of spillovers and their impact on workers’ productivity

  19. Essentials of natural gas microturbines

    CERN Document Server

    Boicea, Valentin A

    2013-01-01

    Addressing a field which, until now, has not been sufficiently investigated, Essentials of Natural Gas Microturbines thoroughly examines several natural gas microturbine technologies suitable not only for distributed generation but also for the automotive industry. An invaluable resource for power systems, electrical, and computer science engineers as well as operations researchers, microturbine operators, policy makers, and other industry professionals, the book: Explains the importance of natural gas microturbines and their use in distributed energy resource (DER) systemsDiscusses the histor

  20. Repelling mosquitoes with essential oils

    Science.gov (United States)

    Riley, L.

    2017-12-01

    Mosquitoes carry diseases than can lead to serious illness and death. According to the World Health Organization, mosquitoes infect over 300 million people a year with Malaria and Dengue Fever, two life threatening diseases vectored by mosquitoes. Although insecticides are the most effective way to control mosquitoes, they are not always environmentally friendly. Therefore, alternative tactics should be considered. In this study, we looked at the repellency of various essential oils on female Aedes aegypti through a series of laboratory assays.

  1. Synergistic effects of targeted PI3K signaling inhibition and chemotherapy in liposarcoma.

    Directory of Open Access Journals (Sweden)

    Shang Guo

    Full Text Available While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%. No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma.

  2. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation.

    Science.gov (United States)

    Koziel, Lydia; Wuelling, Manuela; Schneider, Sabine; Vortkamp, Andrea

    2005-12-01

    During endochondral ossification, the secreted growth factor Indian hedgehog (Ihh) regulates several differentiation steps. It interacts with a second secreted factor, parathyroid hormone-related protein (PTHrP), to regulate the onset of hypertrophic differentiation, and it regulates chondrocyte proliferation and ossification of the perichondrium independently of PTHrP. To investigate how the Ihh signal is translated in the different target tissues, we analyzed the role of the zinc-finger transcription factor Gli3, which acts downstream of hedgehog signals in other organs. Loss of Gli3 in Ihh mutants restores chondrocyte proliferation and delays the accelerated onset of hypertrophic differentiation observed in Ihh-/- mutants. Furthermore the expression of the Ihh target genes patched (Ptch) and PTHrP is reactivated in Ihh-/-;Gli3-/- mutants. Gli3 seems thus to act as a strong repressor of Ihh signals in regulating chondrocyte differentiation. In addition, loss of Gli3 in mice that overexpress Ihh in chondrocytes accelerates the onset of hypertrophic differentiation by reducing the domain and possibly the level of PTHrP expression. Careful analysis of chondrocyte differentiation in Gli3-/- mutants revealed that Gli3 negatively regulates the differentiation of distal, low proliferating chondrocytes into columnar, high proliferating cells. Our results suggest a model in which the Ihh/Gli3 system regulates two distinct steps of chondrocyte differentiation: (1) the switch from distal into columnar chondrocytes is repressed by Gli3 in a PTHrP-independent mechanism; (2) the transition from proliferating into hypertrophic chondrocytes is regulated by Gli3-dependent expression of PTHrP. Furthermore, by regulating distal chondrocyte differentiation, Gli3 seems to position the domain of PTHrP expression.

  3. Role for HIF-1α and Downstream Pathways in Regulating Neuronal Injury after Intracerebral Hemorrhage in Diabetes

    Directory of Open Access Journals (Sweden)

    Zhen Yu

    2015-08-01

    Full Text Available Background/Aims: HIF-1α is accumulated in the cellular nucleus and cytoplasm under conditions of oxygen deprivation and engaged in pathophysiologic changes of homeostasis by modulating the expression of several target genes. As an endogenous signaling protein, HIF-1α contributes to in neuroprotection, erythropoiesis, and apoptosis modulation. The purpose of this study was to examine the role played by HIF-1α in regulating neurological injury evoked by intracerebral hemorrhage (ICH through its downstream product, namely vascular endothelial growth factor (VEGF. In particular, we examined the effects of diabetic hyperglycemia on HIF-1α response in the processing of ICH. Methods: ELISA was used to measure HIF-1α and VEGF; and Western Blot analysis to examine the protein expression of VEGFR-2 and Caspase-3. Neurological Severity Score and brain water content were used to indicate neurological function and brain edema. Results: HIF-1α and VEGF were significantly increased in the brain after induction of ICH in non-diabetic control rats and diabetic rats; however, the amplified levels of HIF-1α and VEGF were attenuated in diabetic rats (Pvs. non-diabetic rats as compared with non-diabetic rats. Also, the protein expression of VEGF receptor subtype 2 was significantly less in the brain of diabetic rats (Pvs. non-diabetic rats. Further, cerebral infusion of HIF-1 activator stabilized VEGF levels, attenuated Caspase-3 and improved neurological deficits induced by ICH and the effects are smaller in diabetic animals. Conclusion: HIF-1α activated by ICH likely plays a beneficial role via VEGF mechanisms and response of HIF-1α is largely impaired in diabetes. This has pharmacological implications to target specific HIF-1α and VEGF pathway for neuronal dysfunction and vulnerability related to ICH.

  4. Coarse and fine sediment transportation patterns and causes downstream of the Three Gorges Dam

    Science.gov (United States)

    Li, Songzhe; Yang, Yunping; Zhang, Mingjin; Sun, Zhaohua; Zhu, Lingling; You, Xingying; Li, Kanyu

    2017-11-01

    Reservoir construction within a basin affects the process of water and sediment transport downstream of the dam. The Three Gorges Reservoir (TGR) affects the sediment transport downstream of the dam. The impoundment of the TGR reduced total downstream sediment. The sediment group d≤0.125 mm (fine particle) increased along the path, but the average was still below what existed before the reservoir impoundment. The sediments group d>0.125 mm (coarse particle) was recharged in the Yichang to Jianli reach, but showed a deposition trend downstream of Jianli. The coarse sediment in the Yichang to Jianli section in 2003 to 2007 was above the value before the TGR impoundment. However, the increase of both coarse and fine sediments in 2008 to 2014 was less than that in 2003 to 2007. The sediment retained in the dam is the major reason for the sediment reduction downstream. However, the retention in different river reaches is affected by riverbed coarsening, discharge, flow process, and conditions of lake functioning and recharging from the tributaries. The main conclusions derived from our study are as follows: 1) The riverbed in the Yichang to Shashi section was relatively coarse, thereby limiting the supply of fine and coarse sediments. The fine sediment supply was mainly controlled by TGR discharge, whereas the coarse sediment supply was controlled by the duration of high flow and its magnitude. 2) The supply of both coarse and fine sediments in the Shashi to Jianli section was controlled by the amount of total discharge. The sediment supply from the riverbed was higher in flood years than that in the dry years. The coarse sediment tended to deposit, and the deposition in the dry years was larger than that in the flood years. 3) The feeding of the fine sediment in the Luoshan to Hankou section was mainly from the riverbed. The supply in 2008 to 2014 was more than that in 2003 to 2007. Around 2010, the coarse sediments transited from depositing to scouring that was

  5. Associations of mRNA:microRNA for the shared downstream molecules of EGFR and alternative tyrosine kinase receptors in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fengfeng Wang

    2016-10-01

    Full Text Available Lung cancer is the top cancer killer worldwide with high mortality rate. Majority belong to non-small cell lung cancers (NSCLCs. The epidermal growth factor receptor (EGFR has been broadly explored as a drug target for therapy. However, the drug responses are not durable due to the acquired resistance. MicroRNAs (miRNAs are small noncoding and endogenous molecules that can inhibit mRNA translation initiation and degrade mRNAs. We wonder if some downstream molecules shared by EGFR and the other tyrosine kinase receptors (TKRs further transduce the signals alternatively, and some miRNAs play the key roles in affecting the expression of these downstream molecules. In this study, we investigated the mRNA:miRNA associations for the direct EGFR downstream molecules in the EGFR signaling pathway shared with the other TKRs, including c-MET (hepatocyte growth factor receptor, Ron (a protein tyrosine kinase related to c-MET, PDGFR (platelet-derived growth factor receptor, and IGF-1R (insulin-like growth factor receptor-1. The multiple linear regression and support vector regression (SVR models were used to discover the statistically significant and the best weighted miRNAs regulating the mRNAs of these downstream molecules. These two models revealed the similar mRNA:miRNA associations. It was found that the miRNAs significantly affecting the mRNA expressions in the multiple regression model were also those with the largest weights in the SVR model. To conclude, we effectively identified a list of meaningful mRNA:miRNA associations: phospholipase C, gamma 1 (PLCG1 with miR-34a, phosphoinositide-3-kinase, regulatory subunit 2 (PIK3R2 with miR-30a-5p, growth factor receptor-bound protein 2 (GRB2 with miR-27a, and Janus kinase 1 (JAK1 with miR-302b and miR-520e. These associations could make great contributions to explore new mechanism in NSCLCs. These candidate miRNAs may be regarded as the potential drug targets for treating NSCLCs with acquired drug

  6. The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway

    International Nuclear Information System (INIS)

    Cohen-Fix, O.; Koshland, D.

    1997-01-01

    Inhibition of DNA replication and physical DNA damage induce checkpoint responses that arrest cell cycle progression at two different stages. In Saccharomyces cerevisiae, the execution of both checkpoint responses requires the Mec1 and Rad53 proteins. This observation led to the suggestion that these checkpoint responses are mediated through a common signal transduction pathway. However, because the checkpoint-induced arrests occur at different cell cycle stages, the downstream effectors mediating these arrests are likely to be distinct. We have previously shown that the S. cerevisiae protein Pds1p is an anaphase inhibitor and is essential for cell cycle arrest in mitosis in the presence DNA damage. Herein we show that DNA damage, but not inhibition of DNA replication, induces the phosphorylation of Pds1p. Analyses of Pds1p phosphorylation in different checkpoint mutants reveal that in the presence of DNA damage, Pds1p is phosphorylated in a Mec1p- and Rad9p-dependent hut Rad53p-independent manner. Our data place Pds1p and Rad53p on parallel branches of the DNA damage checkpoint pathway. We suggest that Pds1p is a downstream target of the DNA damage checkpoint pathway and that it is involved in implementing the DNA damage checkpoint arrest specifically in mitosis

  7. Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene

    Science.gov (United States)

    Ifere, Godwin O.; Equan, Anita; Gordon, Kereen; Nagappan, Peri; Igietseme, Joseph U.; Ananaba, Godwin A.

    2010-01-01

    Background The purpose of our study was to show the distinction between the apoptotic and anti-proliferative signaling of phytosterols and cholesterol enrichment in prostate cancer cell lines, mediated by the differential transcription of caveolin-1, and N-myc downstream regulated gene1 (NDRG1), a pro-apoptotic androgen-regulated tumor suppressor. Methods PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 72 h, followed by trypan blue dye exclusion measurement of necrosis and cell growth measured with a Coulter counter. Sterol induction of cell growth-suppressor gene expression was evaluated by mRNA transcription using RT-PCR, while cell cycle analysis was performed by FACS analysis. Altered expression of Ndrg1 protein was confirmed by Western blot analysis. Apoptosis was evaluated by real time RT-PCR amplification of P53, Bcl-2 gene and its related pro- and anti-apoptotic family members. Results Physiological doses (16 µM) of cholesterol and phytosterols were not cytotoxic in these cells. Cholesterol enrichment promoted cell growth (Pphytosterols significantly induced growth-suppression (Pphytosterols decreased mitotic subpopulations. We demonstrated for the first time that cholesterols concertedly attenuated the expression of caveolin-1(cav-1) and NDRG1 genes in both prostate cancer cell lines. Phytosterols had the opposite effect by inducing overexpression of cav-1, a known mediator of androgen-dependent signals that presumably control cell growth or apoptosis. Conclusions Cholesterol and phytosterol treatment differentially regulated the growth of prostate cancer cells and the expression of p53 and cav-1, a gene that regulates androgen-regulated signals. These sterols also differentially regulated cell cycle arrest, downstream pro-apoptotic androgen-regulated tumor-suppressor, NDRG1 suggesting that cav-1 may mediate pro-apoptotic NDRG1 signals. Elucidation of the mechanism for sterol modulation of growth and apoptosis signaling

  8. Cyber essentials a pocket guide

    CERN Document Server

    Calder, Alan

    2014-01-01

    Every year, thousands of computer systems in the UK are compromised. The majority fall victim to easily preventable cyber attacks, carried out with tools which are freely available on the Internet.   Cyber Essentials is the UK Government's reaction to the proliferation of these attacks. It requires that organisations put basic security measures in place, enabling them to reliably counter the most common tactics employed by cyber criminals. From 1 October 2014, all suppliers bidding for a range of government ICT contracts - in particu

  9. Microsoft Windows Operating System Essentials

    CERN Document Server

    Carpenter, Tom

    2012-01-01

    A full-color guide to key Windows 7 administration concepts and topics Windows 7 is the leading desktop software, yet it can be a difficult concept to grasp, especially for those new to the field of IT. Microsoft Windows Operating System Essentials is an ideal resource for anyone new to computer administration and looking for a career in computers. Delving into areas such as fundamental Windows 7 administration concepts and various desktop OS topics, this full-color book addresses the skills necessary for individuals looking to break into a career in IT. Each chapter begins with a list of topi

  10. Axure RP 6 Prototyping Essentials

    CERN Document Server

    Schwartz, Ezra

    2012-01-01

    Axure RP 6 Prototyping Essentials is a detailed, practical primer on the leading rapid prototyping tool. Short on jargon and high on concepts, real-life scenarios and step-by-step guidance through hands-on examples, this book will show you how to integrate Axure into your UX workflow. This book is written for UX practitioners, business analysts, product managers, and anyone else who is involved in UX projects. The book assumes that you have no or very little familiarity with Axure. It will help you if you are evaluating the tool for an upcoming project or are required to quickly get up to spee

  11. Linear feedback controls the essentials

    CERN Document Server

    Haidekker, Mark A

    2013-01-01

    The design of control systems is at the very core of engineering. Feedback controls are ubiquitous, ranging from simple room thermostats to airplane engine control. Helping to make sense of this wide-ranging field, this book provides a new approach by keeping a tight focus on the essentials with a limited, yet consistent set of examples. Analysis and design methods are explained in terms of theory and practice. The book covers classical, linear feedback controls, and linear approximations are used when needed. In parallel, the book covers time-discrete (digital) control systems and juxtapos

  12. Overview of the essential tools

    International Nuclear Information System (INIS)

    Mount, R.P.

    1989-01-01

    The essential tools needed for the analysis of HEP experiments are software, networking, data handling, and CPU power. Leaving most software topics to other papers, this paper describes how we can use today's hardware effectively for HEP data analysis. It describes a new but viable model for HEP computing and data handling on a single site, and outlines the challenge of extending this environment to the wider university-based community. Finally it touches on the revolution in software design that may be triggered by the revolution in computing technology. (orig.)

  13. Essentials of Electromagnetics for Engineering

    Science.gov (United States)

    de Wolf, David A.

    2000-11-01

    Essentials of Electromagnetics for Engineering introduces the key physical and engineering principles of electromagnetics. Throughout the book, David de Wolf describes the intermediate steps in mathematical derivations that many other textbooks leave out. He covers in depth the concepts of fields and potentials and then progresses to magnetostatics, Maxwell's equations, electrodynamics and wave propagation, waveguides, transmission lines, and antennas. At each stage, de Wolf stresses the physical principles underlying the mathematical results. He also includes homework exercises, a separate chapter on numerical methods in electromagnetics, and a broad range of worked examples to illustrate important concepts. Solutions manual available.

  14. A genetic screen in Myxococcus xanthus identifies mutants that uncouple outer membrane exchange from a downstream cellular response.

    Science.gov (United States)

    Dey, Arup; Wall, Daniel

    2014-12-01

    Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Dissection of Signaling Events Downstream of the c-Mpl Receptor in Murine Hematopoietic Stem Cells Via Motif-Engineered Chimeric Receptors.

    Science.gov (United States)

    Saka, Koichiro; Lai, Chen-Yi; Nojima, Masanori; Kawahara, Masahiro; Otsu, Makoto; Nakauchi, Hiromitsu; Nagamune, Teruyuki

    2018-02-01

    Hematopoietic stem cells (HSCs) are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability. Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network. Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events. We here tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity. Each CR contains tyrosine motifs that enable selective activation of signal molecules located downstream of the c-Mpl receptor upon stimulation by an artificial ligand. Signaling through a control CR with a wild-type c-Mpl cytoplasmic tail sufficed to enhance HSC proliferation and colony formation in cooperation with stem cell factor (SCF). Among a series of CRs, only one compatible with selective Stat5 activation showed similar positive effects. The HSCs maintained ex vivo in these environments retained long-term reconstitution ability following transplantation. This ability was also demonstrated in secondary recipients, indicating effective transmission of stem cell-supportive signals into HSCs via these artificial CRs during culture. Selective activation of Stat5 through CR ex vivo favored preservation of lymphoid potential in long-term reconstituting HSCs, but not of myeloid potential, exemplifying possible dissection of signals downstream of c-Mpl. These CR systems therefore offer a useful tool to scrutinize complex signaling pathways in HSCs.

  16. Emerging treatments for essential thrombocythemia

    Directory of Open Access Journals (Sweden)

    Okoli S

    2011-12-01

    Full Text Available Steven Okoli, Claire HarrisonDepartment of Haematology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UKAbstract: In 1934, Epstein and Goedel used the term hemorrhagic thrombocythemia to describe a disorder characterized by permanent elevation of a platelet count to more than three times normal, hyperplasia of megakaryocytes, and the tendency for venous thrombosis and spontaneous hemorrhage. Over the last 75 years, and particularly in the past 6 years, major progress has been made in our understanding of essential thrombocythemia (ET and its pathogenesis with the identification of the highly prevalent JAK-2 V617F and other mutations. Current management of this condition is based upon historical data and with treatments that have not changed significantly for nearly two decades. This study discusses this and recent progress, highlighting exciting new data with old and new drugs, as well as which patients in particular should be evaluated for these new therapies.Keywords: essential thrombocythemia, interferon, JAK inhibitor

  17. Economic demand and essential value.

    Science.gov (United States)

    Hursh, Steven R; Silberberg, Alan

    2008-01-01

    The strength of a rat's eating reflex correlates with hunger level when strength is measured by the response frequency that precedes eating (B. F. Skinner, 1932a, 1932b). On the basis of this finding, Skinner argued response frequency could index reflex strength. Subsequent work documented difficulties with this notion because responding was affected not only by the strengthening properties of the reinforcer but also by the rate-shaping effects of the schedule. This article obviates this problem by measuring strength via methods from behavioral economics. This approach uses demand curves to map how reinforcer consumption changes with changes in the "price" different ratio schedules impose. An exponential equation is used to model these demand curves. The value of this exponential's rate constant is used to scale the strength or essential value of a reinforcer, independent of the scalar dimensions of the reinforcer. Essential value determines the consumption level to be expected at particular prices and the response level that will occur to support that consumption. This approach permits comparing reinforcers that differ in kind, contributing toward the goal of scaling reinforcer value. (c) 2008 APA, all rights reserved

  18. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2014-07-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  19. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  20. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  1. Propagation of temperature disturbances in bounded flows downstream of a nozzle block

    International Nuclear Information System (INIS)

    Krebs, L.

    1979-12-01

    The early detection of cooling disturbances in a fuel element of a sodium cooled reactor is a must for safety reasons. One possibility of achieving this goal is by measuring and analyzing the coolant temperature at the fuel element outlet. Assessment of the potential of this method requires knowledge of the flow phenomena downstream of the fuel element. As a fluid dynamics model of a fuel element a nozzle block is used, the bores of which correspond to the subchannels between the fuel rods. The studies are conducted in water which has kinematic properties comparable to those of sodium. The velocity and temperature fields downstream of the nozzle block are examined for two REYNOLDS numbers. To simulate a disturbed cooling condition, water with a temperature higher by ΔT anti T = 10 K is injected through one subchannel of the nozzle block. At the same time, the volume injected is varied. The central channel and one side channel close to the wall are selected as injection sites. Statisticl analysis of the measured velocity and temperature signals covers the following parameters: Linear averages, intensities, probability densities, spectral power densities, autocorrelation functions, integral turbulence lengths, dissipation lengths, dissipation, skewness and flatness values. On the basis of FOURIER's differential equation of heat conduction a theoretical model is developed to describe both the average temperature field and the intensity field in the flow downstream of the nozzle block. Comparison of measurements and calculations furnishes good agreement and indicates that extrapolation of the model to sodium as a fluid is possible. Supplementary to the measurements and calculations details of the water test rig and the anemometer measuring system used for velocity and temperature measurements are shown in the Appendix. (orig.) 891 GL/orig. 892 KN [de

  2. Downstream Fining of Polydispersed Gravity Currents Along a V-Shaped Valley.

    Science.gov (United States)

    Besson, C. K.; Meriaux, C. A. M. D.

    2014-12-01

    Turbidity currents belong to the class of currents transporting sediments, whose deposits exhibit downstream grain size fining. In this study, the objective was to better understand the relationship between downstream fining and grain sizes at the source. To this end, we performed four lock-exchange experiments of polydispersed and turbulent gravity currents flowing along a 5-m long V-shaped valley. The particle volumetric concentrations were typically 3%. The four currents were made of 1) Silicon Carbide (SiC), 2) Glass Beads (GBs), 3) a combined poorly sorted SiC/GBs, and 4) a moderately sorted combined SiC/GBs. We used the Morphologi G3 tool developed by Malvern Instruments Corporate (Malvern Instruments Ltd, UK) for the grain size analyses. We first established a criterion for identifying the appropriate number of grain size classes nbclassfor characterizing the grain size distributions. We considered the four statistical indicators that are the arithmetic mean size dmean, the standard deviation σd, the skewness Skd, and the kurtosis Kd, and show that the four indicators for the initial grain size distributions reach plateaux when nb_class≥ 20. Hence we chose nbclass=20 as being our appropriate bin width. These four indicators were then calculated for samples taken along the deposits to establish the grain size distributions along the deposits. The subsequent profiles of dmean, σd, Skd, and Kd with distance from the lock show highly variable behaviours between the different initial distributions. In particular, the distance over which the loss of the largest grains of the initial distribution occurs [dmean> dmean(initial)], can cover up to half the runout length. Curiously, the different rates of fining estimated from the curves (dmean/ dmean(initial)) as a function of downstream distance (x/x_runout) do not appear to be well correlated with the sedimentation velocities based on dmean(initial). This is currently being investigated.

  3. A method for comparing impacts with real targets to impacts onto the IAEA unyielding target

    International Nuclear Information System (INIS)

    Ammerman, D.J.

    1991-01-01

    The severity of the IAEA accident conditions test requirement (IAEA 1990) of an impact onto an essentially unyielding target from a drop height of 9 meters encompasses a large fraction of all real world impacts. This is true, in part, because of the unyielding nature of the impact target. Impacts onto the unyielding target have severities equivalent to higher velocity impacts onto real targets which are not unyielding. The severity of impacts with yielding targets is decreased by the amount of the impact energy absorbed in damaging the target. In demonstrating the severity of the regulatory impact event it is advantageous to be able to relate this impact onto an essentially unyielding target to impacts with yielding targets

  4. Corrosion mechanisms downstream the nuclear cycle: from processing-recycling to transmutation

    International Nuclear Information System (INIS)

    Balbaud-Celerier, F.

    2010-01-01

    The author gives a detailed overview of his scientific and research activities in the field of material behaviour in environments met during the downstream part of the nuclear cycle. In the first part, he presents his works on material corrosion in concentrated and high temperature nitric acid, and more particularly on the phenomenon which governs this corrosion: the nitric acid reduction mechanism. In the second part, he reports researches performed within the frame of hybrid reactor development for the processing of future fuels. In both parts, he also discusses the perspectives for new researches and developments

  5. Advances in downstream processing of biologics - Spectroscopy: An emerging process analytical technology.

    Science.gov (United States)

    Rüdt, Matthias; Briskot, Till; Hubbuch, Jürgen

    2017-03-24

    Process analytical technologies (PAT) for the manufacturing of biologics have drawn increased interest in the last decade. Besides being encouraged by the Food and Drug Administration's (FDA's) PAT initiative, PAT promises to improve process understanding, reduce overall production costs and help to implement continuous manufacturing. This article focuses on spectroscopic tools for PAT in downstream processing (DSP). Recent advances and future perspectives will be reviewed. In order to exploit the full potential of gathered data, chemometric tools are widely used for the evaluation of complex spectroscopic information. Thus, an introduction into the field will be given. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. European downstream oil industry safety performance. Statistical summary of reported incidents 2009

    International Nuclear Information System (INIS)

    Burton, A.; Den Haan, K.H.

    2010-10-01

    The sixteenth such report by CONCAWE, this issue includes statistics on workrelated personal injuries for the European downstream oil industry's own employees as well as contractors for the year 2009. Data were received from 33 companies representing more than 97% of the European refining capacity. Trends over the last sixteen years are highlighted and the data are also compared to similar statistics from related industries. In addition, this report presents the results of the first Process Safety Performance Indicator data gathering exercise amongst the CONCAWE membership.

  7. Has dyke development in the Vietnamese Mekong Delta shifted flood hazard downstream?

    Science.gov (United States)

    Van Khanh Triet, Nguyen; Viet Dung, Nguyen; Fujii, Hideto; Kummu, Matti; Merz, Bruno; Apel, Heiko

    2017-08-01

    In the Vietnamese part of the Mekong Delta (VMD) the areas with three rice crops per year have been expanded rapidly during the last 15 years. Paddy-rice cultivation during the flood season has been made possible by implementing high-dyke flood defenses and flood control structures. However, there are widespread claims that the high-dyke system has increased water levels in downstream areas. Our study aims at resolving this issue by attributing observed changes in flood characteristics to high-dyke construction and other possible causes. Maximum water levels and duration above the flood alarm level are analysed for gradual trends and step changes at different discharge gauges. Strong and robust increasing trends of peak water levels and duration downstream of the high-dyke areas are found with a step change in 2000/2001, i.e. immediately after the disastrous flood which initiated the high-dyke development. These changes are in contrast to the negative trends detected at stations upstream of the high-dyke areas. This spatially different behaviour of changes in flood characteristics seems to support the public claims. To separate the impact of the high-dyke development from the impact of the other drivers - i.e. changes in the flood hydrograph entering the Mekong Delta, and changes in the tidal dynamics - hydraulic model simulations of the two recent large flood events in 2000 and 2011 are performed. The hydraulic model is run for a set of scenarios whereas the different drivers are interchanged. The simulations reveal that for the central VMD an increase of 9-13 cm in flood peak and 15 days in duration can be attributed to high-dyke development. However, for this area the tidal dynamics have an even larger effect in the range of 19-32 cm. However, the relative contributions of the three drivers of change vary in space across the delta. In summary, our study confirms the claims that the high-dyke development has raised the flood hazard downstream. However, it is not

  8. Has dyke development in the Vietnamese Mekong Delta shifted flood hazard downstream?

    Directory of Open Access Journals (Sweden)

    N. V. K. Triet

    2017-08-01

    Full Text Available In the Vietnamese part of the Mekong Delta (VMD the areas with three rice crops per year have been expanded rapidly during the last 15 years. Paddy-rice cultivation during the flood season has been made possible by implementing high-dyke flood defenses and flood control structures. However, there are widespread claims that the high-dyke system has increased water levels in downstream areas. Our study aims at resolving this issue by attributing observed changes in flood characteristics to high-dyke construction and other possible causes. Maximum water levels and duration above the flood alarm level are analysed for gradual trends and step changes at different discharge gauges. Strong and robust increasing trends of peak water levels and duration downstream of the high-dyke areas are found with a step change in 2000/2001, i.e. immediately after the disastrous flood which initiated the high-dyke development. These changes are in contrast to the negative trends detected at stations upstream of the high-dyke areas. This spatially different behaviour of changes in flood characteristics seems to support the public claims. To separate the impact of the high-dyke development from the impact of the other drivers – i.e. changes in the flood hydrograph entering the Mekong Delta, and changes in the tidal dynamics – hydraulic model simulations of the two recent large flood events in 2000 and 2011 are performed. The hydraulic model is run for a set of scenarios whereas the different drivers are interchanged. The simulations reveal that for the central VMD an increase of 9–13 cm in flood peak and 15 days in duration can be attributed to high-dyke development. However, for this area the tidal dynamics have an even larger effect in the range of 19–32 cm. However, the relative contributions of the three drivers of change vary in space across the delta. In summary, our study confirms the claims that the high-dyke development has raised the flood

  9. Downstream process for production of a viable and stable Bacillus cereus aquaculture biological agent

    CSIR Research Space (South Africa)

    Lalloo, R

    2010-03-01

    Full Text Available , 604 Robertson JL (1998) The use of probiotics in the diet of dogs. 605 J Nutri 128:2730S–2732S 606 Brar SK, Verma M, Tyagi RD, Valéro JR (2006) Recent advances in 607 downstream processing and formulations of Bacillus thuringien- 608 sis based..., Menasveta P (2000) Some recent issues and innovations in 630 marine shrimp pond culture. Rev Fish Sci 8:151–233 631 Gatesoupe FJ (1999) The use of probiotics in aquaculture. Aquacul- 632 ture 180:147–165 633 Guetsky R, Shtienberg Y, Elad Y, Fischer E...

  10. Particle collection by a pilot plant venturi scrubber downstream from a pilot plant electrostatic precipitator

    Science.gov (United States)

    Sparks, L. E.; Ramsey, G. H.; Daniel, B. E.

    The results of pilot plant experiments of particulate collection by a venturi scrubber downstream from an electrostatic precipitator (ESP) are presented. The data, which cover a range of scrubber operating conditions and ESP efficiencies, show that particle collection by the venturi scrubber is not affected by the upstream ESP; i.e., for a given scrubber pressure drop, particle collection efficiency as a function of particle diameter is the same for both ESP on and ESP off. The experimental results are in excellent agreement with theoretical predictions. Order of magnitude cost estimates indicate that particle collection by ESP scrubber systems may be economically attractive when scrubbers must be used for SO x control.

  11. Downstream natural gas in Europe - high hopes dashed for upstream oil and gas companies

    International Nuclear Information System (INIS)

    Eikeland, P.O.

    2007-01-01

    Access for independents to retail gas markets was a central concern in European policy reform efforts in the 1990s. Upstream oil and gas companies reacted with strategic intentions of forward integration. By late 2004, forward integration was still weak, however. An important explanation of the gap between announced strategic re-orientation and actual strategy implementation lies in the political failure of EU member states to dismantle market barriers to entry for independents. Variations between companies in downstream strategy implementation are explained by variations in business opportunities and internal company factors. [Author

  12. Price rigidity in the downstream petroleum industry in New Zealand. Where does it happen?

    International Nuclear Information System (INIS)

    Delpachitra, Sarath B.

    2002-01-01

    This paper examines the pricing behaviour of the downstream petroleum product market in New Zealand using multivariate error correction models. The unique feature of these models is the use of actual weekly wholesale and retail prices of diesel and unleaded petrol to measure the relative rigidity of domestic prices. The results suggest that price adjustments in domestic markets in response to price changes in world crude oil markets and refined product markets are very weak. Domestic wholesale prices appear to be the key variable in determining retail prices. Lack of competition in the wholesale sector is found to be the main reason for weak price adjustments

  13. Price rigidity in the downstream petroleum industry in New Zealand: where does it happen?

    International Nuclear Information System (INIS)

    Delpachitra, S.B.

    2002-01-01

    This paper examines the pricing behaviour of the downstream petroleum product market in New Zealand using multivariate error correction models. The unique feature of these models is the use of actual weekly wholesale and retail prices of diesel and unleaded petrol to measure the relative rigidity of domestic prices. The results suggest that price adjustments in domestic markets in response to price changes in world crude oil markets and refined product markets are very weak. Domestic wholesale prices appear to be the key variable in determining retail prices. Lack of competition in the wholesale sector is found to be the main reason for weak price adjustments. (author)

  14. Downstream natural gas in Europe-High hopes dashed for upstream oil and gas companies

    International Nuclear Information System (INIS)

    Eikeland, Per Ove

    2007-01-01

    Access for independents to retail gas markets was a central concern in European policy reform efforts in the 1990s. Upstream oil and gas companies reacted with strategic intentions of forward integration. By late 2004, forward integration was still weak, however. An important explanation of the gap between announced strategic re-orientation and actual strategy implementation lies in the political failure of EU member states to dismantle market barriers to entry for independents. Variations between companies in downstream strategy implementation are explained by variations in business opportunities and internal company factors

  15. Production of structured lipids: acyl migration during enzymatic interesterification and downstream processing

    DEFF Research Database (Denmark)

    Xu, Xuebing

    1997-01-01

    Production of structured lipids by lipase-catalyzed interesterification attracts great interests recently. Structured lipids are defined, in this article, as triacylglycerols which contain both medium or short chain fatty acids and long chain fatty acids, each groups locating specifically in the sn......-2 position or sn-1,3 positions of glycerol backbone. These kinds of lipids are reported to be promising for both enteral and parenteral nutrition. However, acyl migration occurs in the reaction stage and downstream purification process. This side-reaction causes by-products which are harmful...

  16. Essential amino acid enriched high-protein enteral nutrition modulates insulin-like growth factor-1 system function in a rat model of trauma-hemorrhagic shock.

    Directory of Open Access Journals (Sweden)

    Xianfeng Xia

    Full Text Available Nutrition support for critically ill patients supplemented with additional modular protein may promote skeletal muscle protein anabolism in addition to counteracting acute nitrogen loss. The present study was designed to investigate whether the essential amino acid (EAA enriched high-protein enteral nutrition (EN modulates the insulin-like growth factor-1 (IGF-1 system and activates the mammalian target of rapamycin (mTOR anabolic signaling pathway in a trauma-hemorrhagic shock (T-HS rat model.Male Sprague-Dawley rats (n = 90, 278.18 ± 0.94 g were randomly assigned to 5 groups: (1 normal control, (2 pair-fed, (3 T-HS, (4 T-HS and standard EN, and (5 T-HS and EAA enriched high-protein EN. Six animals from each group were harvested on days 2, 4, and 6 for serum, gastrocnemius, soleus, and extensor digitorum longus sample collection. T-HS significantly reduced muscle mass. Nutrition support maintained muscle mass, especially the EAA enriched high-protein EN. Meanwhile, a pronounced derangement in IGF-1-IGFBPs axis as well as impaired mTOR transduction was observed in the T-HS group. Compared with animals receiving standard EN, those receiving EAA enriched high-protein EN presented 18% higher serum free IGF-1 levels following 3 days of nutrition support and 22% higher after 5 days. These changes were consistent with the concomitant elevation in serum insulin and reduction in corticosterone levels. In addition, phosphorylations of downstream anabolic signaling effectors - including protein kinase B, mTOR, and ribosomal protein S6 kinase1 - increased significantly in rats receiving EAA enriched high-protein EN.Our findings firstly demonstrate the beneficial effect of EAA enriched high-protein EN on the metabolic modulation of skeletal muscle protein anabolism by regulating the IGF-1 system and downstream anabolic signaling transduction.

  17. Retention of ferrofluid aggregates at the target site during magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Asfer, Mohammed, E-mail: asfer786@gmail.com [School of Engineering and Technology, BML Munjal University, Haryana (India); Saroj, Sunil Kumar [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India); Panigrahi, Pradipta Kumar, E-mail: panig@iitk.ac.in [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India)

    2017-08-15

    Highlights: • The present in vitro work reports the retention dynamics of ferrofluid aggregates at the target site against a bulk flow of DI water inside a micro capillary during magnetic drug targeting. • The recirculation zone at the downstream of the aggregate is found to be a function of aggregate height, Reynolds number and the degree of surface roughness of the outer boundary of the aggregate. • The reported results of the present work can be used as a guideline for the better design of MDT technique for in vivo applications. - Abstract: The present study reports the retention dynamics of a ferrofluid aggregate localized at the target site inside a glass capillary (500 × 500 µm{sup 2} square cross section) against a bulk flow of DI water (Re = 0.16 and 0.016) during the process of magnetic drug targeting (MDT). The dispersion dynamics of iron oxide nanoparticles (IONPs) into bulk flow for different initial size of aggregate at the target site is reported using the brightfield visualization technique. The flow field around the aggregate during the retention is evaluated using the µPIV technique. IONPs at the outer boundary experience a higher shear force as compared to the magnetic force, resulting in dispersion of IONPs into the bulk flow downstream to the aggregate. The blockage effect and the roughness of the outer boundary of the aggregate resulting from chain like clustering of IONPs contribute to the flow recirculation at the downstream region of the aggregate. The entrapment of seeding particles inside the chain like clusters of IONPs at the outer boundary of the aggregate reduces the degree of roughness resulting in a streamlined aggregate at the target site at later time. The effect of blockage, structure of the aggregate, and disturbed flow such as recirculation around the aggregate are the primary factors, which must be investigated for the effectiveness of the MDT process for in vivo applications.

  18. Essential AOP: The A Calculus

    DEFF Research Database (Denmark)

    De Fraine, Bruno; Ernst, Erik; Südholt, Mario

    2012-01-01

    Aspect-oriented programming (AOP) has produced interesting language designs, but also ad hoc semantics that needs clarification. We contribute to this clarification with a calculus that models essential AOP, both simpler and more general than existing formalizations. In AOP, advice may intercept......-oriented code. Two well-known pointcut categories, call and execution, are commonly considered similar.We formally expose their differences, and resolve the associated soundness problem. Our calculus includes type ranges, an intuitive and concise alternative to explicit type variables that allows advice...... to be polymorphic over intercepted methods. We use calculus parameters to cover type safety for a wide design space of other features. Type soundness is verified in Coq....

  19. The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Eisenmann, David M

    2015-01-01

    In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

  20. Combined 15N-Labeling and TandemMOAC Quantifies Phosphorylation of MAP Kinase Substrates Downstream of MKK7 in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Nicola V. Huck

    2017-12-01

    Full Text Available Reversible protein phosphorylation is a widespread posttranslational modification that plays a key role in eukaryotic signal transduction. Due to the dynamics of protein abundance, low stoichiometry and transient nature of protein phosphorylation, the detection and accurate quantification of substrate phosphorylation by protein kinases remains a challenge in phosphoproteome research. Here, we combine tandem metal-oxide affinity chromatography (tandemMOAC with stable isotope 15N metabolic labeling for the measurement and accurate quantification of low abundant, transiently phosphorylated peptides by mass spectrometry. Since tandemMOAC is not biased toward the enrichment of acidophilic, basophilic, or proline-directed kinase substrates, the method is applicable to identify targets of all these three types of protein kinases. The MKK7-MPK3/6 module, for example, is involved in the regulation of plant development and plant basal and systemic immune responses, but little is known about downstream cascade components. Using our here described phosphoproteomics approach we identified several MPK substrates downstream of the MKK7-MPK3/6 phosphorylation cascade in Arabidopsis. The identification and validation of dynamin-related protein 2 as a novel phosphorylation substrate of the MKK7-MPK3/6 module establishes a novel link between MPK signaling and clathrin-mediated vesicle trafficking.